CORNELL UNIVERSITY
THE
lower Veterinary Library
FOUNDED BY
ROSWELL P. FLOWER
for the use of the
N. Y. STATE VETERINARY COLLEGE’
: 1897
RC
251. ©11'1909 University Library
Diseases of metabolism and of the blo
iit
Cornell University
The original of this book is in
the Cornell University Library.
There are no known copyright restrictions in
the United States on the use of the text.
http://www.archive.org/details/cu31924000242358
MODERN CLINICAL MEDICINE
DISEASES OF METABOLISM
AND OF THE BLOOD
ANIMAL PARASITES.
TOXICOLOGY
EDITED BY
RICHARD C. CABOT, M.D.
INSTRUCTOR IN CLINICAL MEDICINE IN THE MEDICAL SCHOOL OF HARVARD UNIVERSITY
AN AUTHORIZED TRANSLATION FROM “DIE DEUTSCHE KLINIK”
UNDER THE GENERAL EDITORIAL SUPERVISION OF
JULIUS L. SALINGER, M.D.
WITH ONE COLORED PLATE AND FIFTY-EIGHT
ILLUSTRATIONS IN THE TEXT
NEW YORK AND LONDON
D. APPLETON AND COMPANY
1909
Ny. 17459
COPYRIGHT, 1906, 1909, By
D. APPLETON AND COMPANY
PRINTED AT THE APPLETON PRESS
NEW YORK, U.S. A.
INTRODUCTION
AttnouGH the statement of Prof. Hoppe-Seyler that “The process of
life of the organism is, in the main, a complete mystery” is still true,
much has been accomplished by the researches of modern physiologists and
clinicians who have endeavored to find the key to this enigma. Perhaps in
no realm of medicine has labor fructified so richly as in the recent study
of metabolism. This has been of value not only in diagnosis but, even more
so, from the standpoint of treatment. It may be confidently stated that the
treatment of some diseases of metabolism, such as diabetes mellitus, gout,
and obesity, now rests on a scientific basis. This advance is almost exclu-
sively due to the labors of the modern German school of physiologists and
internal clinicians.
What is true of the pathology of metabolism may also be asserted of
diseases of the blood. The study of maladies whose etiology and pathology
were formerly obscure has now been simplified, their relations classified, and
the whole arranged in exact scientific order. The processes of blood forma-
tion and blood degeneration, while not yet forming an open book, have in
part been clearly portrayed. That therapy has not kept pace with this ad-
vance affords an opportunity for the physician of the twentieth century,
but much has already been accomplished, and many problems have been
solved. For this progress also the medical world is indebted to modern
research.
The object of this volume is to present a picture of diseases which were
formerly designated as of “obscure causation,” and to outline their treat-
ment. Tach article is the work of a master in his special field of labor.
In the translation an endeavor has been made to adhere as closely as
possible to the individual style of each contributor without the subserviency
of clearness in the text.
iti
iv INTRODUCTION
I am indebted for much valuable service in the preparation of this volume
to my secretary, Miss M. A. Clarke.
In anticipation of the fact that many points in regard to these affec-
tions will be searched for by the reader, and to facilitate this, an endeavor
has been made to add a comprehensive and full general index.
JuLius L. SALINGER.
1729 Norte 42np Srreet, PHILADELPHIA.
EDITOR’S PREFACE
We have in English no discussion of the Constitutional Diseases which
treats with any fulness the problems arising when we consider the reasons for
what occurs in these diseases.
The rationale of the symptomatology, the rationale of treatment (i.e.,
in diabetes) is here admirably set forth by clinicians each of whom speaks
with authority.
The writers have wisely confined themselves for the most part to thorough
discussions of certain points in each of the diseases considered—making no
fatuous attempt to compress a huge subject into narrow limits. They have
brought their subjects up to date and given very frankly their personal views
on the points at issue.
For the manner and for the matter of their work, therefore, we are in-
debted to our Teutonic brethren, and we are glad that the book will now find
a large circle of readers.
Ricuarp C. Cazor.
190 MarLBoroucH STREET, Boston, Mass.
LIST OF CONTRIBUTIONS
The Quantitative Analysis of Disturbances of Metabolism in the Clinic.
By W. WEINTRAUD, Wiesbaden.
Over-nutrition and Under-nutrition. By C. v. NoorpEn, Frankfort-on-Main.
Diabetes Mellitus. By B. Naunyn, Strassburg.
Diabetes Insipidus. By D. Guruarpt, Strassburg.
Gout. By W. Exsrern, Gottingen.
Obesity. By W. Exsrern, Gottingen.
Myzxedema with Special Reference to Organotherapy. By C. A. Ewatp,
Berlin.
Addison’s Disease. By L. Reiss, Berlin.
Acromegalia. By C. Brnpa, Berlin.
Chronic Articular Rheumatism. By W. His, Basel.
Pentosuria. By F. Buumenrwat, Berlin.
Blood and Blood Examination. By A. Lazarus, Charlottenburg (Berlin).
The Anemias. By P. Euriicu, Frankfort-on-Main, and A. Lazarus, Char-
lottenburg (Berlin).
Chlorosis. By E. Grawirz, Charlottenburg (Berlin).
Leukemia. By W. von Levuse, Wiirzburg.
Pseudo-leukemia (Hodgkin’s Disease and Banti’s Disease). By H. SENnaror,
Berlin.
The Hemorrhagic Diatheses. By M. Lirren, Berlin.
The Animal Parasites of Man. By E. Prtprr, Greifswald.
Important Poisons and Their Treatment. By R. v. Jaxscu, Prague.
vii
CONTENTS
TuHE Quantirative ANALYsIS OF DistuRBANCES OF METABOLISM IN THE CLINIC
Introduction
Consumption of Food in iis Healthy
A. The Laws of Nutrition
Energy Metabolism per Square Meter of Body Surface
B. The Methods for Estimating the Calory Requirement of the Body
C. The Energy Requirement of the Healthy
D. The Albumin Minimum
KE. The Requirements for Albumin begun
The Food Requirement of the Sick
The Degree of Oxidation ,
The Maintenance Diet and the Proteid Hecuhoment of the Sick :
Disturbances in the Absorption of Food
Concluding Remarks
Over-NutRITION AND UNpDER-NUTRITION .
1. Conception of the “Condition of Nutrition”
. Increase of Flesh and Increase of Fat
. Occurrence and Consequences of Under-Nutrition
. Occurrence and Consequences of Over-Nutrition
am w bv
. Indications for Hypernutrition and Hyponutrition .
A. Over-Nutrition .
B. Under-Nutrition
6. Remarks Regarding the Technic of Over Mutittton aad Und ANabiibn
A. The Technic of Forced Feeding
B. The Technic of Antifat Cures
Drasetes MELLITUS i
I. Glycosuria and Diabetes
II. The Various Forms of Diabetes; Diabetic Predisposition
III. Mild and Severe Forms: of ai Course, Symptomatology. and Com-
plications .
IV. The Theory of the Toei of Diabetes
V. Practical Therapy .
VI. Tables
Short Popular Dietetic Rules for Diabetics ;
ix
103
108
x CONTENTS
PAGE
DiaBetes Insiprpus go, Gg ye ag Cs . S 110
Symptoms and Clinical Course 112
Diagnosis . 121
Treatment : y of 38. oH. Gel SO Go ae oh. 8 is a . 339
Prophylaxis 2. 6 «© «© «© &® © #® «© «© «© «© «© «@ « 848
LEUKEMIA 3 eo my GS WBN. ree, Se mt ae Te. Es. ee, EA
Composition of the ‘Bed R. Se ote 1S , Ge: i oe Ah wm. Gn 1 48
Symptoms and Blood-Changes . . . . . . . 2. 348
Diagnosis. .. ous ke CMS a Ta. GHD cu CRE OS vei: OF 6k 371
Disgrosiss..) x. 4. -g (6 (@ GG Bobo So oe Se Go eS bs 3875
Etiology. 2s ewww BT
Course, Duration and Result . . . . . «. . . «. « . 878
WBherapy a. 4 os a oH we BL SS So ok Gn io Me 378
Banti’s Disease F sca. Ge. GL ve: Seo OR Ke ae! ve SRE Sg 381
Tue Hemorruacic DIATHESES . a ‘ . A ‘ 3 ‘ < 3 4 388
Scurvy = 4 Gh GE RS Ee oe Re de, 3888
History 2. 2. 6 8 ee eee ee 888
Etiology 2. 6 6 ete we 898
Pathological Anatomy . . - + ee ee 899
x CONTENTS
PAGE
Symptomatology . . . . ».« «© »© « »« «6 « « « 401
Diagnosis . ee a 2)
Prognosis Sb sh aah ME : #8 410
Prophylaxis and Treatment. . . . . «© © « | - . 410
Hemophilia (Bleeder’s Disease) 3 , . ‘ - 5 3 3 . 413
Pathological Anatomy OB on o> ome Gy ae ce cht, aty of 7480
Symptomatology and Course : se oR a eee . 484
Local Hemorrhages upon a Hemophilic Basis ie Tihs Ahem ae . 442
Prognosis Ba 4 : eo 8 ao Se. mo & : . 451
Treatment : , F 4 ‘ ‘ ‘ : : . 452
Morbus Maculosus Werlhofii (Purpura)
(Purpura Simplex, Hemorrhagica, Rheumatica seu Peliosis, Rheumatica
Schoenleinii) : : ‘ ; ‘ ‘ . 457
Definition 3 : P ¥ : ‘ . : . 457
Etiology . » BS oe ee pp & © o oes
General Clinical Picture : ‘ ; . : s & , a . 469
Pathological Anatomy Pe ee ee ee ee . 487
Special Symptomatology . . . . . . 2. w . - . 490
Treatment . ‘+ . ‘ : : é 7 3 3 - 496
Tue ANIMAL Parasires oF Man ; a ne ne ee A 3 . 501
Protozoa . : r : 3 5 e s ‘ : . - : . - 505
Trematodes A . : ; ; mp > ce he ca of . : - 508
Cestodes : ‘ é : ‘ * ; ‘ 2 F ‘ . 3 . 514
Prognosis . é 3 ‘ ‘ “ ‘ . 3 3 3 : 3 . 624
Therapy : ij ‘ : . F e - ‘ - 3 s : . 625
Echinococcus Disease. ‘ ga hs ‘ ; Sy ws , ‘ . 526
Symptoms ee oR wae wee GE, 58D.
Treatment : 7 2 2 . ‘ 7 3 2 5 ‘i a . 533
Echinococci of Various Organs . F R P F ‘ 7 , ‘ . 884
Nematoda, Thread-Worms : r : : : - : é a , 544
Ankylostomiasis—Uncinariasis_ . ¥ : : 5 2 e : r ‘ . 560
Arthropoda : : ike 8 Fl : 2 ‘ ‘ é : . 565
Fly Larve (Maggots) . . F - : ‘ F 5 7 3 : 573
ImporTANT Poisons AND THEIR TREATMENT . 5 . ‘ . 4 ‘ ‘ . 579
LIST OF ILLUSTRATIONS
FIG.
1. Incipient Myxedema
2. Advanced Myxedema
3. Myxedema in the stage of recovery
4. Réntgen picture showing Heberden’s nodes
5. Metatarso-phalangeal articulation with beginning chronic arthritis
6. Subcutaneous nodules upon dorsal tendon sheaths in chronic exudative polyar-
thritis .
7. Patellar cartilage after an attack of gout
8. Radiograph of hand of a gouty patient
9. Hemometer. (After v. Fleischl-Miescher)
10. Hemometer. (After Sahli)
11. Hemometer. (After Sahli)
12-13. Hemophotograph. (After Gaertner)
14. Hemocytometer. (After Thoma)
15. Microscopie picture with blood-corpuscles. (After Landois)
16. Absorption spectra of hemoglobin. (After Jandois)
17. Relapsing Fever spirilli. (After v. Jaksch)
18. Use of forceps in blood examination
19. Small copper kettle for staining solutions
20. Ehrlich’s eye-piece with iris diaphragm
21. Case of Hodgkin’s disease
22. Genealogical tree of the bleeder family oe (After Lossen)
23. Genealogical tree of a bleeder family. (After H. Gocht)
24. Genealogical tree of a family showing Daltonism. (After Horner)
25. Genealogical tree of a hemeralopic family. (After E. Ammann)
26-28. Leydenia Gemmipara. (After von Leyden-Schaudinn)
29. Trichomonas Vaginalis. (After Kunstler)
30. Balantidium Minutum. (After Schaudinn)
31. Nyctotherus Faba. (After Schaudinn)
32. Distomum Hepaticum, Linné : Re. is
33. Distomum Westermanni and ovum. (After Katsurada)
34. Distomum Spathulatum and ovum. (After Katsurada)
35. Ova of Distomum Hematobium
36. Ova of Tenia Solium
xiii
PAGE
181
182
183
247
249
252
253
254
278
279
279
280
282
282
288
291
294
294
301
373
416
417
419
420
505
507
508
508
509
510
510
512
515
XIV LIST OF ILLUSTRATIONS
FIG. PAGE
37. Ova of Tenia Saginata . 2. wwe eee
38-42, Tenia Confusa, Ward. (After Guyer) SR Oe Oe we Ce Og OTF
43. Tenia Africana. (After v. Linstow) e mp te ci 2 ch wl cee -e 4018)
44, Tenia Asiatica. (After v. Linstow) : ‘ : j , o & Js O19
45. Cercocyst from Cyprinotus Incongruens, 1900 ib -Gp “he, car oe. -2ieuold
46. Hymenolepis Lanceolata, Bloch . i 060. Se. CL Go. 520
47. Head of Hymenolepis Lanceolata, greatly enlarged a a a 520
48. Proglottid of Hymenolepis ere bie 2h . ». « §20
49. Bothriocephalus Grandis. Proglottid and ovum. (After Ijima and Kurimoto) 521
50. Tenia Echinococcus a Si GSO OS : ee m4 . 527
51. Head of Tenia Echinococcus ee im 1485 Mite Sb or . 527
52. EExpectorated Echinococcus membrane. * . , - ‘ ‘ . 538
53. Filaria Embryos 3 4 3 ‘ : a ‘ P ‘ ‘ . 547
54. Ankylostoma Duodenale é ‘ . - ; : r : ‘ ‘ r 561
55. Ova of Ankylostoma Duodenale ee ; . he MG mh & . 561
56. Larva of Ankylostoma Duodenale . ‘ e © ‘ . 561
57-58. Sarcopsylla Penetrans, Sand-flea . . . . wo oR 8 : : . 573
COLORED PLATE
Bioop CELIS . . . . . eS ‘ : Soe & Ob Facing 302
DISEASES OF METABOLISM
ess
THE QUANTITATIVE ANALYSIS
OF DISTURBANCES OF METABOLISM
IN THE CLINIC
By W. WEINTRAUD, Wrespapen
Contents: Introduction—Normal metabolism: A. The laws of nutrition;
B. The methods for estimating the calory requirement of man; C. The
normal energy requirement; D. The albumin minimum; E. The require-
ments for storing up albumin.—The food requirement of the sick: The
degree of oxidation; maintenance diet and albumin requirement; dis-
turbances of absorption of food.—Concluding remarks.
INTRODUCTION
Durine the past decade the scientific researches of internal medicine have
been made chiefly in the clinico-chemical laboratory.
Prepared and.developed by physiology, the pathology of metabolism offered
a fruitful field for study, hence it was not surprising that numerous young
investigators soon found here their sphere of activity. A flood of researches
in metabolism was the result. Clinical literature of the latest epoch bears
the lasting impress of these workers. Many interesting questions concerning
the laws of metabolism can be regarded as decided, chiefly by the theoretic
conclusions based on these clinical studies, but an eminently practical issue.
has also been attained: Based upon these fundamental laws, a rational therapy.
of nutrition has been evolved which affords an extraordinarily fruitful field
for professional usefulness.
It is interesting to recount, in extenso, the valuable discoveries which have.
come from the clinico- chemical laboratories, and have brilliantly justified,
their raison W@étre.
The problems which arose for solution, as soon as investigation passed
beyond the mere examination of urine for albumin and sugar, were manifold.
Often they led into the realm of physiology, and thus it happened that many
obscure points in the physiology of digestion and metabolism were brilliantly
illuminated by the labors of clinicians, and experimental investigation in the
clinical laboratory has especially enriched our knowledge of the physiology of
metabolism.
With energy and thoroughness, therefore, researches into the pathology of
metabolism were pursued clinically. The wards of the hospitals offered rich
material and abundant: opportunity for observing the course of metabolic
processes under abnormal conditions, and the desire to study physiological
questions at the bedside was as much promoted by stimulus from the physio-
logic laboratories of Hoppe-Seyler, Ludwig, Voit, Pfliiger, Salkowski, and
2 : 1
2 : ANALYSIS OF DISTURBANCES OF METABOLISM
Baumann as by the desire to find a key to the comprehension of pathologic
processes. ;
The practical result of these labors may be noted in the extraordinary
interest manifested everywhere to-day in modern dietotherapy. For this rea-
son it is worth while to cast a retrospective glance over the long road which has
led to this satisfactory result.
The scientific study of metabolism began when Lavoisier, in 1780, desig-
nated chemical processes in the animal economy as the source of heat accom-
panying all processes of life. He taught us that the food products in the
body utilized the oxygen breathed in with the inspired air and decomposed,
producing carbonic acid; that this process is therefore analogous to the
combustion of organic substances outside of the body, and is an oxidation
process which is the most important source of animal heat.
A long time elapsed before the discovery of the law of conservation of
energy also permitted new conceptions in the realm of biology (R. Meyer). In
opposition to the view that, besides combustion, still other independent sources
of heat were present in the circulation of the blood (friction, etc.), the opin-
ion became general that all expressions of force whiclht are recognized in the
living organism (i.e., production of heat and capacity for work) were sus-
ceptible of a uniform explanation. They originate from the energy which is
furnished the body by the food. By tireless and long-continued original
researches, Rubner proved conclusively that the law of the conservation of
energy, the correctness of which R. Meyer and Helmholtz proved in the realm
of physics, deserves proper recognition also in biology. The supply of energy
contained in the food passes through the animal body without diminution.
Thus the law of the permutation of forces, which had its origin in Lavoi-
sier’s discovery of combustion as the source of energy for the organism, was
conclusively demonstrated by Rubner.
It was an important epoch in the development of the laws of metabolism
when Justus von Liebig demonstrated the identity of the proteids of the ani-
mal and vegetable organisms in their chemical properties, and explained the
relations of the albumin products of the food to the nitrogenous products of
decomposition in the urine. We owe to him the knowledge that it is albumin,
fat, and carbohydrates which are the basis of metabolic processes. He was
the first to emphasize the fact of the unequal importance of the products neces-
sary for structural formation in the animal organism. He assumed that the
albumin introduced with the food alone reconstructs that which has been
destroyed by the activity of the body, and called albumin the plastic (tissue-
forming) food product, contrasting with it the N-free products (fat and
carbohydrates) as respiratory products. These alone, he supposed, were
attacked directly by the oxygen in the air, and by their combustion protected
the plastic products, the albumin, from oxidation.
But this theory of a division of all food products into two opposite groups
could not be maintained, and the theory of Liebig that the oxygen taken up
in respiration caused the disintegration of the food products, and that its
amount decided the degree of metabolism was also later proven to be unten-
INTRODUCTION 3
able. We know to-day that the causal relation between oxygen intake and
food consumption as accepted by Liebig does not exist, but that in the living
protoplasm of the cell exists the cause of the decomposition going on in the
organism.
Food decomposition does not take place in the blood and fluids, as was
assumed at that time, but in the tissues, where the decomposition is produced
by the chemical activity of the cells.
The type and rate of metabolism are determined neither by the presence
nor by the absence of oxygen, but only the energies dormant in the protoplasm
of the cells—energies whose multiplicity the investigations of our own times
are constantly impressing upon us.
The amount of decomposition which takes place in the cell is decided alone
by the energy requirement of the entire organism, so that the total consump-
tion of the body is made up of the metabolism of all the cells. These cells,
however, show a wonderful adjustment to the requirements of the organism,
not only quantitatively but, on account of their specific properties, qualita-
tively as well.
It is not the oxygen that by its affinity to the individual constituents of the
body dominates the chemical processes that occur there. If oxygen ruled, the
readily oxidizable substances, such as uric acid, could not be so uniformly
present in unaltered form in the excretions, while substances which are only
oxidized with difficulty, such as the fats, are completely burned. It is the
specific force contained in the protoplasm of the cells which causes the meta-
bolic processes in the animal economy.
Among these processes the splitting up of complex chemical bodies into
simpler bodies, while oxygen is at the same time taken up, plays an important
role. But besides mere splitting up, and splitting up with absorption of water
(hydrolytic dissociation), other processes of reduction and synthesis are
largely active, and occasionally all are combined in a single cell.
Hence, as Rubner maintained, life cannot be described under the general
idea of a process of combustion ; we must rather say that while life exists there
is constantly an employment of energy and a transference of the same into
other forms (activity and heat).
Physiologic and pathologic chemistry will aid us still further in analyzing
the chemical changes which occur during the processes of metabolism. The
evolution of the individual protein substances contained in the cell, and the
disclosure of their composition by the production of split-products, constitute
the one method which has been followed with success in solving the problems
here involved. But the protoplasm of the living cell and the proteid which
we have produced from it by the aid of our chemical methods are quite differ-
ent things. So also the products of decomposition which arise in the destruc-
tion of the cell protoplasm in the body are quite different from those which
we make by splitting up albuminous substance in a test tube. In the one case
dead albumin, in the other living albumin is decomposed, and as we appre-
ciate this great difference we seem to drift yet further from the solution of the
1 Hofmeister, “Chemie der lebenden Zelle,” Vortrag, 1901.
4 ANALYSIS OF DISTURBANCES OF METABOLISM
problem of life. Yet even here the ingenuity of our scientists has found a way
to probe more deeply into the cause of things, and, though still in the first
stages, the most recent investigations upon organs kept alive outside the body
(saturated with blood, autolysis) have been followed by important results
which permit us to expect more surprising conclusions in the future.
On the other hand, it must be emphasized that although our knowledge
of the chemical processes of metabolism is still comparatively primitive, the
laws of metabolism have been decidedly advanced by a more physical consid-
eration of the processes. The dynamic conception of the transition of food
products, thought out by Rubner, furnished a basis for labors in the clinical
pathology of metabolism upon which a superstructure might be raised with
ease and certainty, and upon this the imposing structure of modern laws of
metabolism in the diseased body was soon erected.
If we take this as our actual theme, we note that in the clinical ‘study of
metabolism in the last few decades quantitative investigations take precedence.
The history of this begins with the publication of E. Bischoff’s book,
“Urea as the Measure of Metabolism” (1853). The method of estimating
the amount of urea by titration, first employed by J. v. Liebig, enabled Bischoff
and Voit to undertake numerous investigations by which they determined the
laws of nutrition in the carnivora.*
Chossat had previously, by careful experiments with starving pigeons,
demonstrated the daily loss of weight and the amount of the excretions; and,
Bidder and Schmidt in their book, “The Digestive Fluids and Metabolism ”
(1852), described minutely the valuable results of their investigations regard-
ing the metabolism of carnivora (cat) under the most varied conditions of
nutrition. They were the first to relate in detail, after an investigation in
which all requirements were fulfilled, how to find in the urine and the feces
the nitrogen ingested in food in the form of meat, and upon this they founded
the law of nitrogen equilibrium.
With the aid of the elementary analysis of urine and feces, and the care-
ful estimation of the factors of respiratory metabolism which were made pos-
sible by the help of v. Pettenkofer, the study of the quantitative analysis of
metabolism in Voit’s physiologic laboratory in Munich soon attained great
technical exactness. With this came the facilities for studying the alterations
of decomposition under most varying circumstances, and particularly with
food of different nature and quantity, and thus it became possible to deter-
mine the laws of the total animal economy.
CONSUMPTION OF FOOD IN THE HEALTHY
A, THE LAWS OF NUTRITION
The estimation of the amount of food required by the healthy human organ-
ism to maintain its equilibrium has been the subject of many experiments by
Voit and his pupils.
1 Bischoff u. Voit, “ Die Gesetze der Erniihrung des Fleischfressers,” 1880.
COMSUMPTION OF FOOD IN THE HEALTHY 5
The more complete the technic, and the more ingenious the investi-
gation, the more certainly the results show that metabolism is determined
by the activities of the body (heat production and force). Then by excluding
all external factors which could increase metabolism, it is shown that the
“resting-energy ” + of metabolism is equivalent in its potential value to the
amount of heat produced. This has unquestionably been proven by Rubner’s
calorimetric investigations.
In rest, the dissipation of heat is the only avenue for loss of force. Dis-
sipation of heat, however, is a function of the surface of the body. If it
determines the ratio of metabolism in rest, this metabolism must in turn be
dependent upon the surface of the body (law of the development of the sur-
face, Rubner).
There can be no doubt that this biologic law also exists in pathology.
Where conspicuous differences in the amount of the resting-energy per kilo-
gram of body-weight exists, an attempt should be made to explain it by the
variation in the amount of’surface before we accept the view that a special
protoplasm, characterized by a more active or sluggish metabolism, plays a
role (in nurslings, in obesity, etc.).
/ TaBLe I
ENERGY METABOLISM PER SQUARE METER OF BODY SURFACE?
Calories per
Weight in | twenty-four
kilograms. | hours in one
square meter.
Atrophie child (cow’s milk)... 0.0.0... cc cece cece cent ence eee eneees 3 1090
Atrophic child (infant milk). ........ 0... cece cece cece e eee eees 3 1036
Breast-fed Child .....s.csssscaescdoasa sss ea ccer we cewwes os deseo 5 1006
Normal child (cow’s milk)...........eeceeeeeeeees Wa ailens SAA 8 1143
BOY. GDI sade ia sesasiecesd 4 ait heenteapmeme at ga daa wbvalereseuas brag ne Seacasein 26 1290
Boy; fal darsiso ss anges eacwegen Hiss edhe as ayavevasneneieio nls Deaaren meade ely 41 1279
MAD catyasnsaieieias oc's 4 aap Atbende Se guerigeaes Aaa tg ckananmmeree 493 11804
Main, aeveccameemacie 23 shu Aedes c's Fae GR een GG, os Sige RaaaE 583 10304
Matti scisa coud $4.32 e4 aoe ewe 4 6236 vA ENTS wes oe maORED 673 10664
MT iv eevaversauersiae vee Peak MORES TEATS Ea RRS P26 68 eo east 713 11164
MAT s sesisicinceeiay aie 6 808 Raj wea DIN GOT Mot wees PTS eee 993 973+
The metabolism which takes place normally in the body of a mammal when
in absolute rest, for the purpose of maintaining life, is always the same, with-
out regard to the source whence it obtains the organic material to fulfil its
needs—whether from albumin, fat, or carbohydrates.
For the maintenance of life the organic food products compensate accord-
ing to their specific energy of tension (law of tsodynamics). The amount of
energy which the individual food products contribute to the processes of
1German: Ruhewerth. ;
2 Rubner, Beitriige zur “ Erntihrung im Knabenalter,” Berlin, 1902, p. 62.
3 Weight with clothing.
4 Calculated from the carbonic acid values,
6 ANALYSIS OF DISTURBANCES OF METABOLISM
metabolism that arise from them, and by their combustion in metabolism
becomes living force, Rubner has calculated at 4.1 calories for one gram of
albumin, 9.3 calories for one gram of fat, 4.1 calories for one gram of carbo-
hydrate. :
These are the figures which are utilized as standards in all clinical inves-
tigations in metabolism (the correspondence of the value for albumin and
carbohydrate is quite accidental).
In these values force is expressed in units of the heat which is generated in
the organism when by combustion of the individual food products their end
products in metabolism are produced. The loss which occurs in the intestines
by insufficient absorption of the food is not considered here. They are, there-
fore, gross values (large calories). To convert them into pure calories, Rub-
ner has calculated a subtraction of 8 per cent. from the average heat value of
the feces on a mixed diet. His latest investigations, by means of the direct
calorimetry in man, have shown that the calculation obtained from chemical
analysis of the standard figures in derived heat corresponds almost perfectly
with the amount of heat in calories taken directly from the calorimeter. The
method commonly used in the clinic to calculate the energy transference from
the calory value of the food introduced is therefore accurate, if no severe
disturbances in absorption are present.
B, THE METHODS FOR ESTIMATING THE CALORY REQUIREMENT
OF THE BODY
The method in use in Voit’s laboratory for determining the degree of
metabolism in a healthy individual under various conditions of nutrition is
by the comparison of intake and output in a trial period of twenty-four hours.
This presupposes that the body within this time rids itself of the total end
products of metabolism that have arisen from the decomposition of organic
substances. This supposition is quite correct for excretion in the respired air
and in the urine. To estimate the contents of the feces (the discharges usu-
ally occurring later here), we need to mark in some way the beginning of the
experimental period. This is usually accomplished without difficulty and
with sufficient exactness by the administration of from 10 to 15 grams of
powdered charcoal or 0.3 gram of carmin at the beginning and at the end of
the metabolism investigation. This method in its high technical completion
was the sine qué non for the quantitative investigation of metabolism at the
bedside.
An accurate estimate of the food ingested during the period of trial and
of the carriers of energy contained in it (albumin, fat and carbohydrates) is
necessary. ‘The excretions, i.e., the urine, the feces and the expired air, are
measured with exactness, and analyzed as to the amount of nitrogen and car-
bonie acid which they contain. From a comparison of ingesta and excreta
the balance is obtained.
I shall quote an example of one of Voit’s experiments: A workman weigh-
ing 69.5 kilograms took in the form of meat, egg, albumin, milk, bread, lard,
butter, flour and sugar a total of 137 grams of albumin, 117 grams of fat, and
CONSUMPTION OF FOOD IN THE HEALTHY 7
352 grams of carbohydrate, containing 19.5 grams of N and 315.5 grams
of C, besides 2,016 grams of water. He excreted in complete rest:
In the urine... is ccncesesanseanvs 17.4 grams N., 12.7 grams C., —‘-1,279 grams water.
Inthe feces oascniosevinayecnsns 21 © Ns 145 “ OC, 83 “ water.
In the respiration............... ee 2486 “ C, 828 “ water.
Total crnseraeveadiie tes 195 “ N, 275.8 “ OC, 2190 “ water.
The body was, therefore, in N-equilibrium; excreted 174 grams of water
and retained 39.8 grams of carbon, which corresponds to a deposition of 52
grams of fat.
This method gives us knowledge of the body-albumin during the investiga-
tion. This is estimated by means of the nitrogen balance, a method which,
since that time, has come into general use.
One hundred grams of albumin contain 16 grams of N. If-the entire
amount of N due to the decomposition of albumin during the trial period
were excreted in the urine, the N figure of the urine need only be multiplied
by 6.25 to determine the amount of albumin metabolism. The other N losses
of the body are slight. A small portion appears in the feces as a residue of
the intestinal secretions and this is sufficiently large to be calculated in each
investigation. The other N losses of the body (loss of hair, scales of the
epidermis and sweat) are so insignificant that they may be ignored in a trial
period lasting twenty-four hours.
Nitrogen equilibrium is then shown when the food-N = urinary-N +
fecal-N.
Voit’s quantitative method of estimating metabolism also permits us to
recognize from the carbon balance whether the body’s need of N-free sub-
stance has been fulfilled by the food given during the trial period or not.
The organism has its very definite calory requirement. With an insufficient
administration of nourishment, the body takes a supply of energy from its
own material component parts. When, in a body previously in equilibrium,
carbon is retained or more excreted than is ingested, a corresponding accumu-
lation or loss of fat is indicated. In the form of carbohydrates (glycogen) the
body does not accumulate any great supply of energy.
In the quantitative estimation of metabolism in the clinic it has been
necessary as a rule to proceed without determining the carbon balance. This
require’ the estimation of the total CO, excretion in the respired air, which
can only be accomplished by means of a large respiratory apparatus such as
that of Pettenkofer. Such an apparatus is expensive and very difficult to
adjust. As many hours are required to make the experiment, it is incon-
venient to employ this apparatus at the bedside.
To compensate for this, the condition of the body-weight has been em-
ployed as a control to determine whether, besides the proteid requirement, a
sufficient energy supply for the needs of the organism is present in the food.
If there is little variation in the material constituents of the body (albumin,
fat and water), this is permissible, especially if the experimental period is
not too brief. Instead of trials of twenty-four hours, therefore, trial periods
of three to four days are usual in metabolism analyses of this type.
8 ANALYSIS OF DISTURBANCES OF METABOLISM
If the test is made for still longer periods, the. weight of the body alone,
with minute estimation of the energy value of the food, may enable us to
recognize the calory requirement.
Forster demonstrated in persons living under ordinary conditions the
food values just sufficient to maintain weight and to enable them to follow
their usual occupations. In numerous investigations with larger groups of
men (in barracks, in prisons and in almshouses) by an analysis of the food
ingested, valuable standards have been established for the amount of food
required by healthy persons. If the individual continues as vigorous as usual
and his body-weight remains unchanged while on a prescribed diet, the con-
clusion is justifiable that the amount of energy contained in the allotment
of food is sufficient for the requirements of the body.
As the metabolism of the body depends upon the needs of all the cells in
the body, and represents essentially a process of combustion, it is obvious
that the intake of oxygen should also be considered in estimating metabolism
in the body. But the estimation of oxygen consumption is not an accurate
measure of the total metabolism, because the same amount of oxygen, accord-
ing to whether it is utilized for the oxidation of alfumin, fat or carbohy-
drates, corresponds to different quantities of heat; also because one gram of
expired carbonic acid, according as it has been formed by combustion of one
or another food stuff, corresponds to very different degrees of heat.
Therefore, only when the nature of the food-materials decomposed in
the body remains the same are consumption of oxygen and excretion of car-
bonic acid a measure for changes in the entire consumption of products.
By means of the large respiratory apparatus of Hoppe-Seyler-Tigerstedt,
the direct estimation of all the factors of the respiratory metabolism of gases
is possible. The apparatus is difficult to manage, however, and the necessarily
long stay in the chamber of the person experimented upon makes its use
inconvenient; therefore, in the sick but few observations have been made
on this plan.
It is much easier to estimate the absorption of oxygen and the production
of carbonic acid with the apparatus of Zuntz and Geppert. In brief experi-
ments, trials are usually made by means of a mouth-piece for only five to ten
minutes, at most for one hour; the O, and CO, in the expired and inspired
air and the amount of O, intake and CO, excretion per minute are calculated
from this.
To calculate the total O, consumption for an entire day from these figures
would lead to error, on account of the great variation in the respiratory
interchange of gases from hour to hour.
Their reciprocal relation, however, furnishes the respiratory quotient,
which gives valuable information regarding the nature of the material de-
composed at the time. It approaches the value of 1.0 in carbohydrate com-
bustion, while during the combustion of albumin alone it amounts to 0.73,
and in combustion of fat to 0.7.
For the quantitative estimation of the interchanges, the enormous amount
of material gathered by Zuntz and his pupils in numerous healthy and sick
persons contributes valuable points. In absolute rest of the body, and in the
CONSUMPTION OF FOOD IN THE HEALTHY 9
intervals of intestinal inactivity, which occur from six to eight hours after
meals, the values for the intake of O, and the excretion of CO, per minute
are quite constant for any healthy individual, and in different healthy indi-
viduals they vary only within certain limits. In these “fasting values” we
have standards, variation from which in one or the other direction denotes
pathologic change.
In conclusion, direct calorimetry must be considered as the exact method
by which to determine the entire transference of energy in the resting body.
This coincides, as already mentioned, with the total loss of heat, the coinci-
dence of which with the heat-equivalent of the food stuffs consumed have
been determined by Rubner in animals by masterly experiments. In man,
and especially in the sick, direct calorimetric estimations to determine the
quantity of the total metabolism have been carried out only in isolated cases
(see below).
C. THE ENERGY REQUIREMENT OF THE HEALTHY
The quantity of food required by a workman while performing “ moderate ”
labor Voit stated to be 118 grams of albumin, 50 grams of fat, and 500 grams
of carbohydrates. This was based upon many experiences taken from daily
life, and corresponds with the results of numerous exact analyses of metab-
olism carried out, according to the method described above, in Voit’s labora-
tory (comparison of the intake and output). For a long time Voit’s princi-
ples existed almost as a dogma. Later the total calory value to which this
diet corresponds (3,055 calories), as well as the large amount of albumin
contained in it, became the subject of lively discussion, in which the clinical
investigators took a prominent part.
If the performance of muscular work increases the energy requirement
of the body above that of rest (and, in fact, it multiplies several times the
heat equivalent to the work done), the calory requirement of the “ workman”
cannot be estimated otherwise than by considering the amount of work to
be performed. The rich statistical material which is now at hand confirms
the requirement of Voit for about 43 calories (which is the amount contained
in the above quantity of food per kilogram of body-weight) for persons doing
active muscular work.
From many observations Rubner calculates as the medium amount for
a twenty-four-hour metabolism in the healthy adult, of average body size,
and weighing 70 kilograms:
Pure Calory per
calories. kilogram.
GHOSE Si cvcetaccterasdccisbes.alereue acorn Dat ee SRS See aa naelremineGrs 2,303 = 82.9
With slight muscular work............ee eee eee eee eees wine e 2,445 = 34.9
With moderate muscular work.........e cess cer ceeceeeeeeeee 2,868 = 41.0
With exhausting muscular Work.........e essere eect een e eens 3,362 = 48.0
With a deduction of 8 per cent. from the 3,055 large calories which are
contained in Voit’s amount of food, this corresponds exactly with Rubner’s
calculations.
10 ANALYSIS OF DISTURBANCES OF METABOLISM
With more justice, Voit’s requirement of 118 grams of albumin has been
the subject of dispute. In the discussion regarding this amount there has
been much difference of opinion. In their conception of the main point in
dispute, the views of different authors were diametrically opposed; and the
conflicting opinions which arose in consequence of this have kept the discus-
sion alive to the present time.
In the food of man, which consists of albumin, fat and carbohydrates,
the albumin bodies grouped in contrast to N-free substances are especially
important. While the latter may be compensated for to a great extent by
each other and also by albumin, according to the measure of their energy
value, a certain quantity of albumin-in the daily food is irreplaceable and
indispensable if the proteids of the body are to be maintained intact.
To determine this indispensable amount of albumin, the minimum which
the body requires to maintain the living substance in a functioning condition
has been the subject of much discussion.
For a time it was believed (Bidder and Schmidt) that this albumin mini-
mum corresponded with the albumin-metabolism of persons kept in a state
of starvation, i.e., that the nitrogen excretion in starvation furnishes a stand-
ard for the nitrogenous metabolism necessary to maintain life, that is, the
actual albumin requirement of the body. All the albumin absorbed from the
intestine in excess of this was to be considered “luxury,” and was supposed,
like the N-free substances, to undergo prompt combustion, in the blood without
becoming organized at all.
Among clinicians, no less a one than Frerichs upheld this theory of “ lux-
ury combustion,” propounded by C. G. Lehmann. 2
Voit opposed the “luxury” theory. In his “ Handbook of the Physiology
of Total Metabolism ” (page 269) he devotes a special chapter to contradicting
this, and furnishes convincing proofs.
According to experiments made in the dog, which of course are to be inter-
preted somewhat differently from human experiments and which in their
general application to man have been attacked by some investigators, the
smallest quantity of albumin which will maintain the nitrogenous equilibrium
of the body (on a mixed diet with N-free food substances) is usually 24 to 3
times Jarger than the nitrogenous metabolism in starvation. In their com-
prehensive experiments E. Voit and Korkunoff* still found the minimum
albumin-requirement to be 111 per cent. greater than the nitrogenous metab-
olism in starvation (and even with very large amounts of starch in the food).
It may therefore be considered as proved that if we give a dog only the
amount of proteid which is decomposed in a state of starvation, this amount
is not sufficient to maintain the nitrogenous equilibrium of the body.
In man the same appears to be true. With sufficient food, the excretion of
urea 1s increased decidedly above the starvation figures. From this experi- .
ence, and upon the basis of investigations on the nutrition of a large number
of workmen, Voit computed as a standard for any sufficient diet the above-
_ 1H. Voit and Korkunoff, “ Die geringste zur Erhaltung des Stickstoffgleichgewichtes
néthige Menge von Eiweiss,” Zeitschr. f. Biol., xxxii, p. 58.
CONSUMPTION OF FOOD IN THE HEALTHY 11
mentioned high requirement (hygienic albumin minimum in contrast to the
phystologic albumin minimum).
It appears, however, that proteid metabolism during starvation, even in
the same individual, has no constant height, at least not during the first days
of fasting. Here it apparently depends upon the composition of the food
which has preceded the experiment and on the food products retained in the
body. It is high if, in the days preceding the fast, a large amount of
albumin has been ingested, and decidedly smaller if for a long time prior to
the starvation period the ingestion of albumin has been slight. Only after
from one to three days will the nitrogen excretion in the urine, varying in
the same individual, show constant figures. This constant figure apparently
depends on the composition of the body, i.e., its albumin and fat condition.
From this, during starvation, it must make up its losses.
The source of the albumin which is so rapidly decomposed during the first
days of starvation is not, according to Voit, the albumin of the organs, but
the much more easily decomposed and soluble albumin of the fluids, the “ cir-
culating albumin.” This quantity, which is increased by a diet rich in albu-
min, also determines the proteid metabolism in the first days of starvation.
A deficiency of albumin in the food diminishes the amount of “ circulating
albumin,” and as this is dependent upon the fixed or organic albumin it indi-
rectly works mischief upon the organs.
A superfluous intake of albumin, on the other hand, increases the amount
of the readily destroyed circulating albumin in the fluids, and hence propor-
tional with the introduction of albumin there is an increased albumin decom-
position which is dependent upon the amount of circulating albumin and the
N-excretion in the urine.
The amount of albumin consumed in a unit of time in the animal body is
dependent to an astonishing degree upon the amount of the albumin ingested.
The capacity of the normal adult organism to maintain its equilibrium with
any amount of albumin—exceeding the minimum—is hardly limited (in so
far as the body’s capacity to take up albumin permits investigation). If the
energy-requirement of the organism is met by the food, the proteid of food
decomposes completely and with extraordinary rapidity. Scarcely absorbed in
the fluids, it is soon destroyed, and in the briefest time its nitrogenous cleay-
age products appear in the urine for excretion in quantities corresponding
exactly with the increased albumin intake. This fact forms one of the most
important points in Voit’s whole theory of nutrition; important both for
pathology and for physiology. Hence it became at once the spur for many
clinical investigations in metabolism.
Many endeavors have been made to explain these facts. They contradict
completely the otherwise applicable law that the amount of decomposition in
the animal body is equivalent to its requirement of energy. For Voit has
shown that with a sufficient amount of food any additional amount of albu-
min, no matter how large, is at once decomposed, so that metabolism (trans-
ference of energy) is greatly increased.
The changes in the total metabolism by variation of the intake other
than those referred to above are slight. The introduction of amounts of
12 ANALYSIS OF DISTURBANCES OF METABOLISM
food whose heat-equivalent is not decidedly above the interchange of forces
in the starving organism does not increase the total metabolism, and with a
diet beyond the amount required by the needs of the body the introduction
of extra N-free material (fat and carbohydrates), no matter how great, in-
creases the interchange of energy only to a certain percentage of the excess
of food.
If the surplus is introduced in the form of fat, only 10.7 per cent. of it
undergoes combustion; therefore almost 90 per cent. is deposited as fat in
the body. If superfluous carbohydrates are introduced, only 15.9 per cent.
goes to increase the total metabolism; 84.1 per cent. is accumulated in the
body and is utilized for fat formation, since the body’s capacity to increase
its carbohydrate material (glycogen deposit) is a limited one.*
Since the amount of metabolism is relatively independent of variations in
the ingestion of nourishment, we have the conditions which make possible a
deposition of fat.
With an abundant introduction of albumin, however, proteid decomposi-
tion increases in exact ratio to the superfluous amount of albumin ingested.
The entire superfluous supply is taken up in metabolism, and the N-excretion
in the urine shows a height corresponding to the increased administration.
In reality it is, of course, only the N-containing complex in albumin which
is excreted, and these products of excretion are at once thrown off. Of the
non-nitrogenous components which remain after excretion, as well as also
the superfluous fat and carbohydrates introduced, only a portion is subjected
to decomposition, if the organism does not require therm to meet its energy
requirements, while a considerable remainder (69.1 per cent.) is stored up in
the body (fat formation from albumin). Only the elimination of nitrogen is
complete.
For this reason albumin occupies an exceptional position among food sub-
stances; the organism requires it for its simple material maintenance. It is,
therefore, difficult to understand why the organism should waste so much of,
and so soon eliminate, this most valuable food product.
A number of explanations for this apparent waste have been offered. It
has been assumed that owing to the circulation of albumin products in the
fluids after albumin nutrition, the individual food stuffs take part in the
total metabolism. On the other hand, a special chemical affinity of the cell
substance for the individual food products has been assumed owing to the
fact that the albumin is most readily absorbed, less speedily the carbohydrates,
and last of all the fats.
Rubner* has lately assumed that the divisibility of the individual food
stuffs explains the different share taken by each in the processes of metabo-
lism. These differences in divisibility have not been sufficiently considered
until now: “A measure of these differences is the size of the molecules. In
the case of fat this amounts to 870, in grape sugar, to only 180. In what
1 This increase in metabolism by introduction of food was formerly explained by an
increase of intestinal activity. Lately the correctness of this view has been doubted.
2 Rubner, “ Handbuch der Ernihrungstherapie,” Bd. i, p. 78.
CONSUMPTION OF FOOD IN THE HEALTHY 13
form the albumin products circulate is not known. Nevertheless, the view
that albumin and allied substances are always bodies of high atomic weight,
has suffered a setback. The albumoses have a molecular weight of from 1,200
to 2,100; the peptones, however, of only about 200, similar to that of sugar.
In-a molecule of fat there are 8,170 calories, in a molecule of grape sugar
only 674, The peptones vary very slightly from the latter value. The vari-
eties of sugar and albumin, therefore, viewed from this standpoint, might
predominate in decomposition without special forces coming into play.”
Gruber * looks upon the prompt splitting up of the albumin of food as a
very necessary process, in fact as an arrangement which is quite indispensable
to rid the organism as soon as possible of the great bulk of soluble albumin
bodies which are unnecessary for its normal condition and which cannot be
utilized. A further increase in the size of the organs in the adult animal is
possible only to a slight degree after the body has reached the limit of growth
fixed by its hereditary germinal predisposition (increase of the size of muscles
as the result of body exercise). To replace the amount of organic albumin
daily destroyed a small portion of the food proteid is sufficient. As the accu-
mulation of the balance in the body would alter the function of the organs,
its immediate decomposition is absolutely necessary in order to keep the com-
position and concentration of the body fluids unchanged in spite of any varia-
tion in the composition of the food.
The prompt splitting up of the food albumin is believed by Gruber to be
the effect of the action of enzymes with which the cells of the adult healthy
organism are richly supplied. This view has much to commend it. We can
thus readily explain the enormous albumin accumulation which occurs in
convalescence from severe diseases, after prolonged starvation, etc., and is
almost independent of the administration of albumin. The absence of the
albumin-splitting enzyme in body cells that have been damaged in their
proteid constituents by disease explains the absence of that rapid splitting and
excretion of proteids which occurs in health.
D. THE ALBUMIN MINIMUM
We have seen that Voit’s requirement of 118 grams of albumin in the
daily food of an adult performing moderate labor is a practical proposition
for rational nutrition, and does not represent the physiologic albumin mini-
mum which the mature body absolutely requires to supply its functioning
organs. Incorrectly viewed, this stimulated a great number of researches in
which the starting point was the question (although it can have only the-
oretic interest), How far may the albumin metabolism be decreased without
the body suffering in any of its albumin constituents? And yet every new
investigator in the solution of this question attempts to establish a standard
and to proclaim a still lower value as the “albumin minimum.” That man
may exist with smaller quantities of albumin, and be capable of work, Voit
himself readily determined in the analysis of metabolism in a vegetarian who
1Gruber, “Einige Bemerkungen zum Eiweissstoffwechsel.” Zeitschr. f. Biol., xlii,
p. 407.
14 ANALYSIS OF DISTURBANCES OF METABOLISM
weighed 57 kilograms. Choosing his diet freely this person consumed, year
in, year out, only 54.2 grams of albumin (with 32.4 grams of pure albumin),
22 grams of fat and 557 grams of carbohydrates, and maintained the same
body-weight.
The investigations in metabolism of Hirschfeld, Klemperer, Peschel,
Kumagawa, Breisacher, and lately also of Siven and Albu, give even smaller
values as the albumin minimum. The following table is a comparative com-
pilation of the food values with which individual persons experimented upon
were able to maintain their N-equilibrium.
TABLE II
Avruon ER, | albumin. | Aibymie [tangpgelaien! Dasa
Hirschfeld..........605 73.0 35.4 0.485 47.4 8 days
Klemperer I........... 63.0 25.1 0.400 80.0 8 “
Klemperer II.......... 65.0 2676 0.41 77.2 8.
Peschel siiosecee ce ina 79.5 34.2 0.43 47.1 g «
Kumagawa ........... 48.0 37.8 0.788 51.6 9 *
Volts sansawew seaneowa 57.0 82.4 0.570 47.5 Usual diet
Breisacher ............ 57.0 51.4 0.900 50.3 30 days
LV CMs so sacer courant Reese 58.9 28.3 0.48 41.4 1 day
DU, sesso reiriniatiraseaiacagaees 37.5 43.13 0.90 37.32 5 days
The albumin interchange in the professional fasters, Cetti and Breithaupt
(calculated from the N-figures of the urine by multiplying by 6.25), gave
on the other hand: +?
CETTI. BREITHAUPT.
First day of starvation.................. 95.3 grams albumin 63.1 grams albumin
Second “ RE i curtaeel gets ohataharen ast 79.3 °“ “ 62.5 « «
Third “ EE sacar asia anetreha eens ae 82.7 “ eS 83.7 ee
Fourth “ SAAR Nee meses. 7.1 * 7 80.5 “ ss
Fifth “ SiO Speers ait daenias easel 67.4 « is 68.9 “ st
Sixth “ BES” ata, Gustine aacavantutalntss 63.6 “ ss 62.2 “ ve
Seventh “ SE etea:th duicisichamataaian trsetet 68.6 *“* ss
Eighth “ Se - aya eotrertcahioua ue nenrexeaty 56.1 “ fs
Ninth “ Ee re ee 68.2 “ ee
Tenth “ ‘i eine wade piaaemiaten 59.7“ es
Therefore, it is evident from the table that with a sufficient calory admin-
istration in food products free of nitrogen the albumin requirement may fall
far below 118 grams, and even below the metabolism under complete with-
drawal of food.
Theoretically this fact, determined by such numerous, painstaking inves-
tigations, is of the greatest scientific interest. But caution has been quite
properly enjoined upon us not to draw far-reaching conclusions from such
1“ Untersuchungen an zwei hungernden Menschen.” Virchow’s Arch., vol. cxxxi,
Suppl.-Heft, pp. 21 u. 68.
CONSUMPTION OF FOOD IN THE HEALTHY 15
tef investigations of the practical laws of nutrition. We need not, with
fliiger, assign to albumin a pre-eminent importance “as the only and imme-
ate source of muscular power,” but, for the permanent nutrition of the
ralthy and the sick, we must still insist upon greater amounts of albumin
an proved sufficient to maintain the albumin condition of the body in the
‘periments above cited.
In fact it is hardly possible to transfer the conditions of an experiment
‘practice, and to find a diet that will give a sufficient degree of energy to
ie body, that will agree, that will continuously be palatable and can be
gested, yet will contain such slight amounts of albumin as were, for exam-
e, present in the experiments of Siven.
This, however, may be seen from all of the previously mentioned experi-
ents—that the N-equilibrium can only be maintained on such a low proteid
iet when we have a sufficient calory supply. In most experiments the calory
ilue of the food reaches the amount which Voit requires for the “ medium
orker” (with nine to ten hours’ daily labor), although the persons experi-
tented upon did not perform very laborious work; in a few experiments
. decidedly exceeds this amount.
Therefore, only with a superfluous calory administration can the albumin
\etabolism be diminished to such slight values.
The calory carriers, carbohydrates and fat, are therefore albumin savers,
nd for practical nutrition this is perhaps the most important conclusion of
rese investigations regarding the albumin minimum.
E. THE REQUIREMENTS FOR ALBUMIN DEPOSITION
According to Voit’s law, the addition of albumin to a diet already suffi-
ient increases albumin metabolism to such an extent that after a few days
[-equilibrium is again reached, yet no decided accumulation of albumin
ecurs. But we should note here in the increase of the energy value of the
sod by the addition of fats and carbohydrates a process to diminish albumin
ietabolism, so that when albumin administration remains the same, albumin
eposition must be the consequence. This gives us reason td hope to increase
ae body albumin by forced feeding.
Unfortunately the energy supply contained in the superfluous food which
s utilized in albumin deposition is not very great, as is shown by Voit’s
ivestigations in the dog. With the addition of carbohydrates upon an aver-
ge 91.5 per cent., and with the addition of fats upon an average 95 per
ant. of the superfluous potential energy accumulates in the form of fat, and
nly 8.5 (or in fact only 5 per cent.) in the form of albumin. In man
ccording to the investigations of v. Noorden,! at most 10 per cent. of the
aperfluous energy supply is utilized to store up albumin in the body.
The experiments of Krug? upon himself, under v. Noorden’s direction,
1. Noorden, “ Verhandlung. der physiol. Geselschaft,” im Arch. f. Anat. u. Physt-
logie, 1893. ;
2 Krug, “ Ueber Fleischmast beim Menschen.” v. Noorden’s Beitriige z. “ Lehre vom
toffwechsel,” Heft 2.
16 ANALYSIS OF DISTURBANCES OF METABOLISM
have shown, however, that a slight accumulation of albumin day by day can
be attained by giving a food of high calory value for a long time. With food
which differed from that of the prior period (when he was in N-equilibrium)
by an increase of 1,710 calories, aloumin remaining the same, Krug retained
decided N-amounts (a total of about 50 grams in fifteen days) and, what is
remarkable, the gain during the last of the fifteen days of forced feeding
equalled that of the first days.
Liithje* has lately obtained still larger N-retention in his forced feeding
experiments in which he increased the total energy administration of the
food, like Krug, and also raised the quantity of albumin decidedly above the
requirement (albumin administration up to 380 grams with~6,035 calories).
The total,retention in twenty-six days amounted to 149.61 grams of N.
This decided N-retention within a short time, even more than the small
values formerly obtained, raised doubts as to whether the N aa in the
body actually indicated a gain in “ flesh.”
Voit has never regarded the N-retention obtained by forced feeding as an
increase of “organic albumin”; he held the view that the albumin saved
under the influence of nutrition remained in the circulation until it was
changed into organic albumin by the slow production of new tissue. As,
however, under the influence of hypernutrition, the plasma of blood and
lymph does not, so far as we know, become richer in albumin, v. Noorden
proposed the hypothesis that the albumin which is saved, and not yet utilized
for the structure of new tissue, is retained as a dead mass in the living proto-
plasm of the cells, analogous to the superfluous glycogen and fat, remaining
there as “reserve albumin,” though with decidedly different conditions of de-
composition than are present in organic albumin. Correspondingly, he
draws a sharp distinction between increase of “reserve albumin” and in-
erease of muscle (by which he understands the increase of living cell albumin).
He believes the latter to be a result of the specific growth energy of the cells,
a function of cellular labor, and not a result of extra nutrition since, as we
have seen, hypernutrition increases only the reserve albumin.
This hypothesis of v. Noorden’s is not in agreement with Pfliiger’s? view
regarding the meaning of the reserved and deposited albumin. In the latter’s
numerous publications on the subject, he maintained that the accumulated
albumin is soon deposited as cell substance in the body of the animal, and
therefore at once takes a prominent part in the total metabolism. Pifliiger
does not regard it as a dead cell inclusion, but as a “ working mass,” and he
also thus explains the increase of albumin metabolism which occurs after
proteid administration as an increase of the “ working cell substance,” upon
the amount of which, in his opinion, the total metabolism is directly de-
pendent.
1 Liithje, Beitrage zur “ Kenntniss des Eiweissstoffwechsels.” Zeitschr. f. klin.
Med., xliv, p. 21.
2 Pfliiger. Arch. f..d. ges. Phys., Bd. lii, p. 1. “ Ueber einige Gesetze des Kiweiss-
stoffwechsels,” Bd. liv, p. 333. “Ueber den Einfluss, welchen Menge und Art der
Nahrung auf die Grésse des Stoffwechsels und der Leistungsfihigkeit austiben.”
Pfliiger’s Arch., Bd. lxxvii, p. 425.
CONSUMPTION OF FOOD IN THE HEALTHY 17
But the enormous amount of N-retention in the forced feeding investi-
ulions of Liithje makes us hesitate to believe that the total amount of
itrogen retained is really deposited as “albumin,” especially as we should be
yrced to assume at the same time that the reserved albumin is deposited
gether with a quantity of water, such as corresponds to the usual relation
atween albumin and water in the cellular elements of the body (one gram
f N = 6.25 grams, albumin = 29.4 grams of flesh).
According to this we should have to suppose that the N-retention of
49.61 grams N, which was attained by Liithje within twenty-six days, corre-
sonded to an albumin deposition of 935.06 grams of albumin, or a flesh
eposition of 4,398.53 grams. The increase in the body-weight of the person
xperimented on amounted to 6,070 grams during this time. If we estimate
ae flesh accumulation from the N-retention, more than two-thirds of the
acrease in body-weight (4,398 grams) must have been due to flesh deposi-
on. The considerable calory excess contained in the administration of food
1 the days in question certainly must have resulted in a deposition of fat.
‘he amount of this Liithje calculates in the usual manner; from the total
alory excess during the entire period (29.656 calories) he deducts the calory
alue of the albumin which has accumulated (935.06 X 4.1), i-e., in round
umber 3,838 calories, and the remainder, amounting to 25.818 calo-
ies, is ascribed to fat accumulation. Twenty-seven hundred and seventy-six
rams of fat correspond to this energy value. ‘The flesh accumulation of
,398 grams, and a simultaneous fat deposition of 2,776 grams coincide
ery imperfectly with an increase in weight of only 6,070 grams. This may,
owever, be readily explained by the assumption that the body during the
iasting period lost a weight of water, corresponding to the difference (1,104
rams).
Te ae feeding experiments of Krug, the same difference was noted.
Vith an increase in weight of only 3,100 grams, the albumin accumulation of
,455 grams calculated from the retained N, and the fat accumulation from
ae calory excess after deducting the albumin calory, amounted to 2,254
rams. Krug assumed without more ado that the body lost 609 grams of
‘ater.
This assumption is certainly justifiable, and a decrease in water during
orced feeding appears quite plausible if we remember that each increase of
1e albumin metabolism (for example, by a large albumin meal) is soon fol-
ywed by a decided excretion of water.
In my opinion the assumption of so large a loss of water is, however, unnec-
ssary. In the previously mentioned calculations, we have always proceeded
o the assumption that the total calory excess of the food not used to store
p albumin must be utilized in fat formation. It has, however, not been con-
dered that an excess of food also invariably increases the total metabolism,
ad, it may now be supposed, increases this out of proportion to the intestinal
bor. A true luxury consumption of non-nitrogenous food substances takes
lace. Only a portion of the superfluous food energy is utilized in accumu-
ition; in man another portion, probably showing individual variation, under-
oes combustion, and is utilized in heat production, the organism replying
3
18 ANALYSIS OF DISTURBANCES OF METABOLISM
to this increase by an increased excretion of vapor. In the investigations in
forced feeding, the fat accumulation, which can only be controlled by an
accurate estimation of the carbon balance, may also be less than authors have
assumed, judging by the caloric excess in the food.
In such a profuse N-retention, the supposition that the accumulation of
nitrogen-containing end products of albumin metabolism may play a réle
appears to be quite unwarranted for the reason that there are no sufficient
proofs that N-containing products of intermediary albumin metabolism re-
main as such in large quantities in the body of the healthy. The view is
much more likely that the N is retained as albumin, and that this albumin
(as a native molecule, however, and without a corresponding participation of
water) enters the cell. As evidence of this Ltithje points to the observation.
that in certain snails albumin is found included in the cells in a crystalline
form.
It seems to me, however, that there is one phenomenon—which appears, so
far as I am aware, in all investigations regarding albumin accumulation if the
analyses in question are carried out—and which goes to show that the albu-
min accumulated in the protoplasm of the cells increases and rejuvenates it
while assimilating itself with the general cell albumin. I refer to the simul-
taneous retention of phosphorus when N is retained, and its increased excre-
tion (as P,O,) during albumin decrease. This is shown in the investigations
of Kayser, and of Jacob and Bergell. It may be recognized also in Liithje’s
metabolism figures, and only lately Kaufmann has called attention to the
decided phosphorus retention which he observed during albumin accumulation
in feeding with egg albumin. The fact that any phosphorus containing albu-
min body especially favors albumin accumulation (as was shown by Réhmann
and his pupils, and also by Zuntz and Caspari) favors this view.
Quite an analogous N-retention (which probably no one will doubt means
an albumin accumulation) Rost* has observed in his metabolism control
experiments in growing animals.
The amounts of nitrogen of the food which were not excreted in the urine
and feces of three young dogs were decidedly greater than could be accounted
for by the increase of body-weight, if the N-accumulation were reckoned in
the formation of muscle albumin. Therefore, as in the investigations of
Liithje, either a loss of water occurred or the retained nitrogen was utilized
to build up a cell protoplasm with higher nitrogen contents than are found in
muscular substance.
When it became necessary, in forced feeding experiments in animals with
meat free of fat, to promulgate a formula for the N-accumulation (Pfliger,
Cremer) certain difficulties naturally arose. The amount of carbon retained
in the organs was greater in comparison with the nitrogen than would corre-
spond to the composition of albumin.
If, with Pfltiger, we reject the possibility of a fat formation from albu-
min, although accepted by Voit’s adherents, we must be content with assum-
1 Rost, “Zur Kenntniss des Stoffwechsels wachsender Hunde.” Veréffentlichungen
des kaiserl. Gesundheitsamtes, Bd. xviii, p. 206.
CONSUMPTION OF FOOD IN THE HEALTHY 19
“unknown tissue-building substance,” and refer the N-retention to its
umulation.
No matter in what form the nitrogen accumulates in the body in forced
Jing, all authors seem to be unanimous in the opinion that the organism
eives a valuable addition.
For this reason, we shall enumerate again the methods which lead to an
rease of the body albumin.
We see N-retention without any increase in the administration of
rogenous foods when we give a calory excess of N-free substances (Krug),
1 a still more decided N-accumulation when the food contains both an
essive calory value and an excess of albumin (Liithje).
That an excess of albumin alone in an adult healthy person without de-
ed increase of the albumin-saving fats and carbohydrates could bring about
albumin accumulation (apart from the slight N-retention in the first
7s, until N-equilibrium is attained) has been looked upon as impossible,
cording to Voit’s principles. Only special circumstances (growth, con-
escence, diminution in body albumin from preceding starvation) would
ke it possible permanently to accumulate albumin in this way.
Bornstein,t however, lately showed in an experiment on himself that it
sossible in man by an increased administration of albumin alone to produce a
lited increase of the albumin contents of the body. By adding to his diet
grams of nutrose daily he accumulated in fourteen days 16 grams of
= 100 grams of albumin, just as, in Pfliiger’s experiments in feeding adult
imals (dog and cat) with fat-free meat, a decided increase in weight was
»duced by flesh deposition. And as Pfliiger looks upon the increase of the
tumin mass of the body as an increase of power, so Bornstein looks upon
» N-accumulation as a sign of a previously sub-standard value of his mus-
lar and albumin apparatus, which was then improved by a deposition of
mumin.
It is an interesting fact that stock raisers * to-day also believe it possible
bring about a production of flesh, in a restricted sense of the word and
der certain circumstances, in adult animals to a more decided extent than
s formerly thought possible. They regard an increased accumulation of
yvumin in the body of the adult animal as decidedly improving the quality
the meat—an improvement which does not depend upon an increase in
iscle bulk or new formation of muscle fibers, but is due to an increase
the juices in which the muscular fibers are bathed.
For the physician these views regarding muscle food are very interesting,
ismuch as it is often necessary for him to treat persons below par in their
iscular activity. In cases in which a further accumulation of fat is never
sirable (anemia, neurasthenia, etc.), Bornstein’s advice to adopt forced
ding with a decided addition of albumin is certainly worthy of considera-
1 Bornstein, “ Ueber die Méglichkeit der Eiweissmast.” Berliner klin. Wochenschr.,
48, vol. ix, p. 791. -
2 Henneberg und Pfeiffer, Journal f. Landwirthschaft, Bd. xxxviii.
20 ANALYSIS OF DISTURBANCES OF METABOLISM
tion. It increases the albumin contents of the body, and also the albumin
decomposition. We know that a man called on to perform work beyond the
usual amount always prefers a diet rich in albumin (the average albumin
metabolism in athletes is about 200 grams of albumin) * and this coincides
perfectly with the views of Pfliiger that, “increased albumin decomposition is
combined with that increased vitality which in the struggle for existence gains
the victory.” ?
More exact and recent investigations in metabolism show that the general
tendency of working organs to attract albumin and to retain it for their
growth is seen in the highest degree in the muscles. Caspari* studied a dog
that, with a certain diet, was in N-equilibrium, yet, with precisely the same
food, continuous N-accumulation occurred when the dog was daily subjected
to considerable muscular exertion. Bornstein* was able to show that the
accumulation of albumin attained by him with the addition of a larger
amount of albumin to an already sufficient diet could even be increased by
daily muscular exercise in moderation (without work about 16 per cent. of
what is ingested is accumulated; with moderate labor about 22 per cent.). He
therefore speaks of a true labor hypertrophy of the muscles, and the investi-
gations in metabolism carried out upon a large scale by Atwater and Bene-
dict ® confirm this view. Without increasing the nitrogenous food of their
experimental persons during the period of labor, they produced an accumu-
lation in albumin (in contrast to an N-loss in the period of rest), although in
the period of labor the additional calories were given wholly in the form of
carbohydrates without any additional albumin.
It is of course obvious that this labor hypertrophy has its limits. Even
with continuous muscular work, an increase of albumin in the food, which
* is also limited by the person’s digestive capacity, will not force a continuous
accumulation of muscle. A condition of equilibrium is attained in which,
however, the body now controls more organic working albumin than formerly,
and possesses increased vitality.
For the treatment of the cases (constantly multiplying in our time) in
which diminished capacity for work is one of the most prominent symptoms,
these new studies in metabolism contain the most valuable hints. For who
will maintain that every patient who comes to us with a body-weight corre-
sponding to his age and his size controls an amount of the organic substances
used in metabolism which corresponds to his maximum or even to his
optimum ?
With the recognition that we can build flesh by the simple addition of
albumin to the food (a point on which Pfliiger’s views and Voit’s teachings
1 Lichtenfeldt, “ Ueber d. Niihrstoffbedarf b. Training.” Pfliiger’s Arch., Bd. Ixxxvi,
p- 177.
2 Pfliiger’s Arch. f. d. ges. Physiol., Bd. i, p. 319.
3 Caspari, “ Ueber Eiweissumsatz und Ansatz bei Muskelarbeit.” Pfliiger’s Arch.,
Bd. Ixxxiii, p. 6509.
4 Bornstein, “ Kiweissmast und Muskelarbeit.” Pfliiger’s Arch., Bd. Ixxxv, iii, p. 540.
: 5 Atwater and Benedict, “Experiments on the metabolism of matter and energy
in the human body.” Washington, 1899. Quoted by Caspari, loc. cit., p. 539.
THE FOOD REQUIREMENT OF THE SICK 21
are sharply contrasted), the saving of albumin by a superfluous calory addi-
tion is not divested of its therapeutic importance. Where a simultaneous
accumulation of fat is not undesirable, this high calory diet will, as a rule,
be the easiest way of accumulating albumin. But here we should always
remember that muscular work is an important auxiliary means of fixing the
retained albumin in the organs of the body, and that a simultaneous high-
proteid diet is not superfluous or even unnecessary. (See the considerable
albumin accumulation in the investigations of Liithje.)
That it is not immaterial in saving albumin whether the calory surplus is
brought about by fat or carbohydrates in the food was shown long ago by
the investigations of Voit and Rubner. Clinical researches in metabolism
have confirmed this. In Kayser’s? researches albumin was lost when he
replaced the carbohydrates by an isodynamic amount of fat, and Tallquist *
also demonstrated that the carbohydrates were capable in a higher degree than
fat of protecting the albumin of the body from loss.
To understand these differences, which apparently cannot be reconciled
with the laws of isodynamics, it is well to remember the experiments of Rubner,
according to which the different food stuffs (in equal excess) increase the
interchange of energy very differently because they are utilized in quite vary-
ing amounts, the fats undergoing combustion in metabolism, less so than the
carbohydrates.
In the practical therapy of nutrition this preponderance of the carbo-
hydrates in comparison with the fats as albumin savers must not permit us
to abstain from the plentiful use of fat for the purpose of saving albumin,
especially in those cases in which carbohydrates are not allowed, i.e. in
diabetes. And since we see here that with an exclusive albumin fat diet
(without immoderate excess of albumin) diabetics are able to preserve their
albumin condition with a relatively slight administration of fat calories, we
might almost believe that the fats under certain circumstances may almost
equal the carbohydrates in their albumin-saving effect. In the very plentiful
use made of fat in modern dietetics we see further evidence of this.
THE FOOD REQUIREMENT OF THE SICK
For all physicians a fair comprehension of the total food requirement of
the diseased organism is the best foundation in prescribing a suitable diet.
Modern nutritive therapy no longer limits itself to the prohibition of this or
that food. It expresses positive opinions in ordering the diet, both as regards
the nature and the quantity of the food.
Only in diseases which run a rapid course may the amount of food con-
sumed be for the time disregarded. Here real starvation may be necessary on
1 Kayser, “ Ueber die Beziehungen von Fett und Kohlehydraten zum Eiweissumsatz
des Menschen.” Diss., Berlin, 1893.
2 Tallquist, “ Zur Frage des Einflusses von Fett und Kohlehydraten auf den Eiweiss-
umsatz des Menschen.” Arch. f. Hygiene, Bd. xli, p. 177,
22 ANALYSIS OF DISTURBANCES OF METABOLISM
account of the altered functions of the stomach and intestines, and we may
make up our minds regarding the quantity and choice of the food, quite inde-
pendently of the actual food requirements of the body.
In convalescence from such maladies and in all protracted diseases, how-
ever, the quantity of the food is important. A proper appreciation of this
in the dietetic treatment of chronic diseases will give the physician his best
results.
The appetite which normally regulates the quantity of nourishment in-
gested, so that metabolism is always exactly covered in spite of all variations
in regard to amount, is no measure for the amount of food required by the
sick. Appetite is no guide when wasting diseases increase the food require-
ment of the body; appetite is equally deceptive when excessive corpulence
makes it imperative to bring about a reduction of the body-weight.
Only an exact knowledge of the amount of total energy metabolism, the
sum of the energy which the body requires and utilizes in the special case,
is a guide to the physician for his dietetic orders in respect to quantity.
THE DEGREE OF OXIDATION
Regarding the degree of metabolism in disease, clinical researches in the
last few decades have given us definite figures.
Without a knowledge of the amount of nourishment consumed, and with-
out a proper consideration of the energy values contained in it, mere observa-
tion at the bedside, and the analysis of the excretions in the urine exclusively,
have frequently led to entirely erroneous conclusions. French literature re-
garding azoturia, and the writings of Bouchard regarding the slowing of
metabolism, contain numerous examples of this fallacy. Increase or slowing
of metabolism had been frequently assumed in. cases in which later control
experiments in metabolism proved the contrary. When the exact methods of
the German physiological schools (Voit, Pfliiger, Zuntz) were employed in
the analysis of the processes of metabolism in the diseased organism the for-
mer conclusions were reversed. In spite of this, we cannot yet claim clear
insight into many pathologic conditions, but we may nevertheless say that
many deeply rooted errors have been corrected by the methodic quantitative
labors of our clinics.
Metabolism in the normal human adult, in complete rest, amounts to
about one calory per kilogram of body-weight and per hour; therefore with a
weight of 70 kilograms, in twenty-four hours it is 1,680 calories (= 24
calories per kilogram). Even with the ordinary exertion of daily life a
decided increase occurs (from about 2,450 to 3,000 calories, ie., 35 to 42
calories per kilogram). Increased ingestion of food, bodily exercise (muscu-
lar labor) and the unavoidable giving off of heat while exercising are the
factors to which this increase of transference may be attributed. The amount,
the time limits and duration of the increase of metabolism resulting from
exercise in healthy persons have been for this reason closely studied.
The hope that differences in the rate of interchange of force in the well
and the sick while at rest could be measured by the estimated intensity of
THE FOOD REQUIREMENT OF THE SICK 23
oxidation (O, decomposition and CO, excretion) which characterizes individ-
ual pathologic conditions has only been fulfilled to a slight degree. On the
other hand, later researches have furnished proofs that the healthy and the
sick differ in the reaction of their organism to influences that increase metab-
olism (administration of food, work performed, and the amount of heat
given off).
To appreciate these differences, the physiology of metabolism must be
briefly considered.
The increase of the processes of oxidation and of heat production, under
the influence of the intake of nourishment, which may be subjectively noted
in a certain feeling of warmth, has been directly measured by calorimetry.
The factors of the respiratory metabolism have also been indirectly con-
trolled.
If a dog’s food is increased upon three different days to 55 per cent.
above its previously determined calory requirement by administering iso-
dynamic amounts of albumin, fat and carbohydrates, its elimination of heat
upon the albumin day rises 19.7 per cent., upon the fat day 6.8 per cent.,
and upon the carbohydrate day 10.2 per cent. (Rubner).
This coincides exactly with the figures which Magnus-Levy ! obtained in
his numerous analyses of the interchange of gases after the administration
of particular foods; he has referred to these in his valuable dissertation on
the influence of nourishment upon respiratory metabolism. He also deter-
mined that the three principal food products increase CO, excretion and O,
consumption in very different degrees. The proteids again take the first
place; they increase the intensity of oxidation from 50 to 60 per cent.; then
follow the carbohydrates, after the administration of which the interchange
of gases is only increased 35 per cent. above the point reached when the stom-
ach is empty; finally the fats, which, if administered in amounts that do
not exceed the normal requirement, scarcely increase the consumption of O,
in man at all, and in the dog increase it only about 10 per cent.
Investigations in man with a freely chosen diet make the increase of
metabolism after a meal very apparent. In the first four hours after break-
fast the O, intake, in comparison to that in a condition of rest, is increased
21, 37, 22 and 10 per cent.; in the first five hours after the midday meal 364,
30, 20, 18 and 18 per cent., and in the first three hours after the evening
meal 33, 31 and 18 per cent. According to this, the increase of the inter-
change of gases for a whole day, in consequence of the administration of
food, amounts to 13 per cent. of the O, intake, and 19% per cent. of the CO,
excretion.
Hosslin found similar figures which are the basis of Voit’s investigations
in metabolism, and if the body’s requirement does not decidedly exceed the
intake of nourishment, we are generally right in counting about 10 per cent.
as the increase of the oxidation processes due to this cause (Zuntz).
That this increase of oxidation is due principally to the increased labor
1 Magnus-Levy, “Ueber die Grésse des respiratorischen Stoffwechsels unter dem
Ejinflusse der Nahrungsaufnahme.” Pfliiger’s Arch., Bd. lv, p. 1.
24 ANALYSIS OF DISTURBANCES OF METABOLISM
of digestion, and that with a superabundant nourishment these increases in
metabolism can be pushed still further, was for a long time the predominant
view (Zuntz and y. Mering). Yet lately authors have come more and more
to the conclusion that the increase in the labor of the digestive organs is not
sufficient to explain the heat production after intake of nourishment. Inves-
tigations on this point have been carried on in patients, and have shown
that the increase in metabolism produced by the administration of food
is very much greater in some individuals than in others. These results have
increased our doubts regarding the correctness of this prevalent opinion (see
below).
Physiologists have determined the increase of metabolism after physical
exertion even more minutely than that following the introduction of food.
The promptness and delicacy of the changes in the amount of oxidation
after muscular labor are almost astonishing.
Increase in the peristalsis of the smooth musculature of the intestine
after the introduction of mineral salts and after the administration of food,
changes of the mechanism of respiration, unconscious muscular effort in
strained positions of the body or when the temperature of the skin is reduced,
all of these factors influence very notably the interchange of gases. Of course
a much more striking variation becomes apparent in tests with muscular activ-
ity of a type which can be mechanically measured.
Regarding the degree to which the process of oxidation may be increased,
when the amount of work is increased, Zuntz and Katzenstein have given us
exact figures. It is an absolute law that O, consumption and CO, formation
increase with the amount of muscular labor. Accordingly, the interchange
of gases is greater when the individual is standing than when he is in the
recumbent posture. The increase is slight if the person is standing in a com-
fortable position; it amounts to about 20 per cent. of the “rest value” if
the person is standing erect as in military drill.
In walking the consumption of products becomes from 2 to 4 times as
great, according to the rapidity of the pace; in rapid hill climbing it is 5
times as great as the normal, and even more.
Proportionally to the interchange of gases the heat production is increased
by work (in comparison to rest values), as Atwater and Benedict have deter-
mined by direct calorimetry. About two-thirds of the energy set free by
increased decomposition is utilized in heat production, and under ordinary
circumstances only one-third in mechanical work. (Under the influence of
practice the utilization of energy for the performance of labor may increase
just as it diminishes under the influence of exhaustion. )
These are the values which have been estimated in the healthy. As to
the way in which labor increases the total metabolism in disease, and how
much useful energy in the shape of chemical activity the diseased body gets
from the increased decomposition and from the utilization of its own muscles,
only very isolated reports are at hand.
From the reply to these questions, conclusions in regard to pathologic
metabolism will inevitably result,
THE FOOD REQUIREMENT OF THE SICK 25
The question most discussed has been whether the effects of cold and
heat decidedly increase the processes of combustion in the body. That remain-
ing in a cold atmosphere produces a great loss of heat will scarcely be doubted,
and in the endeavor of the body to maintain its own temperature a decided
loss in heat in consequence of cooling cannot be prevented, at any rate not
without an increased consumption of its combustible material. The ques-
tion to be chiefly considered is, whether the irritation of cold upon the sur-
face of the body produces chemical changes in the interior, and thus directly
increases the intensity of combustion. Speck disputes this, and considers
that some physical regulation is responsible for the preservation of body tem-
perature by limiting the loss of heat to the slightest amount. In his opinion,
the involuntary muscular contractions which result as the effect of cold are
the cause of the increase in the interchange of gases which has been observed.
As a matter of fact, Loewy,! in his investigations of the influence of cold
upon the respiratory metabolism, was unable to determine an increase of O,
consumption in all cases of intelligent persons who understood their bodily
functions and who maintained completely flaccid muscles during the investi-
gations. This corresponds with the experience of Wolpert, which is of prac-
tical importance, that “the temperature of the air of the work-room, during
work within the limits of 5° C. and 25° C., exerts no especial influence upon
the degree of CO, excretion, either during rest or during strenuous corporeal
labor.” (In contrast to this are the views of Liebermeister, according to
whom the heat loss from the effect of cold causes directly an increase of heat
production.)
Regarding the increase of oxidation processes which are generated by the
action of heat upon the body, when the conduction of heat by evaporation is
prevented, we have some interesting figures obtained in the experiments on
the respiratory metabolism which v. Mering had performed in his clinic by
Winternitz,? Lohse,’ and others. In contrast to the decided increase of oxida-
tion produced by the hot-water bath, as shown by these investigations, the
effect of a hot-air bath upon metabolism is quite insignificant in consequence
of a prompt physical regulation (sweating) (Salomon).+*
According to the few researches at hand (Schattenfroh,> Wolpert *) we
may assume that the influence of heat and cold in the metabolism of the sick
is quite different from that in the healthy. In the obese, for example, at least
1A. Loewy, “ Ueber den Einfluss der Abktihlung auf den Gaswechsel des Menschen.”
Pfliiger’s Arch., Bd. xlvi, p. 189.
2H. Winternitz, “Ueber den Einfluss heisser Bader auf den respiratorischen Stoff-
wechsel.” Klin. Jahrbuch, 1899, Bd. vii—‘ Ueber die Wirkung verschiedener Bader
auf den Gaswechsel.” Hab.-Schrift, 1902, Nauenburg.
3 Lohse, “ Ein Beitrag zur Lehre von der Einwirkung des heissen Bades auf den
menschlichen Stoffwechsel.” Diss., Halle, 1900.
4 Salomon, “ Ueber die Wirkung der Heissluftbider und elektrischen Lichtbider.”
Zeitschr. f. didt. u. physik. Therap., Bd. v, Heft 3.
5 Schattenfroh, ‘“ Respirationsversuche an einer fetten Versuchsperson.” Arch. f.
Hyg., Bd. xxxviii, p. 93.
6 Wolpert und Broden, “Respiratorische Arbeitsversuche bei wechselnder Luft-
feuchtigkeit an einer fetten Versuchsperson.” Arch. f. Hyg., Bd. xxxix, p. 298,
26 ANALYSIS OF DISTURBANCES OF METABOLISM
under certain circumstances, the regulation is quite different from that in the
lean person. In the latter, the greatly increased heat produced by hard
physical exercise may be completely removed by radiation and conduction;
in other words, by increasing the temperature of the skin, and this is attained
by increased activity of the circulation of the blood. In the obese this method
is unavailing, and the secretion of sweat must vicariously take the place of
the insufficiently active blood-current. Even in rest and in sleep, the obese
person, particularly in a very warm atmosphere, throws off more moisture in
a humid atmosphere than in a dry one. As regards the endurance of high
temperatures the person with great deposits of adipose tissue is easily over-
come, even in rest, and especially so on exertion. Besides the insensible per-
spiration which must be counted in heat regulation, the obese loses greatly
by the sensible perspiration which exudes from the skin, and there is no doubt
that as a result of this his metabolism (through changes in the blood com-
position) is very different from that of the lean individual when exposed to
changes of temperature.
The numerous and practical methods given us by physiology for estimat-
ing the degree of oxidation in health make it obvious that pathologic condi-
tions should be studied and classified from the same point of view: Is the
intensity of the processes of combustion increased or diminished, or unaltered ?
It is well known that Bouchard+ has described an important group of
diseases (diabetes, obesity, gout) as the consequence of a “slowing of metabo-
lism,” and lately has extended the scope of this disturbance of metabolism
still further so as to include in this group other pathological conditions.
Formerly such facts as the increased excretion in the urine of incomplete
products of combustion (uric acid, oxalic acid), maintenance of life on a
lessened amount of food, the deposition of fat with a normal intake of food,
decrease of body temperature at rest, etc., led him to ascribe the condition
to a slowing of metabolism. To-day he attributes to a “slowing of metabo-
lism” any disease which is shown by statistics to occur frequently in asso-
ciation with diabetes, obesity, or gout, or which he supposes to have a genetic
relationship with these diseases.
Such a division, justified perhaps from the standpoint of clinical inves-
tigation, has absolutely no foundation in exact quantitative analyses of metabo-
lism. Where exact analyses have been carried out we find diseases grouped in
an entirely different manner. In quite a number of pathological conditions
which are to be considered here, we have exact analytic data concerning the
intensity of the processes of oxidation and it will be interesting to consider the
results from this standpoint.
1 Bouchard, “Troubles préalables de la nutrition in Traité de Pathologie générale,”
Tome iii, p. 179.
THE FOOD REQUIREMENT OF THE SICK 27
In the following table, the “rest values” for O, consumption and CO,
excretion, in various diseases, have been compiled.
DISEASE.
Oa.
per min.
c.c.
AUTHOR.
Fasting and Rest Value:
Healthy Individuals Minim. ..
Healthy Individuals { Minim. . .
Healthy Individuals } AiO:
Max.....
Healthy Man (average from
AL, CPI AlS) ois se asscrepdsaglerd vee sue
Graves’ Disease..................
Very severe case .............,
Acute case........ ise sbudsoterecduecens
Graves’ Disease, 26 years (4 trials).
Graves’ Disease, 24 years.........
Before Thyreoid-Gland Feed-
ing, 124 kilograms...........
During Thyreoid-Gland Feeding.
Before Thyreoid-Gland Feeding. .
During Thyreoid-Gland Feeding.
Myxedema....... cscs eceeeeeuee
After Thyreoid-Gland Feeding.
Fever: long-continued.........
Second Week of Enteric Fever...
Pneumonia (inc.)..........0. 000s
Enteric Fever: ;
6. Ne 89.8% 6. 52 .ccncaten oo seeas’
6 aC eee ee
Enteric Fever:
14, TX. 366 cccaceeee esas eaws
18: TX; SO6Gesicose ce eve saa:
Pneumonia:
28. VIII. 86.1°.............64.
Tub. Pulm.:
20, VIN 872 cues ees ae wies
22, VILL. 87.2" eas sa cceees aes
Enteric Fever Convalescence :
Ath Day of Convalescence......
13th Day of Convalescence.....
30th Day of Convalescence.....
Enteric Fever Convalescence :
18th Day of Convalescence.....
35th Day of Convalescence.....
Pneumonia-Convalescence :
1th Day... ..... cece eee eee
3.27
4.40
3.89
6.64
Pe RoR CHOI Ww CoCo
— Zeitschr. f.
5
Owe,
eo
co ee owe mo wo we Oy ee wow RoW W WH WWR HF CP
Oe wo 29S CH OD HO OW PRO WE
| Geppers Arch, f. exp.
Pathol., Bd. xxii, p. 367.
t Katzenstein, Pfliiger’s
Arch., Bd. xlix.
| Kraus, Zeitschr. f. klin.
§ _ Med., Bd. xviii, p. 21.
Magnus - Levy, Pfiliiger’s
Arch., Bd. lv, p. 23.
klin. Med., xxxiii, p. 294,
Stive, Arb. aus. d. st. Kran-
kenhaus Frankfurt a. M,,
1896, p. 47.
Thiele u. Nehring, Zeitschr.
f. klin. Med., xxx, p. 47,
t Stiive, loc. ctt., p. 45.
Magnus-Levy, Deutsch.
med. Wochenschr., 1896,
p. 492.
Fall 5) Kraus, Zeitschr. f.klin.
Fall 6 }
Fall 2.
Fall 3.
5
Med., xviii, p. 177.
Riethus, p. 240.
| Svenson, Zeitschr. f. klin.
Med., xxxvi, p. 94,
foe)
28 ANALYSIS OF DISTURBANCES OF METABOLISM
Os | COs, Respir. A
, min. er min. : UTHOR.
Wee eres P c.c. Quotient.
Diabetes:
1. Severe case...... 0.6.0 eee ee 4.06 3.14 U7
2. Very severe case........-46- 4.54 2.97 66 :
8. Very severe case..........-- 3.99 2.71 .68 Leo, Zeitschr. f. klin. Med.,
4, Mild case......... eee eee 3.05 2.66 3 Bd. xix, p. 117.
5. Mild case. siccic xs cees cence 3.04 2.31 16 | |
6. Mild ae ....00.4 052 aaa. 3.51 2.73 78 |)
Di abOUES sis cecsia sia avs. meayesenn dcosetee 3.96 2.93 .74 |Sttive, loc. cit, p. 49.
Severe CaS€........--. cere eee 6.28 4.425 wt
Severe Case. ... 0... ccc e eee eee ee 5.164 | 3.795 .617 | | Weintraud und Laves, Zeit-
(Nine-hour investigation with | schr. f. phys. Chem., Bd.
Hoppe-Seyler’s respiration-ap- | xix, Heft 6.
paratus with simultaneous ad- 5.744 | 3.65 64
ministration of food during
the investigation.)...........J
Anemia, pernic. progress.........] 4.58 8.22 “1 Y/Y
ChIGLOSIS’. <2s¢vessaae antasn wis canes 5.11 3.7 72 «| 4 . F
apse oc ace enone rae ame Oh a cc ac dee ca
Secondary Anemia after hemor- Cc lia
rhage from hemorrhoids..... 4.58 8.45 yt)
CHIOLOSISi sc aia- ausinigsterew avers suengcae 3.47 2.96 85 Thiele u. Nehring, Zeitschr.,
Chilorosiss«saseas xecsiaid eesa ene 3.15 2.92 92 f. klin. Med., Bd. xxx, p.
Chlorosisic<...ccccgseece eperseees 3.38 3.29 975 56.
Secondary Anemia.............. 4.18 3.58 86 |) Thiele u. Nehring, loc. cit.,
Langer Anemia 4.15 ii .70 | p. 59
evere Anemia.............200- 4.26 LOM caesiaices : :
Same patient with continued im- Bitar Tain eerie eis
provement...........+.e00ee 3.83 3.85 | wo... - eae
Obesity:
Dr. Dr. Gew., 94 kilograms..... 2.71 1.95 | ..... v. Noorden, Lehrbuch, p.
Fri. N., 70 kilograms.......... 3.33 QiBd | ceca t 448.
Fr. Mal., 69.5 kilograms........ 3.45 2.77 804 |}
Fr. St., 76 kilograms........... 2.48 1.87 . 756
Fri. E. Kr., 77 kilograms....... 2.94 2.39 -812
Fr. Kr., 88 kilograms.......... 3.74 2.39 .637
Bee is ee Ee pienceeerinete 2.40 1.85 eel
r. Ha., 111.4 kilograms....... 2.88 2.31 .802 ; : c
Fr. Schu., 138.3 kilograms... .. a2 | top | at | egonee Few), Zeileebrit ©
Hr, A.S., 80.2 kilograms....... 3.22 | 2.42 750 By, Ey RE Bee
Hr. Mar., 80 kilograms......... 3.48 2.83 .814
Hr. Stab., 91.5 kilograms....... 2.82 2.04 721
Hr. Dr. Da., 92.7 kilograms..... 2.83 2.382 821
Hr. Ha., 96 kilograms.......... 2.41 1.87 117
Hr. D. O., 109 kilograms....... 2.82 2.37 .840
Fy, Eckmann,..............0.. 2.7 1.98 74 |Thiele u. Nehring, loc. ett.
Ps nosh arag meman @rteesieing & 2.8 2.26 .81 | Stiive, loc. cit., p. 46.
Aged:
Fr, Kr., 75 years..........0008- 4.25 3.36 768 |)
Fr. Kl., 71 years..........00005 3.16 2.55 807 | | Magnus-Levy, Zeitschrift f.
Hr. A. Kr., 71 years........... 3.42 2.70 79 klin, Med., xxxiii, p. 266.
Hr. J. K., 78 years ..... cece eee 2.61 2.61 725
a :
oy, 24 years, 11.5 kilograms...| 9.76 8.16 84 ‘ F
Gat 6) von, 182 kilograms. | 743 | 604 | “eI a Sornperies par i
Girl, 20 years, 61 kilograms. ...| 3.56 | 2.90 a) ochschr., 1895, p. 652.
Among pathological conditions in which investigation of the respiratory
metabolism has invariably shown an increase, GRAVES’ DISEASE occupies the
first place.
THE FOOD REQUIREMENT OF THE SICK 29
Magnus-Levy,' by his many valuable physiological researches in this realm,
was the first to attempt to estimate the factors of respiratory metabolism in
Graves’ disease (Basedow’s disease). He found the O, intake and the CO,
excretion decidedly greater, even 50 per cent. greater, than the rest values of
healthy individuals. At the same time his results showed that the admin-
istration of thyreoid extract in normal persons resulted in the same increase
of the interchange of gases.
These investigations also furnished the first experimental proof that there
are toxins in metabolism which cause increased activity in the cells of the
body during rest, and this discovery furnished a clue for the understanding of
the disturbance in metabolism observed in Graves’ disease (emaciation, sweat-
ing, sensations of heat) as well as the clinical symptoms after thyreoid gland
feeding, which are in many points similar.
A year before this practical use had been made of the effects of metabolism
thus elucidated, when Leichtenstern ? determined the actual loss in weight of
obese persons after thyreoid gland administration, and with this inaugurated
a medical treatment for obesity.
The quantitative investigations in metabolism which followed the clinical
advice of Leichtenstern, the loss of weight after thyreoid administration, and
the attempts to analyze the constituents of this loss first demonstrated that
there is a decided loss in proteids and water. But some of the investigators *
soon observed that, even when N-equilibrium was completely maintained,
there was decided loss in weight which could only be explained by loss of water
and fat. Analysis of the respiratory metabolism showed an enormous increase
in the intensity of the processes of oxidation, and thus confirmed the clinical
observation that in the losses of weight which are observed during thyreoid
feeding it is particularly the body fat which is subject to increased oxidation.
But it is certainly not on the body fat alone that the overflooding of
metabolism with thyreoid secretions exerts its deleterious action in severe cases
of Graves’ disease.
Even if we take the largest increase over “rest metabolism” which has
ever been observed in Graves’ disease (about 50 per cent. or 1,800 calories),
an additional consumption of 900 calories or about 100 grams of fat in the
daily food would cover the loss. Yet as a matter of fact exact quantitative
investigations in metabolism have shown that we are not always successful in
maintaining the equilibrium of body-weight (Fr. Miiller),* even by a very
profuse administration of nourishment, and only in mild cases, when condi-
tions are favorable for a profuse intake of nourishment (good appetite), can
the proteid constituents of the body be preserved (Scholz) .°
The etiologic relations and the clinical contrasts between Graves’ disease
1 Magnus-Levy. Berl. klin. Wochenschr., 1895, Nr. 30.
2 Leichtenstern, “Ueber Myxédem und iiber Entfettungscuren mit Schilddrtisenfiit-
terung.” Deutsche med. Wochenschr., 1894, Nr. 50.
3 Grawitz, Miinchener med. Wochenschr., 1896, Nr. 14.
4 Fr. Miiller, Arch. f. klin. Med., vol. li, p. 36.
5 Scholz, Centralbl. f. inn. Med., 1895, Nr. 438.
30 ANALYSIS OF DISTURBANCES OF METABOLISM
and MYXEDEMA (or sporadic cretinism) make it advisable to include these
diseases here.
They are the only ones in which a diminution of the normal oxidation
has been proven with certainty to be intimately connected with disease. The
values which Magnus-Levy * obtained in a case of sporadic eretinism (for 0,
intake 2.8 to 3.0 c.c., for CO, excretion 2.4 to 2.5 cc. per kilogram and
per minute) are near the lowest normal limits, and when taken in connection
with the clinical symptoms (low temperature, diminished formation of sweat,
inactivity of the muscles) the few analyses of metabolism which have been
made justify the conclusion that in this instance a diminution of metabolism
was actually present, and was due to the nature of the disease.
In no other diseases in which up to the present time the interchange of
gases has been determined is the explanation of the results obtained so simple
and clear as it is in Graves’ disease and in myxedema. Nevertheless, the
figures obtained have considerably modified the prevailing views regarding
the intensity of the processes of combustion in special diseases, and by this
means have broadened our insight into their pathogenesis, and have furnished
us much help regarding their treatment.
For a long time it was supposed that in revER the processes of oxidation
were increased. Nothing was more obvious than to connect the higher tem-
perature of the body with an increased use of carbon-containing material in
the body.
Regarding the degree of the increase of oxidation in the fever of human
beings experimental investigations in animals could only give us imperfect
standards (May*). Researches which Kraus® carried out in febrile human
beings have, however, shown that fever is possible without decided increase
of the oxidation processes (measured according to Zuntz’s method which shows
the relation of the factors of metabolism). This is particularly true of such
individuals as have had fever for a long time—those suffering from inanition
(Robin et Binet *).
In acute infectious fevers, the O, consumption amounts to scarcely more
than 20 per cent. above the normal. Previous to this, higher values have
frequently been obtained for the increase in oxidation, but this has been due
to accidental factors such as greater muscular activity owing to dyspnea,
increased muscular tonus in the chill of fever, etc.
The-amount of increase in the interchange of gases, which Kraus and
Riethus*® have shown to be attributable to some febrile infections, is suffi-
1 Magnus-Levy, Deutsche med. Wochenschr., 1896, p. 491.
2 May, “Der Stoffwechsel im Fieber,” “ Experimentalle Untersuchungen.” Zeit-
schrift f. Biol., vol. xxx, p. 1.
3 Kraus, “ Ueber den respiratorischen Gasaustausch im Fieber.” Zeitschr. f. Klin.
Med., vol. xviii, p. 160.
4 Robin et Binet, “ Etudes cliniques sur le chémisme respiratoire.” Arch. génér. de
méd., 1896, Juin et Octobre.
5 Riethus, “ Beobachtungen iiber den Gaswechsel kranker Menschen und den Einfluss
antipyretischer Medicamente auf denselben.” Arch. f. exp. Path. u. Pharm., vol. xliv,
p. 239.
THE FOOD REQUIREMENT OF THE SICK 3l
ciently explained by the increase in proteid decomposition which forms part
of every febrile process and, as it appears, bears a much more intimate rela-
tion to febrile processes than the increase in oxidation (Traube, Naunyn‘).
The investigations which are constantly multiplying make it obvious that
there is no constant and direct relation between the height of the temperature
and the degree of the increase of oxidation. Febrile conditions occasionally
show a conspicuously low consumption of oxygen, and afebrile cases con-
spicuously high.
The indications to be derived from this, in regard to the regulation of
nutrition in fever patients, are obvious. It is not the absolute height of the
fever which endangers the metabolism of the body, and for this reason it
should not be our only care to study minutely the diet of our patients. On
the contrary, it is the toxins produced by infection which prove injurious
to the nutritive condition of the body, and in all cases in which the physician
recognizes these deleterious consequences, he must arrange the dietary accord-
ingly. Remembering this he will not disregard the dietetic indications of
many afebrile infectious diseases (some forms of pulmonary tuberculosis).
In contrast with fever, in which the increased combustion causes much
less difficulty than the toxogenous proteid decomposition (see below) is the
nutrition of CONVALESCENTS. Here these difficulties are usually slight.
Analysis of the diet, under which debilitated patients after long-continued
under-nutrition are able to increase in weight, has frequently shown aston-
ishingly low energy values. Fr. Miiller ? in a case of stenosis of the esophagus
after intoxication from caustic potash studied a fearfully emaciated patient,
who gained 3.5 kilograms in three weeks, under a diet of only 24.7 to 30
calories per kilogram. Among G. Klemperer’s* patients there were some
who throve very well on a diet containing only 13.5 to 18 calories per kilo-
gram. A patient of Nebelthau’s* who was greatly emaciated in consequence
of stubborn vomiting, accumulated very considerable amounts of albumin
despite a quite insufficient proteid and calory administration after she had
remained for four days without any food.
Without doubt the processes of oxidation are here decreased to a certain
degree. The metabolism is diminished to the minimum which is absolutely
necessary to maintain life. Correspondingly, the formation of heat is slight
(tendency to chilliness), and the power of bodily activity is limited.
There is no objection to our assuming that this diminution of metabolism
in chronic under-nutrition is a true slowing of metabolism. This makes it
possible to maintain life even under very unfavorable external conditions,
and is apparently produced gradually by adaptation and habit.
Sudden withdrawal of nourishment does not diminish the total metabolism
1 Naunyn, Berliner klin. Wochenschr., 1869, Nr. 4.
2 Fried. Miiller, “ Stoffwechseluntersuchungen von Krebskranken.” Zeitschr. f. klin.
Med., vol. xvi, p. 496.
3@. Klemperer, “ Ueber Stoffwechsel und Ernihrung in Krankheiten.” Zeitschr. f.
klin. Med., vol. xvi, p. 550.
4 Nebelthau, “ Ein Beitrag zur Kenntniss der Acgtonurie.” Centralbl. f. inn. Med.,
1897, p. 977.
32 ANALYSIS OF DISTURBANCES OF METABOLISM
to anything like the same degree. In the estimations which Zuntz and Leh-
mann* carried out in the professional faster Cetti, the “rest-values” for
O, consumption and CO, excretion during the days of starvation (on the
average 4.78 and 3.34 c.c.) were but little lower than during the days pre-
ceding the fast (5.35 c.c. O,, and 3.90 c.c. CO,). In investigations in the
case of the faster Breithaupt, the average values prior to the fast and after
it had begun were almost exactly the same.
Whether the ease with which patients convalescent from acute febrile
disease compensate for their loss in weight depends upon the same capacity to
economize in metabolism which enables patients in a state of chronic under-
nutrition to gain weight even on a diet of low calory value is a mooted ques-
tion. Svenson? has recently thrown light upon this question by investiga-
tions of metabolism in convalescence from pneumonia and from enteric fever.
His figures (see Table on page 27) do not show a tendency to economy
in the processes of combustion. On the contrary, in the first afebrile days
after a severe enteric fever, he found a slight diminution of the respiratory
values ; true convalescence with increase in weight was being characterized by
high values, and metabolism was therefore increased. Hence the increase in
weight cannot be explained by assuming a diminution of consumption. On
the contrary, the balance is positive because the intake of nourishment with
the usual increased appetite of convalescence is decidedly greater than the
energy value of the average food of maintenance (60 to 90 calories per kilo-
gram).
The “rest-value” for metabolism in convalescence then is in any case
increased and this is particularly true of the metabolism after work, as
was shown by Svenson’s further researches. The convalescent is able to
utilize in muscular work only a small portion of the energy set free by the
processes of combustion, and therefore has a higher CO, consumption per
kilogram meter than the healthy man. There is no economy of metabolism
here.
DIABETES MELLITUS was for a long time looked upon as a disease in which
metabolism was increased. The enormous ingestion of food which, because
unsuitable, is often insufficient (in spite of its great energy value) to satisfy
the appetite which accompanies diabetes mellitus, and to maintain nutrition,
naturally led to this view, at a period when a deeper insight into the econ-
omy of metabolism of the diabetic was not yet possible.
The quantitative analyses of metabolism which, because of therapeutic ex-
periments in diet, were carried out especially often in diabetics, soon showed,
however, that with suitable food, the usual calory intake was sufficient to
maintain the equilibrium of metabolism even in severe diabetes.
The diabetic perversion of metabolism cannot be due to an increased inter-
change of products since it is possible with a diet which contains only 25
1Zuntz und Lehmann, Virchow’s Arch., vol. exxxi; Suppl.-Heft, pp. 50 und 91.
2 Svenson, “Stoffwechselversuche an Reconvalescenten.” Zeitschr. f. Klin. Med.,
vol. xliii, p. 86.
THE FOOD REQUIREMENT OF THE SICK 33
calories per kilogram to maintain the patient for weeks in an active con-
dition.*
On the contrary, observation proves that metabolism in the diabetic may
occasionally be abnormally slow, and the experience accumulated by many
careful investigations of the nutrition of diabetics demonstrates that, in many
cases, it is in fact slower than the metabolism of a healthy person. I say in
many cases, for this is by no means true of all. A pathologic diminution of the
nutritive requirement is by no means the rule in diabetes. If, however, we
give for a long time a diet which is apparently superfluous but, in reality,
quite insufficient—because improper—under the influence of this chronic
under-nutrition the same diminution in- metabolism may occur that also
occurs in other persons who are under-nourished (see above). Hence it
becomes possible to support life on less food than is necessary for healthy
people and to increase the diabetic’s weight with a diet which is only just
sufficient for the needs of a normal person.
Correspondingly, the rest values for O, consumption and CO, excretion
that have been determined in diabetes neither exceed nor fall below the limits
which we have come to recognize in the normal individual (Voit and Petten-
kofer, Leo,? Weintraud and Laves,’ Stiive *).
The same is proven by the investigations of Magnus-Levy in cout, which
Bouchard, as is well known, includes with diabetes among diseases character-
ized by decreased metabolism.
In the various forms of anemia (chlorosis, secondary and pernicious
anemia) we might expect diminution of O, intake, in view of the more or
less marked diminution of the oxygen carriers in the blood, especially if we
remember the fatty degeneration of organs, which is frequently observed in
anemia.
Experimental investigation, however, has decided against this view. In-
deed the values determined for 0, intake and CO, output have been shown
to be near the upper physiological limits. In those cases of pernicious anemia
which are characterized by increased proteid decomposition, this limit has
even been several times exceeded (Meyer, Magnus-Levy).® A diminution of
metabolism due to impoverished blood cannot therefore be assumed (Kraus,"
Thiele and Nehring) .®
1 Weintraud, “ Untersuchungen tiber den Stoffwechsel im Diabetes melitus.” Bibl.
med., Cassel, 1893.
2 Leo, “ Ueber den respiratorischen Stoffwechsel und Diabetes.” Zeitschr. f. Klin.
Med., vol. xix. :
3 Weintraud und Laves, “Ueber den respiratorischen Stoffwechsel im Diabetes.”
Zeitschr. f. phys. Chemie, vol. xix.
4 Stiive, Arbeiten aus dem stidt. Krankenhaus Frankfurt a. M., 1896, p. 49.
5 R. Meyer, “ Ueber O, Verbrauch und CO, Ausscheidung bei Animien.” Dissert.,
Bonn, 1892.
6 Magnus-Levy, Berliner klin. Wochenschr., 1895, p. 351.
7 Kraus, “ Ueber den Einfluss von Krankheiten, besonders von aniimischen Zustiin-
den, auf den respiratorischen Gaswechsel.” Zeitschr. f. klin. Med., vol. xxii, p. 449.
8 Thiele und Nehring, Zeitschr. f. klin. Med., vol. xxx.
4
‘
34 ANALYSIS OF DISTURBANCES OF METABOLISM
It is remarkable that in certain forms of opEsiTy no diminution of the
physiologic processes of combustion can be determined. Clinicians have
noted two classes of cases, (a) those in which overeating and deficiency of
muscular labor were the obvious causes of the accumulation of fat, and (b)
those in which even a normal amount of food resulted in accumulation of
fat, and even with a decided diminution of nourishment it was impossible to
bring about a reduction in weight.
v. Noorden? reports the case of a man weighing 102 kilograms who—in
spite of the fact that his food during three months did not exceed 1,720
calories per day, and that as an inspector of a country district he had every
day plenty of exercise—lost only a kilogram of weight in three months. In
a lady weighing 86 kilograms he failed to produce the slightest diminution
in weight in the course of six weeks, though he reduced the food to 900 to
1,000 calories. In a woman weighing 145 kilograms, Stadelmann? reports
that with a diet containing but 1,500 calories per day she not only throve but
even gained one kilogram per week in weight. Only when nutrition was
reduced to 1,000 calories did she begin to lose weight, while on 1,200 calories
she gained in weight for a time. (Compare the criticisms of these reports
in Rubner.)*
In the light of these observations the question constantly arises, whether
the tissue elements of obese persons do not require a slighter amount of mate-
rial to perform their normal functions, and whether the very ready accumula-
tion of fat is not due to the fact that the organs function more economically
than under normal conditions. yv. Noorden was the first to study this ques-
tion by exact experimental investigation, and in his excellent text-book, The
Pathology of Metabolism, which stimulated so many later researches in metab-
olism, he worked out in two cases of obesity the first figures representing the
consumption of oxygen and the excretion of carbonic acid. (See Table.)
Researches by Magnus-Levy followed these (Table). All the “minute-
kilo-values” taken with an empty stomach are low, in fact near the lowest
limit of the normal standard figures. “ But they are not so low that a dimin-
ished oxidation energy of the cells must be assumed, especially if we consider
that the values per kilogram as calculated in the obese become lower the more
fat the body accumulates. But in metabolism during quiet respiration this
factor is not operative. In studies regarding the intensity of the process of
combustion fat cannot be looked upon as of the same value as flesh and gland
substance” (Magnus-Levy). Thus when it appeared that analysis of the
respiratory metabolism (according to the Zuntz-Geppert method) would yield
no support for the belief that there is a diminution of the processes of com-
bustion in the obese, new researches by Jaquet* suggested the method by
which in the corpulent an economy of the food material introduced produces
the gradual deposition of fat.
1v. Noorden, “ Die Fettsucht,” in Nothnagel’s Handbuch, p. 31.
2 Stadelmann, Berliner klin. Wochenschr., 1901, Nr. 25.
3 Rubner, Beitriige zur “ Ernihrung im Kindesalter,” Berlin, 1902, p. 31.
4 Jaquet und Svenson, “Zur Kenntniss des Stoffwechsels fettstichtiger Personen.”
Zeitschr. f. klin, Med., Bd. xli, p. 375.
THE FOOD REQUIREMENT OF THE SICK 35
According to a diagram proposed by Magnus-Levy+ the total metabolism
of an individual may be considered to be composed of three factors:
1. The entire metabolism in rest and with an empty stomach.
2. The metabolism which is necessary to sustain the work (glandular and
intestinal) that results in the assimilation of food introduced.
3. The metabolism which is necessary for useful or useless movements of
the body.
Metabolism thus estimated amounts:
INGE .oip2es.d as apeataintans daca Daieansiae Aaa iene to 1,600 calories.
OT Die gead oe go caeday stuns waters eames ere ATA Te to 240 “
Hor32 4 puseceecsnwewee aye aeigiiesichie ncteemienstes te to 860 “*
Total. ccnsscuaceascnarcaces beaten: 2,700 -
In fact it is unlikely that an obese person requires less energy than a
healthy person for the maintenance of his vital functions, for normal activity
of the heart and respiration, for the rest metabolism of the glandular activity
and for the maintenance of body heat. v. Noorden mentioned the possibility
that for 3 he saves something, because the development of heat which accom-
panies physical exercise per kilogram of working protoplasm and per kilo-
gram-meter of physical exercise is less in him than in the average person, but
Magnus-Levy expressed his doubts of this. It was therefore particularly in-
teresting that Jaquet found the value for 2 diminished in his corpulent patient.
The increase of the products of combustion due to ingestion of nourishment
was decidedly less and of shorter duration in his three obese patients than
in normal persons. It was shown that during a period of digestion reckoned
as fourteen hours, the obese require 21.84 liters O, less than a normal person
under similar circumstances. With this amount of O,, 11 grams of fat can
be burned, and a daily saving of 11 grams of fat corresponds to an accumula-
tion of 4 kilograms of fat a year. Thus the analysis of respiratory metabolism
opens a path for the understanding of the pathogenesis of constitutional
obesity.
Practical rules for the nutrition of the sick cannot be immediately deduced
from these clinical studies regarding the amount of respiratory metabolism in
the diseases which have been mentioned, valuable as they are for our knowl-
edge of disturbances of metabolism.
The knowledge of O, consumption and CO, excretion, conveyed to us in
the clinical investigations which are almost exclusively carried out by Zuntz’s
method, with simultaneous estimation of albumin metabolism (by N-estima-
tion in the urine) can give at most but approximate conclusions regarding
the part played by individual food substances in combustion. The respiratory
quotient gives us some information but the absolute value of the transference
of energy in a unit of time cannot be calculated from the “ minute-values ”
for 0, and CO,, because, as was mentioned above (page 8), the same amounts
of carbonic acid and oxygen correspond to entirely different degrees of heat,
1 Magnus-Levy, Zeitschr. f. klin. Med., Bd. xxxiii, p. 299.
36 ANALYSIS OF DISTURBANCES OF METABOLISM
according as we are dealing with combustion of albumin, of fat, or of carbo-
hydrates.
A complete, correct calculation of force-transference and heat-transfer-
ence is only possible if the excretion of carbon and of nitrogen is minutely
investigated for a considerable period of time, and then from both of these
the implication of proteids and of fat is estimated in metabolism. From the
hour or minute values, fixed conclusions cannot be drawn regarding the total
calory requirement ; they are therefore not final. We may hope, however, that
prolonged investigations of the interchange of gases (with Pettenkofer’s or,
even better, with Hoppe-Seyler’s apparatus) will give us more valuable con-
clusions for pathology, and decidedly broaden our knowledge regarding total
metabolism.
The cases in which the entire interchange of forces in pathologic condi-
tions has been determined by sufficiently exact technical investigations are up
to the present time very few. We owe them mostly to the labors of Rubner.
In his researches in artificial nutrition carried on with Heubner* in a
normal and in an atrophic nursling, intake and output were directly estimated
in every way, and by calorimetric analysis it was possible to determine the
actual figures for the interchange of forces. It was shown that there is no
abnormal form of decomposition (force-transference) in the atrophic child.
The diet necessary for maintenance in the atrophic child and in the healthy
nursling correspond very well if we make allowance for small differences in
digestion and in the temperament of the children (influence of body rest,
motion and sleep). If they are given an excess of food, both utilize about
the same percentage for heat production, and about the same percentage is de-
posited in the tissues. The only peculiarity of the atrophic child is a lessened
power of intestinal absorption, and hence a more profuse production of feces.
In a technically complete investigation of metabolism in an obese child,
Rubner? was unable to determine any diminution of interchange of forces.
Despite his pathologic predisposition, the boy required no less food than a
healthy boy of the same weight tested by Camerer.
On the other hand characteristic differences in the processes of decompo-
sition were found by Sonden and Tigerstedt * in their investigations of metab-
olism in men of various ages. They conclude from these that there is a greater
life energy during youth, in contrast to the metabolism of the aged, in which
a lessened consumption may be recognized. The heat production amounted:
In boys of 35.2 kilos weight........... ccc cece ee eeee to 1,322 calories
In men of 67.8 kilos weight..................... 0008 to 1,016 =“
In an aged man of 62.8 kilos weight.................. to 924 “ #
1 Rubner und Heubner, “Die natiirliche Ernihrung eines Siiuglings.” Zeitschr. f.
Biol., Bd. xxxvi, p. 1. “ Die kiinstl. Erniihrung eines normalen und eines atrophischen
Siiuglings.” Zeitschr. f. Biol., Bd. xxxviii, p. 315.
2 Rubner, Beitriige zur “ Ernaihrung im Knabenalter mit besonderer Beriicksichtigung
der Fettsucht,” Berlin, 1902.
3 Sonden and Tigerstedt, “ Untersuchungen tiber die Respiration und den Gesammt-
stoffwechsel des Menschen.” Skand. Arch. f. Physiol., 1895, Bd. vi.
THE FOOD REQUIREMENT OF THE SICK 37
In view of the criticisms which Camerer and Rubner have devoted to these
investigations we shall, however, withhold acceptance from the conclusions
which Sonden and Tigerstedt have drawn from their researches in regard to
the varying intensity of the processes of metabolism in the young and in the
aged. (See Table.)
THE MAINTENANCE DIET AND THE PROTEID REQUIREMENT
OF THE SICK
Besides the complete technic and investigations which can be carried on
by means of complicated apparatus, we can use at the bedside a simpler method
to determine the total metabolism, viz.: the calculation of the tension power,
based upon the food which has been consumed. The demonstration in Rub-
ner’s studies that to supply suitable energy the food of man must be adapted
to his condition of life permits the conclusion that if the individual, although
ill, maintains his body-weight, the supply of force present in his food corre-
sponds with his metabolism (interchange of force).
The calculation of the energy value of food from the standard figures
given by Rubner is simple, and is in general use to-day. The only question
that arises is whether the control of the body-weight and the frequent com-
putation of the N-balance is sufficient to indicate all important changes in
the material condition of the body.
But for the clinical pathology of metabolism this is certainly sufficient,
and with the proviso that this assumption is justifiable, the quantitative anal-
yses of metabolism in patients, now coming into common use, give us valuable
points for the administration of food suitable for the maintenance of the
organism in special diseases, either hypernutrition or hyponutrition.
A few of these investigations have been mentioned. It would extend this
article too much if I were to enumerate them all; and some of them will be
referred to later. (See absorption. investigations.)
v. Noorden’s systematic tests of the energy value of food and his methods
of producing a rapid increase in weight, will be described explicitly.
In eight women who were confined to their beds weight began to increase
when the food reached the following values: 26, 26.5, 19, 32, 33, 36, 36, 38.5,
39 calories per kilogram and per day. Upon the average 32 calories per kilo-
gram. F
In five women who were out of bed for two to three hours during the day,
increase in weight began when the value of the food reached 28, 31.5, 34, 36.5,
36.5, 40 calories per kilogram and per day. Upon the average 34 calories.
In four women who spent most of the day out of bed, and occasionally
walked about in the garden, increase in weight began when the value of food
reached 32, 37, 37, 41 calories. Upon the average 37 calories per kilogram.
Although these figures demonstrate that increase of weight occasionally
occurs even when the calory value of the food is very slight (27 calories), never-
theless v. Noorden cautions us that food in which the calory value is less than
30 calories per kilogram should not be used. The increase in weight with
small calory values is usually limited to patients in whom prolonged under-
nutrition has led to a decided diminution of the amount of water in the body,
38 ANALYSIS OF DISTURBANCES OF METABOLISM
so that the increase in weight observed may be referred more to a satiation
of the demand of the tissues for water than to an actual gain in substance.*
Yet it cannot be doubted, in view of these experiments, that, in emaciated
individuals, administration of food of very slight calory value may compen-
sate completely for the food requirement and the interchange of force, and
may even permit an increase in weight. For if, in spite of a slight calory
administration, N-equilibrium has been maintained for a long time and albu-
min actually accumulated, there cannot be a calory deficit for any length
of time. Later investigations in metabolism show that the N-balance is to a
great extent independent of the calory supply. The stimulation of albumin
accumulation which results from muscular exertion as well as from growth
makes possible an N-retention even with an insufficient calory supply and an
actual loss in weight (Caspari*).
But there are many observations showing that after prolonged under-
nutrition, such as occurs in disease, the body may, up to a certain point, adapt
itself to a smaller amount of food. It limits itself to the functions absolutely
necessary to maintain life, and under these conditions the slightest increase
in food soon brings about an increase in weight as well as a retardation of
the pathological processes, under the action of which the body has become so
reduced. The lessening of body-weight, upon whose maintenance, according
to Pfliiger, the energy of metabolism is dependent, becomes here the direct
cause of a diminished rate of metabolism.
The emaciation which is the invariable consequence of many diseases finds
its chief expression in the decrease of body-weight, so that frequent weighings
of the body in chronic diseases are, as Gerhardt says, almost as valuable as
the temperature record in acute diseases. The variations may, however, be
due to various causes.
When patients suffering from gastric disease are emaciated this is often
due wholly to the poverty of the calory value of their food, as was first emphat-
ically stated and clearly proven by v. Noorden. The fear of pain, or a false
estimation of the nutritive value of individual foods, may have aided in bring-
ing this about. If food of normal calory value be given, the loss in weight
ceases.
Other patients (Graves’ disease), as we have noted, lose weight, in spite
of a calory intake sufficient for the healthy, because the intensity of the
process of combustion is decidedly increased. If the capacity for taking food
is great, as in many afebrile tubercular patients and in many cases of Base-
dow’s disease, the calory contents of their food need only be increased beyond
the usual needs of the healthy, and they will not only attain their N-equi-
librium, but will very soon begin to accumulate fat.
This, however, does not succeed in all cases. Fr. Miiller* was the first
1 vy. Noorden, ‘‘ Stoffverbrauch und Nahrungsbedarf in Krankheiten.” Arbeiten aus
dem stiddt. Krankenhaus zu Frankfurt a. M., 1896, p. 3.
2 Caspari, ‘Ueber Eiweissumsatz und Ansatz bei der Muskelarbeit.” Pfliiger’s
Arch., Bd. 1xxxiii, p. 509.
3 Fr. Miiller, “ Stoffwechsel bei Krebskranken,” Zeitschr. f. klin, Med., Bd. xvi,
p. 496,
THE FOOD REQUIREMENT OF THE SICK 39
to note in his cancer patients that in malignant cachexia, even with a plenti-
ful calory supply (with sufficient albumin elements in the food), it was often
impossible to attain N-equilibrium. Gartig* confirmed these reports.
Here a toxin damages the protoplasm of the cells, and the albuminous
débris of cells, decidedly beyond the requirements of the pathologic organism
for albumin, enters the circulation, there to suffer complete destruction.
In fever patients, in whom the extraordinarily high urea figures obtained
by former investigators (Traube and Naunyn) were for a long time empha-
sized, we now have numerous analyses of metabolism some of which show
that the destruction of tissue in acute cases of fever cannot be entirely pre-
vented by any mode of nutrition (v. Leyden and Klemperer *).
The same is also true of certain severe forms of anemia. Yet the increased
decomposition of albumin does not always occur in impoverished conditions
of the blood. We know this from the researches of v. Noorden, who conducted
exact analyses in metabolism in severe chlorosis, which prove beyond doubt
that such patients, with the ordinary calory supply and without particularly
large amounts of albumin, are able to maintain their N-equilibrium (Lip-
mann-Wulff*). On the other hand, there are certain clinical cases character-
ized by a severe course, the so-called pernicious anemias, some of which are
to-day explained by the presence of intestinal parasites; in these the proteid
metabolism is pathologically increased. Even the first clinical observers of
the disease (Striimpell, Eichhorst) found in these patients high urea values,
though of course these figures, without simultaneous observation and analysis
of the food, did not prove anything. Exact analyses of metabolism which
Rosenquist * lately carried out in patients with bothriocephalus-anemia have
determined with certainty that, at any rate in this form of pernicious anemia,
there is an increased decomposition of albumin. These researches constitute
conclusive proof of the law of so-called toxogenous decomposition of albumin,
for they illustrate how, shortly after the expulsion of the parasites (five to six
days later), an accumulation of albumin, formerly impossible, was attained.
As the blood changes here depend upon toxic action, after the removal of
which normal regenerative changes take place, so also the pathologic decom-
position of albumin may be readily stopped by expelling the parasites.
The indications for preventing the threatening tissue destruction in febrile
and cachectic patients are much more obscure. Yet this is often of para-
mount importance in dietotherapeutic endeavors.
Practical experience shows that the two methods which improve the albu-
min balance in the healthy are also applicable here. By the administration
of a liberal albumin diet, the N-loss may be diminished during fever (Bauer
and Kiinstle) ; the same result can be obtained by giving a profuse calory
supply of N-free substances. For both processes excellent methods are found
1 H. Gartig, “ Untersuchungen tiber den Stoffwechsel in einem Fall von Care, Gisoph-
agi.” Diss., Berlin, 1890.
2». Leyden und G. Klemperer, “ Ernihrungstherapie in acuten Fieberkrankheiten.”
“Handbuch d. Erniihrungsther.,” Bd. ii, p. 408.
3 Lipmann-Wulff, “ Ueber Eiweisszersetzung bei Chlorose.” Diss., Berlin, 1891,
4 Rosenquist, Berl, klin. Wochenschr., 1901, p. 666,
40 ANALYSIS OF DISTURBANCES OF METABOLISM
in the tables of v. Leyden and Klemperer (loc. cit.). That the carbohydrates
in themselves are superior to the fats as albumin savers (see page .21) and
that they are especially valuable in the diet of fever and cancer patients as
compared with albumin and fat (the administration of which is frequently
limited by an unconquerable repugnance and by difficulty in digestion), is
clearly shown by experience at the bedside as well as by experimental study.
In fever artificially produced May? found a limitation of the combustion of
albumin as a result of the profuse intake of carbohydrates.
In spite of the pathologically increased toxogenous decomposition of albu-
min the laws which normally control the metabolism of albumin are still
active in wasting diseases. This fact should always be borne in mind, and
measures based upon it should be employed in the dietetic treatment of such
cases. Hirschfeld? succeeded by forced feeding in attaining an N-accumu-
lation in tuberculous febrile cases. v. Noorden, in his text-book, mentions
quite a number of patients with temperatures of over 101.3° F. in the late
weeks of typhoid cases running a slow course, also patients with sepsis and
pulmonary tuberculosis, who on a diet rich in albumin but not of particularly
high calory value were able, at least for two weeks, to maintain their body-
weight.
Whether nitrogen-equilibrium actually existed in these cases cannot be
determined from the figures given. There is a great difference as regards
the N-balances in febrile and those in non-febrile convalescents for, with the
same calory supply, we can produce in afebrile cases a decided gain in albu-
min while in febrile cases we can scarcely maintain the nitrogen-equilibrium.
The “intoxication necrosis” of the tissues which occurs in febrile dis-
eases as well as from under-nutrition, and the deleterious effects of which
cannot be prevented by any known means, is followed in convalescence by a
-remarkable endeavor of the enfeebled cells to recuperate. They attempt to
gorge themselves with albumin, and the balance of metabolism which termi-
nated in a nitrogen deficit suddenly begins to show an N-retention (Diinsch-
mann, v. Leyden and Klemperer, loc. cit.).
The great rapidity with which this N-retention may occur despite a nor-
mal calory supply and normal proteid supply has been noted in numerous
studies of metabolism.* In this connection Liithje’s* latest experiments in
forced feeding have shown what can be done by means of abundant food dur-
ing convalescence. In his studies of convalescents from enteric fever, N-reten-
tion of from 10, 12 to even 14 grams of N per day, corresponding almost to
100 grams of albumin within twenty-four hours, was repeatedly observed.
This N-addition is all the moré remarkable because, in my opinion, we
must assume that the retained nitrogen is utilized for the production of living
protoplasm, and therefore is utilized in the total metabolism. —
1 May, “ Der Stoffwechsel im Fieber.” Zeitschr. f. Biologie, Bd. xxx, p- 41.
2 Hirschfeld, Deutsch. Arch. f. klin. Med., 1882, Bd. xxx, p. 28.
3 Albu, “ Ueber den Eiweissstoffwechsel bei chronischer Untererniihrung.” Zeitschr.
f. klin, Med., Bd. xxxviii, p. 250; here also the other literature.
* Liithje, Beitriige zur “ Kenntniss des Eiweissstoffwechsel.” Zeitschr. f. klin. Med.,
Bd. xliv, p. 22. ;
THE FOOD REQUIREMENT OF THE SICK 4l
With such an amount of N-retention there is no possibility that we are
producing only a temporary retention of N-containing products of metabo-
lism (proteid destruction). Further such an enormous increase cannot take
wholly the form of circulating albumin (in Voit’s sense). Neither can we
call it “reserve albumin” (v. Noorden), if this term is meant to imply that
the albumin accumulated during convalescence is a different kind of albu-
min from, and subject to other laws of destruction than, the ordinary albumin
of the organs.
In the person experimented upon by Liithje, whose diet for twenty days
averaged 62.5 grams of N," after a reduction to 16.7 grams N, N-equilibrium
was attained, not at once indeed, but within three or four days; and even after
eight days, when the research was stopped, but small losses of nitrogen were
shown.? In view of the obvious tendency toward N-equilibrium in this case
there is no reason to assume that, in the subsequent period, all the nitrogen
(166.78 grams) which had accumulated during twenty days of the albumin
period was again lost. At any rate, there was no loss in weight, although
the patient after leaving the clinic and while living on a freely chosen diet
probably did not consume a very large quantity of albumin.
Apparently then the amount of his living cell substance probably remained
large. Consequently, in later investigations in the same person larger quan-
tities of albumin were required to bring about a large N-retention, a phe-
nomenon quite in accord with the views of Pfliiger, according to which the
degree of the albumin metabolism is dependent upon the amount of living
cell substance of the body.
We are, therefore, justified in holding the view that the N-retention in
convalescents is not due to the retention of N-containing urinary products
of metabolism, but to an actual accumulation of albumin which is equivalent
to an increase of living protoplasm and, in a certain sense, to an increase in
the activity of the body. Moreover, we must not always consider the muscles
of the body alone, and for this reason the designation, “ muscle-food,” had
better be avoided. Richness in albumin (increase of the juices of the flesh)
is only the necessary pre-requisite for great power in the musculature, and it is
exercise and only exercise which increases power, on which capacity for work
is directly dependent.
On the other hand a decided retention of nitrogen, which -does not mean
an accumulation of albumin (or an increase of living protoplasm), is fre-
quently met with in renal diseases. Disturbance of the nitrogen-equilibrium
is usual in these affections.
It is evident without further elucidation that in nephritis which is a con-
sequence of disease of the excretory organs urinary substances are prone to
remain in the body, and we are therefore not far wrong, when we find rela-
tively small amounts of nitrogen in the urine (in comparison with the
1 Corresponding to the enormous administration of 390 grams of albumin per day.
2 For which the further decrease of N-administration to 15.6 grams N is to be made
partly responsible.
42 ANALYSIS OF DISTURBANCES OF METABOLISM
amount of nitrogen administered in the food), in concluding that the cause is
deficient excretion of nitrogenous products of albumin metabolism (Fleischer,
vy. Noorden and Ritter *).
Because of this fact, as well as because days with increased N-excretion
often follow these periods of decided N-retention, the N-elimination in nephri-
tis is in a very “ unaccountable and bizarre state which, according to v. Noor-
den, characterizes the metabolism of renal patients.”
But we are here dealing wholly with disturbances of excretion; there are
no changes in the amount of albumin metabolism (no toxogenous albumin
decomposition).
In investigations of the metabolism of gouty patients we are often con-
fronted with irregularities in the excretion of urea, apparently in consequence
of functional insufficiency of the organs of excretion, which is natural if we
remember that renal disease often complicates gout (Vogel,? Schmoll *).
It is interesting to note that Rosemann ® lately found in a healthy, or appar-
ently healthy, young man during a long investigation in metabolism carried
out for a different purpose, a decided N-retention with subsequent increased
excretion of urea. In this case there were no sufficient grounds for the assump-
tion of any renal disease. On the other hand, the person experimented upon
had suffered for years from a cutaneous affection (occasional attacks of urti-
caria), and it is conceivable that, in consequence of this, the excretion of
water through the kidneys had in the course of years become diminished in
favor of that through the skin; and that, therefore, the N-elimination by
means of the urine had suffered. However, the excretion of water in the urine
during the period of N-retention was never so slight in this case that the
urine could not have excreted more nitrogen. Rosemann, therefore, expressed
the opinion that a prolonged ingestion of iodin was responsible for the dis-
turbance of N-excretion (the person experimented upon had suffered from
a cutaneous affection for years, and up to within fourteen days of the test
had taken potassium iodid), but at the present time proofs are wanting that
the secretory activity of the kidneys can be thus influenced by the use of iodin,
even for a long time.
I believe that every one who has made many quantitative researches in
metabolism has occasionally met with healthy persons in whom, in spite of
the most careful regulation of the amount of the food, it was impossible to
attain N-equilibrium. In such persons the daily N-excretion constantly
varies up and down when we are attempting to get at the average figures. Oc-
casionally there are periods of relatively low excretion lasting several days
: 1 Fleischer, Klinische und pathologisch-chemische Beitriige zur “Lehre von den
Nierenkrankheiten.” Deutsches Archiv f. klin. Med., vol. xxix, p. 129.
20. Noorden und Ritter, “Untersuchungen tiber den Stoffwechsel Nierenkranker.”
Zeitschr. f. klin. Med., vol. xix, p. 197.
8 Vogel, v. Noorden’s Beitriige zur “ Lehre vom Stoffwechsel,” 1894, Heft 2, p. 118.
# Schmoll, “ Stoffwechselversuche an einem Gichtkranken.” Zeitschr. f. klin. Med.,
vol. xxix, p. 510.
5 Rosemann, “Ueber die Retention yon Harnbestandtheilen im Korper.” Pfliiger’s
Archiv, vol. Ixxii, p. 467,
THE FOOD REQUIREMENT OF THE SICK 43
followed by similar periods of increased N-excretion. This phenomenon is
particularly frequent and familiar when the subject is on a régime rich in
albumin (more than 20 grams of N in the daily food).
In contrast with these irregularities of the excretion of nitrogen in the
urine which occasionally occur in the healthy, and more frequently in renal
disease and in gout, we have the N-retention which is observed in cachectic
patients during the formation of transudates and edemas.
Concerning this quite a number of investigations have been made, par-
ticularly in patients with hepatic cirrhosis. Several times during the reac-
cumulation of an ascites (after paracentesis) the nitrogen balance has been
estimated (Schubert, Marischler and Ozarkiewicz?). That the N-retention
which is noted in these cases does not indicate an actual albumin accumulation
is clear. The retained nitrogen is not utilized as albumin to build up tissue
but goes to form edema or ascites. Authors have therefore often spoken of
a “pathological ” N-retention, and explained it by the hypothesis that while
the organism normally possesses the faculty of destroying albumin and digest-
ing it, this function is now lost. Most probably, however, purely mechanical
disturbances of absorption here play a réle in causing the retention of N.
These disturbances depend upon changes in the amount of mineral salts in
the fluids of the body, the osmotic changes being dependent upon variations
in the concentration of these salts which cooperate with the active properties
of the endothelia to govern absorption.
There is no considerable interest in the often-discussed question whether
the albumin in these re-accumulating transudates (ascites) comes from the
albumin of the food, or whether the body albumin is utilized. The question
becomes meaningless if we discard Voit’s differentiation of two varieties of
albumin in the body (organic albumin and circulating albumin). This deci-
sion cannot be arrived at by analysis of the mineral metabolism in such cases,
for the albumin of the food has been absorbed, taken up into the fluids of
the body, and thence also into the cell protoplasm; thence together with the
organic albumin it issues in the fluids of pathological transudates.
DISTURBANCES IN THE ABSORPTION OF FOOD
In determining the food requirement of a patient, we must consider (a)
changes in the amount of oxidation due to the disease, (b) consumption of
albumin due to toxic influences, and (c) other factors, important among
which are the losses of energy which the body suffers by giving off food sub-
stances which it should retain.
These losses are so manifold and so various that it is impossible to place
them side by side as equivalents. Some of these losses are not susceptible to
quantitative estimation; on the other hand, in so far as they are due to
1 Schubert, “ Ueber den N- und Cl-Umsatz wiihrend der Bildung und nach der Punk-
tion des Ascites bei Lebercirrhose.” Dissert., Breslau, 1895.
2 Marischler und Ozarkiewicz, “ Stoffwechsel bei abnehmendem und zunehmendem
Ascites,” Arch. f. Verdawungskrankh., vol. v, p. 222,
44 ANALYSIS OF DISTURBANCES OF METABOLISM
faulty absorption of food—and this is to be especially discussed here—they
can be well controlled and have in fact been thoroughly investigated.
The loss in material which the body suffers from profuse sweating is rela-
tively slight. But the heat equivalent that corresponds to the evaporation
of one liter of sweat amounts to no less than 580 calories. We are justified,
therefore, in speaking of “ exhausting sweats.”
The food requirement of the patient is decidedly increased by muscular
work. We know that even simple muscular tension, without any accompany-
ing effort, is expressed in an increase of the respiratory metabolism. It is not
essential, therefore, that there should be a pathologic tendency to movement
which constantly keeps the entire musculature in action, as in many insane
patients, or that severe convulsions should produce such shock. On the con-
trary, even the restlessness of a patient in bed with increased respiration and
cardiac action and mild tremor, as frequently occurs in the susceptible
patient, will bring about an increase of oxidation. The degree of such in-
crease in metabolism cannot, however, be determined quantitatively.
The conditions are still more difficult if we attempt to estimate the loss
of substance which the diseased body suffers in the discharge of transudates,
in suppurating wounds, in profuse expectoration, in severe albuminuria, in
long-continued hemorrhage, and the like. There can be no doubt that, in all
eases in which there is loss of the body albumin, the diet must be arranged
to compensate for it if loss of weight is to be prevented.
The conditions are much plainer when, in consequence of qualitative dis-
turbances of metabolism, the affected organism suffers loss because the food
products are not oxidized to their normal end products, and, in consequence,
material which is still capable of oxidation is present in the blood, and is
excreted unoxidized or imperfectly oxidized in the urine.
The sugar which the diabetic excretes in the urine is lost to the body as a
source of power. If we fail to take account of this we overestimate the actual
food-requirement and energy-interchange of the diabetic. With a suitable
diet, in fact with a diet of the same calory values, we can produce equilibrium
of metabolism in the diabetic as in the healthy. Only the food must be given
to him in such a form that he can utilize it.
By other products also, which, in disturbances of metabolism, are found
in the urine (acetone, aceto-acetic acid, 8-oxybutyric acid, cystin, homogen-
tisic acid, ete.) energy is occasionally lost to the body.
The organism always loses energy when there is insufficient assimilation
of food in the intestines. This occurs in the healthy, but is frequently
and decidedly increased in the sick. Its amount may be accurately deter-
mined.
In the healthy estimation of the calory value of feces such as are dis-
charged by those on a mixed diet has led Rubner to assume a reduction of
8 per cent. from the raw calory value of the ingested food as the average
amount of energy thus lost. This calculation, however, is valid only under
conditions in which the feces are made up chiefly of the unabsorbed residue
THE FOOD REQUIREMENT OF THE SICK 45
of intestinal secretions, and do not contain remnants of food. These condi-
tions are realized only when absorption is normal and the food is suitable.
This assumption, however, is not true in health if the diet contains sub-
stances in a form difficult of absorption. In the sick, in whom the mechan-
ism of digestion as well as the mechanism of absorption is disturbed, the
estimation of the food lost in the feces is absolutely necessary, for we cannot
estimate it by simple subtraction.
The analysis of feces is therefore very important in all quantitative clin-
ical investigations of metabolism. The results, compared with an exact esti-
mation of the food ingested, give a clear idea of the amount of food assim-
ilated in the intestinal canal.
Voit demonstrated in his laboratory the energy-value of the food of healthy
persons by thus estimating the part which remained undigested in the intes-
tine and in the feces when the subject was given various diets, simple-or mixed.
This forced us to investigate the manifold pathologie conditions which com-
plicate the mechanism of digestion and the processes of absorption and to
study the absorption of and utilization of food in these conditions.
The researches undertaken in this direction are extremely numerous, and
only their most important results can be summarized here.’
In by far the majority of these studies we have limited ourselves to esti-
mating accurately the nitrogen and the fat during the period of investigation.
In view of the fact that the disappearance of carbohydrates during their pas-
sage through the intestinal canal is accomplished not only by absorption
through the intestinal mucous membrane, but also by decomposition (fer-
mentation), and hence that the residue of carbohydrates found in the feces
does not give a reliable measure of the actual amount used, carbohydrate esti-
mation in feces has been quite commonly neglected in these investigations.
Only lately A. Schmidt+ has minutely investigated this question, and in his
“fermentation test” has given a method for determining accurately those
portions of the undissolved carbohydrates which are susceptible to the fluids
of digestion, yet have escaped absorption. His proposition to utilize always
the same trial meal (qualitative and quantitative) for the quantitative estima-
tion of the absorption of albumin and fat in disease deserves the fullest
consideration.
The investigation of the absorption of food in pathologic conditions, in so
far as technic and quantitative estimation are concerned, has now reached a
high degree of perfection.
Comparatively few of the numerous researches in metabolism have given
noteworthy and positive results concerning the assimilation of food.
The researches of Fr. Miiller? in the metabolism in jaundice, which are
the earlier quantitative investigations at the bedside, should be mentioned
first, since they determine a very important decrease in fat absorption in
cases of occlusion of bile from the intestine.
1A. Schmidt, Deutsches Arch. f. klin. Med., Bd. lxi, pp. 280 und 545; Verh. gr. f.
innere Med., 1898 und 1899. : be
2 Fr, Miiller, “ Untersuchungen tiber Ikterus.” Zeitschr. f. klin. Med., Bd. xii, p. 45.
46 ANALYSIS OF DISTURBANCES OF METABOLISM
But also the negative results of many investigations which showed nor-
mal or almost normal absorption in such pathologic states—conditions in
which with a certain degree of justice it might have been supposed that more
serious disturbances were present—have given a basis of support for the
dietetic treatment of such cases, and have shown the fallacy of many diet
lists based upon erroneous ideas.
I refer to the excellent monograph of Ad. Schmidt and J. Strassburger,*
in which the results of their researches in this subject are compiled, and I
shall limit myself to mentioning a few researches. ;
The mal-assimilation of food which Fr. Miiller found in patients with
stasis of bile is limited almost exclusively to fat. Miiller found in the feces
of his patients fat amounting to 87.4 per cent. (against 22 per cent. in the
healthy). The loss in fat often amounted to 50 to 70 per cent. of the fat
administered as food. :
The same decided decrease of fat absorption was afterward observed in
occlusion of the pancreatic juice from the intestine without complications
(Deucher).? In a case of carcinoma of the head of the pancreas, in which no
stasis of bile was present, only 17 per cent. of the fat introduced was absorbed ;
therefore, the simultaneous action of pancreatic juice and bile is necessary
for a sufficient absorption of fat in man.
On the other hand, it appears from the reports of investigations that
neither bile nor pancreatic juice is necessary for the complete splitting up of
fats in the intestinal canal. Not only the fatty stools of the jaundiced patient
(Fr. Miiller), but also (according to Deucher) the feces in occlusion of the
pancreatic duct contain fat which is chiefly in a split-up form (up to 80 per
cent.) ; therefore, Deucher teaches that we cannot count upon the absence of
free fatty acids in the feces as evidence of disturbances in the pancreatic
function.
Predominance of free fatty acids, naturally, not at the cost of the neutral
fats, but, on the contrary, at the expense of the soaps (Deucher), means pre-
sumably a decrease or absence of the pancreatic juice secretion.
By others * in individual cases, a lessened fat splitting has also been ob-
served in connection with occlusion of the pancreatic juice from the intes-
tine. Volhard* has shown that, although the decomposition of neutral fats
is primarily the function of the pancreas, in cases of occlusion of the pan-
creatic juice, fat splitting occurs not only through the action of bacteria, but
also through the action of the gastric juice which also contains a fat splitting
ferment. There is need of further investigations with due consideration of
this factor.
1 Ad. Schmidt und J. Strassburger, “ Die Fiices des Menschen,” Bonn, 1901. °
2 Deucher, “ Stoffwechseluntersuchungen bei Verschluss des Ductus pancreaticus.”
Correspondenzbl. f. Schweizer Aerzte, 1898, Nr. 11.
3 Fr, Miiller, loc. cit., Weintraud, “Die Bedeutung des quantitativen Stoffwechsel-
versuches ftir die Diagnostik innerer Krankheiten, insbesondere von Pankreaserkrank-
ungen.” Die Heilkunde, 1898, Heft 2.
4 Volhard, “Ueber das fettspaltende Ferment des Magens.” Zeitschr. f. klin. Med.,
1901, Bd. xliii, p. 397.
THE FOOD REQUIREMENT OF THE SICK 47
Except in the cases just mentioned a decided diminution in the absorption
of fat, e. g., as a result of disturbance of the gastric chemism, has not yet been
observed. With insufficient or increased HCl in the gastric juice, and also in
complete achylia (apepsia), the fat appearing in the feces does not amount
to more, or to but very little more, than the usual percentage.
On the other hand, unusually large amounts of fat are found in the dis-
charges in disease of the intestine (amyloid degeneration,’ tabes mesenterica,?
chronic intestinal tuberculosis with chronic tubercular peritonitis, fatty diar-
thea [Biedert *]).
Regarding the laws of albumin absorption in the sick, v. Noorden® has
demonstrated the surprising fact that the absence of HCl in the gastric
juice, in spite of its great importance for the peptonizing of the albumin bodies
which is necessary for their absorption, nowise influences the assimilation
of the latter. Patients with disease of the stomach, with anacidity and with
hyperacidity, showed a quite normal power of albumin absorption in the
intestine.
But later, in cases of apepsia gastrica® and of pernicious anemia? in
which not only HCl but also the digestive ferments of the gastric juice were
absent, slight diminution in the absorption of albumin was observed. It
must, however, be remembered that in these conditions there is often not
only independent disease of the mucous membrane of the stomach, but (as the
anatomical findings in individual cases have also shown) actual atrophy of the
glands in the intestinal mucous membrane. Hence it is easily understood
how, in the absence of any peptic effect upon the albumin in the stomach,
the vicarious intestinal digestion which ordinarily occurs does not produce
complete absorption.
The slight albumin losses in the feces, which amount to from 11 per cent.
to 15 per cent., instead of 7 per cent. as in health, in these cases and also in
complete occlusion of bile from the intestinal canal, are in sharp contrast with
the great losses which occur in occlusion of the pancreatic juice (Deucher,
Weintraud, loc. cit.).
In extensive disease of the intestinal mucous membrane (as in an atrophic
nursling) ,* in intestinal amyloid disease,® in extensive intestinal tuberculosis *°
great losses of nitrogen have been observed in the feces.
1 Fr. Miiller, loc. cit.
z Ad. Schmidt, loc. cit.
8 Weintraud, loc. cit.
+ Biedert, Jahrbuch der Kinderheilkunde, Bd. xxviii, p. 21.
5, Noorden, “ Die Ausniitzung der Nahrung bei Magenkranken.” Zeitschr. f. Klin.
Med., Nr. 17, p. 137.
8 Strauss, “ Untersuchungen tiber die Resorption und den Stoffwechsel bei Apepsia
gastrica.” Zeitschr. f. klin. Med., Bd. xli, p. 280.
TErben und Steyskal, “ Klinisch-chemische Studien.” Zeitschr. f. klin. Med., Bd.
xl, p. 165.—Morazewski, “ Stoffwechselversuche bei schweren Animien.” Virchow’s
Archiv, Bd. clix, Heft 2.
8 Rubner und Heubner, “Die kiinstliche Erniihrung eines normalen und eines atro-
phischen Siuglings.” Zeitschr. f. Biologie, Bd. xxxviii, p. 315.
9 Miiller, loc. cit.
W Weintraud, loc. cit.
48 “ANALYSIS OF DISTURBANCES OF METABOLISM
Conditions of stasis, as in disease of the heart, do not cause decided loss
in albumin absorption (Grassmann‘) neither are diarrheas of mild grade
combined with a decrease in the assimilation of albumin in the intestine (v.
Hosslin).?
We know from the researches of v. Mering that the absorption of carbo-
hydrates in the intestinal canal (in the form of sugar) does not take place
so much by the chyle tracts as by means of the circulation, and that they
are introduced through the roots of the portal vein into the general circula-
tion. We might expect that circulatory disturbances in consequence of stasis
of the portal vein and in uncompensated valvular disease would seriously
interfere with the absorption of albumin.
The investigations of Grassmann in persons with valvular disease did not
show any such influence from disturbance upon the circulation, and many
later studies of assimilation have not demonstrated a decided decrease in
carbohydrate absorption. Even in Deucher’s investigations in patients with
occlusion of the pancreatic juice from the intestines, the absorption of carbo-
hydrates is complete. Nevertheless, the pancreatic juice contains the most
active saccharifying ferment known.
The negative results obtained probably depend in part upon the unreli-
ability of the method previously in use. It was therefore a matter of great
importance when A. Schmidt with a uniform diet (test diet), and by means
of a new method (fermentation test), taught us to discern the finer disturb-
ances in the absorption of carbohydrates.
In numerous investigations undertaken in association with Strassburger *
he succeeded in recognizing a pathological condition (in which the clinical
symptoms were not very pronounced, but, nevertheless, were sufficiently char-
acterized by an incomplete digestion of starch) as a not uncommon disturb-
ance of function of the small intestine (in a broader sense, including the
pancreas and the upper large intestine). Only by a quantitative study of
metabolism can a positive diagnosis be made (intestinal fermentative dys-
pepsia). ‘
In conclusion we must refer to the great importance of quantitative clin-
ical researches in absorption, in the healthy and in the sick, as helping us to
decide upon the merits of the nutritive preparations with which chemical in-
dustry has flooded the market during the last ten years. The new albumin
preparations, in particular, have thus instigated researches in the clinic, and
the studies in metabolism upon which the employment of neutrose, eucasin,
tropon, plasmon, and roborat are based are certainly not few. The degree of
absorption as shown by quantitative investigations in metabolism, together
with practical experience at the bedside, will always be the best measures of
the actual value of such food preparations.
1Grassmann, “Die Resorption der Nahrung hei Herzkranken.” Zeitschr. f. Klin.
Med., Bd. xv, p. 183.
2 v, Hosslin, Experimentelle Beitriige zur “ Frage der Ernihrung fiebernder Kranker.”
Virchow's Archiv, Bd. Ixxxix, p. 95.
’ Schmidt und Strassburger, Deutsches Arch. f. klin. Med., Bd. xix, p. 570.
CONCLUDING REMARKS 49
CONCLUDING REMARKS
In the pursuit of knowledge regarding metabolism in pathological condi-
tions, also in the nutrition of the sick, in the last twenty years, it would
be unjust to ignore the importance of the dynamic point of view in the inves-
tigation of the processes of metabolism, which to-day dominates pathology
as well as physiology.
On the other hand, however, we cannot be too careful—when relying upon
a law based upon the combustion value of individual food products—in con-
sidering the quantitative exclusively, or even to such an éxtent as has been
the custom of the average student of metabolism in the last few years.
Primarily it is practical experience at the bedside which should dictate
the diet, and not theoretical knowledge of food requirement, however well
founded. The patient cannot be nourished with calories alone, and it would
certainly restrict the further progress of our knowledge of the laws of nutri-
tion if we should consider the caloric value of the individual foods more, and
the individual digestibility and tolerance, the manner of preparation, etc., of
foods less.
All honor to the calory reckoning of the food—it is of inestimable value
in the treatment of chronic diseases—but we must beware of carrying it too
far. In practice we have a sufficiently well-founded dietetic treatment, espe-
cially in acute disease, without calory reckonings.
But apart from this limitation of its value in practical dietetics, which is
not to be misunderstood, the purely dynamic conception of processes of metab-
olism has not always influenced our scientific understanding and research in
these problems in a fortunate way.
Upon one of the first pages of Hoppe-Seyler’s Physiologic Chemistry,
these words are italicized: “The process of life of the organism is, in the
main, a complete mystery.”
When we read, however, in modern clinical researches in metabolism, that
in the form of albumin, fat or carbohydrates only such and such calories are
to be allowed in the diet, or are to be eliminated from the diet, in order to
increase or to diminish the proteids or fat of the body, or definitely to influ-
ence the activity of the organism in this or that direction, we might almost
believe that the veil had long been lifted from the mystery, while in reality
we are as far from a solution as we were in the period in which Hoppe-Seyler
wrote the foregoing words.
In the modern pathology of metabolism the view is constantly becoming
more prominent that the calory carriers of the introduced food are simply
decomposed in the daily metabolism of the body without having become an
integral constituent of the organism. This prevents us from studying the
great problem of life, and the investigator gets his inspiration not from the
hope of a speedy solution of the problem but purely in the exhilaration of
steady work and steady progress upon the path already trodden; still the goal
itself must never be lost sight of.
This, however, is the case if the view is accepted as final that the mystery
5
50 ANALYSIS OF DISTURBANCES OF METABOLISM
of life was long ago solved by the hypothesis that the organism is a machine
in which the food products undergo combustion somewhat as in an oven,
thereby becoming a source for the production of heat and force.
This is what Liebig assumed for the N-free foods (carbohydrates and
fats), which he therefore designated as respiratory materials; because they
undergo combustion without taking part in the structure of the body he did
not consider them true foods. In true metabolism, in the decomposition of
products, in labor and in the regeneration of tissue destroyed thereby, they
have no part according to his conception. And when Voit explained the
decided increase of albumin decomposition upon adding albumin to an already
sufficient diet by an increase of “ circulating albumin,” and (in place of the
“luxury consumption” of albumin, which was the current theory) showed
the special conditions of decomposition of circulating albumin, making it
responsible for the increase in albumin decomposition, then it was proclaimed
that albumin also may be decomposed without being taken up into the organic
parts of the body. Thus the opinion became more deeply rooted, favored by
the purely dynamic conception of the food products as carriers of energy,
that without any entrance of the food into the tissue of the living cells, the
condition of the body could be influenced by the food in the circulation, where
the nutritive products were supposed to be built up by transference into higher
stages of oxidation. In this manner the organism was supposed to be able to
utilize its food and the energy resulting to cover its losses in heat and mechan-
ical labor.
This conception found decided support in the demonstration by Voit that
muscular labor does not go hand in hand with an increased albumin decom-
position.
Many objections may be raised, however, to such a conception of the
processes of nutrition. Since this conception occurs particularly in the arti-
cles on metabolism written by clinical pathologists it is probably to be ex-
plained by the historical development of the pathology of metabolism on the
basis of Voit’s law of metabolism and nutrition.
Certainly much would have been otherwise if the principles which Pfliiger
advocated in his numerous publications had been accepted.
In many clinical researches of metabolism the subject of investigation can
only be comprehended after considering its historical development.
I shall only refer to the question, still mooted,! whether alcohol is a
nutrient and an albumin saver. As a carrier of energy alcohol is of even
greater importance than the carbohydrates, the recognized albumin savers
Sie gram of alcohol = 7 calories, one gram of carbohydrates = 4.1 calo-
ries).
How could this question have been so long disputed if alcohol, following
the dynamic laws, simply undergoes combustion in the body, and in this
manner offers its energy value to the organism? And why, in the numerous
clinical investigations of metabolism in regard to the albumin-saving action
2 R. Rosemann, “ Ueber die angebliche eiweisssparende Wirkung des Alkohols.”
Pfliiger’s Arch., Bd. xxvii, p. 405; here also the other literature.
CONCLUDING REMARKS 51
of alcohol, does it so constantly strike us that the results of research are con-
flicting and permit different explanations?
Because the whole process is without doubt quite different from our ordi-
nary dynamic conception of it. Alcohol, after absorption, is not only decom-
posed into carbonic acid and water, and thus converted into a definite amount
of heat, but, moreover, it enters the protoplasm of the cells where all oxida-
tion takes place, and there modifies the destruction of the protoplasm.
For the same reason the carbohydrates and fats do not act isodynamically
in regard to albumin saving, as would be the case if the supply of heat repre-
sented by them became free in the circulation. In fact the carbohydrates
are more active than the fats in the physiologic experiments.
By the appearance of acetone bodies after the complete withdrawal of
carbohydrates, pathology indicates that not only quantitatively, but also quali-
tatively, the destruction of the cell protoplasm occurs in different ways, accord-
ing to whether the carbohydrate molecule or the fat molecule is found in the
cell which dominates the processes of decomposition.
It has already been mentioned that the newer facts regarding the condi-
tions and the occurrence of the accumulation of albumin are very difficult to
reconcile with Voit’s laws of albumin metabolism.
The fact that gelatin, and as Mann? has lately shown, also elastin, even
although they are inferior to fat as calory carriers, are far superior as albu-
min savers, certifies beyond doubt that the nitrogen-containing food mole-
cule of the body-cell in which decomposition takes place brings with it
something else than the calories—something which influences metabolism,
independently of the calories which it brings.
Analogous with this is the remarkable observation of Loewi,? who fed a
dog with N-free starch and cane sugar as the sole carriers of nitrogen and
with soluble products of continuous pancreas digestion until the complete
disappearance of the biuret reaction. Thus he managed to produce nitrogen
equilibrium. Therefore, the dog must have formed albumin synthetically
from the nitrogen carriers in solution (from amido acids, ammonia, purin
bases and hexon bases).
This proof was necessary to throw light upon many physiologic and patho-
logic processes of metabolism. I shall mention only one more:
According to the dominant teaching, it was formerly very difficult to
answers questions which arose as to the origin of muscular power. Voit was
the first to show that increased muscular labor is not expressed by a decided
increase of albumin decomposition (in the balance of metabolism), and, in
opposition to the views of Liebig who believed albumin decomposition to be
inseparably combined with the activity of the organs, regarded the nitrogen-
free food products as the source of energy from which the organs, without
suffering in their substance, derived energy for their functions.
Now the newer investigations of Caspari actually show an accumulation
1 Mann, “ Ueber das Verhalten des Elastins im Stoffwechsel des Menschen.” Arch.
f. Hygiene, Bd. xxxvi, p. 166. :
2 Loewi, “ Ueber Eiweisssynthese im Thierkérper.” Centralbdl. f. Physiol., Bd. xv,
p. 590.
52 ANALYSIS OF DISTURBANCES OF METABOLISM
of albumin (nitrogen retention) during forced muscular labor. Is it possi-
ble that the muscular machine acts so wonderfully that it is not subject to
wear and tear, but actually develops during this condition, while it transfers
the energy supplied by the carbohydrates into living force? Or are the con-
ditions in reality quite different, and are nitrogen-free substances really
burned in the muscle during its work, or, on the contrary, does it decompose
the specific albuminous protoplasm of the muscle cell so that the nitrogen
also at once decomposes like the albumin of the muscle, and is utilized for
the reconstruction of muscular albumin? Verworn assumes that in muscular
activity the biogen molecule which represents living albumin decomposes into
atom groups containing nitrogen and non-nitrogenous atoms, of which only
the latter are excreted in metabolism, whereas the former regenerate to com-
plete biogens. That we must recognize synthetic processes if we are to make
such an assumption, cannot be thought remarkable after what has been said.
For does not the animal organism evolve from inorganic iron such a highly
complicated molecule as is represented by hemoglobin? It produces syn-
thetically nuclear albumin from its components, etc.
If we dismiss the view that each molecule of food which is absorbed, and
is required by the organism to maintain its vital functions, is at once in all
its constituents decomposed into end-products of metabolism and quantita-
tively excreted, then many other points in the pathology of metabolism for-
merly difficult to understand will be made clear.
When nuclein decomposition occurs in the body, the phosphoric acid ex-
cretion is frequently not uniform with the excretion of alloxur bodies; appar-
ently because phosphorus is retained for the purpose of nuclein synthesis, for
the regeneration of the nuclein which has been lost.
After complete withdrawal of carbohydrates, the amount of sugar excreted
in severe cases of diabetes (as has lately been frequently observed) may
exceed the quantity which may be assumed to be formed from albumin. Be-
fore we speak of a sugar formation from fat, we should think of a renegera-
tion of the N-containing part of the albumin molecule after splitting off the
carbohydrate group, perhaps with the aid of the atom groups taken from
the fat molecule. This is, however, quite different from a direct sugar forma-
tion from fat expressed in chemical equation. It is simultaneous splitting
and synthesis, a work of the living cell, whose effort toward regeneration
becomes greater the more its protoplasm is involved in decomposition.
In the study of the pathology of metabolism, we must escape from the
narrow confines of views which, in the discipline of student days, were of
certain value to us, but which must no longer be a barrier to development.
The opinion must probably be discarded that the amount of decomposi-
tion of animal protoplasm (living substance), that is, the amount of metabo-
lism necessary to maintain life, is equal in all individuals and at all times.
_ Of course the common estimation of the amount of total energy consump-
tion in clinical metabolism investigations is not decisive in judging this
question. Slight, and even scarcely noticeable differences in the activity of
different individuals (greater muscular exertion, etc.) may produce vary-
ing degrees. Hence the difference of two values obtained under similar con-
CONCLUDING REMARKS 53
ditions of research should not have too great importance attached to it, as the
identity of the conditions is only apparent.
Nevertheless the low nutritive values which are sufficient to maintain life
after prolonged under-nutrition. and in some cases of diabetes are of no
importance. That in some obese persons an exireme diminution of the
calory supply is actually necessary before they begin to lose weight also makes
it likely that here a fundamental property of the living cells is changed, so
that the degree of their energy of decomposition has been diminished. And
the contrary experience that, in some perfectly healthy persons, even with
a food very rich in calories, it is impossible to produce an increase in weight,
makes us doubt whether in this case the amount of food is really the decisive
factor in the interchange of energy. On the contrary, cases of this kind
make it more likely that there is an increased energy of the cells and so an
actual “ luxury consumption.”
In practice these individuals do not always present such conspicuous ezter-
nal signs of a lively temperament that the increase in metabolism can be ex-
plained by an increased activity of the muscles; and we are the more inckined
to search for an individual anomaly of protoplasmatic activity, if such en
assumption can be in consonance with the dominant teaching.
The dynamic theory, which has been of inestimable value in making us
recognize in biology the force of the law of conservation of energy, naturally
lays particular stress only upon the intake and output of the organism. But
this theory does not exclude intermediary metabolism from consideration in
the future. The importance of inorganic salts will then appear in its proper
light; they are indispensable in the food; nevertheless, because they do not
bring tension power (calories) into the organism they have no part assigned
to them in the dynamic conception of the processes of metabolism and
nutrition.
Again we must remember that in the animal organism we have not only ten-
sion energy consumed, but sources of energy newly formed (ferments).
Although researches in the realm of the pathology of metabolism will be-
come much more complicated, when all these facts are borne in mind the
desirable result will be attained that clinical pathology of metabolism will
become deeper but less expansive.
OVER-NUTRITION AND UNDER-NUTRITION
By C. v. NOORDEN, Franxkrort-on-Main
In modern therapy, dietetic cures are becoming more important from
year to year, particularly those which are intended to influence the entire
nutritive condition. Originally confined to the domain of internal diseases,
they have become familiar to the surgeon and gynecologist, and no less valu-
able to them than to the specialist in clinical medicine. It is well worth
“ia to consider the salient features of these cures, without expecting that
much that is new will be promulgated. For the fundamental laws are well
known, though their application to practice is eternally new. When the indi-
viduality of each patient has to be considered, the rules lose their supposed
uniformity and their diagrammatic aspect. Uniform and self-evident as the
method is when formulated in theory, in practice each particular dietetic
treatment brings with it new difficulties, new demands, and when the art of
the physician has succeeded, he invariably experiences the gratification of an
artistic triumph.
1. CONCEPTION OF THE “CONDITION OF NUTRITION”
When we speak of a person’s “condition of nutrition” we mean, in the
first place, his development of adipose tissue; but not only this is to be con-
sidered, for the state of the muscles is of no less importance. Their devel-
opment is not always proportionate to the amount of fat. There are many
persons who are deficient in fat and weak in muscle, and many who are rich
in fat and strong in muscle. But there is a third class who are of strong
muscular power and deficient in fat, and a fourth who are lacking in muscle
and rich in fat.
Of most importance, of course, is the condition of the muscles, all the
more so since with powerful muscles we expect a normal composition of the
blood and of the most important glandular organs. In every treatment by
which we hope to influence the “ condition of nutrition” the protection of the
muscles must be kept in mind, or, stated more generally—the living and func-
tioning protoplasm of the body must be protected, and if possible improved,
so that the maximum of its development may be attained.
How great is the amount of fat on the body—leaving out of considera-
tion pathologic leanness, pathologic obesity and special instances (see below)
—is of less significance. There is no generally accepted standard for a nor-
mal amount of fat. Between emaciation on the one hand and obesity on the
54
INCREASE OF FLESH AND INCREASE OF FAT 55
other hand, there is a wide space for the conception of a “medium state of
nutrition.” Although this conception permits no positive statement as to
the amount of superfluous fat, no definite body-weight, no distinct relation
between weight and size, age and sex, that can be called normal, it must,
nevertheless, be maintained that, for each individual, there is a definite stand-
ard for the condition of nutrition, particularly with regard to the amount of
fat. To recognize this optimum is the duty of the physician, and presup-
poses much thought and experience. Good judgment will take into considera-
tion the state of health, the competency of all the organs, and the entire mode
of life. A few examples will illustrate this. Experience teaches us that
persons who are predisposed to tuberculosis are endangered by leanness, and
that a certain degree of corpulence protects them. Neurasthenics, as a rule,
feel better if they have a large amount of adipose tissue. For patients suffer-
ing from disease of the heart, Bright’s disease, and emphysema the slightest
amount of superfluous fat is an evil, and in diseases that affect the organs
of motion, obesity is, at least, the cause of great annoyance. Persons who
perform hard labor continue in better health and are more capable of working
if their adipose tissue is not too greatly developed. Those who have passed
the prime of life, and are no longer compelled to work hard, bear a certain
development of corpulency better than those just beginning the struggle for
existence. These points will be amplified in the description of the indica-
tions for over-nutrition and under-nutrition.
It follows from what has been said that in all treatment by which we
attempt to influence nutrition, we must first of all try to maintain and
improve the muscles; in certain cases, however, we attempt nutritive cures
in which increase or diminution of adipose tissue represents the sole aim of
the treatment. Even in these, however, the state of the muscles must not be
lost sight of. The importance of this must be emphasized, for very frequently
it is forgotten. We sometimes see patients with weak muscles who in the
process of “strengthening” are fattened by various means, and when the
cure is done we find obese subjects with feeble muscles. Again we see corpu-
lent persons subjected to such irrational antifat cures that not only the fat
but also the muscles and blood are depleted, and the activity of their func-
tions permanently injured.
Our theme will be the question: How far can and should the general
condition of nutrition, 1. e., of muscle and fat, be influenced by dietetic treat-
ment?
2. INCREASE OF FLESH AND INCREASE OF FAT
To accomplish the most important point, the accumulation of muscle,
dietetic treatment has, unfortunately, but limited powers. Theoretically it
appears to be most difficult to maintain the musculature of the body in anti-
fat cures. The animal experiments of physiologists have invariably shown
that with under-nourishment fat disappears from the body, but that albumin
also decreases. To this loss of body albumin, that is to say, waste of muscle,
we owe the serious consequences which frequently surprise those who carry
out a too rapid antifat cure. Discussions regarding the admixture and
56 OVER-NUTRITION AND UNDER-NUTRITION
amount of nourishment which will most surely produce a loss of fat without
impairing the muscular condition have been carried on for years, and reached
their acme in the debates at the Congress of Internal Medicine in the year
1885, and in the literary war waged between Ebstein and Oertel. The views
were based rather upon theory than upon practical experience. Investigations
regarding metabolism during antifat cures had not yet been attempted. A
few years later when, independently of one another, F. Hirschfeld and v.
Noorden-Dapper worked out this problem experimentally, contradictions at
first resulted. The former found it almost impossible to produce a loss of
fatty tissue without a simultaneous decrease of the body albumin. The other
two authors proved by numerous investigations that this goal may be reached,
and even without special difficulty, provided the leap from a plentiful diet to
one of abstinence is not too sudden. All the authors who later devoted them-
selves to similar researches have confirmed this. The satisfactory result of
these studies of metabolism has had, it appears to me, great influence upon
the practical work of physicians, and has encouraged them—certainly not to
the detriment of the patient—to attempt careful antifat cures, where pre-
viously they refrained from them because in every antifat cure—even if only
transiently—the supply of body albumin was jeopardized. According to other
investigations in metabolism as well as in my own, and also according to later
researches of Dapper and myself, careful planning of the ingestion of nour-
ishment so that the albumin supply of the body will not be decreased may
obviate this danger, but by no means removes all other difficulties. For, in
numerous cases, it is evident that the muscular power of the patient must not
only be maintained but increased. This end also may be practically achieved,
and will crown the success of a thoughtfully carried out antifat cure. It pre-
supposes that the patient must become accustomed, from the beginning of
the treatment, to an increasing amount of bodily exercise. We must utilize
the well-known physiological fact that, if we exercise a muscle, it gains not
only in strength but also in bulk. It is true that investigations of metabo-
lism in which the combustion of albumin has been tested during dietetic
antifat cures with and without systematic, muscular exercise have not yet
been carried out; but we hardly require them, for clinical experience demon-
strates how readily strength and size of muscles may be increased during
dietetic antifat cures.
Formerly (in opposition to the facts) we regarded the preservation of
the stability of the organic albumin in antifat cures as difficult, even impos-
sible. Yet, at the same time, it was not doubted that by forced feeding it
was very easy to accelerate not only the formation of adipose tissue but also
of the animate protoplasm of the body, and particularly to strengthen the
muscles. The proposition, however, is by no means so simple as it appears.
That albumin metabolism is diminished and N-containing material accumu-
lates in the body on over-feeding with albuminates, particularly with fat, and
to a still greater degree with carbohydrates, had been long known from animal
experiments by Bischoff and C. v. Voit and their pupils. Investigations in
man—especially the researches of Bleibtreu and Krug—have confirmed this,
and Bornstein and Liithje in their latest studies in metabolism have demon-
INCREASE OF FLESH AND INCREASE OF FAT 57
strated the surprising fact that the amounts of nitrogen which remain in the
body in over-nutrition may be raised in an astonishing degree. There can be
no doubt, therefore, that an increase in the body nitrogen may be secured by
the quality and quantity of food. In all probability we may go further and
say that this increase of nitrogen means increase of albumin, i.e., the N which
remains accumulates in the body in the form of albumin. Here our knowl-
edge for the present ceases. C. v. Voit has called attention to the fact that,
in an adult animal, the albumin accumulated by excessive nutrition is stored
up in a form readily decomposed and must therefore be differentiated from
true organic albumin. Hence he proposed the name “circulating albumin.”
Since it is, however, extremely unlikely that this albumin actually “ circu-
lates,” i.e., that it is present in the circulating fluids, and as it is very much
more probable that it is deposited in the cells, I have suggested the term
“reserve albumin.” This term has now been generally accepted. It is meant
to imply that the albumin, like the fat globules and glycogen granules, is
absorbed into the body of the cell, and is deposited there for a time (as reserve
material) without becoming an integral constituent of the cell protoplasm.
According to this, in the investigations conducted with me by Krug, and in
my Text-Book of the Pathology of Metabolism, I have regarded it as unproven
and improbable that the increase of body-albumin which may readily be
attained is synonymous with increase of muscle. Increase of muscle should
mean the increase of living cell-albumin. But the mass of blood-cells and
gland-cells unquestionably is but little influenced, and this is especially true
of muscle. With few exceptions (prominent among them E. Pfliiger and
Bornstein) later authors have accepted this view, and in a recent excellent
and instructive, as well as critical, dissertation by Liithje, who has produced
by far the greatest increase of body-albumin, we find the same opinions ex-
pressed. If increase of albumin (so readily attained) were synonymous with
increase of true muscle tissue weaklings could without great difficulty be
transformed into robust, muscular people. But this is of course impossible.
Every one knows that over-nutrition will produce corpulent persons, but not
athletes.
Increase of muscle is a function of the specific growth energy of the cells,
i.@., of cellular activity rather than of excessive nourishment. Hence we see
plentiful and permanent increase of muscle:
1. In every growing body.
2. In the fully grown body when it is gradually accustoming itself to
increased labor (work hypertrophy of the muscles).
3. When; from previously insufficient nourishment or from disease, the
muscular tissue of the body has been diminished, and subsequently profuse
nourishment makes up this loss. It is a fundamental error to look for the
primary cause of this variety of muscle accumulation in food; it is an expres-
sion of the regenerative energy of the cells. This is a mighty power. It shows
itself, as investigations in the metabolism of convalescence have demonstrated,
even when there is no question of forced feeding, and indeed when the calory
supply is so slight that fat must certainly be lost in the body, and even a
healthy person would lose body albumin.
58 OVER-NUTRITION AND UNDER-NUTRITION
Of course, under circumstances otherwise favorable for the accumulation
of albumin, muscular development takes place more certainly and more rap-
idly with very profuse nourishment than with scant food. Usually, however,
in adults otherwise healthy—provided we consider long periods of time and
not brief intervals—muscle-increase is independent of an excess of food.
Muscle growth is dependent on food supply only because the body is better
supplied by over-nutrition with reserve products (glycogen, fat, reserve albu-
min), and because better food and the somatic and psychical stimulation
resulting from it produce greater capacity for work. To this greater capacity
of the muscles and secreting glands for work and the stimulus for blood for-
mation which arises thereby, the body owes its power of accumulating proto-
plasm as well as fat, and—what is more important—of permanently retain-
ing it.
cer this point of view, it appears that under special conditions (after
wasting disease or after prolonged periods of hunger and under-nutrition) we
may hope by over-alimentation to promote the formation of new protoplasm,
and particularly of muscular substance. The natural regenerative endeavor
of the organism will aid us. If, however, we are treating persons who,
although weak, are sufficiently well nourished, the chances for increased mus-
cular development are much more uncertain.
In such debilitated individuals, especially in convalescents, the accumula-
tion of flesh will be greatly favored, if from the onset, or as soon as the
strength at all permits it, forced feeding is combined with muscular exercise.
This, however, contradicts a widely prevalent custom; for, in the original
methods of Playfair-Mitchell, most patients who were to undergo forced
feeding were advised either to go to bed or to keep as quiet as possible. In
certain cases, for example, in very irritable nervous persons, this may be fully
justified. Generally, however, it appears to me after years of experience that
early and sufficient activity of the muscles is much more beneficial when we
desire to nourish our patient. The increase in weight is not less than in rest
cures, and it is gratifying to note that the patients gain in muscular strength
and activity at the same time that they increase in weight and size. There
is very little danger that, in consequence of muscular exercise, much of the
fat which has heen acquired with difficulty may be again lost, since the in-
ie of appetite induced by muscular exercise easily makes good the material
used up.
In view of what has been said it is obvious that in forced feeding, as well
as in carefully and wisely conducted antifat cures (for obesity), the increase
and strengthening of the muscles is almost independent of the loss or accumu-
lation of fat. Insufficient nourishment in obesity favors the loss of muscle;
superfluous nourishment both in normal nutrition and when it is below par
favors the accumulation of muscle. But muscle-loss and muscle-increase are
not in immediate dependence upon, or in exact proportion to, the quantity of
food. An individual factor always intervenes; an elective property of the
organism rather than the bulk of food produces muscle-accumulation.
The conditions are quite different in losses and accumulations of fat.
Here the law may be definitely stated, When the supply of nourishment is
os: ‘Saree at a eae.
OCCURRENCE AND CONSEQUENCES OF UNDER-NUTRITION 59
less than the requirement for maintenance, fat is always lost; when it is
greater than the requirement for maintenance fat is always accumulated. In
the former case we speak of under-nutrition, in the latter case of over-
nutrition.
Although I shall be repeating what is known to most readers, it is neces-
sary to devote a few lines to the definitions of food necessary for maintenance,
of over-nutrition, and of under-nutrition.
In proportion to the requirement of the cells, according to the amount of
work required of them externally and internally in heat production, etc., the
body arranges the use of material for combustion. When the combustion
value of the food is equal to the demand, the equilibrium of metabolism in
the body is preserved. The amount of food which is necessary for this we
call “ food necessary for maintenance.” Most normal persons, if left to them-
selves and following their own inclinations, usually take neither more nor
less food than is necessary for maintenance; variations in this balance of
nutrition may occur, but the deficiency of one day is made up the next. Con-
sequently it is the rule that normal adults remain for years and decades at
about the same weight. The proportion of food which is necessary for the
equilibrium of metabolism, calculated per day and for each kilo of the body-
weight, must have a combustion value of from thirty to thirty-five calories in
complete rest (in bed), thirty-five to forty calories with hght exercise, forty
to forty-five calories with moderate exercise, and forty-five to sixty calories in
exhausting muscular labor.
For children these figures are to be raised about one-third, for the aged
they are to be lowered about one-fourth. There are no decided differences
between males and females. These figures relate to a “moderate condition
of nutrition”; in the obese they are from twenty to twenty-five per cent.
lower, in very thin persons they are just as much higher, for while fat in-
creases the body-weight it takes no part in metabolism. This ratio will enable
us to calculate the amount of food necessary in the individual case with suffi-
cient exactness for practical purposes.
3. OCCURRENCE AND CONSEQUENCES OF UNDER-NUTRITION
As soon as the supply of -food (i.e., its combustion value) falls below that
required for maintenance we have a state of hyponutrition. The under-nour-
ished body does not accommodate its combustion processes to a lower scale—
except perhaps in the most extreme marasmus and in the death agony. When
the supply is less than the requirement, it lives upon its own body substance.
In the obese, as we have seen, this process may be limited to the adipose
tissue while the albumin, that is, the muscle, is preserved. In normal and
mal-nutrition, however, apart from exceptional cases (in convalescence after
acute diseases, or after periods of hunger), the supply of albumin in the body
may also be slowly consumed, and the person not only loses fat but becomes
weaker in muscle. We rarely resort to systematic under-nutrition except in
the treatment of obesity. Whether or not treatment for obesity is indicated
does not depend wholly upon the degree of corpulence, but also upon many
60 OVER-NUTRITION AND UNDER-NUTRITION
other conditions, particularly upon the healthy state of certain organs, for ex-
ample the heart and the kidneys. To this we shall refer later. But very often,
without our interference and against our will, our food produces the character-
istics of hyponutrition. This occurs in many diseases. We are unable to main-
tain the balance of nutrition either because patients refuse to take a sufficient
supply, or because diseases of certain organs (for example, the stomach)
necessitate a limitation. In acute diseases which run a rapid course the dan-
ger is not great, for what has been lost is rapidly regained in convalescence.
But in chronic diseases the body is often more weakened and damaged by con-
tinued under-nutrition than by the disease itself. It then becomes one of
the most important duties of the physician to increase the amount of food
at least to the point of maintenance, and, if possible, to make up what has
been lost by forced feeding. He will then often have the pleasure of noting
that not only does the state of nutrition improve, but that this improvement
acts favorably in the cure of the disease. In some maladies, for instance, in
not too far advanced tuberculosis of the lungs, this is the rule.
At least as frequently as in actual disease we meet persons who are really
not ill but under-nourished. This results from caprices of appetite, from
unfounded fear of injury from this or that food (for example, fat substances),
from disturbances of appetite which are slight or which are taken too seri-
ously, from poverty, ete. Thus they have become accustomed to a too slight
ingestion of nourishment. Sometimes this is habitual from youth, and such
persons if left to themselves never attain the acme of nutrition (muscular
and fatty tissue) of which they seem capable, judging from their constitution
and build. Adipose tissue is scant, and the muscles, no matter how suscep-
tible of development, and no matter what efforts are made to strengthen them
by exercise, continue weak, for everything that is attempted is frustrated by
the oxidation-processes of the body.
Others first manifest the symptoms of chronic under-nutrition after they
have reached adult life. These are mostly persons in whom there is a neuro-
pathic taint, and in whom the various forms of nervous dyspepsia develop.
Still others have become neurasthenic and hysterical only in the struggle for
existence against adverse circumstances. Organic causes which would pre-
vent a sufficient ingestion of food are not present, but manifold nervous dis- -
turbances interrupt the distinctive connection between actual food-require-
ments (tissue hunger) and appetite (gastric hunger). Gradual loss of weight,
disappearance of adipose and muscular tissues, lessening. of the bodily and
mental powers, are the inevitable consequences. These patients, to the detri-
ment of their health, often seek a cure by unsuitable means, by gymnastic
exercises and sports, by mountain climbing, by exhausting cold-water cures
(frequently in so-called nature-cure institutions), where they hope to build up
their nervous system. This acts at first like a whip, apparently increasing
and stimulating their activities But the oats are lacking, and in a short
time there is a relapse to the former condition. The treatment is all the more
harmful because the food, during the time spent in these exhausting cures,
is weakening rather than strengthening. The patients and their “ Natural-
Healer ” proceed from the view that a too profuse animal diet has disordered
OCCURRENCE AND CONSEQUENCES OF OVER-NUTRITION 61
the nervous system. Meat and eggs are withdrawn and the patients are put
upon a vegetable diet. To this no special objection can be raised, provided
it is carefully chosen; but too frequently it is lacking in nourishment. This
has been so abundantly proven as to need no further consideration at this point.
4. OCCURRENCE AND CONSEQUENCES OF OVER-NUTRITION
If the food (i.e., its combustion value) exceeds what is necessary for
maintenance we have the condition of hypernutrition. In over-nutrition the
organism does not increase its processes of combustion, or, at least, does so
to a very slight extent. Perhaps the increase of oxidation which arises from
over-nutrition has been for a time underestimated, as the latest investiga-
tions of Fr. Miiller appear to prove. Theoretically this increase is interest-
ing, but it is too slight to be of practical importance.
The increase of oxidation is not due to a stimulation of the cells to a greater
katabolic activity, in other words, to a greater rapidity of metabolism, but
only to the greater labor which is put forth by the mechanism of mastication,
the stomach and intestines, the digestive glands, the organs of circulation and
respiration, etc., in order to work up and utilize the greater mass of food.
After deducting the slight amounts spent upon the increased labor of diges-
tion, ete. (about 7 per cent. to 20 per cent. of the energy supplied by the
food), a large residue from the superfluous food remains, which accumulates
as reserve material, and serves to increase the body mass. We call this “ food
surplus” (= the difference between food ingested and food used up in metab-
olism).
Aside from slight differences it is of no importance to the processes of
metabolism whether the surplus of food occurs from: excess of albuminates.or
of N-free food, or whether the increased supply comes from one source only
(the albumin or the fat or the carbohydrates). A surplus of carbohydrate
nourishment favors almost exclusively the production of adipose tissue, pro-
vided special circumstances do not promote the increase of protoplasm (see
above).
In an especial case (B. Krug’s experiment upon himself carried out under
my direction) the following calculations were made:
Dr. Krug (perfectly well and in a moderately good state of nutrition),
after a period in which he had been abundantly nourished, took for fifteen days
in addition to his ordinary food a daily total of 1,710 calories, consisting of
fat and carbohydrates. This sum represented “surplus nourishment”; for
the fifteen days it amounted to 25,650 calories. Of these 23,051 calories were
utilized by the body.
1,720 calories = 7.46 per cent. albumin accumulation, and
21,331 calories — 92.54 per cent. accumulation of fat.
Whether the production of albumin was equivalent to accumulation of flesh
could not be decided.
It follows from the preceding statements that after the ingestion of a
surplus amount of food only an accumulation of fat can certainly be counted
62 OVER-NUTRITION AND UNDER-NUTRITION
upon. It is quite uncertain whether an accumulation of muscle will take
place; with an equal amount of surplus nourishment the gain in muscle
varies from case to case. It is sometimes lacking, in’ other cases it occurs to
a greater or less extent. But it may be prophesied with mathematical cer-
tainty that in over-nutrition fat will accumulate. How much is dependent
upon the amount of food, and how much upon the amount of work performed
by the body? A disproportion between the supply of food and the assimila-
tion of food, to which the accumulation of fat (and ultimately obesity)
owes its origin, can be brought about:
1. By an increase of the food above an average normal consumption ;
2. By diminution of exertion (muscle laziness) with an average normal
amount of food ; .
3. By a combination of superfluous food and diminished exertion.
We frequently meet with cases of over-nutrition, but we are not so often
called upon professionally to combat this condition as we are to treat under-
nutrition. Occasionally, however, we are called to deal either with obesity or
with persons who, by continuing their present mode of life, are in danger of be-
coming too fat. Every corpulent person has behind him a period of over-nutri-
tion ; not, perhaps, because he has eaten more than others who have not become
fat, but he has eaten more than his individual constitution and bodily func-
tions enabled him to utilize. It is immaterial whether this superfluous inges-
tion of food has arisen in consequence of a preference for albumin, for fat,
for carbohydrates, or for alcohol; we meet with obesity among decided meat-
and-fat eaters as well as among those who prefer starchy foods, sweets, and
beer. We observe it among those who perform hard manual labor, but who
more than compensate for their great metabolism and output of energy by a
profuse intake of food ; we observe it also in those who, although they eat little,
consume an amount of food out of proportion to their slight physical activity,
slight metabolism and slight output of strength. To elaborate this in indi-
vidual instances would be to consider the etiology and pathogenesis of obesity,
which is not the purpose of this article (the reader is referred to my mono-
graph on obesity in Nothnagel’s Handbuch der speciellen Pathologie und
Therapie).
Whether in the development of corpulence there is an increase of the mus-
cles depends,-as we observe daily, upon external conditions. The rule holds
good that only those obese persons who utilize and, in spite of their corpu-
lence, exercise their muscles have strong and firm muscles. In such people
we see the picture of the so-called “ plethoric obesity.” Those who live much
indoors have flabby and weak muscles, often so weak that serious consequences
may be the result. Distressing yet convincing proofs are thus furnished to
show how loose is the connection between over-nutrition and increase of muscle.
5. INDICATIONS FOR HYPERNUTRITION AND HYPONUTRITION
Having explained the changes of metabolism which occur in the organ-
ism in under-nutrition and over-nutrition, we must briefly discuss the indi-
cations for forced feeding and for antifat cures.
INDICATIONS FOR HYPERNUTRITION AND HYPONUTRITION 63
A. OVER-NUTRITION
Group 1. In chronic wasting diseases—Considered historically, over-
nutrition in pulmonary tuberculosis, or rather in tuberculosis of any type,
is to be placed in the front rank. Even the old custom of administering cod
liver oil in “scrofula” and tuberculosis belongs to this category. We have
gradually been forced to acknowledge that its action is not specific but due to
the fat which it contains, that is, to its high nutritive value. Brehmer was the
first, and Dettweiler the next, systematically to employ over-nutrition in
tuberculosis. The success of this method is surprising, as any one can see in his
daily experience. By over-nutrition, as now carried out in all institutions
for the cure of pulmonary tuberculosis, in hospitals, in the homes of the
patients, or wherever it may be attempted, we do not attain a cure for tuber-
culosis, but the favorable results which have been attained up to now in treat-
ing tuberculosis are inseparably associated with over-nutrition. Here, better
than anywhere else, it may be noted how beneficially the improvement in the
general nutrition acts upon the resistance of the tissues. J have already
alluded to this elsewhere, and, after further experience, I wish to reiterate
that the modern treatment of pulmonary tuberculosis by over-nutrition is
in danger of accomplishing too much. Pulmonary patients who had formerly
been emaciated sometimes after treatment become corpulent; this is not to be
regarded as desirable, but as a disadvantage. For obesity always throws in-
creased work upon the respiratory and circulatory organs, and in this way
makes demands upon the diseased organ which it should be spared. But apart
from these extreme cases, over-nutrition in pulmonary tuberculosis may be
designated as one of the most valuable agents in the realm of dietetic therapy.
Over-nutrition as a prophylactic measure produces even more favorable
results than in tuberculosis that has already developed. It is especially valu-
able in children and adolescents who have suffered from a previous tubercu-
lous disease of the glands, joints and bones—and hence are liable to a later
“pulmonary tuberculosis ”—as well as in those who without such preceding
affections are likely to become tuberculous on account of general weakness
and hereditary predisposition. The majority of consumptives attacked in
the second or third decades of life have been, as Brehmer once correctly re-
marked, small eaters from youth. Under circumstances such as these the
early resort to forced feeding, combined with exercises to harden the mus-
cles and properly develop the body, is one of the most beneficent and grateful
tasks of the family physician, all the more grateful if this method be insti-
tuted early in life when the body is still in the stage of growth and the
accumulation of muscular tissue takes place more readily than in later years.
Cures based on forced feeding practically play a less important réle in
all other chronic wasting diseases than in tuberculosis. Most important, per-
haps, is over-nutrition in syphilis, a disease which frequently, and especially
in its early stages, markedly influences nutrition, and in its subsequent course
(in the so-called tertiary forms) almost invariably produces extensive tissue-
disintegration. The old custom, originating centuries ago, and not yet rooted
out, was to place these patients upon a scant, meager diet, and to weaken them
64 OVER-NUTRITION AND UNDER-NUTRITION
by laxative drinks. In contrast to these old usages, an excessive or forced
administration of nourishment has shown itself to be much more efficacious,
Many protracted cases of tertiary syphilis can be cured only when the body
has been thus strengthened by over-nutrition.
Diabetes mellitus may also be counted among the chronic wasting diseases,
naturally within certain limitations, as there are numerous cases of diabetes
mellitus in which, vice versa, definite relations to obesity exist. Where this
is not the case (as in the severe forms of diabetes, particularly that occurring
in youth), emaciation is combined with the disease, partly as the result of
losses in sugar, and partly as the result of peculiarities of the diet. To inter-
fere, to replace by over-nutrition not only what has been lost and if possible
to raise the patient’s state of nutrition above the average, is important, for
experience teaches that a good state of nutrition will often avert many of the
dangers of the disease.
Diabetes insipidus must also be mentioned, Unfortunately, we know
little regarding the pathogenesis and the minute disturbances of metabolism
which take place in this disease. The most conspicuous symptom in all severe
cases is the decided emaciation and loss of strength, which cannot be reason-
ably explained from the loss of water by the body. If we leave out of con-
sideration the gradual restriction of the intake of water, and a few purely
symptomatic drug indications, the especial and systematic improvement of
the nutrition by a long-continued, forced diet is the only measure which
promises success. In view of the rarity of these cases, I shall briefly report
a case under treatment by me three years ago for diabetes insipidus. The
disease occurred in a man aged fifty, and was credibly reported to have fol-
lowed a severe shock sustained in a railway accident; it had existed for about
fifteen months. The patient’s previously normal state of nutrition had suf-
fered acutely during this time, the loss in weight amounting to more than
25 kilograms. The daily amount of urine varied between 9 and 13 liters. In
this case, by a plentiful addition of cream and butter to his diet (between 250
and 300 grams of milk fat daily), weight was increased 20 kilograms within
four months. After the first six weeks, the urine had already diminished to
between 5 and 6 liters, and, after two months more, to 3 to 4 liters. The once
markedly debilitated patient had, in the meantime, become strong again and
fully capable of working. He continued strong until attacked the following
winter by pneumonia to which he succumbed. According to the statements
of his relatives there had been no increase in the amount of urine.
Finally, among the chronic wasting diseases, we must mention exoph-
thalmic goiter (Basedow’s disease). Probably from a thyreogenous auto-
intoxication (Mobius, Fr. Miiller, A. Magnus-Levy) an increase of the proc-
ess of metabolism occurs, i. e., an increase both in the assimilation of albumin
and in the combustion of fat. In consequence of this, if the patients take
.only the amount of food which is the average for normal persons, this proves
insufficient, and they therefore consume their own body substance (protoplasm
and fat). Only by over-nutrition can we safeguard them from this. By over-
nutrition it is possible at least to conserve the fat, or we may even hope to
merease it. According to the researches of Fr. Miiller, we cannot count on
INDICATIONS FOR HYPERNUTRITION AND HYPONUTRITION 65
maintaining and developing the muscular tissue even by forced feeding so
long as the disease progresses. Nevertheless, forced feeding carried on per-
sistently is remarkably successful; the patients accumulate valuable reserve
material, and experience shows that they are much better than when exposed
to progressive emaciation by dietetic negligence. But though it is necessary
to promote the nutrition of the patient, it is not to be supposed that a very
energetic and rapid forced feeding is here indicated. Great care is neces-
sary; for patients who present severe forms of Graves’ disease, and whose
nutritive condition has been correspondingly damaged, suffer also from car-
diac weakness. To maintain their balance of nutrition, they require upon
the average from 15 to 20 per cent. more food than a person in normal health
of the same weight and build, and of course if we are to attain an increase in
weight, still more food is necessary. But according to my experience, the
cardiac difficulties frequently increase if we proceed too rapidly with forced
feeding. Indeed the cardiac weakness which results may be dangerous. Last
year an able author reported a case in which, in a short time, an increase of
weight of 22 pounds was brought about by over-nutrition. In spite of this
desirable result, collapse occurred in which the patient succumbed. I believe
it cannot be doubted that this too rapid over-nutrition was responsible for
the unfavorable outcome. I have, myself, not seen such serious results from
over-nutrition in Basedow’s disease, but I have observed exacerbations which
made me fear collapse. Hence, there is need of proceeding slowly in all
severe cases; we must be satisfied if at first only the rapid loss of weight is
stopped. When this has been accomplished, and the weight maintained for
several weeks, forced feeding should be again resorted to, but an increase of
about a pound a week should not be exceeded.
Group 2. In functional nervous diseases.—We are indebted to S. Weir
Mitchell for having pointed out the deleterious effects in neurasthenic and hys-
terical persons of a poor state of nutrition—whether this dated from the onset
or developed in the course of the disease. He still further demonstrated, by
innumerable and convincing examples, that with systematic over-nutrition
(forced feeding) not only the state of the nutrition but also the activity of
the nervous system could be restored.
Nearly twenty years have passed since the publication of these views by S.
Weir Mitchell and since that time forced feeding in the treatment of neuras-
thenia and hysteria has become the common method of nearly all physicians.
The results thus attained are the foundation and the corner stone of the
reputation which numerous clinics and sanatoria have acquired in the treat-
ment of these cases. Retrospectively speaking, this therapeutic accomplish-
ment which we owe to S. Weir Mitchell is of the highest significance. The
treatment of Weir Mitchell and Playfair, the latter of whom did a great
deal to popularize the method, consists of several factors:
1. Isolation of the patient.
2. Rest in bed, lasting according to the circumstances of the case from
one to several weeks.
3. Over-nutrition; beginning with small amounts of food, and gradually
increasing to high values.
6
66 OVER-NUTRITION AND UNDER-NUTRITION
4. Massage and faradization of the muscles during the rest in bed; careful
hydrotherapy to stimulate the circulation.
For numerous cases, especially those in which excessive irritability of the
nervous system is prominent among the clinical symptoms, no more valuable
treatment can be outlined to-day than the Weir Mitchell-Playfair plan. But
it has been demonstrated that the diversity of the cases necessitates numerous
modifications. ‘The other factors associated with hypernutrition- (especially
isolation, rest in bed, massage, etc.) are frequently not only unnecessary, but -
actually a hindrance to success. The diet which Weir Mitchell proposed may
be modified as occasion requires. Any one conversant with the laws of nutri-
tion and with general therapy may with ease select what is suitable for each
individual case.
My experience leads me to state that I frequently employ only limited
isolation, i.e., the removal of the patient from his usual surroundings and
activities, but rarely insist on prolonged rest in bed. In my opinion, the
latter should be avoided whenever possible, for reasons previously men-
tioned.
The indications for forced feeding, according to the experiences of the
last twenty years, are present in functional neuroses combined with mal-
nutrition, whether the poor state of nutrition is to be looked upon as the
cause of the neurosis, or whether the neurosis by its influence on the intake
of nourishment and digestive processes produces secondarily a damage to the
nutrition of the body. In the former case, we can well hope to remove all of
the pathologic phenomena together with their cause. In the latter case we
are at least combating a symptom from which the disease constantly receives
new stimulus.
' Here also, as in the case of exophthalmic goiter—although not for the
same reasons—I must caution against immoderation. Many neurasthenics are
easily fattened, and, after six to seven weeks, may show a gain of 30 or 40
pounds in weight. But during such rapid augmentation of body-weight new
disturbances not infrequently appear which, in themselves unimportant, are
over-estimated and exaggerated by the suspicious neurasthenic and hysterical
patient. For this reason, I limit the acquisition of weight desired to about
20 pounds, which, according to the individual case, may take from four to
five weeks. Then a halt must be called, and after an interval, forced feeding,
if necessary, may be begun again.
Group 3. In all individuals with a poor condition of nutrition it is im-
portant to determine whether this faulty nutrition has been the hindrance
to the full development of their power, to the natural building up of their
bodies (in children and young persons), to recuperation after excessive bodily
and mental labor, or to convalescence after diseases. The guide for the physi-
cian must be not only the present, but the thought of what the future may
bring. The various special indications cannot be individually described with-
out entering into the wide realm of general pathology. I should like to
repeat (see above) that for every person there is a different optimum of
nutrition. Only experience will enable the physician to estimate and recog-
nize this optimum in individual cases. He who trains himself from this point
INDICATIONS FOR HYPERNUTRITION AND HYPONUTRITION 67
of view possesses weapons against disease (existing and threatening) than
which there are none more effective.
Of course in all of these cases, even more than in Groups 1 and 2, the
development of the muscles must be considered, for by the accumulation of
fat alone nothing is gained. Therefore, systematic muscular exercise must
be added to forced feeding. The form which this exercise takes is of minor
importance. I prefer exercise in the open air (walking, mountain climbing,
gymnastic exercises, games, bicycling, etc.), provided we are certain of not
overdoing, to massage or indoor gymnastics. Gymnastics with apparatus
deserve consideration only when exercise in the open air is contra-indicated
for special reasons, or when development of special muscle groups is desirable.
As a rule, it is wise to regulate forced feeding and muscular exercise in
this third group of cases, so that only a gradual increase of weight results.
We are then much more certain of a permanent and substantial gain. In
cases belonging to the first and second group, increases in weight of about
12 to 15 pounds within four weeks—with certain exceptions (see above)—are
worth striving for, and sometimes, as in neurasthenics, particularly rapid
results are important as suggestive curative agents. But in cases of the third
group it is better to have this increase in weight distributed over months
instead of weeks. From this it may be further concluded that these persons,
who need not so much an instant recovery from a morbid condition as a general
strengthening of the body, should not be treated in hospitals or sanatoriums,
or only temporarily. Few can bear removal from the ordinary routine of daily
life for so long a time, for the air of the sanatorium is rich in psychical con-
tagion. The treatment, and especially the regulations for forced feeding and
slow increase of the body-weight, must therefore be planned according to the
patient’s circumstances, occupation, habits, and position in life. With strict
regulations we are less likely to reach our goal than if the constraint of an
institution is abolished. Of course a complete change from the previous mode
of life which led to the unsatisfactory condition is the first step. Then we
can easily learn whether a simple increase of food without any special regula-
tion of its quality, quantity or distribution is sufficient, or whether any par-
ticular food must be added to the diet to make the success certain, and, lastly,
whether this addition should come from the albumin group, from fats or
from carbohydrates.
B, UNDER-NUTRITION
Antifat cures are undertaken almost exclusively in obese persons; rarely,
if ever, in persons normally or insufficiently nourished. What rule is to
guide the physician in the important problem: Is an antifat cure to be begun
or not? I desire to refute the opinion so frequently expressed that antifat
cures always belong to the so-called “weakening cures.” The popular views
in regard to this are very exaggerated. I maintain positively that an anti-
fat cure begun for proper reasons—and provided that the choice of the
method, the rapidity with which it is carried out, and the loss of weight are
adjusted to the individual condition—never deserves the name of a “ weaken-
ing cure,” but may always be conducted without injury to the patient, and
68 OVER-NUTRITION AND UNDER-NUTRITION :
will always be beneficial to the whole body. It will be noted that this favorable
opinion is based upon a number of provisos which, although apparently sim-
ple, require careful consideration and good judgment.
I shall mention only the most important of the indications as these have
been elsewhere extensively discussed.*
1. Simple obesity in otherwise healthy persons.—(a) Extreme obesity is
almost always an indication for an antifat cure. The dangers which may
result from a further gain of fat are great, and we must endeavor to prevent
them. Certain modifications are required by the age of the patient. In chil-
dren and in adolescents up to about the twentieth year, we should be content
with preventing an extreme development of obesity, and only from time to
time, during short periods of from four to five weeks, should an effort be made
to reduce the superfluous fat (intermittent antifat cures). In the aged antifat
cures are prohibited, as almost invariably there is a rapid loss of strength.
(b) Moderate obesity (body-weight about 15 to 25 kilograms above the
average for the age, sex and height) is most frequent and at the same time
best suited for treatment. In most cases it can be let alone without any great
danger to health, but it cannot be denied that corpulence brings many evils
in its train; for if any acute disease occurs (infections, diseases of the heart,
of the lungs, of the kidneys, the joints, ete.) or after unusual exertion (such
as over-strain of the heart) the obesity may become dangerous. Here, also,
the rule holds that in the aged this treatment must not be attempted, and
in childhood and in youth only in slow tempo and with the greatest caution.
(c) Slight obesity (body-weight upon the average 5 to 15 kilograms above
the normal) in healthy persons never necessitates an antifat cure, but, if the
corpulence steadily increases, measures may be taken to check its further
development. Nevertheless, very often, particularly in women, the aid of a
physician is sought because of a desire to reduce weight and to attain slen-
derness. In many cases the physician will all the more willingly comply
with the wishes of his patients as he may thus gain control of their entire
mode of life, in which usually much should be amended. Although in the
effort to reduce early obesity, and in the timely regulation of detrimental
habits, vanity rather than bodily ill is sometimes the motive power, we as
physicians should not criticise this. It may amuse us, but it must be wel-
comed as a therapeutic opportunity.
Care is always necessary. Many a woman, as the result of a too rapid and
too far reaching antifat cure, acquires in exchange for her moderate corpulence
various derangements of the abdominal organs, such as constipation, ruptures,
gastrectasis, movable kidney, sometimes also of the uterus; or, after the dis-
appearance of fat, the liver and gall-bladder are more exposed to the pressure
of the corset, the flow of bile is impeded, and gall-stones result. All these
evils are much more frequent in slight corpulence than when it is marked.
In the latter the antifat treatment is rarely carried to such an extent that
decided pressure changes occur in the abdominal cavity; enough fat always
remains to protect the viscera and preserve them from injury.
1v, Noorden, “Sammlung klinischer Abhandlungen,” Heft 1, Berlin, 1900.
THE TECHNIC OF OVER-NUTRITION AND UNDER-NUTRITION 69
It may be said in general that slight obesity does not especially demand
slow and careful reduction of weight, although, to prevent excessive corpulence
and for many other reasons, this is often very desirable.
%. Indications for antifat cures when obesity is complicated by other
diseases.— Diseases of various kinds, from slight functional disturbances of
vital organs to severe anatomical changes, may influence the physician in his
decision of the antifat question. More frequently than otherwise, it is the
complicating conditions that we meet which lead us to combat obesity.
Such complications may lead us to undertake an antifat cure when if we
found a normal condition of all the organs there would be no indication for
treatment.
Among the disturbances whose course and prognosis are influenced by
obesity, and which for this reason may necessitate the reduction of moderate
and even slight corpulence are the following:
Disturbances of the organs of circulation, such as valvular diseases, myo-
carditis, myocardiae degeneration of the heart, fatty heart, or better, cardiac
weakness in obesity, arteriosclerosis, aortic aneurism, etc.
Renal diseases, particularly contracted kidney, on account of the implica-
tion of the heart and the arteries which is always associated with it.
Certain chronic diseases of the respiratory organs, such as chronic bron-
chitis, pulmonary emphysema, extensive bronchiectases, bronchial asthma,
adhesive pleurisy ; kyphoscoliosis also may be here included.
Chronic articular rheumatism.
Gout in all severe forms.
Other diseases characterized by loss or difficulty of motion or locomotion,
for example, hemiplegias, chronic diseases of the spinal cord, some cases of
peripheral paralysis, many surgical affections of the bones and joints, large
varices, chronic ulcer formation upon the leg, deformities of the lower
extremities, ete.
Diseases of the nervous system. That neurasthenics and hysterical per-
sons in general are in better condition when their fat is somewhat profusely
developed has already been mentioned; therefore these are the patients who
frequently require forced feeding (see above). But as these neuroses do not
always disappear under forced feeding, neither does corpulence always pre-
vent their appearance. Where the neurosis is combined with corpulence, care-
ful antifat treatment and the re-establishment of the normal nutritive con-
dition may be indicated, and may be as potent in relieving the neurosis as
forced feeding is in thin, poorly nourished persons.
6. REMARKS REGARDING THE TECHNIC OF OVER-NUTRITION
AND UNDER-NUTRITION
It is an old axiom which constantly demonstrates itself anew that dietetic
cures originating with this or that author, and advised for this or that disease,
degenerate in practice into mere formule. The “ cure,” the method, is forced
upon the patient, instead of the method being adjusted to the patient and its
main principles applied to the unending variety of cases. Routine precludes
70 OVER-NUTRITION AND UNDER-NUTRITION
success in this field, and frequently does more harm than good. There is no
single “best method” of over-nutrition, and no single best method for the
removal of fat, but there is for each individual case one and only one best
method. It must be constructed by the physician upon the scientific laws of
nutrition, whether a celebrated name is attached to the method or not. Hard
and fast dietetic rules are most widely developed in the realm of antifat cures.
There are obesity cures according to Harvey-Banting, Oertel, Ebstein, Hirsch-
feld, Schweninger, Kisch, Pastor Kneipp, etc.
I do not intend either in over-nutrition or in under-nutrition to dwell
upon the individualities of the methods, but I shall emphasize the main points.
A. THE TECHNIC OF FORCED FEEDING
Over-nutrition presupposes that the ingestion of food is to be greater
than the requirement. How great the surplus of food is to be depends upon
the rapidity with which the process is to be carried out. Apart from particu-"
lar indications (for example, in Graves’ disease, see above) the capacity of the
digestive organs should decide this question.
How the requirements of the patient can be approximately determined
from the body-weight has been related.
According to the calculations which I made in a large number of cases
treated by forced feeding I obtained the following results (I must admit in
this connection that the figures had not been theoretically determined prior
to beginning forced feeding, but were gained empirically during the treat-
ment): With a daily excess of food of about 500 to 800 calories, we get an
increase of weight of from 600 to 1,000 grams in a week; with a daily in-
crease in food of 800 to 1,200 calories, weight increases from 800 to 1,200
grams per week; with a daily excess of food of from 1,200 to 1,800 calories,
weight increases from 1,200 to 2,000 grams per week.
Quite properly the question arises, not only how many calories-should the
food contain, but also how much albumin and N-free substances are included
in it.
The albumin bodies theoretically considered have no great value in in-
creasing weight. The average albumin content of ordinary diet (100 to 110
grams) may be somewhat increased in forced feeding, but hardly more than
50 grams. Still larger quantities of albumin can be utilized only in excep-
tional cases as the bulk of the food becomes too great, and also because all
albuminous foods produce satiety to a marked extent. Even the preparation
of purified albumin products (casein, nutrose, tropon, plasmon, roborat, aleu-
ronat, ergon, etc.) has not changed this. From 20 to 30 grams during the
day are useful; larger quantities, if their use be prolonged, as a rule spoil the
appetite, whether we administer them in milk, soups, sauces, pap, in the form
of pastry or otherwise. No matter to what form we add the 50 grams of albu-
min, which I have designated as the most that can be used, it is certain that for
increase of weight little is gained by this; it only furnishes about 205 calories.
I hold that in general, allowing for exceptions, the daily administration
of from 120 to 130 grams of albumin is quite sufficient. My best results
were arrived at by keeping within these limits, Nevertheless, it must be
THE TECHNIC OF OVER-NUTRITION AND UNDER-NUTRITION 71
emphasized that occasionally the mere increase of the amount of albumin is
beneficial; for example, in preparation for true forced feeding, or, if there is
‘ repugnance to great quantities of N-free food, during a “ vacation period ” of
from eight to fourteen days which the patient may have to take in his forced
feeding treatment. Under these conditions temporary forcing of the albumin-
intake at the expense of the N-free substances renders the body more receptive
to the later action of the true forced feeding. For these purposes the purified
albumin preparations, such as plasmon, etc., are more suitable than meat.
From 50 to 60 grams of plasmon may be given with advantage during the
day. There is no difficulty in administering this amount, as, in this period,
we no longer increase the N-free substance. During longer periods, however,
little can be expected from such an exclusive increase of the albuminates.
Among the substances free from nitrogen we may choose between the
administration of fats or of carbohydrates, or may administer both in almost
equal proportions. In principle it is immaterial, as fat and carbohydrates
compensate for one another according to the law of isodynamics. One hun-
dred grams of fat are equal to 224 grams of carbohydrates, and vice versa.
As a rule the marked increase of carbohydrates is preferable, provided always
that they are better tolerated than fats. In some patients this is unquestion-
ably true, but in the majority certainly not. If we desire to add about 1,200
calories of N-free substances, we require either 129 grams of fat or 300 grams
of carbohydrates; many other mixtures may be used; for example, 200 grams
of carbohydrates and 40 grams of fat, or 100 grams of carbohydrates and 85
grams of fat.
For more than ten years I have preferred to increase the administration
of fat, for I have found that a larger amount of carbohydrates—300 to 400
grams a day—is not well borne for any length of time. When, under the
constraint of treatment in an institution, the patient is forced to take the
large amounts of food which are necessary if we use the carbohydrates alone,
we see only too frequently, after the restraint is removed, a period of anorexia
during which much of the body-weight gained with so much difficulty is lost.
Accordingly, the composition of the nourishment during forced feeding
should be about as follows:
120 to 130 grams of albumin (490 to 530 calories).
300 to 350 grams of carbohydrate (1,230 to 1,435 calories).
This nourishment (720 to 1,965 calories) forms the basis to which as
much fat may be added as is necessary to make the proposed calory total:
i.e, from 200 to 300 grams of fat (1,860 to 2,730 calories) or even more.
Frequently a portion of the required calory excess may be given in the form
of alcohol, whereby certain amounts of fat are protected from oxidation and
preserved for the organism (9.3 grams of alcohol protect about 7 grams of
fat from oxidation).
The amount of water to be added, provided special indications do not
necessitate exact regulation, may be according to the desire of the patient.
As a rule, if much carbohydrate is given the amount is greater than if much
fat is administered,
72 OVER-NUTRITION AND UNDER-NUTRITION
B, THE TECHNIC OF ANTIFAT CURES
In antifat cures the intake of nourishment must be smaller than the
demand, and in the obese this cannot be estimated very readily. The practi-
cal need will be satisfied if for an obese person the average normal require-
ment, amounting to about 2,500 calories, is given and is combined with slight
or moderate bodily exertion. On this basis I have proposed the following
scale in antifat cures: +
First grade of antifat diet—To this belong antifat cures in which the
diet may be reduced to about four-fifths of the normal requirement, i.e., to
about 2,000 calories. Success follows this only when we are treating robust
persons who are able to take sufficient bodily exercise. The action is usually
slow; we must not count in the beginning upon losing more than from three
to four pounds, and later two to three pounds, of weight per month.
Second grade of antifat diet—In this category the antifat cures belong
in which the diet is reduced to three-fifths of the usual requirement, there-
fore, to about 1,400 to 1,500 calories. This diet may very readily be adapted
to the mode of life of most patients, so that they can follow their occupations
without hindrance. The rapidity of cure depends upon the amount of physical
exercise they can take. If exercise is difficult or impossible (as in many
women, in very lazy persons, in certain diseases, particularly in paralysis and
with threatening signs of cardiac weakness), the action of diet alone is quite
slow (about two to three pounds a month). In vigorous persons who, besides
pursuing their daily occupations, can devote an hour to an hour and a half
daily to mountain climbing, bicycling, rowing, exercise in the gymnasium, etc.,
at first losses in weight of four to six pounds, later of two to four pounds, a
month are the result. For a time, as for instance during a vacation in the
mountains, these losses may without excessive exertion be increased to 11
pounds a month or more.
Third grade of antifat diet—To this belong antifat cures in which the
diet is less than three-fifths, or even only two-fifths of the usual requirement,
i.e, about 1,000 to 1,400 calories. In this class belong the well-known diet-
aries calculated to produce decided and rapid action, those of Banting-Harvey,
Oertel, Ebstein, and others, as is shown by the following tables:
Dizt SCHEME ACCORDING TO Albumin. eats Fat. Calories.
Bante oc cacceg sea sone e a aie one ee ne 172 81 8 1,100
Oertel { Maximum........ 170 120 45 1,600
ee a Minimum........ 156 vi) 25 1,180
HbStey acnwves ee seas camels pszaln ee dale'sa ake 102 47 85 1,300
Hirschfeld { Maximum........ 139 67 65 1,400
Nea Netagias te Minimum........ 100 50 41 1,000
Kisch | Plethoric obesity. . 160 80 11 1,086
Peeowgey ase Ii ry Anemic obesity ... 200 100 12 1,116
Ve NOOFGOD Sy a cdeewisceanea cea $40 owt anna 155 112 28 1,866
1. Noorden, “ Die Fettsucht ” in Nothnagel’s “ Handbuch der speciellen Pathologie
und Therapie,” Wien, 1900, p. 110.
THE TECHNIC OF OVER-NUTRITION AND UNDER-NUTRITION 73
A diminution of food to about two-fifths of the usual requirement is
looked upon as the utmost that may be wisely attempted in the obese patient.
The amount and rapidity of the loss of weight depend in the main on
the accompanying conditions. If the patient is inactive, the loss in weight
amounts to from 6$ to 13 pounds in a month. The greater reductions are
noted in the medium, the slighter decreases in the most marked grades of
obesity. If auxiliary measures, such as systematic muscular exercise, hydro-
therapeutic agents, mineral spring cures, etc., are utilized, the loss in weight
may readily be increased to 22 to 33 pounds in a month.
The following table showing the success which Dapper attained in his
sanatorium at Kissingen, in which the diet scheme was based upon that pro-
posed by me, is instructive:
Loss of weight
during the
time in
kilograms.
Weight at Duration of
Men. the onset the treatment
in kilograms. in weeks.
NuMBER.
129.5
104.5
99.5
114.5
104.5
112.0
104.5
111.0
74.0
101.0
97.0
97.0
112.0
107.0
116.0
74.7
96.0
110.0
128.
107.0
106.7
113.5
133.7
114.0
105.8
me
oo
ve ee
et
ot
nm
ao
re
ee Se
tt wm
SCWWODBRKSTOMDMCHOCHKEOVWH OOK OPO
AaaLhPrLALWAPERHLOHPTOHROaAarRhOH
CUNSMAMAANMNSSIOONNSN FBIM OTH
£
coud seul sell el
In what proportions the main constituents of the food, albumin, fat, and
carbohydrates, are to be arranged in the antifat diet of milder and medium
grades is of minor importance. The restriction of food is not so complete
that danger from uniformity of the diet is to be feared. On the other hand,
the question as to how we are to act in antifat cures of the third degree has
been much discussed. It cannot be considered of vital importance, for prac-
tical experience has sufficiently demonstrated that with a high intake of albu-
min (Banting, Oertel, Kisch, v. Noorden) as well as with a low intake of
albumin (Ebstein, Hirschfeld) satisfactory results have been attained. The
investigations in metabolism of the last few years are in accord with this.
I regard the question as one of technic rather than of theory or principle.
74 OVER-NUTRITION AND UNDER-NUTRITION
Experience appears to prove that in numerous patients the administration
of large amounts of meat—equivalent to a high intake of albumin—is much
better than small ones. Meat is not only the most important food for most
persons, but also the one most desired. Nevertheless, there are many corpulent
persons, especially women, who dislike large amounts of meat, and in whom
any antifat diet that consists largely of meat will certainly suffer shipwreck.
Nothing can be more unwise than, for the sake of theory, to force the admin-
istration of albumin up to a certain height; the requirements of the individual
case and nothing else should be considered. But we must insist on not less
-than the minimum of about 100 grams of albumin. Above this, theoretically,
the limit cannot be definite. In practice, about 180 grams of albumin per
day should rarely be exceeded.
No less warm than the question of the administration of albumin is the
discussion, whether, among the substances free from nitrogen, more fat or
more carbohydrate should be given. The important point is, that the total
of these, according to their calory values, must be diminished so ‘that the
total amount of food reaches the degree aimed at in the antifat diet. But
both the fat and the carbohydrates must be reduced below the average amount
if the administration of nourishment is to be limited to two-fifths or three-
fifths of the average requirement (see above). If only the one or the other
is forbidden or limited—whether it be the fats or the carbohydrates—sufficient
of the other remains in the diet to render the result dubious. Whether in
the simultaneous limitation a little more fat (Ebstein, Hirschfeld) or a
little more carbohydrate (Banting, Oertel, Kisch, v. Noorden) remains is of
subordinate importance. Only the calory total of both, not the chemical
constitution—whether fat or carbohydrates—is of significance. I regard it as
only a question of technic how far the limitation of one or of the other is to be
carried. The wishes, the manner of life, and the peculiarities of the patients,
not the principles of treatment, are the determining factors. But from my
own experience I should like to emphasize the fact that, as a rule, we attain
better results if the fats are limited as much as possible, and somewhat more
of carbohydrates are permitted in the food; for the carbohydrates furnish
a larger volume, satisfy more readily, and permit a much greater variation
in the diet.
Alcohol, of course, must not be given with a free hand in antifat cures.
As already remarked, it saves fat and in this manner favors its accumulation.
Many persons owe their excessive adipose tissue, primarily, to the immoderate
use of alcohol. Nevertheless, almost all authors have ascribed to alcohol a
subordinate place in antifat cures—and quite properly so, since in practice
its stimulating effect cannot always be dispensed with. But where it is possi-
ble—particularly in young, robust people—it is wise to exclude alcohol on
account of its high calory value.
In antifat cures the question of the allowance of water is usually discussed.
Among laymen, and also among physicians, the opinion prevails that the
intake of fluids favors the accumulation of fat. This is unquestionably incor-
rect. How easy and cheap would it be for the farmer if the administration
of water favored fattening! On the other hand, the statement that antifat
THE TECHNIC OF OVER-NUTRITION AND UNDER-NUTRITION 75
treatment is favored by limiting the amount of water cannot be pronounced
unqualifiedly incorrect. We must be quite clear that this fact has no bearing
on the relation between the administration of water and decomposition of
fat—as taught by Oertel and Schweninger—but that water has its effect by
influencing the intake of food. Many persons eat decidedly less when forbid-
den to take as much fluid as they have been accustomed to doing. They cer-
tainly eat less if the simultaneous ingestion of fluid and solid food is for-
bidden. The lessened ingestion of food will then promote the disappearance
of body fat. But this result cannot always be counted upon, for among the
obese we meet many whose appetite is not influenced in the least by limiting
the intake of fluid. They naturally remain fat, or even deposit more fat, no
matter how much they are tormented by the thirst cure.
I have formulated the present status of the question in the following state-
ments ; +
1. A limitation of the intake of fluid, according to Oertel and Schwen-
inger, has not the slightest influence upon the decrease of body fat or upon
the increase of fat metabolism.
2. The primary effect of limitation of fluid upon body-weight depends
upon the losses of water from the blood and the tissues. This may be utilized
therapeutically :
(a) To improve the circulatory conditions in endangered failure of the
heart (in cases of valvular disease, disease of the heart muscle, arteriosclero-
sis, contracted kidney) ;
(b) In patients with a tendency to immoderate production of sweat, and
for the purpose of combating hydrorrhea ;
(c) In some patients it is a valuable auxiliary remedy through suggestion.
3. The influence of the limitation of water upon fat metabolism, particu-
larly in decreasing the amount of fat, is only indirect, and comes into ques-
tion only under special conditions, namely:
(a) If, by decreasing the fluid intake, the circulatory disturbances pres-
ent are to be compensated; there may be then a possibility of favoring the
combustion of fat by muscular exercise.
(b) When, by decreasing the fluid intake, the appetite of the person for
fat-producing foods is diminished. This result may appear in a marked
degree, more frequently in slighter degree, or not at all.
4. When no special indications are present the intake of water is not to
be limited in the obese, as, without this, we attain the same end and the
limitation of water in such cases is only an unnecessary hardship for the
patient.
That, in antifat cures, under-nutrition is not the only agent to be em-
ployed, but that this is to be assisted by systematic muscular exercise, has been
reiterated. I shall not enter into individual points, but will only refer to
other chapters of this book in which the treatment of obesity has been explic-
itly described.
Here it is only necessary to indicate the important points that should
1 Therapie der Gegenwart, April, 1900.
76 OVER-NUTRITION AND UNDER-NUTRITION
be remembered in all curative methods in which over-nutrition and under-
nutrition come into play. The better the physician understands the general
laws of these cures, the more readily will he be able to meet the indications
of the individual case. The successes of dietetic therapy may only too readily
become matters of routine. Many practitioners adhere too closely to definite
diet schemes which have been proposed by this or that celebrated author, or
.they even hand to the patients a so-called diet list which refers only to the
disease, and not to the patient, and which means the annihilation of indi-
vidual dietetic therapy. Only the intimate union of practical experience with
a comprehensive understanding of fundamental theoretic laws will enable the
physician to choose rightly in every case. He must always bear in mind that,
although there are many methods of securing over-nutrition and under-
nutrition, for the special case there is but one best method. :
DIABETES MELLITUS
By B. NAUNYN, Srrassspure
Contents: J. Glycosuria and Diabetes. II. The Various Forms of Dia-
betes; Predisposition. III. Mild and Severe Forms of Diabetes; Course,
Symptoms and Complications. IV. Theory and Treatment. V. Prac-
tical Management. VI. Tables; Diet Lists; Scheme of Food Values;
Dietetic Rules for Diabetics.
I, GLYCOSURIA AND DIABETES
Glycosuria, Levulosuria, Lactosuria and Pentosuria. Physiologic and Alimentary
Glycosuria. Alimentary Glycosuria e saccharo; Non-Diabetic and Diabetic Forms.
Spontaneous Non-Diabetic Glycosurias.
By the term “glycosuria”? we mean the appearance in the urine of true
grape-sugar (dextrose, glucose), which is dextrorotary. We also speak of
“levulosuria,” when we mean the excretion of levulose, a fruit sugar which
is levorotary. “ Lactosuria” means the excretion of milk-sugar (lactose).
A sugar containing five atoms of carbon, in its molecular composition known
as pentose, may also appear, hence the term “ pentosuria.”
Lactosuria may occur during pregnancy and in nurslings, and has nothing
in common with diabetes. Pentose may be found in the urine after the inges-
tion of cherries, plums and beer, and occasionally also in diabetic urine, but
its réle in diabetes is quite obscure.
On the other hand, there are cases of diabetes mellitus in which levu-
losuria takes the place of dextrosuria and levulose plays the part in the
disease which ordinarily is assumed by dextrose. Such cases are, however,
very rare, not more than half a dozen being known.
Glycosuria (dextrosuria) is the cardinal symptom of diabetes mellitus,
but not every case of glycosuria is of a diabetic nature. There is a so-called
physiologic glycosuria; in other words, a normal individual may excrete dex-
trose in his urine, but the quantity is always extremely small. Disregarding
for the present so-called alimentary glycosuria, the percentage of sugar in the
urine of healthy individuals is seldom more than 0.05 per cent., although it
may reach 0.1 per cent. or even 0.2 per cent.
It is fortunate that the amount of sugar in normal urine does not react
to the ordinary tests. Trommer’s (or Fehling’s) and also Fischer’s test only
give a positive reaction in urine when the amount of sugar present is abnor-
77
78 DIABETES MELLITUS
mally high; i.e. over 0.1 per cent., and only when this quantity of sugar is
present can it be quantitatively estimated. If on boiling urine in an alkaline
solution of copper sulphate (Trommer’s test) we immediately, not subse-
quently, obtain a red or reddish-yellow precipitate, or if on warming the
urine with phenylhydrazin and acetic acid on a water-bath for half an hour,
a distinct crystalline sediment is deposited, we may be sure that the glycosuria
is not physiologic. As possible sources of error there may be mentioned the
presence in the urine of lactose, pentose, and combinations of glycuronic
acid (after the administration of chloral, chloralamid, etc.). Lactose and
pentose as well as combinations of glycuronic acid have a considerable power
of reduction, but we may readily distinguish them from dextrose by the
fermentation test and by polarization.
In diabetes, then, we are concerned only with hyperglycosuria, or, in
other words, with cases in which the sugar exists in such quantities as to
react readily to the above mentioned tests. But hyperglycosuria may exist
independently of diabetes. The so-called alimentary glycosuria is a case in
point: a person whose urine does not contain sugar partakes of sugar or
sugar forming substances (starchy material, dextrin) in sweetened foods and
liquids, beer, bread or potatoes, etc.; if sugar then appears in the urine so
that it may be detected by means of any of the ordinary quantitative tests,
this condition is designated alimentary glycosuria.
In diabetics whose urine is temporarily free from sugar, this is of quite
regular occurrence. It also takes place in non-diabetics, but with this differ-
ence, that in the diabetic the sugar producers in the food—the flour in bread,
etc.—if consumed in large amounts give rise to glycosuria almost as surely
as the sugar itself, while this condition only occurs in the non-diabetic from
sugar and not from starchy substances.
Therefore, glycosuria after the ingestion of sugar need not be diabetic,
but may be produced in normal persons even up to several per cent., provided
the sugar (grape-sugar, milk-sugar, or cane-sugar) is given upon an empty
stomach in amounts of 100 grams and over. If such a glycosuria occur after
the consumption of 100 grams of sugar (usually grape-sugar is used) when
the stomach is no longer empty, we are dealing with abnormal glycosuria,
i.e., alimentary glycosuria e saccharo. This may indicate diabetes or be the
first sign of the development of the disease; in other words, the person in
question may develop diabetes sooner or later, but not necessarily; the indi-
vidual need not be a diabetic, nor even become one.
Taking as a criterion the nature of the processes concerned, let us now
attempt to differentiate between diabetic and non-diabetic glycosuria.
In the diabetic, the organs which are concerned in the consumption of
sugar have suffered damage and are incapacitated for work; they fail to extract
the sugar from the blood which is brought to them, or they return it to the
circulation, as they are incapable of utilizing it. Thus a hyperglycemia and
consequent glycosuria arises, provided the amount of sugar in the blood is
more than 0.2 per cent.—0.3 per cent., and this is a diabetic hyperglycemia
and glycosuria. The condition depends upon obstruction to the normal drain-
age of sugar from the blood by the organs of sugar metabolism, and it is for
GLYCOSURIA AND DIABETES 79
this reason that sugar is excreted by the kidneys. But the organs whose
function it is to burn sugar cannot take up from the blood and consume an
unlimited amount of sugar, even if they and all the other organs are per-
fectly sound and function normally. It is true that a flooding of the blood
with sugar can hardly occur in health through the ingestion of starches, even
in the largest amounts, as these are absorbed too slowly, but it may readily
occur after ingestion of large quantities of readily absorbable sugar solu-
tions. That alimentary glycosuria (e saccharo) may be explained in this
manner is evident from the fact that in most of these cases the sugar
(for example, milk-sugar or levulose) is excreted in the sam¢ form in which
it is introduced. This explanation is also favored by the circumstance that
alimentary glycosuria occurs more readily when the stomach is empty, for, as
is well known, absorption is then more rapid. This pathologic but non-
diabetic alimentary glycosuria (e saccharo) is’probably due, therefore, to an
abnormally hastened absorption: of the sugar solution.
Finally, non-diabetic glycosuria, i.e., glycosuria despite a normal condi-
tion of the sugar-consuming organs, may occur when the renal secretion has
become so increased that sugar and other solids are drawn out of the
blood in abnormally large quantities and excreted with the urine. Perhaps
it may be possible to explain in this way the fact that, after the ingestion of
much beer or champagtie, sugar (even several per cent.) is occasionally found
in the urine.
It is possible, however, that in these “beer glycosurias” the damaging
influence of the alcoholic beverage upon the liver is also a factor; the possi-
bility is obvious enough, since, in cirrhosis of the liver, alimentary glycosuria
is frequent. In these cases we are then concerned with diabetic glycosuria,
i.e, with the complication of cirrhosis of the liver and diabetes mellitus.
This example shows how difficult it is to separate alimentary glycosuria
from the diabetic form, and there are many other illustrations of this diffi-
culty. Thus, in traumatic neuroses true diabetes may occur. On the other
hand, alimentary glycosuria (e saccharo) is a particularly frequent symptom
in traumatic neuroses. And one cannot look upon this sign, in all cases,
as indicating diabetes—at any rate in the overwhelming majority of cases
such a condition does not arise. In exophthalmic goiter the same state of
affairs exists. Taken all in all, in every alimentary glycosuria, including the
“@ saccharo” variety, it is necessary to observe great caution in deciding
whether this is a sign of diabetes or not. Alimentary glycosuria following
the ingestion of starch must always be looked upon as a sign of true diabetes.
“Experimental ” glycosuria in the human being does not play a great
role, although it occasionally occurs—for example, glycosuria after poison-
ing with coal gas, or with phloridzin for purposes of malingering. These
conditions must be understood in order to recognize that they are not cases
of diabetes.
In all cases of spontaneous glycosuria (non-alimentary) the greatest care
is necessary before deciding whether they are to be looked upon as signs of
diabetes or not. We must be sure that pentose or glycuronic acid in the urine
is not mistaken for glycosuria; when lactosuria occurs in pregnancy or in
80 DIABETES MELLITUS
the puerperal state, we must know that this has nothing to do with diabetes.
As an example of true glycosuria appearing spontaneously in man, yet not
the expression of diabetes, I can only mention the form occurring in cholera
asiatica and cholera nostras.
All other forms (unless proofs are present to the contrary) should be
looked upon as diabetic; but we need to know what is meant by diabetes, i. e.,
the disease of this name as it occurs in the human subject.
Il. THE VARIOUS FORMS OF DIABETES;
DIABETIC PREDISPOSITION
Acute Diabetes, the Acute Form Terminating Fatally and the Acute Form Resulting
in Recovery—Transitory, Nervous (Cerebral Trauma), and Pancreatic Glycosuria
Representing the Shortest Course of Acute Diabetes Mellitus Terminating in Recovery.
Chronic Diabetes Mellitus as an Expression of an Hereditary Predisposition. Its
Three Varieties: (a) The Pure Form, (b) Diabetes of the Aged, and (c) Organic
Diabetes Mellitus. Etiology of Diabetes Mellitus and the Possibility of its Cure in
the Light of Hereditary Predisposition—the Heredity of Diabetes Mellitus. One Form
or Several Forms of Diabetes?
Diabetes is generally considered a chronic affection, but it may take an
acute course and be either rapidly fatal or readily curable.
Well studied cases with an acutely fatal course have been reported; for
instance, Wallach reports the case of a chemist who was accustomed to make
weekly examinations of his own urine. The urine was always free from sugar
until suddenly a severe glycosuria appeared, and within five weeks the man
died in diabetic coma.
The question of acute cases that terminate in recovery is less simple.
Schmitz reports the case of a four-year-old child of a diabetic mother.
The anxious mother had the urine of the child examined frequently, and it
was always free from sugar up to November 22, 1871. On November 26th,
the child was attacked by a gastric fever, and on the 27th the sugar contained
in the urine amounted to 5.8 per cent. The child was put upon strict diet,
and on the 13th of December the urine was again free from sugar. Although
the patient gradually returned to the usual saccharine and amylaceous diet
the urine remained normal for twenty years. Whether it is correct to say
that the diabetes had already been cured upon the 13th of December is at
least very questionable, for at that time, and for a long period afterward, the
child lived upon a very strict diet, which later was even more restricted, so
that very little was expected from its carbohydrate metabolism. On Decem-
ber 13th, the recovery was probably only relative.
Zinn observed a child attacked by diabetes mellitus after scarlatina; the
patient, after ten weeks, even upon “mixed diet” showed no sugar in the
urine; unfortunately the observations in regard to the recovery were only
continued for a few months.
Similar conditions may be observed in all cases of true diabetes in which
recovery takes place.
Diabetes after cerebral injuries also occurs as an acute disease which may
THE VARIOUS FORMS OF DIABETES 81
terminate in recovery. As a result of trauma of the brain we note cases of
diabetes that are severe, even very severe; then there are cases which run a
milder course similar to those of Schmitz and Zinn mentioned above; finally,
there are cases after cerebral injuries, in which transitory glycosuria, without
any further consequences, occurs and lasts but a few days. What right have we
to deny that these transitory glycosurias represent the mildest forms of dia-
betes mellitus? The same lessons which are taught us by the study of diabetes
after cerebral injury in the human subject are paralleled as regards pancreatic
diabetes by experiments upon animals; extirpation of the pancreas produces
the most severe forms of chronic diabetes; transitory lesions of the organ
produce mild ephemeral glycosuria.
In my opinion we must admit that diabetes may occur as an acute affec-
tion, and this conclusion has some practical importance; spontaneous, true,
acute diabetes is certainly very rare, but transitory, spontaneous (?) gly-
cosuria may be explained in this manner:
Although the course of the disease is for the most part chronic, the con-
ditions are not accurately designated if we call diabetes “a chronic disease” ;
in the majority of cases there is an innate hereditary predisposition, a weak-
ness of sugar metabolism, which, sooner or later, in combination with other
causes, or even without such, may lead to insufficiency of sugar metabolism
and thus give rise to the disease.
According to this, three forms of the disease may be differentiated :
1. Diabetes mellitus of young individuals (those between thirty and forty
years of age) (“pure diabetes”’).
In this form the hereditary weakness of sugar metabolism, without the
association of any special disease of an organ, progresses to insufficiency.
This occurs at an early period of life, owing to a particular severity of the
pathologic predisposition, and, in keeping with this, the cases are for the most
part serious.
2. Diabetes of the aged, the usual mild diabetes of old persons; the saying
that “the age of an individual depends upon the condition of his arteries ”
is also true in these cases; usually, arteriosclerosis is the underlying condi-
tion and with this all factors are operative which favor its development; lux-
urious living and, above all, the use of alcohol.
It is readily seen that the least severely predisposed cases are the ones in
which this form of diabetes is most likely to appear; perhaps this accounts
for its relatively mild course. ;
3. Organic diabetes; this refers to cases in which disease of a particular
organ is the immediate cause of the affection. As examples, there may be
mentioned: (a) among the diseases of the liver, cirrhosis and, rarely, chronic
cholelithiasis; (b) among diseases of the nervous system, apoplexy, chronic
encephalomalacia, cerebral syphilis, dementia paralytica, tabes dorsalis, cere-
bral trauma of all kinds, the various functional neuroses, particularly the trau-
matic ones, and paralysis agitans; (c) diseases of the thyreoid gland (Graves’
disease), and (d) diseases of the pancreas.
Experimental evidence would seem to show that the pancreas takes the
first position among the organs which cause diabetes, since by extirpation or
82 DIABETES MELLITUS :
by a more or less extensive resection, true diabetes may be produced. Our
investigations in man, however, only correspond with this in so far as extir-
pation of the pancreas and disease of the pancreas also cause diabetes in the
human subject. On the other hand, diseases of the pancreas have only in
rare instances been determined with certainty as the cause of diabetes; these
affections are pancreatic calculi, pancreatic cirrhosis, neoplasms and cysts.
If we have disease in an organ which is very influential in sugar metabo-
lism, as, for instance, the nervous system or pancreas, this suffices to produce
diabetes, even without a previous predisposition; if, however, a predisposi-
tion exists, disease of one of the vital organs is not absoluteby necessary.
Slight general disturbances are sufficient to bring about an insufficiency in
sugar metabolism. Thus the varying etiology of diabetes mellitus becomes
comprehensible, and we learn to recognize as causes not only the above men-
tioned organic diseases, but also many severe or mild general affections:
influenza, enteric fever, scarlatina, erysipelas, phlegmons, syphilis, and,
finally, the most manifold forms of trauma, surgical operations, psychical dis-
turbances, bodily or mental over-exertion, indigestion and excesses of all
kinds; all of these are occasionally of etiological significance in diabetes
mellitus.
This conception of diabetes mellitus as an expression of an hereditary
weakness of metabolism makes clear at once what we can expect as regards
the cure of diabetes. °
One can speak of actual cure only in those cases in which the disease
appears as the result of an affection of one of the principal organs; if an
affection of the organs in question improves, then diabetes may actually be
“cured.” That this occurs is certain (in man) in the case of diabetes as the
result of brain injuries.
If, however, as in most cases, the cause of diabetes must be referred to
hereditary predisposition, we must at once assume a skeptical attitude in
regard to the cure, all the more so if the predisposition is the only causal
factor. Where other causes are associated with this, e. g., cirrhosis of the liver,
infectious diseases, especially syphilis (we may remark in passing that syphi-
lis plays but a very slight réle in the etiology of diabetes), arterio-sclerotic
circulatory disturbances, we have more reason to hope that, by treatment or
by cure of the causes simultaneously present, sugar metabolism may again
become sufficient, but the predisposition remains, and with it the danger that
any fresh damage may bring about a relapse.
Many cases may be explained in this way; for example, an elderly person who may
have suffered many years ago with diabetes, is apparently cured; i.e., he returns to his
usual mode of living without paying much attention to his “cured ” diabetes. The
urine is free from sugar; he is then attacked with influenza, or undergoes some marked
psychical disturbance, and the glycosuria at once returns quite severely; or he has to
submit to an operation, and after the operation a coma ensues, coma diabeticum, the
urine containing many per cent. of sugar.
We are justified in assuming (as we have) an hereditary predisposition
for many cases of diabetes, apart from what has already been said, by the fact
of the heredity of the disease. In most cases of diabetes, heredity is a factor;
MILD AND SEVERE FORMS OF DIABETES 83
it has been proven in more than 30 per cent. of my cases, and becomes more
frequent the more closely I investigate. This hereditary predisposition is
true of all three varieties, and can be demonstrated in a like number of cases
of the organic form, in diabetes of the aged, and in “ pure diabetes.” The
hereditary factor in diabetes is related to the neuropathic taint and to the pre-
disposition to gout and obesity. In many families gout or some variety of
neurosis or psychosis occurs alternately with diabetes, and if, in such diabetic
families, one of the members is conspicuously fat, this is very suspicious of
diabetes. These are, incidentally, the cases for which the improperly used
term “ diabetes of the obese” should be reserved, the cases, namely, in which
obesity points to diabetes.
It is often said that as the cases of diabetes are quite different, and as these
etiologic differences correspond with differences in the course and the symp-
tomatology, diabetes should no longer be looked upon as a single disease. We
should no longer speak of “ diabetes mellitus,” but of “various forms” of
diabetes mellitus. But in answer to this we must again emphasize in all
forms of diabetes the hereditary predisposition. This is the common bond
which holds these various forms together; it is operative in each of the
varieties which are to be differentiated etiologically. In every type of the
disease, in nervous diabetes, as well as in liver diabetes, in diabetes after
infections, in diabetes of the aged, and in “ pure” diabetes, 30 per cent. (or
more) are hereditary cases.
Further, we do not know at present whether the pathogenesis of glycosuria,
i.e., the disturbance in metabolism which causes it in the different cases, is
as multiform as the etiology; on the contrary, the glycosuria which occurs in
all the various types of diabetes mellitus (so far as this point has been inves-
tigated) is hyperglycemic in origin, i.e., the condition is due to an increase
in the amount of sugar in the blood. This is only true, however, of diabetes
mellitus as it occurs in man; we can produce in animals and in man an experi-
mental glycosuria which is not hyperglycemic, i. e., the form due to phloridzin.
In animals even the most marked phloridzin glycosuria produces no note-
worthy increase of sugar in the blood.
We cannot, therefore, see any sufficient reason for speaking of “ various
forms” of diabetes, but we do distinguish a mild and a severe form of the
disease. This distinction will be observed throughout the following descrip-
tion of the symptomatology and it will also be seen that we have taken full
account of the differences in etiology between different groups of diabetic cases.
III. MILD AND SEVERE FORMS OF DIABETES; COURSE,
SYMPTOMATOLOGY AND COMPLICATIONS
Mild and severe forms of diabetes mellitus. The importance of complicating organic
disease in the symptomatology of the mild cases. Differentiation of the various symp-
toms according to whether they are due to the organic disease or to diabetes mellitus.
Hyperglycemia as a cause of the latter. The albuminuria of the diabetic.
In practice we cannot avoid differentiating between mild and severe cases,
or the mild and severe forms of diabetes mellitus. It is true that this is only
84 DIABETES MELLITUS
a difference of degree; the nature of the affection depends upon the same
process in the mild and in the severe cases, and transitional forms are by no
means rare.
Well developed cases of the mild and of the severe variety resemble one
another as little as an epileptic migraine resembles typical severe epilepsy,
or even less. When, in a severe case of diabetes, 4 to 15 or more liters of urine
are passed with a specific gravity of 1.025 to 1.040, or even 1.060, and a per-
centage of sugar from 5 per cent. to 12 per cent. daily (200 to 1,500 grams
of sugar daily), it is obvious that there must be an enormously increased
intake of nourishment; yet it is easy to understand that in spite of this the
patient emaciates, becomes debilitated, and soon perishes. The course of the
disease in such cases is necessarily brief. Often within a few weeks the body-
weight falls to 60 kilograms in a man or 50 kilograms in a woman, and in
spite of all endeavors to prevent this, the patient’s condition becomes pro-
gressively worse; in from one and a half to three years increasing cachexia,
diabetic coma, or pulmonary tuberculosis, terminates life.
Mild cases of diabetes may exist undiscovered for years, even decades,
until a complication or an accident leads to the discovery of the glycosuria;
so vague may this condition be. In such cases only 10, 30 or 50 grams of
sugar are excreted daily, with a normal or slightly increased amount of urine
in twenty-four hours, and this state of things may go on indefinitely, although
the patient before, as well as after, the discovery of the sugar pays but slight
attention to his condition. If he limits the amount of beer, bread and starchy
food and gives up sugar and potatoes entirely, this will suffice to keep his
glycosuria within the limits above mentioned, whereas, in a severe case, even
the strictest diet only brings about an amelioration, and the patient’s whole
life becomes a combat with glycosuria, a battle for existence. If glycosuria
is a symptom in a mild case of diabetes, in a severe case it is the disease, the
fatal disease itself. The loss of sugar in the urine, the impossibility of com-
pensating for it by an increased nourishment, and the consequences, among
which coma is common, are the conditions from which the patient suffers and
to which he finally succumbs.
In the severe cases glycosuria itself is, in a certain sense, the main disease,
since usually in cases of “pure” diabetes no disease of any special organ can
be found. It is not necessary to discuss the question whether in these cases
of “pure” diabetes we are justified in looking upon a disease of some special
organ—generally the pancreas—as the cause of the disturbances of metabolism.
On account of my own position in regard to pancreatic diabetes I have par-
ticularly interested myself in this question; but it is impossible to prove in
these severe cases, either from the symptoms and signs present during the
life of the patient, or at the autopsy, anything which points to disease of the
pancreas or of any other organ. There are, as has already been mentioned,
cases of diabetes due to disease of the pancreas, pancreatic calculi, cirrhosis of
the pancreas, ete., but they are rare.
The mild cases rarely belong to the type classified as “ pure” diabetes ;
more frequently the symptoms point to hepatic diabetes, to nervous diabetes,
or to diabetes of the aged (arterio-sclerotic diabetes). Nevertheless, “ pure ”
MILD AND SEVERE FORMS OF DIABETES 85
diabetes may occasionally run a mild course, and cases of the other form may
sometimes be severe; this latter course is most frequently seen in the diabetes
which occurs after trauma of the brain.
Not infrequently the symptoms of the accompanying disease (hepatic,
nervous, or arterio-sclerotic) are much more prominent than the slight gly-
cosuria, and so it happens that the cirrhosis, or the tabes, in spite of the com-
plicating diabetes, runs the same course which it would have assumed without
the associated condition. In arterio-sclerotic diabetes, as the disease develops,
the arterio-sclerosis may become more and more prominent, presenting circu-
latory disturbances, cardiac asthma, angina pectoris, dropsy, congested liver
and albuminuria; in all of these cases we may note that, as they progress,
the glycosuria decreases and finally disappears.
Although in many of these cases the glycosuria does not become promi-
nent, nevertheless, the diabetes and the diabetic disturbances of metabolism
usually do not fail to produce evil consequences; on the contrary, there is
quite an array of complications and symptoms which appear frequently in
mild cases; pruritus pudendorum, vaginitis, vulvitis, balanitis, phimosis, ure-
thritis, impotence, fermentation of the urine in the bladder (with pneuma-
turia), and as a consequence of this, cystitis and pyelonephritis; itching of
the skin, urticaria, eczema, the most manifold ulcerating dermatoses, furun-
culosis, carbuncle, lymphangitis, boils, intermittent claudication, gangrene of
the toes, necrosis of internal organs, pulmonary gangrene, pulmonary tubercu-
losis; also a host of nervous diseases; encephalomalacia, column degeneration
of the spinal cord, neuritis, polyneuritis, neuralgia, peripheral paralyses (par-
ticularly paralysis of the facial nerve), malperforant, very frequently loss
of the patella reflex which occasionally ushers in the remarkable picture of
pseudo-tabes diabetica.
It is impossible to bring this confused array into any systematic arrange-
ment; any one of these symptoms, or complications, may appear alone as the
first sign of a diabetes, latent up to them; each of these conditions may remain
the only one, or be succeeded in any order by any of the others.
For some of these conditions diabetes alone cannot be held responsible ;
thus arterio-sclerosis is the true cause of gangrene of the extremities with its
occasional prodrome, claudicatio intermittens, perhaps also of malperforant.
This is true, even though these lesions occur during the course of a case of
diabetes. In the peripheral paralyses and neuralgias, the neuropathic predis-
position doubtless often plays a part, and the diabetics that suffer from poly-
neuritis are, as far as I know, all alcoholics.
Naturally the question next arises whether diabetes has any influence at
all in the production of these lesions; for example, in cardiac asthma or in
angina pectoris of the diabetic; take the case of an old diabetic, with a
glycosuria of from 3 per cent. to 4 per cent., from 50 to 60 grams of sugar
per day, suffering from cardiac asthma or angina pectoris; there is slight
venous stasis of the liver, occasionally slight albuminuria; nothing abnormal
can be detected in the heart. Nevertheless, there is a well-grounded suspicion
that a beginning cardiac insufficiency, perhaps due to°myocardiac degenera-
tion and perhaps to arterio-sclerosis, is present, Removal of the glycosuria
86 DIABETES MELLITUS
helps but little; digitalis, however, soon brings relief. We must not be too
certain that, in these complications of diabetes, glycosuria does not play a
part, and we should never fail to attempt to remove the glycosuria, for there
are cases, like the one just described, in which no result can be obtained with-
out this method of treatment. It should remain a rule that wherever there
is even a possibility that the symptom present is of a diabetic nature, the
attempt must be made to reduce the glycosuria.
We are compelled, then, seriously to consider glycosuria as the cause of
these symptoms. Glycosuria may produce symptoms in two ways: First, by
the loss of sugar; of this we have already spoken and shall have to refer to
it again frequently; in mild diabetes the loss of sugar is not important, and
glycosuria as such is only to be considered as the cause of urinary fermenta-
tion and its consequences, such as pneumaturia, cystitis, pyelonephritis,
pruritus pudendorum, balanitis, vaginitis, etc. In mild diabetes it is the
hyperglycemia that we hold responsible for symptoms.
As long as the diabetic excretes sugar, the sugar contents of his blood is
increased above the normal and there is hyperglycemia. In marked glycosuria
(above 1 per cent.) the hyperglycemia amounts to over 0.2 per cent. and in
the severe grades of glycosuria it may amount to 0.7 per cent.; if the gly-
cosuria is slight (4 per cent. to 1 per cent.), or if the urine of the patient
is free from sugar, the hyperglycemia is very slight, scarcely amounting to
more than 0.1 per cent. (which is almost normal), and then the condition is
not serious.
Diabetic hyperglycemia may certainly be held responsible for the loss of
resistance of the diabetic—even of the mild cases—toward infections; at least
it has been experimentally proven that many of the pathogenic microbes flour-
ish better in the tissues which contain sugar. I shall include, besides this,
the cutaneous affections and the neuralgias as among the complications de-
pendent upon the hyperglycemia, basing my opinion upon the results of the
therapeutic removal of glycosuria. Removal, perhaps, implies too much; it
would be more correct to say reduction, for to render the hyperglycemia
innocuous, it is almost always sufficient to reduce the glycosuria to the limit
mentioned above.
Regarding the symptomatology and complications of diabetes, I must limit
myself to what has been previously mentioned. The other important symp-
toms not yet enumerated, for instance, coma, will be spoken of elsewhere;
only in regard to albuminuria I should like to add a few words.
Albuminuria has one significance in mild and another in severe cases F
in mild cases, the albuminuria is the expression of a renal affection inde-
pendent of the diabetes, although in some cases arteriosclerosis or hepatic
cirrhosis may represent a connection between these diseases and the diabetes.
In severe diabetes, the albuminuria may be referred directly to the diabetes;
it is the consequence of the excessive functional irritation from which the
kidney suffers owing to the continued polyuria.
Perhaps the abnormal constitutents of diabetic urine, possibly the sugar
itself, may irritate the renal elements. But this diabetic albuminuria is not
nephritic in origin, i.e. it does not denote nephritis; and we should err
THE THEORY OF THE TREATMENT OF DIABETES 87
greatly if we were to diagnosticate nephritis on this account. What is found
at the autopsy is the large, slightly hyperemic “ diabetic kidney ” which shows
none of the changes that we expect to find in nephritis.
The transition of diabetes into nephritis, which is frequently mentioned,
is, therefore, very questionable; the true diabetic albuminuria of severe cases
is not nephritic, and the albuminuria of the mild cases is not diabetic, but
frequently due to an independent nephritis. It is true that a genuine nephritic
albuminuria not infrequently takes the place of glycosuria; for when the
arterio-sclerotic or other form of chronic nephritis which may appear becomes
really severe, the albuminuria becomes more pronounced, whereas the sugar
disappears from the urine.
IV. THE THEORY OF THE TREATMENT OF DIABETES
Diabetic glycosuria has a tendency to increase during a decrease in the patient’s
tolerance, whereas during sugar-free periods the tolerance usually increases. Hyper-
compensatory hyperglycemia. Dietetic aglycosuria as a theoretic postulate. The rela-
tive importance of carbohydrates, albumin, fat, and alcohol for the diabetic. Difficulties
in supplying sufficient nutrition; temporary under-nutrition not always avoidable.
Acidosis diabetica with acetonuria and diaceturia. The secondary increase of albumin
waste and the secondary decrease of the powers of oxidation in diabetics. Acidosis an
expression of the disproportion between over-abundant tissue-destruction and the less-
ened powers of oxidation. Acidosis as a cause of the diabetic (dyspneic) coma.
The only method of treatment of real value in diabetes is the dietetic.
(We shall refer later to the medical treatment.)
The foundation for the dietetic treatment in diabetes was laid one hundred
years ago by an English physician, Rollo, but it is only of late years that this
method of treatment has become general. Rollo discovered the correct method
empirically, but, as is frequently the case, the theoretic foundation had to be
worked out before his treatment obtained general recognition, and it required
great labor to establish this theoretic foundation. But it is not for this reason
that I intend to enter somewhat more minutely into these theoretic considera-
tions of the treatment of diabetes, but because we cannot otherwise obtain
such clear ideas of diabetes as are required for the practice of medicine.
THE FIRST FUNDAMENTAL PRINCIPLE in the treatment of diabetes to which
I refer is this: .
Diabetic glycosuria usually increases with time, while the tolerance of the
patient decreases.
The tolerance of the diabetic depends upon the relation between the
amount of sugar excreted and the quantity of sugar and sugar producers (par-
ticularly the carbohydrates) ingested.
In the following example, for the sake of simplicity, I shall estimate the
entire amount of the carbohydrates in the food as bread.
A patient receives 500 grams of meat, 3 eggs, 400 grams of vegetables deficient in
carbohydrates (salad, spinach, ete.), 100 grams of fat (cheese, sausage), in which there
is some albumin which need not be taken into account, butter and fat in the food, 100
grams of wheat bread, 100 grams of cream and the necessary wine, coffee and water. He
excretes two and a half liters of urine, with 3.5 per cent. sugar, that is, on the average,
88 DIABETES MELLITUS
88 grams of sugar per day. If he lives for months, with this glycosuria, it is to be
expected that with the same nourishment he will excrete more sugar; for example, 4
per cent., that is, upon an average, 100 grams per day; in other words, his tolerance
(for carbohydrates) has decreased.
This lessening of tolerance, due to the glycosuria, may not take place if
the glycosuria is very slight and does not amount to more than from ten to
twenty grams in a day; but in cases in which the glycosuria shows such an
increase as in the example just quoted, the patient’s tolerance is bound to
diminish within a short time.
THE SECOND FUNDAMENTAL PRINCIPLE which is a necessary complement
to that mentioned above is as follows:
When the diabetic is free from sugar, his tolerance usually increases.
For example, a diabetic on the diet previously mentioned excretes 88 grams of
sugar. To diminish the glycosuria his allowance of bread is reduced; this decrease in
food, however, is not sufficient; bread must be withdrawn entirely to render the patient
free from sugar; as soon as even ten grams of bread are allowed he begins to excrete
sugar again, although only from six to eight grams per day. Next the patient remains
for four weeks without bread and his urine becomes free from sugar. After this, if the
physician is careful, from twenty to thirty or forty grams of bread may gradually be
given without being followed by an excretion of sugar; the patient’s tolerance, during
the sugar-free period of four weeks, has been materially improved.
How may both these conditions be explained? The improvement of toler-
ance during the sugar-free period exemplifies Hoffmann’s law that “ by lessen-
ing the work of any diseased function the latter may be improved,” which law,
however, if we are honest, is, in the case of diabetics, little more than a lengthy
statement of the facts which are to be explained.
There is more hope of success in the attempt to explain the aggravation
of the patient’s intolerance of carbohydrates during every decided glycosuria.
The amount of sugar in the blood, as is well known, is quite constant in man,
at least it never falls below a certain point (about 0.8 per cent.) ; if, for exam-
ple, after severe muscular exertion, sugar almost disappears from the blood,
a fresh supply is sent from the carbohydrate storehouse (the liver) ; this
may be called a process of compensation. If now, after severe sugar losses,
it is desirable that a great amount of sugar be quickly brought to the blood,
it appears (according to some facts the explanation of which I shall not give
at this point) that a hypercompensation occurs. Hence arises the paradoxical
conception that loss of sugar produces hyperglycemia! If this seeming para-
dox is really true, and if it holds good even for the diabetic with an already
existing hyperglycemia, then a spontaneous increase of diabetic hyperglycemia
by hypercompensation becomes comprehensible, Therefore, as long as sugar is
lost by the urine, a steady increase of hyperglycemia leading to a still greater
glycosuria is to be expected.
Whether these attempts at explanation are correct or not, the two laws
themselves to which they refer are as near the truth, I think, as can be deter-
mined to-day. And as the aim of the therapy of diabetes they show us this:
to render the patient free from sugar and to keep him aglycosuric.
This conclusion is identical with that arrived at in the end of the last chap-
THE THEORY OF THE TREATMENT OF DIABETES 89
ter regarding the meaning of diabetic hyperglycemia. We there said that
hyperglycemia is the cause of most of the complications and many of the
dangers of diabetes mellitus, and the patient is safe only when he is excreting
little or no sugar.
Therefore, there can be no question that in every case of diahetes the
therapeutic indication is to render the patient aglycosuric, or sugar-free. It
is obvious that the treatment is to be begun as soon as possible, so that little
time may remain in which the disease may unfold its tendency to develop
ad pejus. If there is any theoretical law as regards treatment which is found
to succeed in practice it is this. The chances for successful treatment are,
ceteris paribus, very much better in recent cases. It is just as important to
insist that the treatment is an obvious necessity in the later course of the
disease, and should also be attempted from the beginning of symptoms by
means of dietetic treatment. For it has been determined only as regards the
dietetic treatment, and not as regards the aglycosuria brought about by drug
treatment, that it increases the tolerance of the diabetic.
There are no theoretic contra-indications (i.e., such as might be derived
from our knowledge of the diabetic disturbances of metabolism) against
carrying out this requirement, although the practical difficulties are fre-
quently great.
The dietetic treatment of the diabetic gains its end by forbidding the use
of sugar and sugar-producing foods as far as possible. The sugar-producing
foods are the carbohydrates and albumin. Even from albumin sugar is pro-
duced in animal metabolism, and in no small quantity, as from 100 grams of
albumin (which amounts to about 400 grams of raw meat) about 50 grams of
sugar, or even more, may be formed. It is important to note that the organ-
ism also produces sugar from those varieties of albumin which contain no
preformed sugar, i.e., those from which it is impossible to extract sugar by
chemical means. An example of such an albumin containing no preformed
sugar is casein, and from this substance the diabetic produces sugar in large
amounts. ;
Sugar production from fat does not play such an important réle as to
influence diabetic glycosuria to any notable extent. For this reason, and on
account of its high calory value, fat is the most valuable food substance for
the diabetic.
According to the very latest investigations (Bjierre) it may be looked
upon as settled that alcohol has nutritive value (indeed, 1 gram of alcohol
upon oxidation furnishes as much as 7 calories) and the diabetic does not
form sugar from this. But its utilization as food is limited, for if it is admin-
istered in large amounts it acts as a poison to protoplasm, increasing albumin
decomposition. It is believed that this toxic action of alcohol is to be feared
when more than 50 grams of alcohol are taken per day.
That the patient must be sufficiently nourished, no matter how strict the
diabetic treatment, is a well-known rule, but by this we do not mean to say
that, temporarily, the patient may not be subjected to hyponutrition; I have
already spoken of this. Under some circumstances, as we shall see, it is even
then permissible for the patient to abstain completely from food for twenty-
90 DIABETES MELLITUS
four hours in order that his urine may become free from sugar. Just so,
it is occasionally necessary to give for a few days so little food that some
of the patient’s body substance is utilized. At the beginning of strict dietetic
cures, it is often very difficult to overcome this consumption of tissue in dia-
betics who have previously lived upon a mixed diet and have excreted much
sugar.
Let me again illustrate. Imagine, for example, a man weighing 65 kilograms, who,
on a mixed diet, has been excreting 600 grams of sugar daily. He is put upon a diet
not absolutely free from carbohydrates. According to Rubner, a man requires for his
maintenance about 35 calories per kilogram, so that this man ought to have sufficient
food to produce 35 X 65, or, in round numbers, 2,300 calories daily.
80 grams wheat bread contain 50 grams starch = 200 calories.
500” boiled or fried meat, medium fat (5 per cent.)—= 750 v2
200 +” cream (30 per cent. fat) = 600 a
200 7% ~=milk =120 ”
100 ” fat, in butter, cheese, fat sausage, bacon, etc. = 900
2,570 calories.
Besides this we will add about 300 to 400 grams of green vegetables, whose calory
value, like that of the albumin partaken of in fat foods (bacon, cheese, fat sausage, etc.),
may be disregarded.
According to this our patient would be plentifully fed, if he were free from sugar,
for a diabetic who excretes no sugar does not emaciate, and consequently does not need
any more food than a healthy person. Unfortunately, our patient continues on this diet
to excrete his full 100 grams of sugar per day. The calory value of these 100 grams
(400 calories) must be subtracted from the total calory value of the food he is ingesting;
2,570 calories— 400 calories = 2,170 calories, which is 130 calories less than the patient
requires, according to Rubner.
In some cases, under favorable circumstances, it is possible to supply these
missing 130 calories by the further addition of fat, but by no means always;
at least, under ordinary circumstances, it is often quite difficult to make the
patient take the 500 grams of meat, 200 grams of cream and 100 grams of
fat mentioned in the dietary above; and we must always avoid throwing too
great a burden upon the metabolism of the diabetic. In short, as a choice of
evils, we must often allow our patient to remain underfed and lose weight,
until his excretion of sugar decreases appreciably. Only when the glycosuria
becomes so slight that the net calory value of the ingested food approaches the
gross calory value, can we expect to avoid the evil of under-nutrition. We
must risk under-nutrition quite often, in severe cases, e. g., when, in order to
abolish the glycosuria, we forbid all bread, and reduce the albuminous (meat)
food considerably.
I know of no successful treatment of severe cases without temporary under-
nutrition, but the physician must be very careful during these periods. We
should be especially cautious in regard to long-continued hyponutrition, such
as entails a loss of weight of more than two kilograms in subjects who have
already reached the minimum weight of 130 pounds in men and 110 pounds
in women, for this loss is difficult to regain.
In the consideration of the theory of treatment in diabetes, some mention
of diabetic acidosis will not be out of place. By this term I mean the forma-
THR THEORY OF THE TREATMENT OF DIABETES 91
tion of B-oxybutyric acid in the processes of metabolism. It never fails to
occur in serious cases, and even in mild cases it appears quite often.
Acetonuria and diaceturia are part of acidosis, for both substances, acetone
as well as acetoacetic acid (diacetic acid), originate from oxybutyric acid. I
must insist upon this view which has many evidences in its favor, among them
the fact that acetonuria and diaceturia only occur when oxybutyric acid is also
found in the urine. I know very well that some prominent chemists have
maintained the direct opposite, but I also know that very prominent chemists
may be mistaken in their reports; for in the very cases in which they found
no oxybutyric acid in spite of the presence of acetone and acetoacetic acid,
and in the specimens which they kindly sent to me for examination in my
laboratory, I succeeded in demonstrating oxybutyric acid in the urine.
Therefore, acidosis, including acetonuria and diaceturia, plays an impor-
tant réle in diabetes. In twenty-four hours oxybutyric acid may be excreted
in amounts above 100 grams, and acetone + diacetic acid up to 15 grams.
As these substances are easily oxidized, their excretion in such large amounts
shows a deficiency in the power of oxidation possessed by the tissues in these
cases of diabetes mellitus. As regards this decrease in the power of oxidation
in the diabetic, the conditions are very similar to those involved in the in-
creased decomposition of albumin. Neither is primarily due to the diabetic
disturbances of metabolism, but since the albuminoid decomposition is only
increased when sugar is wasted and passes out unutilized in the urine, this
weakness of oxidation may be referred to the lack of oxidation of sugar.
The oxidation of sugar, however, does not fail because the general power
of oxidation is diminished, but vice versa. Since for other reasons the sugar
is not oxidized, the general power of oxidation becomes lessened; of all the
products which are consumed in the organism, sugar is the most readily com-
bustible, and in the fire which thus arises in normal metabolism, other less
readily oxidizable substances are consumed, a process designated by physiolo-
gists as secondary oxidation. Owing to the facts just mentioned, the same
substances which produce acidosis may occur in other conditions—in non-
diabetic persons whenever carbohydrates and sugars are withheld entirely.
In the diabetic, too, they usually appear when the carbohydrates are excluded
from the food. They may be excreted, however, in severe diabetes, with
marked glycosuria, even when carbohydrates are eaten in large amounts. Here
acidosis indicates that the sugar metabolism of the body has fallen so low that
in spite of the plentiful ingestion of carbohydrate food, very little of it is
consumed. The fire which lights the secondary oxidation processes is almost
extinguished, and thus the total power of oxidation of the organism is dam-
aged. It must be remembered that this condition is due to the disproportion
between the products ready for oxidation in metabolism and the power of
oxidation. In diabetic patients tissue decomposition goes on too rapidly for
their power of oxidation; their nourishment is both improper and too profuse,
yet by limitation of their metabolism and careful diet it is often possible to
restore to par the power of oxidation, and thus cause the acidosis to disappear.
Tt has been necessary to discuss acidosis quite in detail because of its
role in diabetic coma. Acidosis is the only certainly known cause of this coma
92 DIABETES MELLITUS
(that is, of many cases of it). We now recognize that it is oxybutyric acid
which produces true dyspneic coma; that is, an acid coma, 1. €., a coma which
is an expression of an over-acid condition of the blood, and this hyperacidity
is due to the presence of a large amount of oxybutyric acid (100 grams or
more), which is formed and which eaters the blood within twenty-four hours.
This fact, and also the danger that by a too rapid withdrawal of carbohydrates
one may cause acidosis, as well as coma, renders it necessary for the physician
to be familiar with this process.
V. PRACTICAL THERAPY
Every therapeutic measure is to be used, but after the dietetic treatment mineral
waters alone are of much service. Prophylaxis; obesity and diabetes mellitus. From
the point of view of dietetic treatment, three forms of diabetes are to be distinguished:
the medium severe, the mild, and the severe. The medium severe cases, their diagnosis
and their importance in practice. The aim of treatment in cases of each form. For the
proper dietetic treatment of every case a quantitative and qualitative estimate of the
entire dietary is necessary. Preliminaries of treatment: Quantitative regulation without
limitation; its result. Further steps toward the abolition of glycosuria and improve-
ment of tolerance, maximal reduction of albuminous food and the twenty-four-hour fast.
Diet lists for the diabetic; there are no foods absolutely permissible. Carbohydrate
nutrition: Bread, cereals, vegetables, fruits; calculation of their relative advantages
and dangers. Meat, fish, and eggs. Fatty foods. Sausage, cheese, bacon, butter, oil,
cream. Drinks: Milk, wine, beer, whiskey, tea, coffee. Artificial foods. Hospital treat-.
ment. Dispensary treatment and “ bath-cures.” Disturbances and dangers arising during
the treatment of diabetes.
I wish to speak first and chiefly of the dietetic treatment of diabetes, but
of course every other therapeutic measure is to be welcomed and utilized. It
should not be forgotten that since almost any disturbance of a diabetic’s gen-
eral health tends to aggravate the underlying disease, common sense teaches us
to treat as carefully as we can any minor ailment from which the patient
may suffer from time to time. If he is syphilitic, carefully planned specific
treatment should be used, as also quinin in malaria, digitalis in circulatory
disturbances, and appropriate treatment for nervous affections. By such treat-
ment we may succeed in improving but, unfortunately, very rarely in curing
the diabetes—that is to say, the glycosuria and the other symptoms which
may be dependent on it.
It is just as evident that the treatment of diabetes must always be a
treatment of the entire organism, i.e., that the mode of life of the patient
must be properly arranged in all respects. From this standpoint, there are
two factors to be considered—mental and emotional rest, and sufficient
muscular exercise; I say sufficient muscular exercise, but no more, for too
much readily increases the glycosuria.
The main point, however, the alpha and omega in the care of the diabetic,
is the dietetic treatment; besides this, mineral water cures (Carlsbad, Neue-
nahr, Vichy) also play a réle, but not drugs. There is scarcely a physician
familiar with diabetes who will resort to drugs to diminish the glycosuria. It
is true there are many remedies which bring this about, and among them
some which produce this effect without diminishing the demand for food or
PRACTICAL THERAPY 93
the actual intake of nourishment. But—they act only in those cases in which
the dietetic treatment alone would suffice, and in which they are, therefore,
superfluous. During the administration of drugs (if we do use them) the
dietetic treatment should never be forgotten, else the case will fail to do well
in the long run. For a few weeks, perhaps, here and there, by the adminis-
tration of opium, occasionally also by the use of antipyrin and other nervines,
the glycosuria may be limited or even removed. Then the action of these drugs
ceases and glycosuria returns to its former height, sometimes even exceeding
it. It appears, as I have already indicated, that the tolerance of the diabetic
is not improved by a drug diminution of glycosuria; and even in an agly-
cosuric condition, in case this is brought about by drugs, the patient’s toler-
ance does not improve as it does under diet.
That we shall ever find a specific remedy for diabetes, must be regarded
as quite unlikely, especially by those who, like myself, look upon the disease
as an expression of hereditary weakness of metabolism; at present we cer-
tainly do not possess such a remedy.
We shall now proceed to the discussion of the dietetic treatment in detail.
This method of treatment has its place not only in the care of confirmed,
true diabetes mellitus, but also in prophylacis.
In families in whom this disease is hereditary there should be great mod-
eration in the use of carbohydrates in any form, i.e., limitation of the sugar
metabolism should be made an unalterable law. But there should also be
moderation in eating and drinking in general. There can be no doubt that
habitual hypernutrition favors the outbreak of diabetes if the predisposition
to it exists. The cases of diabetes mellitus complicating obesity (even in
full-blooded individuals with arteriosclerosis) are almost all to be included in
this category. Alcoholism, at least that form that goes hand in hand with
over-nutrition, also plays a part in the etiology of diabetes.
In individuals with a hereditary predisposition and marked obesity due to
over-nutrition, diabetes should always be watched for, and an occasional exam-
ination be made of the urine voided four hours after a breakfast in which at
least 100 grams of bread and about 30 grams of sugar have been consumed ;
or, for greater certainty, a test for glycosuria alimentaria e saccharo should
be made, and the case should then be judged with the necessary reserve.
In confirmed diabetes, dietetic therapy has for its object the elimination
of glycosuria if possible. This occurs very readily in some cases, in others it
is difficult, and in some it may be impossible; even when it may be accom-
plished, although with difficulty, there are, unfortunately, many cases in which
the results scarcely compensate the physician and patient for the required
trouble. ar:
The amount of energy that should be put into the treatment varies in
different cases, and much labor will be saved the physician and the patient
if this fact is recognized from the onset; on this account it is convenient to
divide diabetics into three groups, a method which I proposed ten years ago.
1. The moderately severe cases.
2. The mild cases.
3. The severe or very severe cases.
94 DIABETES MELLITUS
We have already learned to differentiate between mild and severe cases,
but in gauging the case from a therapeutic standpoint we need to recognize
also a group of moderately severe cases. The mild cases are so benign that
they offer a splendid prospect for therapy and usnally require but little treat-
ment. The severe and very severe cases, on the other hand, are so malignant
that even after the most energetic therapy the results obtained are slight and
unsatisfactory because incomplete or transitory. In the group of moderately
severe cases are included a great many which occupy a middle position, being
by no means so benign that they do not require continued observation and
proper treatment, but by no means so malignant that they should be left to
their fate; by a more or less strict plan of treatment, they may be preserved
in fair health and moderate activity for many years. Among the cases which
at the beginning of treatment must be included in this intermediate group,
there are not a few which prove to belong to the mild form, but which, on
account of unfavorable influences, have passed temporarily into the moder-
ately severe form. In this group we also find some which belong to the severe
or very severe forms, but have not yet reached the full development of the
disease.
Let us illustrate:
A man aged fifty, with an inherited predisposition to diabetes. Ten days previously,
he undertook a lengthy and fatiguing excursion in the Black Forest, ate and drank more
than usual, and was thoroughly drenched by a heavy rain. Since that time, he has had
a voracious appetite, extreme thirst, marked diuresis, and has lost much weight. His
urine contained 8 per cent. of sugar(!). His daily dietary was restricted quantitatively
to about one pound of meat, several eggs, coffee with rich cream but no sugar, green
vegetables (no potatoes or beets), no cereals, 80 grams only of wheat bread, his meals
to be prepared without flour; one bottle of wine was allowed. Within a few days his
glycosuria had disappeared. The case has continued to run a mild course up to the
present time (twelve years subsequently). Since the acute attack, the patient’s diet,
for the most part, has been restricted as above, although at times it has been relaxed
to the extent of allowing sweet champagne; the sugar in the urine has never risen above
0.5 per cent.
At the beginning of treatment this case appeared very desperate, but it
soon became a clear example of the mild form of diabetes.
To illustrate again:
A peasant, thirty-three years of age and of a diabetic family. For five weeks following
an accident he complained cf hunger, thirst, loss of flesh, lassitude, and cramps in the
calves of his legs. Patellar reflexes present; no complications; weight 48 kilograms;
internal organs sound. After eight days on regulated diet including fat meat, with 150
grams of milk, and 20 grams of wheat bread, the sugar in his urine was still 4 per cent.
— 5 per cent. (75 to 100 grams of sugar a day). Only after the complete withdrawal of
bread and increase of milk to 200 grams did the urine gradually become free from sugar.
After this on a diet with 200 grams of milk and 50 grams of bread he remained aglyco-
suri¢ for several months, but even then he had to rigidly conform to rules in order to
prevent the reappearance of glycosuria. In this fashion he has now lived for years. His
weight is 56 kilograms.
This is a typical case of the medium severe form; severe at its onset but
under continuous, moderately strict dietetic treatment taking a rather favor-
able course.
PRACTICAL THERAPY 95
The following is another typical example of this group:
A bookbinder, seventeen years old. No family history of diabetes. For five weeks,
without apparent cause, he was continually hungry, he lost weight, was extremely weak,
and had a non-gonorrheal urethritis. Organs sound; knee-jerk normal; weight 45 kilo-
grams. On a diet of 220 to 300 grams of meat, green vegetables, 250 grams of milk and
300 grams of bread, there was a glycosuria of 6 per cent.— 150 to 200 grams of sugar
a day. Only upon complete withdrawal of bread while still taking 25 grams of milk,
did he become free from sugar. After a sugar-free period of one month, he could take
more milk and a small quantity of bread without excreting sugar. He gradually became
accustomed to a larger allowance of bread and milk, being careful never to take enough
to produce glycosuria. This tolerance gradually inereased until he could ingest 170
grams of bread and 100 grams of milk without sugar appearing in the urine.
The patient remained in this condition, outside the hospital, for two years. After
this (probably because he did not adhere to the same diet) sugar was again excreted,
and did not disappear on very strict diet—so that the case became severe.
The object in quoting these examples is to show clearly the existence of
a moderately severe form of the disease. At the outset, cases like those just
quoted may readily be looked upon as extreme, and thus great harm may
result. Among the points on which the recognition of medium severe cases
rests the most important is this, that after partial withdrawal of carbohydrates
(for example, 200 grams of milk and 50 grams of bread), no matter how
marked the glycosuria has previously been, it immediately and decidedly
decreases, usually falling below 100 grams. Besides, in these cases of medium
severity, the amount of acidosis as determined by the ferric-chlorid and ace-
tone reaction is slight, and the amount of urine is not great (4 and, at most,
5 liters per day). All these conditions may also exist in severe cases.
After determining to which group a given case belongs, the physician must
outline the method of treatment as follows:
1. Mild cases are to be made aglycosuric, and maintained in this condition
until continuous observation for at least six months has demonstrated that
the disease shows no tendency to progress. Later, a permanent increase of
glycosuria above 0.5 per cent. should not be permitted. Such a transitory
increase need cause no anxiety, but as soon as it becomes greater the case is
to be treated as at first by strict limitation of the diet.
2. Cases of the medium severe form are to be made aglycosuric by strict
treatment if this is necessary. Then, in case they do not prove to be mild
cases, they are to be permanently maintained in this condition. Even a mild
glycosuria is not to be permitted, and anything causing a transitory increase
of glycosuria is to be absolutely avoided, as it threatens the already greatly
endangered tolerance. It is possible that there are individual cases which
at the onset belong to the medium severe group, but which may be rendered
mild, and then the indulgences possible for cases of the mild forms may be
permitted; but such cases are certainly not frequent.
3. The nature of the severe and very severe cases becomes manifest when
on the first attempt to produce aglycosuria the feebleness of their tolerance
appears. In these cases, our primary object is to bring the patient to the
point at which life can be maintained without-a deficit; but this can rarely
be brought about, unless we can limit, and that decidedly, the loss of sugar in
96 DIABETES MELLITUS
the urine. We must make an attempt to diminish the glycosuria, and see how
far we are successful. Now and then, we can accomplish more than we had
hoped, and a better tolerance may follow a regulation of the diet and a reduc-
tion of the glycosuria, so that we may succeed in maintaining the patient’s
equilibrium of metabolism with a very slight glycosuria and with a fair con-
dition of health for years, even after all hope had seemed to be gone.
This is the chief task of the physician, easy in some cases, more difficult
in others, and in many almost impossible. Although the treatment of the
different groups of cases varies, one general rule applies to all. We should
determine the exact quantitative and qualitative diet for every diabetic who
comes under treatment. Prout exaggerated when he stated (1820) that the
quantity of the food, that is, the quantitative restriction, is more important
for the diabetic than its quality; but his maxim that all of the diabetic’s food
(including meat) is to be determined quantitatively, holds good, because noth-
ing more unfortunate can befall a diabetic than the overtaxing of his general
powers of metabolism. I consider the restriction of labor of the whole metab-
olism to be an important advance in the therapy of diabetes. There are no
foods which the diabetic can be allowed to eat in unrestricted amount; the
quantity of each must be measured. We must see that he does not get too
much carbohydrate food, or too much animal food, and that he has just enough
fat, neither too much nor too little.
I am proceeding on the supposition that the patient is to be treated not
in a hospital but in his own home. First of all, we must determine quantita-
tively for several days the amount of each food ingested. For this purpose it
is only necessary to know the amount of each carbohydrate (flour, bread,
sugar and milk) used in the preparation of his meals. If this plan is carried
out, there is no difficulty later. Each variety of food should be served on a
separate plate, and the amount weighed. Sauces are not considered, and bread
is weighed separately. If the patient cannot afford this, or if he is unwilling
to do it, he should either go to a hospital where others will look after his food,
or we must relinquish the attempt to regulate the whole diet quantitatively.
We may be able to get along without weighing the food in very mild cases in
which a moderate reduction of the carbohydrates is sufficient to control the
disease.
Still, most patients, even those in limited circumstances, can arrange to
weigh their food. Usually a simple quantitative regulation of the diet, with
liberal allowance for the wishes and inclination of the patient, and without
too strict limitation, may be followed by good, even remarkably good results;
at any rate, we may thus ascertain the maximum of the glycosuria on a given
diet and thus establish the necessary basis for further dietary regulations.
An example will best serve to make this intelligible.
A woman, forty years of age, no hereditary history obtainable, has suffered for four
months from extreme hunger and thirst; there is copious diuresis; loss of weight 20
kilograms. Present weight 58 kilograms; no organic disturbances or complications; no
acidosis; reflexes normal. The patient asserts that she has been on a diet, that is, that
she has eaten but little bread, etc. During the first three days of treatment, she ate as
before and was found to be excreting 24 to 3 liters of urine with 6 per cent. to 7 per cent.
(= 150 to 200 grams) of sugar per day. Then the diet was regulated quantitatively,
PRACTICAL THERAPY 97
taking the wishes of the patient into consideration. She received daily 500 grams of
milk, 100 grams of bread, 200 grams of meat, 4 eggs, 200 grams of vegetables with ten
per cent. of fat, 50 grams of butter, and 75 grams of fatty cheese or sausage, ete., with
tea, coffee, and water ad libitum, and a half liter of wine. This diet was abundant, and
gave the patient 35 calories per kilo of body-weight. She remarked that she had not
eaten much more before treatment, not even of bread. During the following days she
excreted 14 to 2 liters of urine, and 3.5 per cent. (= 50-70 grams) of sugar daily. At
the same time she felt stronger and improved each day. No acidosis.
This is, in itself, a truly remarkable result of quantitative regulation of
‘the diet. Of course, there was some restriction, but the patient hardly
noticed it.
In this case, the milk and the bread must be still further reduced until
the sugar has disappeared entirely.
Our patient preferred not to have the milk in her diet reduced. The bread was there-
fore reduced to 40 grams, but after four days upon a diet containing 60 grams of bread
she still excreted sugar, but when the milk was reduced to 300 grams and the bread to
40 grams there was no glycosuria. On this diet she remained aglycosuric, so that after
‘fourteen days it was deemed possible to increase her food. For the sake of precaution,
100 grams of milk were withdrawn, but 10 grams of bread were added. She remained
free from sugar. After three days 100 grams of milk were added, and the patient
continued free from sugar; again after three days 10 grams of bread were added, and
100 grams of milk withdrawn. Thus she continued upon a diet of 500 grams of milk
and 100 grams of bread for six weeks, when she was aglycosuric and in apparent full
health, having attained a weight of 62 kilograms.
She remained under observation. Occasionally, as the result of an indiscretion in
diet, a slight, transitory glycosuria occurred, and then the patient would live on 50
grams of bread for a few days, or would desist altogether from eating bread for a whole
day, then return to 50 grams of bread for a few days, until finally she became perfectly
aglycosuric on a diet of 100 grams of bread.
The removal of glycosuria is by no means always so easy and simple.
Very often more stringent methods must be employed; carbohydrates, flour
foods, and even milk, must be wholly excluded before the patient becomes
entirely free from sugar, and frequently even this is insufficient and nothing
remains but the reduction of albuminous food. The albumin nutrition may
then be restricted to 200 grams, even to 150 grams of cooked meat (reckoning
albumin as meat), so that the patient does not receive more than 40 to 50
grams of albumin. In the severe cases this limitation of the albumin nour-
ishment is one of the most important points. Its effect is often much greater
than can be explained by the withdrawal of the sugar formed from the albu-
min. For example: With 100 grams of albumin (besides the necessary fat)
40 grams of sugar are excreted; after a reduction to 60 grams of albumin,
sugar disappears in a few days. That 40 grams of sugar are formed from 40
grams of albumin is hardly possible; therefore, the aglycosuria cannot be due
to the limitation of sugar intake (in albumin). I have long been convinced
that it is the limitation of food and the resulting disencumbrance of the
entire metabolism which brings about this favorable result. The metabolism
of the diabetic is not deficient in only one respect, namely, that with which
we are concerned, the working up of the sugar molecule and its preparation
for oxidation. His metabolism is deficient as a whole—witness the weakness
of the powers of oxidation as expressed unmistakably in the acidosis.
8
98 DIABETES MELLITUS
In the severe cases which we are now considering it is almost always neces-
sary to limit the entire amount of food (albumin and fat included) so that
its total calory value will be lowered, even below the minimum required by
Rubner (35 calories per kilo of body-weight). Under-nutrition need not be
feared; my diabetics, at least those who are treated in the hospital, get along
with 30 calories, and even less, per kilo, without losing body-weight.
When the excretion of sugar has fallen to the minimum, about 0.5 per
cent., and not more than 10 grams of sugar per day are excreted, aglycosuria
may finally be brought about by giving the patient no food for twenty-four
hours. He may be allowed water ad libitum, for it is unnecessary in this con-
dition that the patient should suffer from thirst. This procedure—a twenty-
four-hour fast—was introduced by Cantani.
Both the reduction of the albuminous foods and the twenty-four-hour fast
seem cruel, or at least drastic, measures, but they really are not so; at least
the author has never had the least difficulty in enforcing them. More diffi-
culty in the strict dietetic treatment of diabetes is encountered in other direc-
tions. We shall speak of this later on.
After glycosuria has been abolished, if we expect to increase the tolerance,
we must maintain aglycosuria for at least two weeks before we can appreciably
add to the food. After the patient has been finally brought to the daily allow-
ance of food which is sufficient for him he must remain upon this diet and
be under observation. It is also advisable at times to institute once a week
a twenty-four-hour fast for carbohydrates, during which period the patient
receives tio bread.
Keeping. the patient for a month or longer without bread, starchy foods
or milk rarely succeeds, but the author knows of several diabetics who have
lived for years on a strict albumin-fat diet with the addition daily of 200
to 400 grams of green vegetables (deficient in carbohydrates), and they have
been able to attend to their business without taking unusual care of them-
selves. One, a man about forty years of age, held the responsible position of
professor at a university.
We must, then, exert all our efforts and all our art properly to regulate
the diet!
In what follows, I shall only mention briefly some of the main rules, the
observance of which will enable the physician judiciously to handle his dia-
betics. We shall see, however, that in order to prescribe a diet, he must be
familiar with the composition of the most common foods as regards fat and
carbohydrates. All recent books on diabetes contain detailed data on this
subject, and the most essential figures in this respect will be given at the
conclusion of this article.
it shall attempt no distinction between what is absolutely (in any quan-
tity) allowable for a diabetic, and what is absolutely forbidden. I consider
such a distinction wrong and dangerous. No diabetic should be permitted
; hs eas use of any food; everything must be ordered him quantita-
twely. :
The amount of carbohydrates permitted is best considered in terms of
wheat bread; and most patients prefer to take the amount of carbohydrates
PRACTICAL THERAPY 99
permitted them in the form of good wheat bread. Some, however, would
rather have it as flour-cakes, and there is no objection to their having it in
the form of any simple carbohydrate that they prefer. If the patients take
their carbohydrates partly as wheat bread and partly in some other way, then
we must subtract the latter amount from the total that is permissible. Sup-
pose, for instance, that the patient is allowed 100 grams of wheat bread =
about 60 grams of starch. He prefers to take part of his starch in another
form, for instance, as oatmeal or rice, in soup, 10 grams being sufficient to
make a large dish of 4 of a liter; or he takes balls of oatmeal, or 25 grams of
oatmeal alone. Oatmeal and rice contain about 75 per cent. of starch. We
can consider the 10 grams of oatmeal as equivalent to wheat bread, and there-
fore we must subtract 10 grams (or to be quite accurate 12 grams) from the
daily allowance (100 grams) of wheat bread. Twenty-five grams of grits or
rice are equal to about 30 grams of wheat bread. Of course, the patient may
have other forms of bread instead of wheat bread. Rolls are useful for this
purpose, the amount of starch being almost the same as in wheat bread. The
rolls may be cut into small slices and spread with butter. Rye bread is also
serviceable; it contains 15 per cent. less of starch, but is heavier and more
compact. Aleuronat bread contains only about half as much starch as wheat
bread, but there are few diabetics who like this bread, although among all the
varieties of so-called “ diabetic bread,” this has the most agreeable taste.
Among vegetables the diabetic should eat only those in which the amount
of carbohydrates does not exceed 5 per cent. (compare the tables), and even
this slight amount of carbohydrates must not be ignored in those cases in
which the removal of glycosuria is difficult. With 300 grams of vegetables
per day, it may amount to as much as 15 grams.
Fruits should be permitted the diabetic if possible. There are plenty of
fruits whose carbohydrates do not exceed 6 per cent. (sugar + pectin). They
must be well cooked and sweetened with saccharin. Almost any kind of fruit
may be given, even such as contain sugar in large amounts, but the amount
of carbohydrates they contain must be deducted from the amount of bread
which is permitted. Only grapes and dried fruits, on account of their high
sugar-contents, are to be excluded. The fact that the sugar contained in fruit
is levulose modifies the case but little, for after prolonged use levulose becomes
almost as injurious as dextrose. Many so-called “ fruits for diabetics” are to
be found on the market; they contain about 2 per cent. to 4 per cent. of sugar,
therefore less than the fresh fruits, even those poor in sugar, but, unfortu-
nately, many diabetics grow tired of them after a time.
In meat, besides the albumin, we must take into account the fat it con-
tains. Considering only the percentage of albumin (25 per cent.), the calory
value of stewed or broiled meat is only 1. When the ordinary amount of fat
is present (10 per cent.) the calory value becomes 2, but we must remember
that in the cooking of meat (broiling, stewing) part of the fat is lost; in fact,
most of the fat is lost in cooking. Excluding the fat, all kinds of meat are
of the same calory value. Liver is strictly forbidden; of other “ glands”
sweetbreads and brain, though not strictly meat, are of equal value on account
of their high percentage of fat. Naturally, fat meat is always preferable for
100 DIABETES MELLITUS
a diabetic ; some fat meats and fat fish contain 20 per cent. of fat or more (see
diet lists).
As a working principle, let us say that a diabetic should not eat more than
500 grams of meat (weighed after cooking), for most patients lose their appe-
tite if they eat more; diabetics who are under close medical supervision may
be permitted more, but it is usually of no benefit.
Eggs are very useful. On account of the large amount of fat in the yolk,
each egg has a value of 75 calories. If we allow more than two eggs, we
should subtract 50 grams for each egg from the amount of meat allowed.
Fat foods are of the greatest value, for fat, as a rule, does not increase
glycosuria and has the enormous nutritive value of 9 calories, while starch
and albumin have only 4. In good sausage (poor sausage often contains
flour and but little fat!) there is 30 per cent. to 40 per cent. of fat; in good
cheese from 20 per cent. to 30 per cent.; poor cheese contains but little fat.
Butter contains 85 per cent. of fat; lard (butter or fat melted), bone marrow,
and vegetable oils almost 100 per cent. Bacon varies greatly in regard to the
amount of fat it contains; it averages about 92 per cent. An enormous calory
value may be obtained in the following foods: 100 grams of Holland cheese
(30 per cent. fat) gives 270 calories, without including the albumin; 100
grams of good butter, 720 calories. Fat and butter may be mixed with vege-
tables so as to make them contain 10 per cent., even 15 per cent. of fat; bacon
and oil in salad, up to 20 per cent. to 40 per cent.
Cheese may be pulverized and added to soups and sauces, and also may
be made into cheese cakes, cheese puddings, etc.
Cream contains 25 per cent. of fat, and is, therefore, very valuable; the
slight amount of sugar it contains (3 per cent. milk-sugar) need scarcely be
regarded. Some cream contains even more fat than this (up to 40 per
cent.). If it is dairied in a very cleanly manner, it is at first very grate-
ful to the taste, but after prolonged administration patients often do not
like it.
Milk is in general use, and, even in the most severe cases, of great value.
But it must not be supposed that the milk-sugar is “harmless” to the dia-
betic, for it is not much less so than dextrose and cane sugar; but milk con-
tains very little sugar, only about 3 per cent. Its carbohydrate contents must
be reckoned, but it also contains 4 per cent. to 5 per cent. of fat. There are
several manufactured preparations of milk which contain a larger amount of
fat, and in which the sugar is decreased; there are even artificial milks free
from sugar—but my patients soon become tired of these preparations.
Other fluids are to be estimated according to their carbohydrate value;
among wines only the southern wines and champagne contain more than 3 per
cent.; these contain 12 per cent. In beer the carbohydrate value is rarely
under 6 per cent. Beer is more harmful than this percentage would lead us
to suppose, as it contains the greater part of its carbohydrates as maltose;
this at once decomposes in the intestines into dextrose, and, for this reason,
the diabetic ingests in beer the most dangerous, most readily absorbable form
of carbohydrate food.
Among alcoholic liquors only rum, cognac, whiskey, etc., are to be con-
2
PRACTICAL THERAPY 101
sidered! No liqueurs! These, and often the so-called “ bitters,” contain enor-
mous quantities of sugar.
Coffee and tea may be looked upon as harmless for the diabetic. Cocoa
contains (without admixture) 15 per cent. of starch, and must be estimated
accordingly.
If it is desirable to increase the menu still further, manufacturing chem-
ists have placed many preparations on the market for the diabetic. The physi-
cian should assist the diabetic to make his life as comfortable as possible,
yet the medical adviser must never allow the reins to be taken out of his
hands; unfortunately, this often occurs.
Which diabetics are to be treated at a hospital (of course, one well appointed
with reference to diabetic treatment), which may be treated at home, and
which should be sent to Carlsbad, Vichy, Neuenahr, etc. ?
The very mild cases, in which only sugar, potatoes and beer must be
restricted in order to inake the urine free from sugar, do not need hospital
treatment, though it is advisable for them to undergo each year, or at least
from time to time, a course of treatment at any one of the previously men-
tioned bath cures. Frequently these cases occur in elderly persons, in whom
a cure of this sort is indicated on account of complicating arteriosclerosis,
disease of the liver, or gout.
It is often wise in such cases, after sugar has been discovered, to send
them at once to Carlsbad; they return free from sugar, and with a greater
docility and willingness to carry out*further dietetic treatment.
If the case is severe, so that it is necessary to reduce to a minimum the
allowance of bread in order to free the urine from sugar, the question whether
the patient should be treated at home or in a hospital must be settled by the
individual circumstances. If the patient is sensible, reliable, and in easy
circumstances, treatment at home should be tried, but we must not be too
optimistic as to results; as soon as signs of unreliability on the patient’s part
are detected, hospital treatment should be urged. If, under treatment at
home, the sugar has been considerably reduced (to about 20-30 grams a day),
we may send the patient to Carlsbad, whence he often returns sugar-free, and
he may then more easily than before be kept aglycosuric; but this applies only
to the mild cases.
Every diabetic whose case is not very mild, or who is not reliable or well-
to-do, as well as every moderately severe and every severe case (that is, every
patient from whose diet carbohydrates must be largely or wholly eliminated,
if only for a time), must, to begin with, have hospital treatment. In a hos-
pital we find out how much can be attained, and we determine the diet on
which the patient will become sugar-free, or will have, at least, only a gly-
cosuria of definite and known intensity. After this he must remain under
supervision, and if the glycosuria again shows a progressive tendency he should
return to the hospital. Poor patients with severe diabetes need hospital treat-
ment at least every year, of six or eight weeks’ duration the first year, and
reduced, if necessary, to four weeks the next year.
In the author’s experience, “ bath cures” rarely benefit these patients, and
often do harm, :
102 DIABETES MELLITUS
DISTURBANCES AND DANGERS OCCURRING IN THE DIETETIC
TREATMENT OF DIABETES
That disturbances of digestion often occur during dietetic treatment has
been known ever since the disease has been treated by a restriction of food.
The more violent disturbances, such as used to occur when our knowledge
was less, for instance, diarrhea, sometimes combined with vomiting, should
now be prevented entirely. They may be avoided in trustworthy patients if
the whole amount of food ingested is quantitatively determined, if too large
a portion of meat is not allowed, and if we bear in mind the sensitiveness of
the patient as regards fat and fatty foods. Some patients lose their appetite
from the beginning, or as soon as carbohydrate food, especially bread, is re-
stricted. This anorexia may be avoided by giving them fruits. If the patient
likes the fruits prepared for diabetics he is very fortunate; otherwise cooked
or uncooked fruits that contain but little sugar may be used. I am loath to
forbid fruits altogether, and even in the severe cases I usually allow as much
as 100 to 200 grams. Milk, also, is very valuable; 4 to 1 liter of milk a day
with a restricted fat-albumin diet often helps the patient over the period of
anorexia without increasing the glycosuria to any extent, and without mak-
ing the patient lose weight. With these precautions, we are not compelled to
break off the dietetic treatment as soon as it is begun, but may go on with it
cautiously as soon as the appetite has improved.
Every disturbance of appetite, however, must be seriously considered, for,
on the whole, cases with anorexia are the most difficult to deal with. In some
of these cases, psychic depression plays a certain part, and if their disease is
not too pronounced, they often get along much better at Carlsbad or Neuenahr
than if they stay at home, or go to a hospital.
In acidosis we have an especially formidable hindrance to strict dietetic:
treatment. In many of the moderately severe cases it appears as soon as the
diet is restricted, or, if already present, it becomes more marked when the
carbohydrates are limited. Then the patient is at once in danger, because
acidosis may lead to coma. Formerly, this often happened when the diet was
restricted too suddenly, and even to-day cases with acidosis are always in
danger if severe gastric disturbances occur. In the absence of gastric irritabil-
ity this danger may be averted by the administration of sodium bicarbonate.
Enough should be given to make the urine feebly alkaline, and 50 or more
grams in twenty-four hours may be necessary. With this precaution we may
endeavor to reduce glycosuria by strict diet even where decided acidosis already
exists. Of course all food end its calory value must be determined with quan-
titative exactness, for, to repeat, it is the disproportion between the quantity
of the products prepared in metabolism for oxidation and the power of oxida-
tion itself which finds its expression in acidosis. In cases with acidosis we
must not think of withdrawing carbohydrates entirely, but should allow 60 to
80 grams of bread, 4 a liter of milk, and as much as 200 grams of fruit. The
latter is here particularly important in order to prevent indigestion.
We may count with certainty on the fact that if the acetone reaction be-
comes marked at the onset, the cause is simply the urinary sodium, that is, the
TABLES 103
alkalinity of the urine. Sometimes the diacetic acid (ferric chlorid) reaction
also becomes marked; but this should not be allowed to occur after the first
few days. In case the reaction becomes still more intense, so that the urine
blackens on the addition of ferric chlorid, milk should be cautiously added to
the diet, and its calory value subtracted from that of the meat, which should
be correspondingly reduced. Otherwise, if the general condition of the
patient remains good, we may maintain an expectant attitude until the ferric
chlorid reaction becomes less marked, which usually occurs in eight to four-
teen days, sometimes earlier or later. When this diminution of acidosis begins
the danger from this source is over; acidosis gradually disappears and will
not cause trouble, even should a further restriction of the carbohydrates be
necessary.
Of course, if symptoms of coma appear we must increase the dose of sodium
bicarbonate until the urine is alkaline. Sometimes 100 grams or more of
sodium bicarbonate must be given in twenty-four hours. In almost every case
of this kind, it is milk which answers our purpose best.
VI. TABLES
Tables of foods: different kinds of meat, fish, eggs, sausages, meat-preserves, and
various kinds of cheese, arranged according to the amount of fat they contain.—Fat,
butter and varieties of milk, with percentages of fat and carbohydrates.—Bread, flour
and vegetables, with percentages of carbohydrates.—Fruits and their carbohydrate
(sugar + pectin) contents.—Beer, wine and spirits, with their amounts of alcohol and
carbohydrates.—Plan for calculating the food-value of the diet in calories.—Short
popular dietary instructions for diabetics.
MEAT WITH PERCENTAGE OF FAT
Percentage Percentage
of Fat. of Fat.
1, Rat! pork: eviiscginsdeaucewe cee sees 37.84 | 27. Groundling.......cceeeeeeeeeees 2.68
2 Very fat mutton................ 36.39 | 28. Medium fat horseflesh........... 2.55
8: River €€l occ ccc atetcaasese say eas 28.37 | 29. Anchovy.....ccescceevecceenees 2.21
4, Fat beef (from ox).............. 26.88 | 80. Roe (deer)........ceceeeeeee ves 1.92
5. River lamprey (smoked or pickled) 25.59 | 31. Plaice.............eeeeeeeee 0.25-1.80
6. a HEMI vs nciscicwaggnd aware 16.89 | 32. Lean cow’s meat...........eeeee 1.78
Me OPTAD ys dred aitia piracy tne ee eatioase bai 15.94 | 38. Fieldfare. wccc.cesscssscsescnnas 1.77
8. Very fat horseflesh.............. 15.64 | 34. Lean beef (ox).......-.-.0...... 1.50
9. Salt mackerel.................6- 14.10) | 85. Partridge oan ce e284 so site te 1.43
10. Salmon (smoked or salted)....... 11.86 | 36. Chicken (lean)............0008 o. «1.42
11. Mackerel (fresh) j BT VATE: wsasae sad acoebreee /aeucncdyesnwiniee 1.18
12. Rabbit (fat)........ S16: | 88. Carp. scaciyete aw sieine si ecicin coma 1.09
18. Chicken (fat).............. .000- E 89. Pipeons oss sso cemewwewnaienaeens 1.00
14. Bloater.... 0.0.0 cece cc eee eee ee a 40. Veal (lean) .82
1D; Bleak aaasaiswanrs ca aalaae.saeoera . 41, Stock-fish .. 78
16. Fat cow’s meat...... 2... .. ee eee : AD. GAC US 5. 4:5.).5:6 85 F294 tegen es 70
17, Fat veal... ..cscsce ews cveseen ss . ABs. PIG cord oMasiesehinsad, og Garmscctgpienece meee 51
18. Fresh herring..............0.04- - 44, Very lean horseflesh (minimum)... .50
19. Swedish anchovy (salt)....... ... 7.05 | 45. Roach... ..ccee sc cece eee eee eens AT
20. Lean pork......... 02. cece eee ee 6.81 | 46; Perch.c: 22144 cccdenusve sinew dese 44
Ble SALMON asesors ie tie daw arent as aiecere widaeag « 6.42 | 47. Codfish........ceecscccesceeeece .39
22. Swedish anchovy (fresh)......... 5.87 | 48. Oysters... 1... cece eee eee eee eens B87
23. Half fat mutton..............65 5.AT | 49) Crab. cc. eccecnccwsmnns crea e845 s 85
24. Medium fat beef (ox)..........4 5.19 | 50. Haddock........... eee eeee enone 80
25.. Sea cel sis ivevescewasen versace s B02 | BL, LOPS i otis doesneceace acd anise dete 20
26. Duck (wild).......... eee cece ee 3.11
104 DIABETES MELLITUS
EGGS
P t
rarme ome
1. Hens’ eggs (average weight, 53 3. Lapwing eggs......++6 awa men ss 11.66
paineh elena hHans ile Sy og xiasaro 12.11 | 4. Carp roe... .. ce cece cece e eee enne 6.00
2. Duckie ges. os si seaside cee saad aers 15.49 | 5. Caviar... cece cece cece e en eeeees 15.70
SAUSAGES AND PRESERVED MEATS
P ti Percentage
sseapee crit
1. Clean, well-smoked, meat-free bacon 92.20 . Pomerania goose-breast.......... 31.49
2. Westphalia sausage.............04 39.88 . Smoked beef.......... cece eeeeee 15.35
3. Cervelat sausage............00005 39.76 . Tinned meat..........6eeeeeeeee 12.63
4, Frankfurters 4. ccscevens coveseas 39.61 . Blood-sausage...... ea Guts daaietis 11.48
5. Westphalia ham................4. 36.48 . Hard smoked sausage............ 11.40
6, Smoked beef-tongue.............. 31.61 @ Dried beef. oss wseiawaes eos awe 5.24
CHEESE
Percentage Percentage
of Fat. of Fat.
1, Noufchatel ics. sinedwewee ee es « 40.80 . Cheshire cheese..........-eeeeee 27.46
2. Stilton cheese.............00000e 34.55 . Holland cheese...............4.. 26.70
8. Stracchino cheese........ ...... 33.67 . Artificial oleomargarin.......... 25.95
4. Roquefort cheese................ 33.44 . Swiss cheese (ordinary).......... 23.54
5. Brick cheese.... «0... 200000, 32.78 . Artificial fat cheese............. 21.70
6. Cheddar cheese............. «0. 82.37 Romadour. ......... ce eeeeeeeee 20.66
7. Edam cheese.............00ee eee 30.26 . Camembert.......... cee cece eee 21.00
8. Gervais cheese..............000e 29.75 SA DVIC 5 21g actenete tiew ex daaalewie Bieees & 20.27
9. Emmenthal cheese.............. 29.67 Parmesan cheese.........-00.+-+ 19.52
10. Gloucester cheese........... veeee 28.08 . Swiss caraway cheese........... 12.11
11. Gruyére cheese...............04. 28.04 . Meager cheese.........-..--.005 6.84
DIFFERENT FATTY FOODS AND VARIETIES OF MILK
(Arranged according to their fat and carbohydrate—sugar—contents.)
Fat. Carbohy. Fat. Carbohy.
1. Plant-oil.........-... 100.00 ........ . Sheep’s milk........... 6.83 4.73
2. Bone-marrow......... 100.00 ........ . Goat’s milk............ 3.94 4.89
8, Artificial butter....... BIG eee ead . Cow’s milk............ 3.65 4.81
4» BUtter .accadin se. e es 83.27 0.8-0.58 . Ass’s milk....... ..... 1.64 5.99
OS LATS 2.2 scacscsocvesessisvecsia ae 100.00 ........ . Buttermilk............ .93 3.73
6. Cream 6. ceaees sess ces 26.75 3.52 . Kumiss from cow’s
7. Condensed cow’s milk MI Regs sends been cd a) 3.10
without addition of Skimmed milk. .... 2... LTA 4.75
cane-sugar.......... 13.19 15.38 WHEY) cithourawadanaass 23 4.70
The liver of fattened geese (Strassburg liver) should by no means be excluded from
the diet on account of its supposedly ‘high percentage of glycogen, for, in fact, this is
slight, and does not: amount to more than from 0.96 per cent. to 2.8 per cent. (of the
fresh liver): -I am unable to find any quantitative reports of the percentage of fat in
these livers, but it’ may safely be.aggumed to be about 30 per cent.
-BREAD, FLOUR AND VEGETABLES
(According to their percentage of carbohydrates.)
R Per cent.
1. Fine flours (arrowroot, sago, maize,
* GUC aca iu catiins wie eos orton ee -ee. 83.31
2. Potato flour ................0.. 80.83
8. Biscuit flour for children........ 77.30
4, Noodles. ...........0. 25 veeees 76.77
De RiCBias ba sg ex saisivecs Cacuiatea ened 76.52
Per cent.
» Oatmeal... ccc ccc een eee 75.95
fs GARGS: io heset'y secaaale x elaivamrene eee 73.30
Wheat rusks...........cccseeees 72.00
. Wheat forrolls................. 72.00
. Barley flour........... ceeeeeee 71.74
. Rye flour........... Pe Nidgees oie 69.66
TABLES 105
BREAD, FLOUR AND VEGETABLES (continued)
Per cent. Per cent.
12. Barley bread............. eee ee 69.06 | 46. Other-wort............c cece eee 9.46
13. Coarse wheat flour, including bran 47. Carrots (large).......... cc ce eee 9.35
for Graham bread............. 65.00 | 48. Beet-root.. 00... cee cece eee ece 9.26
14, Oatmeal gruel................2. 64.73 | 49. Sceallion........ 0... eee cee eee 9.08
15;, Oat: bread sss sess sake ees sce 64.21 | 50. Radish...............00.0.0000.,. 8.48
16. Leguminose ..................0. 64.05 | 51. Kohlrabi, underground (tuber)... 8.18
DT, TROUS sca dnin cre cacalann teen Seeds oe 63.00 | 52. Carrots (small).................. 8.18
18. Coarse wheat bread.............. 58.00 | 58. Parsley...........0.0.0c00 ca ees 7.44
19) Rye breads i.e. snsieerteweses a AO 20: | Obs DID oc wc aectyaitlact! wed oiaih orsbs ahi 7.43
20. Soldiers’ bread...............0.. 49.00 | 55. Green horse beans,...........006 7.35
21. Pumpernickel.................0. 47.00 | 56. Pumpkin......... 0c... ccc ceca 7.33"
22, So-called Graham bread......... 39.00 | 57. Turnip leaves................2. 7.28
23. Aleuronat bread (Strassburg make) 34.30 | 58. Watermelon.................... 7.14
24, Aleuronat bread (after Ebstein)::. 27.50 | 59. French beans!..............0008 6.60
25, PAS (GLY) iyscc ews Games Yar wens 52.36 | 60. Leek (bulb and root)............. 6.53
26. Beans (Ary). eake ssid eure acne s 49.01 | 61. Red cabbage...... ....... ..00. 6.25
27. Lentils (dry)..... Ee oarpranuemere ves 53.46 | 62. Brussels sprouts........ ........ 6.22
28. Bishop’s-cap....... ee 43.31 | 63. Cabbage (Savoy)..............., 6.02
29. Truffles (air dry)............... 87.40 | 64. Kohlrabi..........00...00..008-
80, Soja beans..... ....ceeeee eee 29.99 | 65. White cabbage
31. Mushrooms (air dry).. .........- 28.99 | 66. Cauliflower..................00,
Ob GANG ies scsscescaSoserata cis Os isles 08 26.31 | 67. Leek (leaves)...............020.
83. Onions (white).............0.005 25.69 | 68. Spinach ............00....e eens
34, Potatoesec.a3 sees 4 arer sawee ees 6 20.69 | 69. “Sugar loaf”............ 0.02005
85. Horseradish ............-+ = -. 15.89 | 70. Tomato....... ccc eee ee eee
36. Black salsify!................06- 15.00 | 71. Radish (small) s
37. Sweet potato (topinambur)....... 14.00 | 72. Roman salad (lettuce)........... 3.55
38. Green garden peas............4. 1200+ | GS. SOrrel cies caueve'ee s save ca Hae 3.43
BOs WOLSRYS a iscusitsintrs a wedesiy selene nesta 11.80 | 74. Mushrooms (fresh).............66 2.91
40! Sugar bests iiss evaceanyaraass 11.72 | 75. Prickly lettuce
41, Green cabbage..........2.. 20068 11.63 | 76. Asparagus.....
42. Eoapery on iia e sie «4 eee ete madara 11.61 | 77. Endive............. ccc eee eee
43. Pale red onions (the tuber)....... 10.82 | 78. Cucumbers......... ........00.
44, Truffles (fresh)......... 0 ccc eee 10.73 | 79. Headed lettuce
45. Red beets...........ce ee eeeeeee 9.56 :
PERCENTAGE OF CARBOHYDRATES IN DIFFERENT FRUITS, ETC.
(Sum of sugar and non-nitrogenous [sugar-producing] extracts [ pectin].)
Sugar. N.-free extracts. Total.
Dextrin.... 3.4
Ti iasiesrs spaces a dmadaela cen peal eeaahoues , { Rene cee oof 13.00 74.40
2. Tocust-beam’.. sacrsieceeee nerve successes oad aie me 67.67 67.67
; ane-sugar :
8. Dried prunes ........ 0. cee eevee eee e es { Geapelneas 44.19 t 17.69 62.10
4, Raisins...........5 3 7.48 62.04
5. Dried apples 42.83 11.40 54.23
6. Dried figs cosine nett Swcasiae aes oe eae sh ese ase ae sia 8 49.79
2 rape-sugar 24.1 ‘
DHL POMS << cermaxiaaririaarvanvees { Cee te t 19.34 48.47
8: Dried! chertiesin.siweswiinus ss ia Wendie asses aanueeeaee 31.22 14.19 45.51
9. Bananas: vcesee vows iv is sa eevee sei ead takoRuced a tee 23.05 23.05
10, Chestnuts (genuine)........... 0. eee e cece eee eee eee beens 38.34 88.84
11. Sunmowertseed ss. s.c:<.5-4 consents seeded Soa gneinle care «baw ah 20.03 20.03
12. POppyis@e eis c srsen sca ces oan welepnasrnadanie dex paanowon eae s 18.74 18.74
18:; WiMeigta pes ccc ciriredeee egies cow er ewingln Kea alvaars 14.36 1.96 16.82
1 Ripe black salsify and sweet potato (topinambur) contain levulose almost exclu-
sively. The unripe roots contain much dextrose, the proportion between levulose and
dextrose in both is inconstant and variable, as the roots are not always quite ripe. In
French beans (59), the substance given as being a carbohydrate is inosite, which is not
a genuine carbohydrate, and is entirely harmless.
106 DIABETES MELLITUS
PERCENTAGE OF CARBOHYDRATES IN DIFFERENT FRUITS (continued)
Sugar. N.-free extracts. Total.
14, Green Zages.... ccc eeu e eee e ence cere teen e eee rereneee 3.16 11.46 14.62
15. Mirabelle plums...........eee seer eee esp Sacaeblaataels - 3.97 10.07 14.14
16, Apples...... cree ceeeee ee cee ‘yaiendnaipte G6 oie reese mies 7.22 5.81 13.038
17. Cherries...... a:hivdhauare.S aulecel cise Bia 8 RHEE Ba SO eNw eels 10.24 1.76 12.00
18. Mulberries. ... 0 ..c2ceec ses ve cecevens Cues Ria aeS 9.19 2.08 11,22
19; PéaTtS,. .c.24 cineemet sae 6 a9 Susisinsye Slecele | eee eee 8.26 3.54 11.80
D0), PRACIOS cies cine ccs 5 esial@iadire Sev 9-4 Rate anes NAS + ees wee SHON 4.48 TAT 11.65
O11. PEUNCS: «a sicycsnaissnn Bais + Aba METS RI Oe FR oes Siewlewe 6.15 4.02 11.07
. 22. Apricots 4.69 6.35 11.04
23. Hazelnuts ay, 9.03 9.03
24, Gooseberries 7.03 1.40 8.43
95: PlUMSPrcciere sak os asjarmde lana a's sintwarsers Waeinele a OMAK 3.56 4.68 8.24
26. Cocoanut Sart 8.06 * 8.06
27. Walnuts ican 7.89 7.89
28, Currants 6.38 0.90 7.28
29. Almonds sat 7.23 7.23
30. Strawberries 6.28 0.48 6.76
81. Whortleberries A 5.02 0.87 5.89
32, Candlenuts (bankulnut)......... 0. cee eee ee eee enone cea 5.88 5.88
88, Blackberries. cccscsan . 044 008 Wows Dew ORTH S Sole CeO 4.14 1.44 5.88
BA. OFAN BOS ia occas dnasccod aicshainiamns: Guna EES S aH gieeet 4.59 0.95 5.54
35. Raspberries.....-... ccc ccc cece reece een eeeeeeteeee 3.86 1.44 5.30
BG Beam Ws wee iss a4 weajaretaaearese @ sie'sveies eta te ddiwidice senate areueaoe'e ates 1.85 1.85
37, Cram bGEniesiss sas iuiseachedusde sos we eetbaner ease OD veee = 1.58 sate 1.58
DIFFERENT KINDS OF BEER
(According to their alcohol and carbohydrate contents.)
Carbo- Alcohol,
hydrates. vol. per cent.
1. Braunschweiger Mumme.........:ccesececceesteeseeerece 52.29 2.96
2. Wheat beer from Celle. .............e ee eee Lae carshee men dgoes 10.45 0.70
Be POLE Basses su e.ahvk soled does) doh Go Rctacaenaus io Bk Signe RS Beda 7.55 5.35
4. Bock beer (Mirzen, Saloon, double beer, etc.).. 7.20 4.74
Bs Rice: beer ga ates tea givin Bicone Kade gs oro eae aKa Sb epee, Ss 6.83 4.02
6; Export beets js 262s suisse sae eas snags va Sees eee = Pes 6.48 4,31
on NIG! cute a Ente ee ee ET REE SEARED 24 dee ARES OME CESS 6.03 4,89
8. Lager orsammer beer... oc ..csccnenee sess citcsanece aust 5.78 8.95
9. Swedish: beehs.05 caches etals qeGeeeeGenae oOo ae ataned ees ts 5.68 3.89
TO. HOB TIS hs DEC B. 6 sata scescsc syaie ser Biss spar acerara aa SMe Daeler Seratere etTE 5.65 5.55
11. Lighter beer varieties (usual yeast and winter beers)......... 5.49 3.46
12. Berlin weiss beer (1878).........ccc eee cen ee cee sec eeeeene 4.28 3.33
13. Belgian, beet, os vi wisidgn ovens ewnedaes eee ee eg Beawenee ees 3.84 6.08
PERCENTAGE OF CARBOHYDRATES (SUGAR + “EXTRACT”) IN WINES
AND SPIRITS Alcohol, Carbohydrates
vol. per cent. (sugar + ‘‘extract”).
1. Russian Dorvy-vodka 62.00 sakey
Q. WMrrack suc. wane anuie sade e palaces sedan d cigs cee y nee 60.05 0.8
8. American whiskey ee 60.00 nant
4, Wrench COgNaCl saws yee Sateen Gee ote sie te sera 55.00 siete
ec HMMM, ce acevereitia scuere tice MME anda arene ole puis teutN alan diane tas 51.40 Siete
6. English whiskey. ........... cc ccc cece eee eee 49.40 or
7 Ordinary brandy (s. schnaps)..........c. cece eereee 45.00 suite
Bi SDONL Yio pk ausntnvieiaiay sea sle-a aeaigvat ators os wears Sam S 20.89 3.53
Op POP esas iegaa anes asaextore: 8s bees desig cls ceixes ss 20.00 6.99
10. Madeivas wccx s csc nuniainwe tae aa viteiciw dans seeevee ace 19.20 5.28
TY, Swedish, punehys sais ccd asses eae a ssivessereesnn wineid-ee dee 00 18.90 33.20
10, MiMGEALEl need too9 4ac9a2- Gamnan dusenen yen « we Lcaeuneeen: 16.05 18.60
‘ ‘ Max 41.00
18;-GieeR WING saciid. sccaseweeees Ya es yaaaen. Goes 15 40 | Min 2 65
14) Tokay: :scumewa, 205906 nestiowed vests ada ta tedeaie veka 14.89 72.4
15. Ruster Ausbruch,............ ccc cee csc uceeucceve 14.72 8.8
TABLES 107
PERCENTAGE OF CARBOHYDRATES IN WINES AND SPIRITS (continued)
Alcohol, Carbohydrates
vol. per cent. (sugar + ‘‘ extract”).
16. Malaga (iii 0% soc stesaiarue each a doinaie s intele ag son eae 14.22 17.27
4%, Ttaliat Withee sic. aecsis cea aeaned oo oveaeamnca sans oe 13.86 3.68
18. Tyrolese wine 12.57 3.67
19. Bohemian white wine...........0.....c.ccc cece ele 12.09 1.99
20. Moselle and Saar wine.............0 ccc cece cceeeucee 12.06 1.804
21, Palatinate wine.... 22... . cece ccc ce ewe neenetettcccs 11.55 2.4
22. AINE WIN Gia. c5.cs esas g:40 4 and dee s wie eats lasiwintete wo 11.45 2.3
28. Bohemian red Wine............cc cece cc cncc cee ceuees 11.16 2.2
24, Rhine-Hessian white wine............ 00 ccc c cece eee 11.07 2.0
25, Baden WANG,
a a
a £ Z
e Ss .
* a
* fe »
MYXEDEMA
WITH SPECIAL REFERENCE TO ORGANOTHERAPY
By C. A. EWALD, Beruw
HISTORY
Av a meeting of the Congress of the British Medic:
don in 1875, various medical curiosities were shown, among them a number
of patients, mostly women, who, on account of their peculiar appearance and
behavior, excited the greatest interest. At first clance one would have thought
that a group of Eskimos or Samoans was present. Their swollen faces of
strange yellow tint, almond-shaped eyes, and stupid expression, their clumsy
figures, the leathery texture of their skin , the scant growth of hair, and their
torpid mental state made them a truly remarkable spectacle. One could
hardly realize that these were children of sea-enco passed Albion, so com-
pletely in them had the characteristic features of the Anglo-Saxon race been
eradicated. As explained by Dr. William Ord, these were cases of myxedema.
We owe the recognition s, and their classification as a special
pathological group to | from cretinism and imbecility, to two
English physicians, Sir William Gull and Dr. William Ord (in 1873 and
1878). The latter physician was also the first to designate the condition
myxedema, on account of the peculiar muco-edematous condition of the in-
tegument, and Charcot later roposed the name “ cachexie pachydermique,”
which, in my opinion, is more suitable. As a matter of fact, the mucus con-
tent of the skin, contrary to the assumption of the first observers, is but slight,
although Shaw believed it to be fifty times greater than in the normal skin.
The general thickening of the skin greatly overshadows this. However, an
aptly chosen name soon takes root, even if it be not quite unobjectionable (I
need only refer to the barbarous word “ appendicitis”), and so it has been
with the term “ myxedema”; every one knows nowadays what is meant by the
term.
Since then twenty-five years have passed, and numerous cases of myxedema
have been described, particularly in England and America. The peculiarities
of the disease have been thorou hly studied, and our understanding of its
nature based upon this study has led to the rapeutic success as far reaching
and as remarkable as any in the entire realm of medicine, excepting only
Serumtherapy.
In Germany, myxedema is comparatively rare.
tion to relate th history of a very characteristic ¢
m, however, in a posi-
Le)
.
i
=
=
-
=
te
!
hy"
=
«Pr
ee <=
a
a
—.
-
180 MYXEDEMA
The patient, a woman aged fifty-five, has been known to me for six years;
the symptoms of the disease developed slowly and insidiously, and for a long
time they were so little characteristic that it was hardly possible to differen-
tiate the condition from the ordinary cachexia of old age. But the. behavior
and appearance of the patient were, even at that time, so peculiar that I had
a photograph: of her taken which is here reproduced (see Fig. 1). Later,
however, the typical symptoms appeared (see Fig. 2). They improved and
nearly disappeared under specific treatment (thyreoid extract), but returned
after some time, the patient having discontinued her treatment. Fig. 3 shows
the patient in this stage of her disease."
ETIOLOGY
Regarding etiology, as little could be determined in my case as in other
cases of myxedema. A tendency to nervous diseases and depressing influences
of a psychical nature are said to be conducive to the development of the dis-
ease. Whether alcohol, syphilis, and tuberculosis, those exterminators of the
human race, play their part in this disease is very questionable, although sev-
eral authorities (Pel, Greenfeld, and Byrom Bramwell) have called atten-
tion to the occurrence of tuberculosis in the families of myxedematous patients,
or in the patient himself. Several cases in the same family have also been
observed.
The sex of my patient confirms the general experience that women are
attacked in the majority of instances, and Sir William Gull entitled his first
communication, “ On a Cretinoid State Supervening in Adult Life in Women.”
Full seven years after the first publication regarding myxedema, a male suffer-
ing from this affection was observed by Savage (1880). In 1894, in a com-
pilation of 127% cases of myxedema, Heinsheimer found only 10 men, ie.,
7.8 per cent.; and this proportion would about correspond to the ratio if we
tabulated all the cases that have been published up to, the present time.
Typical myxedema is a disease of adults, occurring most frequently be-
tween the thirty-fifth and fiftieth years of life. It is, however, by no means
limited to these ages, but may occur earlier, as the so-called infantile myx-
edema, or even later (which is quite rare).
SYMPTOMS
The symptoms of myxedema consist of :
1. Changes in the external integuments (skin, hair, nails), and the absence,
or, more strictly speaking, the degeneration of the thyreoid gland.
2. Disturbances of the cerebral and nervous functions.
3. Disturbances of nutrition (of metabolism) and of circulation.
1 The literature up to 1896 is almost complete in CO. A. Ewald’s “The Diseases of
the Thyreoid Gland, Myxedema and Cretinism,” in Nothnagel’s “Special Pathology and
Therapy,” xxii, Part I; for later articles see Ewald’s article “ Organotherapy,” in
Mendel’s Jahresbericht fiir Neurologie und Psychiatrie.
orn {0 me for ty
Isilowly, and tna!
wndly pose fy i
OL aye, But Me
NR $0 eedin
Need (see Bg 1), |
%). They inp.
Teoid extract, but nh:
her treatment Tig ie
tuned in my eas ne
eases and depres i
to the Lerelopmet th
iis, those external
very questionable, alte
Branovell) have eal:
nlies of mysedematos je:
the same famuy have
eal experience that we:
r Williaa Gl eal:
ening in Adult Lifeiate
anding myseden, 3
fe (188), In tt
mer found only I 08.
it correspond fo the ni
1 up tothe prea i
oecurning ms fn
Tt is home Wr”
y
a3 the scaled int’
Fie. 1.—W. M., Acrep Forry-rreut; Incipient MyXeDEMa,
jel
gp
net : rp oral
y's arte
Fic. 1.—W. M., Acrep Forry-r1eur; Incierent MyxepeMa,
>
verrvoee
«ee
“9
Fic. 2.—W. M., Acep Firry-rwo; ADVANCED MyXEDEMA.
Fic. 3.—W. M., Acep Firry-THREE ; MyXEDEMA IN THE STAGE OF RECOVERY AFTER THE
EMPLOYMENT OF 39.2 GRAMS OF THYREOIDIN.
184 MYXEDEMA
These features are not equally developed nor even all present in every case,
and my case was no exception to this rule.
Of greatest importance in the diagnosis of the disease are the cutaneous
symptoms. They make it possible for us to recognize the malady, prima visia,
so to speak, and after a comparatively brief examination of the patient. They
give the patient the characteristic stamp which I attempted briefly to portray
at the beginning of this article.
1. Most frequently the disease begins unnoticed and insidiously, with a
gradual swelling of the skin, at first in the face, then in the hands, arms, feet
and legs; finally and least noticeably upon the trunk. In the cheeks, around
the eyelids, and upon the chin, puffiness is noticed; the lips and nose become
swollen and thickened, the palpebral fissure is diminished by the swelling of
the eyelids, and a hard, elastic edema of the whole face produces a stupid,
dull expression. The tongue is thick, clumsy and too large for the mouth;
the soft palate, the uvula, and the postpharyngeal wall, as well as the larynx,
are swollen. Hence the voice becomes rough and hoarse with a peculiar deep
sound. The gums also swell, bleed readily, and retract from the teeth, which
have a tendency to caries and frequently drop out without any change of
structure. The lobes of the ear are also coarse and misshapen. Upon both
sides of the neck above the clavicle, swellings appear, which are soft to the
touch, and from about the size of a plum to that of a hen’s egg. These pads
are not due to swollen glands, but consist of fat, connective tissue, and conyo-
lution of vessels (veins). The extremities appear swollen and shapeless, the
hands like paws; wider shoes and larger gloves become necessary.
The skin is pale and looks anemic; occasionally it has a marbled appear-
ance; to the touch it is cold, unelastic, hard and coarse. If pressure is made
with the finger a slight impression is made, but the pitting does not remain.
As a rule, this swelling is by no means uniformly distributed over the entire
body. It attacks preferably either the face and the supraclavicular region or
the extremities. Occasionally it disappears temporarily at the beginning of
the disease (Ord), and then recurs, wandering here and there. The skin is
dry, rough, desquamates decidedly, and not even by means of diaphoretics can
sensible perspiration be induced, while insensible perspiration is lessened from
40 to 60 per cent. in comparison to the normal. The nails show longitudinal
fissures and become brittle. The hair of the head and eyebrows falls out,
and soon large areas are formed which are perfectly bald.
Besides these striking changes there is a further defect which indeed can-
not always be determined with certainty during life, but which in my patient,
for example, was readily demonstrated; I mean the absence of the thyreoid..
In place of the lobes of the gland normally situated upon both sides of the
wind-pipe, the smooth wall of the trachea may be palpated from the cricoid
cartilage to the jugulum. I shall revert later to this remarkable condition,
and to its importance in pathogenesis.
2. The disturbances of the cerebral functions mostly set in with headache,
sometimes with a feeling of anxiety, and a heaviness in the limbs. The
patients move about slowly and with uncertainty. The power of co-ordination
is diminished, as is frequently shown in the attempts at walking. The patient
SYMPTOMS 185
then conveys the impression of being under the influence of a high grade of
nervous irritability with severe muscular tremor, so that it is impossible to
maintain an erect attitude.
The patient’s appearance is peculiarly quiet and suggests mental limita-
tion, an impression which is increased by the fact that the head is mostly bent
forward so that the chin is held, or, more correctly, falls upon the chest, for
the patient cannot keep the head erect. The power of thought lessens, and
its exercise is apparently difficult. There is loss of memory, particularly in
regard to the true duration of the illness; now and then actual hallucinations
appear. Speech itself is peculiar, being monotonous with a nasal or rough
quality, and this, combined with a certain tendency of the patient after hav-
ing once begun to speak to continue uninterruptedly like a wound-up clock-
work, is looked upon by Ord as especially characteristic. JI must admit that
this latter condition has not yet been noticed by me in my very much more
limited experience. Finally, actual convulsions and coma have been observed.
The reports in regard to reflexes, cutaneous sensation, and electric irritability
vary. In my case no disturbance of these functions was present. The tendon
reflexes were prompt, and electric irritability both for the faradic and constant
current was normal. The sensation of cold, and the lowered body tempera-
ture which is the cause of this, may be considered as due in part to the nervous
disturbances. The temperature in the axilla varies between 96.8° F. and
98.6° F. The patients feel “as if they were living in an eternal winter.”
Unquestionably, this sensation of cold depends upon the inability of the
patients to regulate the body temperature so as to correspond with variations
in the external temperature; they suffer particularly in cold and frosty
weather. On the other hand, there is deficient energy of oxidation, a dimin-
ished heat production, in the organism.
This leads us to the discussion of the last point:
3. Disturbances of metabolism and of the circulation. The former is
decidedly decreased. The urea or N-excretion as well as the respiratory metab-
olism (Magnus-Levy) is decreased. Albumin is occasionally found in the
urine, sometimes only in traces, sometimes in larger amounts. According to
the observations of Byrom Bramwell, as well as of Hun and Prudden, albumin
is found in about 18 per cent. of the cases. In rare instances at the acme of
the myxedematous stage, mucus is also found in the urine. In the blood there
is a slight oligocythemia or a polycythemia. In women there is amenorrhea.
The pulse is small, low and weak. Hemorrhages from the mucous membranes,
particularly from the nose and mouth, are not rare.
I have now sketched the most important symptoms. I omit the rarer ones
as, for example, synovitis of the knee-joint, premature climacteric, tremor of
the eyelids, contractures of the hands and feet, salivation. The characteristic
symptoms of the affection under discussion are limited to tissue changes, par-
ticularly of two organs, the skin and the thyreoid gland. The connective tis-
sue of the corium is loosened, its individual fibers thickened and hyperplastic.
The cell nuclei and the fibrillary elements of the gelatinous substances be-
tween the individual fat lobes are increased. It seems as if the skin were
saturated with a fluid or semi-fluid substance. Whether this actually con-
186 MYXEDEMA
sists of mucus, i.e., of an edematous fluid containing considerable amounts of
mucin, is not yet certain. This much, however, is assured, that the degree of
this infiltration may vary decidedly in individual cases. In my patient there
is now only slight swelling of the eyelids and of the cheeks, but at the height
of the disease the entire face, shoulder-girdle, hands, forearms, and feet showed
swelling which was everywhere unmistakable, and here and there extreme.
In a case observed by Kast (Ponfick) the thickening of the skin was so
extreme that numerous fissures formed, with intertrigo-like excoriations
which were followed first by a phlegmon of the arm and later by a general
fatal sepsis.
In the internal organs usually no changes are found apart from the pre-
viously mentioned atrophy of the thyreoid gland, but occasionally cirrhotic
processes in the liver and kidneys, endarteritis obliterans, and enlargement of
the pineal gland have been noted.
The changes in the thyreoid gland are undoubtedly the most remarkable
feature of this disease. In most cases, even during life, we observe that it
is impossible to palpate the lobes of the thyreoid gland in the neck. It may
be said that this condition is found in about 80 per cent. of the cases. In
some instances, however, the atrophy of the gland cannot be determined with
certainty, and in a few an enlargement has been noted. Yet in these cases,
in so far as accurate observations have been obtained, there has always been
found a strumous degeneration of the organ, which may also have resulted in
a loss of function. I have been able to collect 36 reliable autopsy reports,
in 33 of which, or 94.4 per cent. of the cases, there was atrophy of the thyreoid
gland. The necropsy reports show that the gland substance had lost its char-
acteristic structure, and had been changed into a more or less shrunken rem-
nant, of hard, fibrous consistence and yellowish white color. Connective tissue
proliferation leads to destruction of the parenchyma, so that only isolated re-
mains of degenerated alveoli can be detected. Very recently Ponfick has
reported an extremely careful histological investigation of the remains of the
gland in a well-developed case of myxedema. He found “ in wide areas almost
total destruction of the follicles; here and there were the remains of rudi-
mentary alveolar structures, all filled with colloid. Besides this atrophy there
was an enormous increase and thickening of the connective tissue structure; in
a word, a picture which markedly resembled the terminal stage of degenera-
tive inflammatory processes, such as are met with so frequently in the kidneys,
liver, ete.”
PATHOLOGY
I need hardly say that this degeneration of the thyreoid gland is the key to
the entire pathological condition. Atrophy of the thyreoid gland is not only
one of the symptoms of the discase; tt is the causative factor. This fact is
absolutely certain in spite of occasional objections. Its recognition forms a
glorious page in the history of pathology. We owe this to the united labors
of physiologists and clinicians, the fruit of which is a therapy which, as re-
gards the certainty of success, may be placed side by side with the most reliable
remedies of our therapeutic armamentarium.
PATHOLOGY 187
I shall attempt to prove this in a few words, thereby taking an opportunity
of referring to related conditions, namely, to sporadic and endemic cretinism,
to infantile myxedema, and to the so-called cachexia strumipriva.
Two observations stand out prominently like landmarks in the great num-
ber of physiologic and clinical experiments and communications which resulted
in the establishment of the importance of the thyreoid gland in the causation
of myxedema. First, the experiment of M. Schiff, the results of which were
for a long time discredited and even ridiculed, but at last completely proven.
In this experiment an animal was subjected to thyreoidectomy, which under
ordinary circumstances would have proved fatal, as Schiff had previously
shown in 1859. But Schiff found that the animal did not succumb if the
thyreoid gland were grafted into the abdominal cavity or under the skin, the
specific constituents of the gland being thus preserved for the organism. Next
came the important communications of Kocher and Reverdin who observed
after the extirpation of the thyreoid gland in man a condition of general
cachexia with physical and mental phenomena which show a marked similar-
ity to the symptoms of myxedema just described, and also correspond accu-
rately to the phenomena developing in an animal after extirpation of the
thyreoid. In other words cachexia strumipriva, produced experimentally or
(in man) as the result of an operation, is identical in nature with genuine
myxedema. Now since in both cases the same defect is present, namely,
absence of the thyreoid, it follows that the resulting insufficiency, that is, the
complete loss of function of the thyreoid gland, is to be looked upon as the
cause of these pathological phenomena.
I cannot here discuss the different phases which the evolution of this view
has undergone. But one stage at least I should like to bring into prominence,
for it shows how difficult the proper interpretation of an experiment may
sometimes be, and how obscured by complicating conditions.
Some investigators did not succeed in producing the symptoms of cachexia
strumipriva (or, more correctly, cachexia thyreopriva, as we are not speaking
of the removal of a goiter) by thyreoidectomy, and consequently were justified
in doubting the causal relation of the thyreoid gland. Then Gley showed
that besides the great mass of the thyreoid there are in animals small, super-
numerary glands, which had already been anatomically described by Sand-
strom. These extra thyreoids, if not removed together with the gland, per-
form vicariously the function of the latter. Only after this circumstance had
been taken into consideration could constant results be obtained. In the
same manner we may explain those observations (which, however, are in the
minority) which show that in some cases cachexia strumipriva did not follow
thyreoidectomy in man. This is because parts of the gland were not removed
at the operation or because a rapid reproduction of the gland took place. But
even a few isolated and trustworthy cases of this kind would not overbalance
the enormous number of positive observations to the contrary.
But let us proceed a step further. All over the world, as is well known,
there are unfortunate individuals whose mental and bodily development is
retarded, so that they present a stupid and misshapen appearance. They are
called cretins, and their disease cretinism. From the fact that such ill-fated
188 MYXEDEMA
persons are met with in isolated regions, and are particularly numerous in
certain localities, and inasmuch as the development and distribution of the
disease are apparently dependent upon the condition of the soil and the water-
supply of the district in which the cretins accumulate, we call these cases
“endemic cretinism.” In other parts of the world they are only occasionally
met with, and we then speak of them as cases of sporadic cretinism. In these
cases as in myxedema there is an insufficient development, or an atrophy and
disturbance of function of the thyreoid gland. Hence we speak of them as an
athyreosis chronica, in contrast to the results produced experimentally in ani-
mals, or after loss of the thyreoid by operation in man in whom this state may
be called cachevia thyreopriva.
Accurate observation and study of the cases belonging to this group show
that endemic cretinism is a condition of physical and intellectual degenera-
tion, which occurs only where there are local predisposing causes, and a degen-
eration of the thyreoid gland produced by these or going hand in hand with
them. The disease begins its development even in fetal life. Sporadic cre-
tinism, on account of its resemblance to myxedema of adults, is in early
life also designated as infantile myxedema. In these cases we find mental
weakness even to idiocy. Like actual typical myxedema, it is an occa-
sional affection of the thyreoid gland with consequent loss of function, ie, a
disease not limited to a definite region. The course of genuine cretinism, as
well as myxedema, is a very chronic one, lasting for decades, so that a cretin
may attain relatively old age provided he does not die of some intercurrent
disease. Cases of sporadic cretinism (infantile myxedema) have, as a rule, a
briefer duration of life, and if not ameliorated by treatment scarcely survive
the third, at most the fourth, decade. Cachexia thyreopriva runs a subacute
course, and unless relieved by medical aid terminates in death after a com-
paratively short time, at the longest four or five years!
THERAPY
This is not the place in which to discuss the clinical symptoms of these
diseases ; that degeneration of the thyreoid gland is unquestionably the causa-
tive factor in all of them is the only circumstance important for us. This is
clear not only from the general correspondence of the external pathologic phe-
nomena, but, in particular,.from the results of therapy founded especially
upon the knowledge of the causal réle of the thyreoid gland in these cases.
The results of thyreoid therapy have proven, a fortiori, that the common cause
of these diseases is an absence of function of the thyreoid, by which, it may be
remarked in passing, they differ from goiter or struma.
Properly speaking, in these cases we are dealing with a substitutiontherapy,
replacing the lost or deficient glandular secretion by the administration of the
glandular substance or its extracts.
The surprising experiments of Schiff, previously mentioned, actually com-
pelled the application of these principles in the human subject, and Bircher
in 1890 by implantation of a human thyreoid in a woman with cachexia
strumipriva first succeeded in obtaining a curative result. Shortly after
THERAPY 189
Horsley proposed, in place of the human gland, to utilize the thyreoid of the
sheep in myxedema and cretinism, and Bettencourt and Serrano noted a rapid
improvement in a woman with myxedema, in whose abdomen they engrafted
one-half of a sheep’s thyreoid. When Murray, instead of employing the entire
gland, subcutaneously injected its glycerin extract, and Mackenzie in 1892
administered the fresh gland or its extract internally with the same effect,
and other observers showed that the dried glandular substance in tablet form
acted in the same manner, the therapy of myxedema and of the related patho-
logic conditions previously mentioned became as simple as it was reliable.
In fact, reports came from all quarters regarding the almost remarkable action
of this “ organotherapy,” which was particularly effective in myxedema, in
infantile myxedema, and in cachexia strumipriva, while endemic cretinism,
owing to its nature, could only be benefited to a slighter extent. The tablets
which were administered were so prepared as to dosage that each tablet corre-
sponded to 0.25 gram of the glandular substance; these were given in increas-
ing doses of from 3 to 7 or 10 tablets per day, until (early or later) symptoms
of intoxication, extreme or mild (the symptoms of so-called thyreoidism)
appear.
It cannot be denied that the use of the entire gland has certain disadvan-
tages, on account of the varying amount of active substance in the individual
gland or tablet, the admixture of products of decomposition, etc. Obviously
it would be desirable to isolate and to utilize the specific active substance.
There have been numerous trials in this direction. At one time it was
hoped that the desired body could be obtained in the form of a ferment, at
another time it was supposed that it could be secured as a fixed chemical com-
bination from the group of proteid substances or even as an alkaloid. I must
mention that S. Fraenkel, in 1895, isolated a substance belonging to the
guanidin group with the empiric formula, C,H,,N,0,, which he called “ thyreo-
antitoxin,” and Drechsel and Kocher, Jr., isolated similar combinations from
the gland. Then Baumann, in 1896, made the surprising discovery that the
gland contained considerable amounts of iodin, and that this iodin was found
in combination with organic substances, chiefly in his opinion with albumin,
and to a smaller extent with globulin. This body Baumann called iodothyrin,
later thyreoiodin, and showed that from the purest thyreoiodin 9.3 per cent.
of iodin could be obtained in a crystalline form. Investigators are not yet quite
unanimous as to the true nature of this thyreoiodin. Tambach assumes that
the iodin is combined with various albumin bodies, and that iodothyrin forms
only a part of the iodin-containing substances of the thyreoid gland. Accord-
ing to Oswald, the iodin combined with albumin has the character of globulin,
for which reason he called it thyreoglobulin. From this, by long-continued
pepsin digestion, iodothyrin and iodin-containing albumoses and peptones can
be split off: Besides these, a nucleoproteid is said to occur which, however,
does not possess the specific action of the gland. Blum denies the presence
of iodothyrin as a primary constituent; he thinks it is not preformed but is
an artificial cleavage-product. However this may be, Baumann in associa-
tion with Roos seemed to prove that thyreoiodin possesses the specific proper-
ties of the natural gland, and acts as a substitute for its curative effects; it
190 MYXEDEMA
also possesses the same toxic action, but has the advantages of a more exact
dosage and absolute purity. These opinions were soon confirmed by others
(Hofmeister, Ewald, Hennig, Goldmann, and others), so that there can be
no doubt that thyreoiodin may be employed in place of the natural gland.
Whether it is actually an equivalent for the complete gland appears doubtful
from the investigations of Gottlieb and Jaquet, who observed in a number of
dogs after thyreoidectomy that thyreoiodin alone did not keep the animals
alive, while Gottlieb by administering an extract from the complete gland
(thyraden), and Jaquet by a substance called by him aiodin (a tannin precipi-
tate of the extract of the gland with physiological salt solution) succeeded
in sustaining them. I might also mention that Cunningham in England
isolated a so-called colloid substance from the gland which is analogous to
Baumann’s thyreoiodin, i.e., the contents of the acini after previous peptic
digestion of the gland tissue. He is consequently of the opinion that this
colloid is the true active extractive product of the gland cell, while Oswald
believes it to be a mixture of thyreoglobulin and nucleoproteid. In a similar
manner, McLennan produced a preparation from iodoglobulin and thyreo-
iodin which has received the name thyreoglandin. In view of all this it is
obvious that the nature of the specifically active substance of the gland has
by no means been definitely decided; on the contrary, each day brings new
reports and new views.
This is true also of another highly interesting discovery which science
owes to Baumann, who was unfortunately too early removed from his sphere
of activity. In a comparative estimation of the iodin contents of glands,
some of which were procured from Freiburg and some from Hamburg and
Berlin, it was shown that the iodin contents of the former were considerably
less than in the glands brought from the two last mentioned cities. The
glands obtained from Freiburg, in the same parts by weight, averaged 2.5
milligrams of iodin; those from Hamburg 3.83 milligrams, and those from
Berlin 6.6 milligrams; in the investigations in North America made by Gideon
Wells, the iodin contents of 20 glands, some from Chicago, some from Balti-
more, Boston, New York, etc., averaged 10.79 milligrams. Now, in Frei-
burg goiter is endemic and frequent, in Berlin and Hamburg comparatively
rare, in America almost unknown. What can be more reasonable than to
connect the slight amount of iodin in the glands from Freiburg (where, as
may be remarked in passing, goiter is found conspicuously often even in the
new-born and in young children) with the prevalence there of goiter? For
many years strumous degeneration has been referred to a lack of iodin in the
water, in the air, in the food, though no convincing proof of this has been
established. Here, for the first time, we seem to have analytic evidence of the
influence of iodin upon the development of goiter, or, more correctly, the
relations of the iodin contents of the thyreoid gland to goiter. I expressly say
“ seem to have evidence,” for to make this assumption a certainty more com-
prehensive investigations are necessary, and I am forced to admit that Oswald
made numerous analyses of glands from Switzerland and from the regions
where goiter occurs endemically and has demonstrated the exact opposite ;
namely, that the amount of iodin in glands from this district was greater than
THERAPY 191
in those obtained elsewhere, while, on the other hand, Rositzki’s researches in
Styria confirmed Baumann’s reports.
No matter how diverse the manufactured preparations may be, their use
evidently checks the previously described symptoms of myxedema, which give
place to complete or almost complete health; therefore all must contain the
active substance, though perhaps some more than others. The skin becomes
soft, smooth and elastic; the edematous infiltration—the myxedema—disap-
pears; the hair which has fallen out is renewed. The general health returns
to the norm, vigor and activity take the place of the preceding debility and
indolence—briefly, so complete a transformation in the condition of the patient
takes place that anything more extraordinary can hardly be imagined. The
same is also true, mutatis mutandis, in the conditions previously described,
viz.: infantile myxedema, cachexia thyreopriva, an abortive form of myx-
edema which has been designated “myxroedéme fruste,” and to some extent
also in cretinism. To enter minutely into this subject would carry us too
far, hence we will only remark that the influence of thyreoid preparations
upon the length and caliber of the bones in infantile myxedema has been ob-
served, and to a certain extent demonstrated, ad oculis, by means of radioscopy.
We noted the curative effect of this remedy upon myxedema in my patient.
As time has gone on the preparations of various English and German firms
have been administered, as well as thyreoiodin pastilles, all with good results
which, however, lasted only as long as the drug was given.
After discontinuing the administration of the remedy for some time—in
my case for a few months—we must always return to it, as signs of myx-
edematous cachexia always recur. These usually consist of chilliness, malaise,
and slight swellings in the face; occasionally, however, severe symptoms of de-
pression appear, particularly of a psychic nature. This is not to be wondered
at, as our substitutiontherapy does not root up the evil, but only re-supplies
some necessary products for metabolism, and for this reason the medication
must be persistently carried on. At times the remedy becomes unneccesary,
and it may be discontinued for a considerable interval, because a certain
reserve accumulates, which, after the cessation of the specific therapy, is only
gradually utilized and consumed by the organism. The same is also true,
according to our present experiences, in cachexia strumipriva, while in infan-
tile myxedema and cretinism this effect does not occur, and from the begin-
ning we must carry on the thyreoid therapy almost continuously.
One of my patients, a highly cultured woman, who has been taking thyreoid
extract for five years, wrote me as follows: “I may say that (inconceivable
as it may appear) under organotherapy the system becomes decidedly accus-
tomed to the taking of thyreoid gland, so that its therapeutic effect is weak-
ened, and the doses must be constantly increased if improvement is to be
expected. On the other hand, when we consider the toxic action, the debility
and tiring of the heart, the damage to the stomach, etc., it appears that one
does not become accustomed to it; the longer the drug is administered the
greater the susceptibility.” The latter remark points to the secondary effects
of thyreoidtherapy, effects which, after prolonged use of the drug, appear to be
more or less severe.
192 MYXEDEMA
This secondary condition has been designated thyreoidism; the disturb-
ances may be separated into the nutritive and the nervous. The urine in-
creases in amount, and its N-containing constituents, as well as the chlorids
and phosphates, are increased. The body-weight decreases and, as was first
shown by Wendelstadt, not over 3 of the loss in weight is of the body albumin ;
the remainder is a decrease of fat and water, so that the increased combustion
of fat may be referred to increased oxidation (Magnus-Levy). In this process
oxidation, during and for some time after the use of thyreoid, may rise 10 to
20 per cent. above the former values; there is therefore an increased metab-
olism. As a nervous symptom we note primarily a decided increase in pulse
frequency and cardiac palpitation, which may be looked upon as a definite
indication that the dose is too large. After this headache, nausea, vomiting,
and general debility may occur. Sometimes these symptoms increase to an
alarming extent, and formerly, when this condition was not sufficiently under-
stood, even fatal cases were observed. Therefore, when these symptoms
appear (which may be soon or late, according to individual susceptibility)
thyreoid preparations must be immediately stopped, and the treatment be
interrupted. These toxic symptoms will then shortly disappear without causing
permanent injury. This teaches the lesson that these preparations should
not be used except on the advice and under the supervision of a physician,
and their sale by an apothecary except upon prescription should be prohib-
ited. How far thyreoidism is a phenomenon of specific intoxication, and
how far toxic products of decomposition generated during the manufacture of
the preparations are concerned in it, is doubtful. Fortunately, we have lately
become able to combat these symptoms of thyreoidism, or better, to prevent
their appearance; as Mabille has proposed, we administer simultaneously with
the thyreoid preparations small doses of arsenic, either as Fowler’s solution or
as arsenious acid. As a matter of fact, in my case I administered no less
than 962 tablets without any deleterious effects, and during three months I gave
3 drops of Fowler’s solution, i. e., upon the whole a minimal amount of 0.16
gram of arsenious acid.
We may consider it as definitely settled that we are able by means of sub-
stitutiontherapy and only in this way to influence the entire constitution to
such a surprising extent, in the pathologic conditions which depend upon
atrophic or degenerative changes in the thyreoid gland. We should mention
here also the value of thyreoid extract in the abortive forms of myxedema
which Hertoghe has described under the designation “ myxoedéme fruste.”
The use of thyreoid preparations should also be considered in local dis-
ease of the thyreoid gland, namely, in the treatment of goiter. Although suc-
cess in treatment is here limited to the so-called parenchymatous goiters of
youth, i.e., to that form of goiter which is not so much the result of degenera-
tive change as of a hypertrophic condition of the glandular tissue, their use is
here of great value. v. Bruns was the first to employ thyreoid gland prepara-
tions in simple goiter with the idea of diminishing the labor of the hyperactive
gland. For it is self-evident that in such cases there is an increased demand
in the organism for the product of the secretion of the gland, either because,
from some unknown disturbance of metabolism, more thyreoiodin was required
THERAPY 193
and so consumed by the organism, or because the supply of iodin was deficient
while the activity of the gland was especially active, thus leading finally to
hypertrophy of the organ. v. Bruns, in fact, observed a decided diminution
in the goiters after the administration of comparatively small doses, and
Ewald, Stabel, and others in Germany obtained similar results. Wells in
1897 compiled 584 cases of simple goiter which were treated with different
thyreoid extracts, of which cases 475, i.e., about 82 per cent., were improved.
Nevertheless, in my experience, the cure is never complete; that is, the goiter
does not completely disappear, although v. Bruns reports this result in about
8 per cent. of his cases. As has been already stated, the best results are seen
in youthful individuals in whom the goiter has not existed for too long a time.
The older the patient and his goiter the slighter the changes which may be
observed in the gland in favorable cases even after four to six days of treat-
ment with thyreoid preparations. Usually, however, this becomes noticeable
only during the second and third weeks of treatment. A diminution in the
circumference of the neck of from’4 to 6 centimeters is frequent; greater re-
duction than this is exceptional. Even in these cases, after discontinuance of
the remedy relapses occur, so that small doses must be repeated from time to
time.
I have the history of two girls, aged nineteen and twenty-one years re-
spectively, the circumference of whose necks after the use of thyreoid prepara-
tions was reduced in one from 37.6 to 35.1 centimeters, and in the other from
33.5 to 32.1 centimeters. Symptoms of thyreoidism did not appear. J must
not fail to mention that equally favorable results have been obtained with
thymus preparations by Mikulicz and Reinbach.
The conditions are very different in another disease which also implicates
the thyreoid gland: Graves’ disease. In this affection enlargement of the
thyreoid, as is well known, is one of the three cardinal symptoms of the dis-
ease—goiter, exophthalmos, tachycardia. But here we are no longer dealing
with a vicarious or compensatory labor hypertrophy of the gland, but with an
active increase of its secretion, which leads to the phenomena of thyreoidism
occurring in the course of the disease. The use of thyreoid preparations in
this malady is contraindicated, even if we omit entirely from consideration the
fact that the cause of Graves’ disease is not to be found in an affection of the
thyreoid gland alone. We know that its cause is multiform and that other
organs—as is shown by the cases without goiter—especially the sympathetic
nervous system, are implicated. As a matter of fact all cautious and unbiased
observers have been convinced of the complete failure of thyreoid therapy in
Basedow’s disease (exophthalmic goiter). Indeed it has been noticed that
its use is not only useless, but often produces a decided aggravation of the
symptoms. = : . :
Although we have up to this point discussed the administration of thyreoid
preparations only as true substitutiontherapy in diseases in which a disturb-
ance of function of the thyreoid can be demonstrated, yet the list of the uses
of the remedy has by no means been exhausted. We know of other dis-
eases, or disease groups, in which, based upon the pharmacodynamic action
of thyreoiodin, this remedy has been employed with more or less success. I
14
194 MYXEDEMA
have stated before that the employment of thyreoid preparations increases
metabolism, and causes a decrease in the fat of the organism; this has been
experimentally proven. What was more natural than to attempt a cure of
obesity by this means? YY. Davies in America, Leichtenstern and Ewald in
Germany, were the first to publish favorable results of this kind. They ob-
tained in obese persoris reductions in weight of 5 kilograms and more in a
few weeks without any special restriction of the food, and without producing
marked debility, restlessness, fatigue, etc. This condition is due, as already
remarked, to an increased combustion of carbohydrates and fat, while albumin
decomposition is but little affected. Schrédt has lately published a case in
which a loss of 16 kilograms of weight occurred in an obese person, and, as
was shown by carefully conducted investigations of metabolism, this was almost
wholly due to combustion of fat. The results are even better if the diet is
regulated simultaneously, i.e., the fats and carbohydrates limited to a certain
extent without, however, insisting on a dietetic cure for the reduction of fat
in the strict sense of the word. Cabot has collected 145 cases of this kind,
and reports favorable results in all but 6 cases. v. Noorden, who is not well
disposed to thyreoid treatment in obesity, nevertheless observed among 14
patients, who, in the course of four or five weeks, had taken upon the average
3 to 4 tablets per day, a reduction in weight of 5.4, 6.0, and 7.8 kilograms,
and had only one complete failure. In thyreoiodin we should, therefore, pos-
sess an almost ideal remedy for obesity if only it were always effective. Re-
ports of failure are, however, not wanting, and in several cases, instead of the
desired loss of weight, symptoms of thyreoidism have appeared. ‘This latter
condition, with or without a simultaneous reduction of body fat, has been apt
to supervene when the laity, without professional advice, have used the thyreoid
preparations either too long or in too large doses. In another article, in re-
ferring to a case of psoriasis treated by the thyreoid preparations, I have dis-
cussed the question asked by Hertoghe, whether success or failure in these cases
does not depend upon the condition of the thyreoid gland of the affected indi-
vidual; i.e., the treatment is only successful in cases in which the obesity
(or the skin disease) is one of the manifestations of an affection produced by
disturbance of the function of this organ, as the gland certainly has a decided
influence upon metabolism.
There can be no doubt, as has been determined from observations in myx-
edema, of the effect of thyreoid in trophic processes of the skin. Hence thyreoid
preparations are administered in various skin diseases, lichen planus, prurigo,
adenoma sebaceum, ichthyosis, xeroderma, lupus, and, above all, in psoriasis ;
of course here also the success is varying and uncertain. In some quite chronic
cases I have seen conspicuous improvement, and it is not too much to say a
cure; in others there was no result in spite of treatment for several months.
In the last case successfully treated, a spare man, aged fifty-three, whom I
showed at the meeting of the Berlin Medical Society on July 18, 1900, the
thyreoid gland could not be palpated. This man had a persistent, freely
desquamating eruption, appearing in large blotches upon the trunk and ex-
tremities, for the cure of which various remedies had been unsuccessfully
employed for years. After the administration for three months of thyreoiodin
THERAPY 195
tablets with arsenic—he received during this time 450 tablets which contained
0.25 gram of iodothyrin and 0.16 gram of arsenious acid—the eruption
almost disappeared, being replaced by small, isolated areas of about the size
of a silver three-cent piece, and by natural, smooth, pink skin. Of 154 cases
collected by Cabot, 63 were improved, 53 unimproved, and 22 aggravated.
This is greatly in favor of my view previously expressed regarding the connec-
tion between these diseases of the skin and disturbances in function of the thy-
reoid gland; for Wells, in a case of scleroderma in a woman aged fifty-one
who had suffered for about one year from the affection, found the thyreoid
gland, post mortem, to be greatly atrophied, so that in the fresh condition it
weighed only 14 grams and when dried only 3.23 grams. The total amount
of iodin was only 2.94 milligrams, i. e., only about one-fourth of the normal.
Microscopically the connective tissue was greatly increased, the intima of the
glandular vessels was proliferated, the lumen of the acini, for the most part
without colloid, changed into small cysts which were filled with colloid mate-
rial. The hypophysis was hypertrophied, it weighed 0.7% gram, its acini were
distended by colloid masses with uncommonly numerous eosinophile cells in
the interacinous tissue. Wells remarks quite properly that if these changes
could be determined constantly in scleroderma the fact would greatly favor a
thyreogenous origin of this disease.
Actuated by the same reasons as in the therapy of obesity and psoriasis,
ete., physicians have used thyreoid preparations in mental discase, in tetanus,
chorea and progressive myopathy. Favorable results in isolated cases have
even been reported, particularly by Bruce from the Royal Edinburgh Asylum,
. by Mabon and Babcock from the St. Lawrence Hospital, and by Reinhold,
Levy-Dorn, Gottstein, and Bramwell in tetanus, etc.; but invariable and con-
vincing results have been obtained more rarely in these affections than in the
diseases previously mentioned. Gauthier, Quénu, Reclus, Ferria and others
have employed thyreoid treatment also in fractures with delayed union of
bones, on account of the fact that the thyreoid gland has a predominant influ-
ence upon the growth of bone; the results were apparently most gratifying,
and the same reason led to the employment of this remedial agent in rachitis.
But here the watchword for the present must be: temporize! Confirma-
tions are wanting; and from this it may be concluded that the treatment has
been tried by others, but without success.
We cannot close this discussion without referring briefly to an organ
apparently in close connection with the functions of the thyreoid gland, and
by embryologic and anatomic analogies also histogenetically parallel with it.
This is the hypophysis, the pituitary body, the anterior glandular part of
which is developed, like the thyreoid, from the ectoderm, a diverticulum of
the posterior pharyngeal wall, the structure of which also consists of acini
which unite and form follicles containing more or less of a colloid substance.
Unquestionably this gland has some relation to osseous growth, for it is
almost invariably enlarged in acromegalia and giant growth. In isolated cases
it has been known to attain the size of a hen’s egg, and the sella turcica 1s
abnormally developed. Nevertheless, this does not yet prove, as most entire
too hastily assume, that the hypertrophy of the gland is the cause of these
196 MYXEDEMA
anomalies of growth. It may be.a mere coincidence, or vice versa, a resulting
condition of disease of the bone, to a certain extent a reflex from the bone to
the gland. After thyreoidectomy in animals the hypophysis is said to hyper-
trophy vicariously (Hoffmeister), and in a few cases of myxedema hyper-
trophy of the pituitary gland has been found. But Ponfick, to whom we
owe two very accurately investigated cases of myxedema recently reported,
found upon transverse section in one case the glandular portion of the hypoph-
ysis enlarged, in the other case a decided destruction of the organ so that
the tubules of the gland were replaced to a great extent by a “ worthless fibrous
mass.” Here also there are evidently contradictions and enigmas which still
await solution, especially as we can state nothing definite in regard to possible
therapeutic results.
Although we are completely in the dark in regard to these last-named
affections, and for the present are compelled to await further investigations,
this much is certain, that in thyreoid therapy we possess a remedy previously
unknown with which to combat a number of chronic diseases, which even a
short time ago were looked upon as incurable, and which it was thought impos-
sible to influence therapeutically. This type of therapy has been designated
organotherapy or opotherapy, éés, juice), and, by a hasty generalization, the
principles which are the foundation of thyreoid gland therapy have been mis-
applied to preparations from other organs. It has been forgotten that, in the
case of the thyreoid gland, we are dealing with successes gained in conformity
with well-founded physiologic and pathologic experiments and observations.
If now we attempt to extend this substitutiontherapy to all the other organs
which are looked upon (more or less correctly) as the cause and seat of cer-
tain diseases, corresponding extracts and preparations from these organs are
thrown upon the market. But it must be remembered that, barring isolated
exceptions, there is no reasonable foundation for any hope of success. Here
the wish has been father to the thought, and views have sometimes become so
extravagant that a certain resemblance to the notorious “ similia similibus”
of homeopathy resulted. As a matter of fact, treatment by organotherapy is
by no means of recent origin, as is commonly supposed.
Park, in a very interesting article in the Buffalo Medical Journal, 1899,
has shown that it may be traced to a very early epoch in the history of medicine.
In China, since remote antiquity, the juice from macerated pigs’ lungs
is said to have been an efficient remedy for pulmonary diseases; for headache,
pigs’ brains are taken; for dysentery and chronic diarrhea, pigs’ intestines
are administered; semen is reputed a potent tonic in chlorosis, anemia, impo-
tence, ete. Tout comme chez nous!
Strictly speaking, the administration of ovarian extract is the only one
of these attempts that is founded upon experimental proof as well as upon
analogy. The administration of pancreatic substance in diabetes (on account
of the experimentally proven relation of the pancreas to glycosuria and dia-
betes, is a therapeutic experiment which, critically examined, is based
upon nothing more than analogy, and lacks direct experimental proof. Re
garding ovarian therapy, i.e., the use of so-called odphorin tablets, Loewy
and Richter have demonstrated experimentally the interesting fact that in
THERAPY 197
castrated bitches the consumption of oxygen falls about 20 per cent., the total
metabolism of gases about 9 per cent. below normal, and that this alteration
of respiratory metabolism continues for a long time after ovariotomy, even
from six to twelve months. If such animals are fed with dried ovaries, the
interchange of gases returns to its former height and even beyond it.
On the other hand, under the influence of odphorin, no increased destruc-
tion of N-containing substances takes place—no interchange more rapid than
in normal animals—nor could similar results be obtained after ovariotomy in
animals by the use of didymin or spermin. This explains Landau’s successes
with the administration of ovarian tablets in menstrual anomalies, during the
climacterium, in chlorosis and hysterical conditions; these good results I can
partially confirm from my own experience.
Other organic extracts and preparations are also known to produce certain
effects upon the organism. Thus adrenal extract increases blood pressure,
preparations made from the spleen and liver have an influence upon leukocy-
tosis, etc. However, these are, as far as can at present be ascertained, only local
effects limited to definite circumscribed areas, and may be compared to the
action of digitalis upon the heart, or of atropin upon the pupil. We cannot
claim for them any specific curative effect.
The successes reported with cerebrin in cerebral affections, with medullin
in diseases of the bone, with didymin, with the extract or with the substance
of the adrenals in Addison’s disease, with pancreatic tablets in diabetes, etc.,
must be regarded as very exceptional, if indeed we credit them at all. These
preparations have not as yet found general acceptance. Consequently, I do not
intend to relate in detail what has been accomplished, or, better, what has
been attempted by their use.
In this field of therapy the same phenomenon is met with which we find
at present in other realms of therapy: professional activity and choice are
influenced more than is desirable from a source outside of the profession. I
mean by the manufacturing chemist. The chemical laboratories, especially
of the anilin works, have lately thrown themselves zealously into the endeavor,
laudable in itself, to produce or to combine chemical bodies whenever a the-
oretic consideration or, more rarely, an animal experiment appeared to show
the existence of a pharmacodynamic property. These endeavors have flooded
the medical market with an endless number of new preparations that are
distributed for trial, and with the hope of a successful trial, to competent and
incompetent judges. Now there is absolutely no curative agent, no matter
how slight the foundation for its use, that does not have its firm believer, and
serve for purposes of investigation. Frequently it is tested in only a few cases
from private practice, and then its epithon ornans “ clinical observation ” is
attached. The results, in the form of reprints, are then sent by the labora-
tory into the world by thousands. Unfortunately the opinions expressed in
these reprints often depend upon autosuggestion or an uncritical spirit in
the author: in other cases the effects produced by the new preparations are
nowise better than the action of old and reliable remedies.
Who knows the preparations? Their name is Legion; they are sent out
with “ first-class recommendations ”—this commercial expression is excusable
198 ‘MYXEDEMA
for, in fact, it is in place here—are put upon the market, and, after a brief
and ephemeral existence, are relegated to the orcus of the medicine closet,
never to see again the light of day!
The natural reaction is a constantly increasing doubt in regard to new
remedies. The fascinating reprints, of which every physician has a plentiful
supply, owing to the activity of the manufacturer, are read or not read, but
are followed very cautiously, for, otherwise, time and money would often be
uselessly spent, even if other and greater injury to the patient does not result
from their use.
Why do I mention all this?
Certainly not to check a spirit of rivalry in the production, nor in the
testing of new remedies by competent physicians, and this J desire.to repeat
with emphasis and to bring out prominently. The advantage which has
already resulted from organotherapy is so obvious that many a failure would
be amply compensated’ for—but I must advise those who busy themselves with
this line of investigation to be more cautious in arriving at conclusions, and
to exercise more patience in collecting and more care in utilizing their
material.
It is not wise to cut the corn while it is yet green; harvesting also is an
art. Whoever has not learned this, whoever works in a field which is too
narrow, i.e., in other words, whoever lacks the necessary experience and the
endowment of a faculty for scientific criticism, should refrain from giving
opinions on such a subject.
To this group of over-hasty, uncritical, and, therefore, untrustworthy pub-
lications, belong those chateaux en Espagne which form the greater part of
that “so-called ” organotherapeutics with which we have been favored in the
last few years. With alarming haste the manufacturing chemists have made
preparations from all of the organs, and offered them to the medical profes-
sion for its kind consideration.
ADDISON’S DISEASE
By L. REISS, Bertin
In recent pathological discussions attempts have been made to refer the
clinical symptoms in a number of general affections to a so-called “ auto-
intoxication ” produced by the decrease or absence of the “ internal secretion ”
of an important organ of the body. Of course this view refers chiefly to those
forms of disease in which clinical and pathologico-anatomical experience
have taught us to recognize the invariable predominance of changes in an
organ having a secretory character. An example which best illustrates this is
the wonderful symptom-picture of myxedema, the direct dependence of which
upon a cessation or absence of function of the thyreoid gland has been lately
proven with all the certainty that can be desired.
To the general diseases, in which, at the first glance, it must be obvious
that similar functional disturbances are causative, belongs also the remarkable
symptom-group which, about the middle of the last century, was first accu-
rately described by the English physician, Addison, and to which, therefore,
his name has been attached. The relation of this clinical picture to a well-
defined disease of the adrenal bodies which is present in the majority of cases
has governed the views of observers from remote times regarding the nature
of the disease, and in spite of the many differences of opinion which have
become prominent in the last decades regarding the pathogenesis of Addison’s
disease, the great majority of physicians maintain that a cessation of the
function of the adrenals is the essential basis of the affection. It is also in
harmony with this view that lately, by a transference of the practical question
of the treatment of this affection by organotherapy, favorable expectations
have been aroused so that many trials have already been made of this
method.
But nevertheless, upon closer observation, the conditions do not appear so
simple. Many of the clinical symptoms cannot be referred without further
consideration to a disturbed function of the adrenals; a constant group of
clinical and anatomical findings cannot be said to have been found, and thus
an accurate weighing of the experiences gathered up to this time leads to the
conclusion that the exclusive dependence of Addison’s disease upon disease
of the adrenals, although in many respects quite likely, has not been absolutely
proven, and does not suffice fully to explain the pathogenesis of the disease.
Under these circumstances, it is instructive to investigate the most impor-
tant points and ascertain whether or not the weight of evidence points to
a direct dependence upon disease of the suprarenal bodies. In the following
199
200 ADDISON'S DISEASE
survey of the present status of our knowledge of the pathology of the affection,
this problem is our chief interest. We hope clearly to demonstrate what the
investigations of the last half century have contributed in explanation of
the disease, and what is left for future studies to elucidate.
A brief description of the clinical picture must precede the rest of my
discussion.
CLINICAL PICTURE OF ADDISON’S DISEASE
The description need be but very brief for, in the portrayal of the clinical
symptoms, the first description given by Addison in 1855 is practically ex-
haustive, and many of the later observations have but supplemented this in
certain respects.
All typical cases of the disease show (simultaneously or serially) the fol-
lowing four groups of symptoms:
1. General adynamia; 2. gastric and intestinal disturbances; 3. general
nervous symptoms; 4. abnormal pigmentation of the surface of the body.
I here emphasize the conception of “ typical cases,’ and do not believe it
advisable in describing the nature of the disease to deviate too far from this
conception. In particular, I do not believe that we ought to include as cases
of Addison’s disease (as has often been done of late) those in which the most
conspicuous symptom, the abnormal pigmentation of the skin, is absent, even
though examples of this kind (of which more will be mentioned later on)
may be important in the explanation of the nature and the pathogenesis of
the disease. The differentiation of characteristic symptom-pictures can
advance our clinical knowledge only when it is carried out with the neces-
sary consistency.
The signs of adynamia as a rule develop very insidiously, showing them-
selves in general malaise with exhaustion upon slight exertion, gradually
increasing to extreme muscular weakness, particularly of the lower extrem-
ities, so that walking may become very difficult. These symptoms cannot well
be referred to a profound disturbance of nutrition of the muscles, for, as a
rule, neither very marked emaciation nor muscular atrophy is present, at least
in the early stages of the disease. A weakened condition of the heart muscle
is also apparent, particularly in advanced stages of the disease. The pulse
is often very small, and, at least in the earlier stages, more often slowed than
accelerated. Subnormal temperature (95° F. or a little above this) has been
repeatedly observed, particularly in the terminal stages of the disease.
The muscular weakness cannot be attributed to a marked anemia, for the
microscopic examination of the blood (which will be referred to more in
detail later) has generally indicated even in a late stage of the disease only
a moderate diminution of the red blood-corpuscles and leukocytosis while
some recent observations have shown a conspicuously large number of eryth-
rocytes. -
The disturbances referred to the digestive canal show themselves in the
earlier stages of the affection by general dyspeptic complaints: Loss of appe-
tite (often extreme), occasionally bulimia; tendency to nausea and vomiting,
sense of pressure in the epigastrium; also disturbance of intestinal activity
CLINICAL PICTURE OF ADDISON’S DISEASE 201
which more frequently leads to diarrhea than to constipation. With this
very often, even early, there are marked pains in the abdomen especially in
the epigastrium, in both lumbar regions, and in the right and left hypochon-
drium, intermittent at first, subsequently often becoming continuous. All of
these symptoms increase late in the course of the disease, and often become
so severe that after a time the gastrointestinal disturbances, with- stubborn
vomiting and often steady diarrhea, rapidly decrease the strength.
The symptoms which may be referred to the nervous system are slight at
the onset of the disease, of a general character, and limited for the most part
to psychical apathy, tendency to headache and the like. Later, attacks of
vertigo and syncope are usually observed, not infrequently also epileptiform
attacks and somnolence. Death occurs most often after coma and convulsive
phenomena.
The most conspicuous symptom of the disease in all well marked cases is
the discoloration of the skin which has given: the affection the designation
of “bronze disease.” Like the other symptoms, this usually develops gradually
from a light yellowish brown up to a dark brownish black (mulatto color,
negro color). It often begins simultaneously with the general asthenia, but
may precede this, in some cases even by a long time (in one recorded case
twelve years). The bronzing appears most often on the places which are
exposed to the air (face, neck, hands), and on those which normally show
most pigmentation (the axille, the areola of the nipple, the linea alba, the
genital region), and thence distributes itself over the rest of the skin. Upon
the uniformly pigmented surface there often develop later circumscribed, still
darker areas; in some cases, on the other hand, we find zones which are without
pigment (leukoderma).
The simultaneous involvement of certain mucous membranes in this pig-
mentation has very properly been emphasized throughout the literature of
Addison’s disease as especially important in. the differential diagnosis from
other discolorations of the skin. Almost invariably the mucous membrane of
the mouth is affected, usually in the form of irregular bluish black spots,
their seat being chiefly upon the mucous membrane of the lips and palate.
According to my experience, the tongue deserves more attention than is usually
given to it. In the cases seen by me it often shows in different areas a very
conspicuous inky stain. Sometimes pigment areas are found upon the vaginal
mucous membrane; exceptionally also upon the conjunctiva palpebrarum and
scleree and upon the vocal cords.
The pigmentation, as a rule, gradually increases in intensity throughout
the course of the disease. Only exceptionally has a diminution been noted
prior to death. Somewhat more often transitory remissions of the bronzing
have been reported. I myself have seen in two cases a bleaching of the skin
lasting several months (with a simultaneous general improvement) and later
increased discoloration.
The course of the symptoms just mentioned is decidedly chronic; only
exceptionally is the onset acute and progress rapid. The severer symptoms
follow the milder; not infrequently they come on some months or weeks prior
to death, with a certain suddenness: Two years may be mentioned as the
202 ADDISON’S DISEASE
average duration of the disease, as determined from a large collection of
cases. The termination is always fatal; in the few cases which have been
described as cured the diagnosis is doubtful.
To complete the description it may be stated that Addison’s disease (par-
ticularly in North Germany) is quite rare, that with the exception of earliest
childhood and extreme old age it attacks all periods of life quite uniformly,
and is more frequent in men (60 to 70 per cent.) than in women. Important
etiologic factors cannot be determined ; in a number of cases prolonged psychi-
cal depression (care and sorrow) appear to play a réle.
Besides those diseases with which:the malady is often associated (tubercu-
losis, and, to a lesser extent, carcinosis) I must mention certain cutaneous
complications which have become known by experience, among which are
especially scleroderma, and in rarer cases prurigo, mycosis fungoides, ete.
GROSSER PATHOLOGICO-ANATOMICAL LESIONS IN ADDISON’S
DISEASE
As regards the pathological anatomy of the disease numerous investigations
in the last few decades have confirmed the findings emphasized by Addison,
i.e., the coincidence of the symptom-complex just described, with disease of
the suprarenal bodies. In the overwhelming majority of the recorded cases,
a profound change in these organs with destruction of the greater part of the
normal parenchyma has been observed. Furthermore, experience has shown
that Addison’s disease is not produced by any and all the pathological changes
of the adrenals but that a definite form of disease of the organ is usually
present, particularly a form of chronic tuberculosis, in which the parenchyma
is rapidly destroyed, partly by caseous degeneration, partly by fibrinous con-
traction. The macroscopic changes according to age and distribution: In the
majority of cases the adrenals are enlarged (occasionally to several times the
normal) ; upon section the tissue in part shows inflammatory swelling with
foci of caseous softening; in other areas, contraction and induration with
hard, cheesy, or calcified deposits. In a small number of cases processes of
contraction are predominant, so that the organ is smaller, occasionally so
small that it can only be found with difficulty. The disease of the suprarenal
bodies in the majority of cases is bilateral but, as a rule, not equally developed
on the two sides. In the interior of the individual organ the cortical and
the medullary substance are as a rule uniformly implicated, so far as can be
noted at the autopsy. Tubercle bacilli have lately been found by many
observers in the foci of disease.
In a small number of cases the adrenals show other forms of disease.
Among these, according to the latest investigations and reports, comparatively
the most frequent seems to be simple atrophy of the organ, a change which
in some instances is so extreme that the adrenal appears to be absent, But
it is very likely that some of these atrophic cases represent only the remains of
inflammatory processes after the absorption of softened foci. In a still smaller
number of cases malignant neoplasms (carcinoma and sarcoma) have been
found in the parenchyma of the organ. Still more rarely other diseases, such
GROSSER PATHOLOGICO-ANATOMICAL LESIONS 203
as amyloid degeneration, gummatous changes, echinococcus disease, ete., occur.
Finally, destruction of the organ by hemorrhage has been occasionally men-
tioned (in cases running an acute course).
An important point is that in a large number of the accurately investigated
cases the neighborhood of the adrenals has also been found changed, so that
as a result of adhesions and abnormal connective tissue changes (apparently
the remains of circumscribed peritonitis) the adrenals have coalesced and
become embedded in the neighboring parts. Among the areas thereby affected
the filaments and plexuses of the abdominal sympathetic (above all, of the
solar plexus and of the celiac ganglia which are situated in the neighborhood
of the suprarenals) have quite often been found embedded in thick masses
of connective tissue.
In the purest cases the changes to be found in the adrenals and in their
immediate surroundings are the only abnormal autopsy findings. Frequently,
however, other changes take place, among them (naturally and primarily)
tuberculous lesions which attack the lungs in about one-third of the cases.
But Addison’s disease does not often complicate cases of advanced phthisis.
Similarly malignant neoplasms of the adrenals may exist alone or be com-
bined with tumors of other abdominal organs,
So far I have purposely considered only the simple typical cases of the
disease. This method I should like to continue for the present, excluding
the cases above referred to, which present the clinical picture of Addison’s
disease but show no changes of the adrenals. The question must now be
asked: May we, and must we, in such pure cases with a typical symptom-
picture and well-developed disease or destruction of the adrenals, refer the
former directly to the latter?
Before deciding this question, two other questions, it appears to me, must
first be solved: (1) May the main symptoms of Addison’s disease be produced
by certain general conditions which are present in the affection? and (2) Can
we believe with our present knowledge of the nature and function of the
adrenals that disease of these may produce the symptoms of Addison’s disease ?
In regard to the first question a number of maladies must be considered
in which, as a result of a profound anemia and cachexia, with the general
symptoms of asthenia (and eventually also gastric and nervous disturbances),
an abnormal pigmentation of the skin may develop. To this group belong
certain cases of malarial cachexia, pseudo-leukemia, pellagra (Neusser), the
so-called vagrant’s disease which is produced by deprivation of all kinds,
advanced stages of tuberculosis and carcinosis, and others. But it is not
likely that any disease of the adrenals exists in these disorders. Moreover,
the discoloration of the skin differs in these cases most distinctly from that
seen in Addison’s disease. In the diseases just mentioned it is usually of
slighter degree than in Addison’s disease, and is far less generally distributed ;
it rarely shows, as in the latter malady, the formation of dark areas on a
background of diffusely discolored skin, and above all the accompanying
pigmentation of the mucous membranes is absent. On the other hand, in
the general diseases enumerated above the principal pathogenic factor is a
204 ADDISON’S DISEASE
disturbance in nutrition and a change in the composition of the blood, which
is generally absent in Addison’s disease: The anemia, as a rule, is only devel-
oped to a moderate degree in Addison’s disease; the red blood count, even
in advanced stages, is rarely below 3,000,000; the hemoglobin also has been
often found comparatively high. The increase of the erythrocytes, which has
been lately determined, is not constant and is still unexplained; in one case
from 6,800,000 to 7,200,000 were found, and, shortly before death, 6,500,000.
" The frequently accompanying leukocytosis, with the relative increase of
lymphocytes which has been recently reported, was not marked enough to
constitute a characteristic change in the blood composition. The pigmenta-
tion seen in tuberculosis is not of importance, inasmuch as changes resembling
Addison’s disease occur only in its late stages; typical cases of Addison’s
disease, however, are rarely the accompaniments of advanced stages of tuber-
culosis.
In answer to the other question, what consequences are, a priori, to be
expected upon destruction of the adrenals, it is necessary to briefly review
the reports concerning the anatomy and physiology of these organs,
ANATOMY AND PHYSIOLOGY OF THE ADRENALS
Formerly the adrenal was assumed to be essentially a part of the nervous
system, and its medullary substance was described as consisting almost exclu-
sively of ganglion cells. But the newer histologic investigations are unanimous
in this, that the cortical substance as well as the medullary substance contains
chiefly parenchyma cells which show a varying size and form in different areas,
are arranged in groups inside of a connective tissue structure, and contain
very abundant pigment, chiefly in the intermediary zone (Virchow). The
rich blood supply of the organs has long been emphasized ; this is shown partly
by the comparatively great number of afferent and efferent large vessel trunks,
and partly by the very dense capillary network (particularly in the medullary
substance). The parenchyma cells are everywhere in intimate relation with
the walls of the capillaries, according to some reports in part directly within
them. Between the cells, excreted “colloid”? masses have of late been fre-
quently observed (Auld). All authors, even the most recent, agree that the
organs (especially their medullary substance) are particularly rich in nerve
elements, i.e., in non-medullated (sympathetic) and medullated nerve fibers
as well as also in ganglion cells deposited in the parenchyma. Numerous
nerves unite the organs with the neighboring parts of the nervous system,
particularly with the semilunar ganglion and the other parts of the solar
plexus; they have even been followed further, and traced into the splanchnic
nerve, the vagus and the phrenic nerve. Some authors have described small
ganglion cell groups situated upon the external part of the capsule of the
adrenal.
The conception of the embryologic development of the adrenals differs
with various investigators; the majority of observers believe that there is
an intimate relation between the medullary substance (which develops sepa-
rately from the cortex) and the (sympathetic) nervous system, either assum-
GROSSER PATHOLOGICO-ANATOMICAL LESIONS 205
ing a direct development of the adrenal medullary substance from the ganglion
of the sympathetic, or a later growth from the sympathetic ganglion cells and
nerve fibers.
In spite of many points which are still obscure the complicated anatomical
structure of the adrenals gives us the impression that they are (ductless)
secretory organs, constructed with a comprehensive innervation apparatus.
Still more complicated, and in many respects uncertain, is our knowledge
of the physiologic function of the adrenals.
For a long time they have been classed with the well known glandular
ductless organs, being designated as blood-vessel glands serving an unknown
purpose. Particular attention was drawn to the adrenals by the first descrip-
tions of the Addison symptom-complex, and this caused a deeper scientific
interest regarding their importance, and the investigation of their function.
And thus, soon after the publication of Addison’s views, a series of experi-
mental researches were begun which had for their purpose the extirpation of
the adrenals in animals, and the observation of symptoms thus produced, in
order to determine the functional importance of these organs.
But the difficulty of such investigations was soon shown in the uncertainty
of the results. This gave rise to the important question, whether the adrenals
were to be looked upon as organs necessary to life. This question was an-
swered definitely in the affirmative by the first investigator, Brown-Séquard ;
in a publication in 1856 he stated that after removal of both adrenals all the
animals died in a short time (one to two days) with prostration and severe
nervous symptoms. But his reports were at first not confirmed by other ob-
servers; on the contrary, there soon appeared a number of communications
(among which I shall mention only those of Philippeaux, Gratiolet, Harley
and Schiff), according to which certain animals, in spite of the loss of both
adrenals, continued to live for a long time (several months), and from which
it appeared likely that the death of the experimental animals was produced
by lesions of neighboring parts (peritoneum, abdominal nerve plexus, etc.).
At this point I must refer to a series of experiments by Nothnagel, who
produced bilateral contusion of the adrenals in a great number of rabbits, a
few of which were still living eighteen months later and showed no gross
lesions.
Thus the vital importance of the adrenals was for a long time a subject
of doubt. But a series of new investigations substantiated the original opinion
of Brown-Séquard. These (conducted by Tizzoni, Abelous and Langlois, de
Domenicis, Cybulski, Szymonowicz and others) showed that in a number of
different animal species (dogs, guinea-pigs, frogs, etc.) death invariably re-
sulted after a complete removal of both adrenals.
The period before death varied (according to the animal and according
to certain auxiliary conditions) from a few hours up to several months. By
careful control experiments it was shown that only the loss of the adrenals
could be the cause of death. An opposite result has been obtained in some
investigations, very few of them recent. This contradiction may be explained
in various ways: Either the observation of the animals may have been too
brief, or the removal of the adrenals was incomplete.
206 ADDISON’S DISEASE
Finally, as an explanation of this problem (as of many others to be men-
tioned later) we must remember the presence of the so-called accessory or
supplementary suprarenal bodies to which Marchand was the first to call
attention. These accessory adrenals are found particularly in the neighbor-
hood of the internal genitalia, which have been experimentally proven to be
capable of decided hypertrophy after removal of the adrenals. In conclusion
it has lately been regarded as settled that after complete. removal of the
adrenals a continued healthy extstence 13 impossible.
More difficult is the decision of the question, what are the disturbances
of function in experimental animals after removal of the adrenals?
In the first place a number of symptoms in these animals may be referred
to general nutritive disturbance (mostly diarrhea) ; further some observers
have noted lowering of temperature and lowered blood-pressure. Such symp-
toms are not consequences of loss of the function of the adrenals, as has lately
been often affirmed. On the contrary, they may find sufficient explanation in
the severity of the operation and in various auxiliary circumstances. It must
be emphasized, too, that up to the present time, no animal experiment has been
successful in producing unmistakably the principal clinical symptom of Addi-
son’s disease, viz., the pigmentation of the skin.
In some more extensive series of experiments a few of the animals lived
for a longer time and some developed areas of pigment upon the mucous
membrane of the mouth or nasal cavity; but it is doubtful whether in these
exceptional cases the operation produced the pigmentation.
On the other hand more conspicuous symptoms relating to the nervous
system were observed in the experimental animals. In those that soon suc-
cumbed there were convulsions, symptoms of vertigo, rotary movements, and
the like; among the animals which lived longer, paralytic conditions, con-
tractures, etc., developed. More profound pathologico-anatomical changes of
the nervous system have been described only by Tizzoni. In his cases there
were lesions in the central nervous system, particularly the medulla oblongata,
the cervical cord and cerebellum, as well as in the abdominal plexus of the
sympathetic, and certain peripheral nerve trunks. In animals that died
quickly the central nervous system showed hyperemia with hemorrhages and
cell infiltration surrounding the vessels; in the cases running a chronic course
the changes were more in the form of column degeneration and atrophy
of the gray substance. The starting point of the process was apparently the
abdominal sympathetic. But nothing analogous to this has been reported by
other experimenters.
Brown-Séquard believed that he could determine important changes in the
blood of these experimental animals, particularly a decided increase of pigment
with pigment emboli in the organs. From this observation he inferred an
intimate connection between the adrenals and pigment formation in the body.
But confirmation of these reports by other observers is lacking. Reliable
results were furnished by prolonged investigations with the injection of the
blood of epinephrectomized animals into healthy animals by Brown-Séquard
and by later observers (particularly Abelous, Langlois, etc.). These experi-
ments showed, after removal of the adrenals, a conspicuous toxicity of the
GROSSER PATHOLOGICO-ANATOMICAL LESIONS 207
blood serum so that when it was injected into animals one of whose adrenals
had been excised death was produced or hastened. From the sum of these
investigations the observers conclude that, after the operation, substances cir-
culate in the blood which under normal circumstances are rendered harmless
by the adrenals; that the latter are therefore protective organs in relation to
certain toxic products of metabolism. Further consideration caused a number
of these observers to emphasize the similarity of the symptoms to those of
curare poisoning. This was true of the animals operated upon as well as
those animals into whom the blood was injected (particularly in regard to
the action upon the nerves). It was also determined that after inoculation
of the blood and serum of dogs into other animals whose muscles were ex-
hausted by tetanizing action was produced similar to that after the removal
of the adrenals. Regarding the substances which appear to be neutralized
by the normal function of the adrenals, these experiments justify us in believ-
ing that they are the toxic products of the metabolism of muscular activity.
Finally I must mention the researches of Jacobi, which appear to prove
an intimate relation between the adrenals and intestinal peristalsis. And this
influence must be looked upon as an inhibitive action exerted on the gut by
the adrenals. Extirpation of the adrenals acted like division of the splanchnic
and produced active intestinal peristalsis while irritation of the adrenals caused
the intestine to remain quiescent. The adrenals accordingly are looked upon
as branches of the splanchnic, and the inhibitive tracts controlling the intes-
tine considered to be fibers which lead from the adrenals to the semilunar
ganglions. It is true these investigations have not as yet been thoroughly
confirmed.
In the reports of experiments up to the present time, therefore, certain
points of support are found for ascribing to the adrenals an important func-
tion in the organism.
This conviction is strengthened and confirmed by other recent investiga-
tions, in which the attempt was made to introduce the active constituents of
the adrenals in the form of an organic extract (watery, glycerin-containing,
ete.) into animals by injection, and to study the action thus produced. I
shall only mention a few of the most important, and the conclusions which
have been drawn from them regarding the function of the adrenals:
After a few earlier observers had determined the toxicity of adrenal
extracts, noting the effect of injections in different animals who showed
symptoms of general body and nervous weakness, Oliver and Schafer (1894
and 1895) were the first to make minute studies regarding this condition.
They found as the most conspicuous action of intravenous injections of the
extract (particularly that obtained from the medullary substance) a transitory
but very decided rise of blood-pressure. Further investigations (cutting the
vagus, injection of atropin, destruction of the medulla oblongata and of the
spinal cord, etc.) proved that this rise in blood-pressure is due to a direct
increase of vascular tonus and general muscle-tone (particularly in the heart
and in the vessels). The extract, besides strengthening the cardiac action,
also slows it. Adrenal extracts which were taken from cases of Addison’s
disease were inactive. The observers conclude: That the adrenals secrete a
208 ADDISON’S DISEASE
substance which reaches the blood, and gives to the muscles the degree of
tension necessary for their functions.
In a similar manner Cybulski and Szymonowicz proved the rise in blood-
pressure (by contraction of the vessels) and the strengthening of the cardiac
activity resulting from injections of suprarenal extract. But upon further
investigation (after severing the vagus and spinal cord, injecting atropin,
etc.) they obtained results which appeared to favor, not a peripheral action
of the extract, but an influence upon the central nervous system, particularly
the vasomotor centers of the cord. They also found marked irritation of the
respiratory center. They therefore assume that the secretion furnished by
the adrenals to the blood is intended to maintain the tonus of the cardiac,
vasomotor and respiratory centers. But the majority of the later investiga-
tions have favored the assumption of a peripheral action of the adrenal
extract. Only v. Cyon believes from his investigations that the rise in blood-
pressure depends for the most part upon an irritation of the vasomotor cen-
ters. On the other hand, the researches of Velich favor the view that the
vascular contractions which he observed after injection of adrenal extract into
the tongue, conjunctiva, ear, intestine and kidneys depend upon an influence
of the extract upon the peripheral vascular apparatus as well as upon the
co-operation of spinal vaso-constrictor centers. Biedl obtained, after complete
destruction of the spinal cord, marked rise in blood-pressure by intravenous
injections of suprarenal extract, so that an irritation of the peripheral appa-
ratus may be assumed. Gottlieb, according to whom the increase in blood-
pressure depends principally upon a strengthening of the cardiac activity,
after investigations in chloralized animals, refers this to an energetic irrita-
tion of the motor ganglion groups which dominate cardiac movement. Lewan-
dowski has further demonstrated in a convincing manner a peripheral action
of the injected suprarenal extract upon the smooth muscles of the eye and of
the orbit (dilatation of the pupil, prominence of the bulbus oculi, etc.),
which is parallel to the vascular action. Finally I must mention the local
vaso-constricting action of the suprarenal extract which has been lately recog-
nized, and which has been used therapeutically upon the conjunctiva (by
advice of Darier), upon the larynx and nasal mucous membrane, and in
intestinal hemorrhages.
In several of the investigations it has been proven that the adrenal venous
blood acts similarly to the extract (Cybulski, Dryer). The rise in blood-
pressure which is thus attained is usually very decided. In some cases it
has been raised above 300 mm. of mercury. After destruction of the spinal
cord, which reduces blood-pressure almost to zero, it can be raised to 160 mm.
by injection, and by repeated injection the pressure can be maintained for a
long time at from 90 to 140 mm. (Biedl). By using a very pure extract
recently produced by Moore and Purinton zpytuay of a gram is sufficient
to maintain in a dog a persistent rise in blood-pressure of from 20 to 40 mm.
of mercury.
Interesting observations have recently been made which show that injection
of adrenal extract into the abdominal cavity of guinea-pigs causes a destruc-
tion of red blood-corpuscles and produces in the spleen and lymph-glands
GROSSER PATHOLOGICU-ANATOMICAL LESIONS 209
hemosiderin deposits similar to those which occur in the so-called hemo-
chromatosis (a pigmentation of the skin resembling Addison’s disease) (Foa).
A recent experiment is also to be mentioned according to which the subcutane-
ous (or intravenous) injection of adrenal extract in animals produces glyco-
suria in the majority of cases (Blum). ’
From these experiments it appears that we must admit an “ internal
secretion” of the suprarenals, and must recognize that these organs furnish
to the blood a substance which acts primarily to raise blood-pressure.
Endeavors to isolate and more minutely to characterize the substance in
the adrenals which raises blood-pressure have not been lacking. These have
lately led to definite and fixed, even though not always uniform, results.
But these endeavors, like the earlier and frequently repeated chemical investi-
gations of the adrenal parenchyma, are not calculated to advance our knowl-
edge regarding the function of these organs. The most important experi-
ments are the following:
The earlier investigations (conducted by Vulpian and Virchow, and dating
from the time when the clinical picture of Addison’s disease was first made
known) were made with a substance which is found in the medulla of the
adrenals and which, with iron chlorid, gives a blackish green color. These
observers first called attention to the similarity of the pigment seen in the
parenchyma of the adrenals (particularly in the intermediary zone) to that
of the rete Malpighii in pathologic discoloration of the skin. Furthermore,
observers have made frequent attempts to isolate a peculiar coloring matter
from the parenchyma of the adrenals but without reaching unanimous results.
Some writers emphasize the brown coloration of the tissue (particularly in
the intermediary zone) which occurs with salts of chromic acid. Several
others have noted small globular structures in the blood of the adrenal veins.
These granules can be colored with chromic acid, and have been looked upon
as products of secretion of the organs. A chromogen with different deriva-
tives has been found by several observers in the parenchyma; by some this
has been believed to be identical with hemochromogen (McMunn).
Among the substances which have been demonstrated in the parenchyma
of the adrenals are leucin and myelin which were referred to in earlier re-
ports, lecithin which has been found in large amounts (Alexander), a related
body resembling jecorin which contains sulphur and phosphorus (Manasse),
and neurin. All these are substances from the presence of which certain
telations between the adrenals and nervous system may be inferred. The
substances which give a green color with iron have been found to be chemically
closely related to pyrocatechin (Krukenberg), and from the extracts of the
medullary substances it is possible to isolate a compound from which, by
boiling with hydrochloric acid, pyrocatechin can be produced (Miihlmann).
These findings also indicate a relation with pigmentation of the skin without
furnishing definite proof of it.
The “substance forming a green color with iron” and the “substances
resembling pyrocatechin” are identical with the products which cause a rise.
in blood-pressure, and for use as substitutes for the adrenal extract in animal
injections have been produced from the organs by complicated chemical proc-
15
210 ADDISON’S DISEASE
esses. Of the numerous investigations of this character which have recently
been conducted three must be particularly mentioned: One of these bodies
has become known as “ sphygmogenin ” (Frankel) and is a syrupy substance
which shows marked reducing property, is easily oxidized, and with a watery
iron chlorid solution gives a dark green reaction. Another substance named
“ epinephrin ” has been obtained by Abel from a watery extract of the adre-
nals as a benzoyl combination. As a result of elementary analysis Abel looks
upon it as an alkaloid belonging to the pyrrhol or skatol group, and obtains
from it by treatment with dilute alkali a dark pigment. Finally, v. Firth,
after prolonged study, believes he has found a still purer body which he calls
“suprarenin,’ and designates as a dioxypyridin having a composition of
C,H,NO, or C,H,NO,. This substance also raises blood-pressure upon sub-
cutaneous injection. How far the previously mentioned bodies actually repre-
sent the important secretions furnished by the adrenals to the blood must
be decided by further physiologico-chemical investigations.
After this brief ‘description of the results which have been obtained from
experiments and chemical investigation in regard to the physiologic action of
the adrenals, we return to the question: Can the clinical picture of typical
Addison’s disease be explained from the lesion, that is, from the destruction
of these organs?
Up to a certain point an affirmative answer may at once be given. We
can reconcile many important symptoms of the disease with a gradual decrease
and final cessation of function which, from the experience we have gathered,
may be ascribed to the adrenals, and we can find abundant analogies between
the condition of the person attacked by Addison’s disease and the experimental
animal that has been deprived of its adrenals.
First of all we recognize in the steadily progressive constitutional disease
which leads to death the same consequences of the loss of vital organs which
we found in the'experiments. That the duration and course here correspond
but little with those in the animal experiments is not surprising. Rarely
does experimental disease in the animal accurately simulate the human dis-
ease, and still less so when, as in this case, the sudden removal of the organs
from the animal (even should the extirpation in part be undertaken at two
different times) is contrasted with a chronic disease in the human being with
very gradual loss of function. The duration of the disease in the human
subject is often many years—indeed disturbances of the adrenals are some-
times of such long standing that in the last periods of life a complete loss of
function of the organ must be assumed. Nevertheless we can sometimes find
analogy for this in the circumstance that for many months, even for years,
it is possible to keep the experimental animal alive. The nature of the general
disease in both cases is similar: In both, emaciation is present, but is not the
predominant symptom ; in both the signs of true anemia are usually of mod-
erate degree. Against this the general asthenia, the permanent and increas-
ing weakness of most muscle groups, becomes particularly prominent in the
clinical picture, and reminds us strongly of the prostration which appears
so constantly in the experimental animal.
GROSSER PATHOLOGICO-ANATOMICAL LESIONS 211
This asthenia in Addison’s disease may also be alleged as valuable proof
of the theory of many observers that the function of the adrenals mainly
consists in the maintenance of the muscular tonus. :
The cardiac weakness so frequently noted in Addison’s disease, which
numerous authors have also observed in the animals operated upon, may in
some respects be regarded as a part of the general muscular weakness. Obvi-
ously this must be looked upon as an expression of the fact that a disturbance
of the adrenals has decreased or abolished the formation of a substance which
increases blood-pressure and strengthens the heart, and which according to
the investigations we have mentioned must be ascribed to the parenchyma
of the organ.
In regard to the manifold disturbances originating in the digestive canal
and its surroundings, practical experience at the bedside coincides with experi-
mental results and theoretic deductions: The majority of the gastric symp-
toms, such as general dyspepsia, particularly loss of appetite, gastric oppres-
sion, eructations, nausea, vomiting, etc., may be referred to the general
affection with its adynamia, anemia, etc. The epigastric, hypochondriac, and
lumbar pains which are never absent, and occasionally form the most distress-
ing of the subjective symptoms, may be directly due to pathologic processes
in the adrenals themselves. Experimental investigators have repeatedly de-
monstrated that the adrenal, particularly its medullary substance, is very sensi-
tive to pain. The frequency, too, with which the adrenal affection attacks
the surrounding areas, in which are found signs of old local peritonitis in the
form of adhesions and connective tissue masses, certainly points to a similar
explanation of these pains. But though we cannot be sure of the connection
between these pains and the chronic and progressive inflammation, a terminal
stage of the Addison symptom complex resembling peritonitis has of late been
frequently described (Ebstein). To explain the intestinal symptoms, the same
factors may suffice, but we may also call to mind the above-mentioned experi-
ments which show a nervous connection between the adrenals and the intes-
tinal ganglia and suggest that inhibitive nerve impulses are normally
transmitted from the adrenals to the intestine, so as to control intestinal
movements. The diarrhea which appears in the terminal stage of the disease
is a particularly strong argument for this view.
It is less easy to ascribe to a simple adrenal defect some of the many
nervous phenomena which accompany the disease. The general nervous symp-
toms and the milder forms of cerebral implication such as apathy, headache,
insomnia, vertigo, attacks of syncope and the like may be related to the ady-
namic and anemic general condition. Nevertheless, these symptoms are often
much greater than can be accounted for by the general asthenic conditions ;
for example, the apathy often changes into increasing psychical depression
with disturbance of the mental functions, showing itself partly by somnolence,
partly by irritability. To this may be added the neuralgic conditions often
observed in the earliest stages, especially affecting the extremities and the
joints, and finally, the usually spasmodic, often epileptiform attacks, accom-
panied by extreme irritability and delirium which lead up to the final coma
of the later course. If this picture is considered, it corresponds neither to a
212 ADDISON’S DISEASE
general nutritive disturbance nor to a simple chronic intoxication; on the
contrary, in many particulars it points to a direct implication of various areas
of the nervous system.
Most difficult of all to understand is the principal clinical symptom, the
bronzing of the skin. It must first be pointed out that in many investigations
of extirpation of the adrenals in animals, even in those animals which were
kept alive a long time, this symptom could never be produced. But too much
stress is not to be laid upon this point, for there is justification for the view,
shared by many observers, that the comparatively early death of the animals
experimented upon may have checked the deposition of pigment. Further,
we do not know whether abnormal pigmentation of the skin occurs in animals
as readily as in man.
But neither do our investigations furnish anything which can be looked
upon as proof that by destruction of the adrenals pigmentation of the skin
is directly caused or even favored. We may concede most readily the possible
truth of the theory (which is frequently expressed) that under normal condi-
tions there is a substance circulating in the body which furnishes material
favoring pigmentation, but which is rendered inoperative by the internal
secretion of the adrenals. That the chemical investigation of the parenchyma
of the adrenals has furnished no positive points of support for this has already
been mentioned. Such a connection, too, is untenable without a demonstrable
pathologic change in certain fluids of the tissues and in the blood; for such
demonstration, however, there is no further experimental evidence, for exam-
ple, in the blood and in the urine.
Of the blood it has already been stated that an estimation of the blood-
corpuscles and the amount of hemoglobin shows for the most part but slight
change, and upon exact counting of the leukocyte varieties no important
deviation from the normal has been found. In these investigations signs of
abnormal amount of pigment of the white blood-corpuscles or of the serum,
analogous to melanemia, have never been observed, nor does the finding of
cells containing blood-corpuscles and pigment granules in the marrow of the
tubular bones, mentioned in one case, permit positive conclusions. Nor is
much added to our knowledge by certain reports, according to which there is
a qualitative change in the blood with increase of reduced hemoglobin and
appearance of methemoglobin (Tschirkoff).
Even slighter deviations from the normal were shown by the wrine in
most cases. Apart from polyuria, which is not infrequently noted, in some
patients an increase in indican, and in one a decided increase of urobilin, has
been found. In one case an abnormal coloring material (urohematoporphy-
rin) was determined spectroscopically (McMunn). Furthermore, there are
reports regarding decrease of urea and creatinin. Opposed to this, however,
are a large number of reports of cases in which a normal condition of the
principal urinary constituents, particularly of indican, of urea or nitrogen,
has been determined. A new amin base (Ewald) obtained from the urine
in a single instance has not been satisfactorily explained.
_ Nevertheless while there is no evidence which points with certainty to a
direct importation of the pigment from the adrenals to the skin, the possibility
GROSSER PATHOLOGICO-ANATOMICAL LESIONS 213
of a process of this kind cannot as yet be excluded. For the formation of
pigment in the organism is a complicated process, and no less so its deposi-
tion in the tissues, particularly in the skin. Regarding the latter process
we are quite well informed by recent investigations, which shall briefly be
referred to here.
According to these, the pathologic deposition of pigment in Addison’s
disease occurs in the same manner as physiologic discoloration of the skin
(in dark races, in pregnancy, etc.) which is apparently distributed in an
analogous manner also in all species of animals. The main seat of the pig-
ment particles, all observers who have undertaken microscopic investigations
of the bronzed skin find to be the cells of the lowest layers of the rete Mal-
pightt. The previous view that the pigment development here is autochtho-
nous (by metabolic activity of the cells) has been almost wholly abandoned.
On the contrary, quite a number of recent investigators (Renaut, Nothnagel,
Riehl, v. Kahlden and others) have proved conclusively that the pigment from
the deeper layers of the coritum is brought to the rete cells by motile cells,
and that the pigment most probably originates in the blood. The findings
resemble one another very much in individual cases; almost always, beneath
the pigment layer of the rete, wandering cells are to be seen carrying pigment
through the corium; in the deeper cutis layers these cells often accumulate
in large groups around the vessels, partly also in their adventitia. A disease
of the walls of the vessels has been described in several cases, in which swelling,
cellular infiltration and small hemorrhages were conspicuous (Riehl), but
this has not been discerned by other observers, and does not appear to play
a role in the process. The mucous membrane of the mouth shows conditions
analogous to those of the cutis.
It is obvious that this process of pigment-deposit in the skin favors the
assumption of an abnormal coloring material admixed with the blood as the
result of adrenal disease, a chromogen, for the existence of which, however
(as I have previously said with emphasis), our knowledge up to this time
gives no points of support. It must also be remembered that if there were such
an over-flooding of the vascular system with pigment it would be very difficult
to explain why no deposits of pigment are found in any areas of the internal
organs. At any rate, it is obvious that besides the hypothesis of the trans-
portation of pigment from the blood to the superficial layers of the skin we
should also consider the possibility that the disease may be due to an implica-
tion of the nervous system, upon whose vasomotor and trophic tracts the walls
of the vessels and the cells of the cutis are dependent to a high degree.
Evidently the unusual formation of pigment substance from the hemoglobin
(normal or modified), and the increased activity of the cells transporting
the pigment, can scarcely occur without the nerve elements being subjected
to an abnormal irritation. Also many irregularities of the pigmentation of
the skin occurring in Addison’s disease, particularly the not infrequent occur-
rence of leukoderma plaques, as well as the combination with other trophic
cutaneous disturbances (sclerodema), point to varying local processes of in-
nervation. Finally, it is not without significance to remember that in many
species of animals characterized by conspicuous staining of the skin (chame-
214 ADDISON’S DISEASE
leons, frogs, etc.) the dependence of “ chromoblasts ” upon the nervous system
(Raymond) has been proven. ;
Thus the most conspicuous symptom of Addison’s disease points with more
emphasis than any of the others to an implication of the nervous system.
Therefore we are forced to the conclusion that even in the most typical cases
a conception of the clinical picture as due to a cessation of suprarenal func-
tion is beset with difficulties.
The perplexities of explanation increase materially when we leave the realm
of purely typical cases of Addison’s disease, and consider the deviations which
the clinical symptoms and pathologico-anatomical findings present under some
circumstances. Unfortunately, these variations from the normal type of the
disease are not very rare. I mean by this, not the many quantitative differ-
ences in individual symptoms whereby it often occurs that one symptom, for
example, gastro-intestinal phenomena, becomes more marked than all others,
or that the bronzing of the skin is very intense in the early stages of the
disease, while at other times, toward the termination of the affection, it is
only very moderate, that at the autopsy the adrenals, contrary to rule, are
found with lesions of fresh degeneration, and in part present well retained
parenchyma and the like. All these variations depend upon the duration,
course and complications of the disease, and partly upon auxiliary conditions
which cannot be controlled. Much more important are the instances of a
lack of coincidence between the main clinical symptom, the pigmentation of
the skin, and the important factor of the pathologico-anatomical picture—
the degeneration of the adrenals. Such exceptions were noted soon after the
publication of Addison’s fundamental description, and have multiplied in
the course of years, so that many modern authors deny wholly the parallelism
between the pigmentation of the skin and adrenal disease.
Two groups of cases are here to be distinguished, and by most observers
have been noted separately: The cases in which in well developed Addison’s
disease with bronzing no affection of the adrenals has been shown, and upon
the other hand, advanced changes in the adrenals without discoloration of the
skin and even in some cases without any severe symptoms. The frequency
of such exceptions naturally cannot be seen in a small group of cases, and
full compilations have up to the present time been very rarely made (Aver-
beck, Greenhow, G. Lewin). Among the earlier reports of this kind Green-
how’s statistics are to be referred to, in which among 172 cases of undoubted
Addison’s disease, disease of the adrenals was absent in 10. The most com-
plete compilation at present is that of Lewin, which includes 561 autopsies;
according to this, typical Addison’s disease with changes in the adrenals is
noted in 88 per cent., without lesion in 12 per cent.; on the other hand there
was adrenal disease with bronzing of the skin in 72 per cent., without such in
28 per cent. of the cases. Now it must be stated, once for all, that most
statistics of this kind which refer to early cases are unreliable on account
of the lack of definiteness in the descriptions of the pathologico-anatomical
conditions of the adrenals. In some cases disease of the adrenals has doubt-
less been overlooked, in others erroneously assumed. Nevertheless the number
PATHOLOGICO-ANATOMICAL CHANGES OF THE NERVOUS SYSTEM 215
of these deviations from the supposed pathology of Addison’s disease is too
great for us to ignore.
For us the exceptional cases in which the clinical picture of Addison’s
disease does not correspond with the adrenal affection are of the greatest
importance. They are the ones which even in carly years caused doubts to
arise regarding the direct dependence of the clinical picture upon disease of
the adrenals, and soon caused investigators to search for another explanation
of many of the pathologico-anatomical findings. That the first point of
attack was usually an investigation into the nervous system is not surprising
when we consider the location and intimate connection of certain parts of the
nervous system, particularly the abdominal sympathetic plexus, with the adre-
nals. At autopsies, special attention has apparently been directed to these
parts by the frequent extension of the disease of the adrenals to the surround-
ing areas, often in the form of circumscribed inflammation and connective
tissue development, more rarely in the form of tumor formation, particularly
in important nerve areas. Thus in the last decades a great number of ana-
tomical investigations, partly superficial, partly very thorough, have been
made of the nervous apparatus surrounding the adrenals, and a great number
of results have been obtained, the most important of which will now be
briefly sketched.
PATHOLOGICO-ANATOMICAL CHANGES OF THE NERVOUS SYSTEM
IN ADDISON’S DISEASE
The parts of the nervous system most frequently investigated, and most
frequently found diseased, are the semilunar ganglia of the solar plexus.
These are naturally implicated by a cireumscribed peritonitis or insidious
connective tissue inflammation developing from the’ adrenals; and thus we
find a decided percentage of cases in which these ganglia are reported as
adherent to their surroundings, enclosed by connective tissue proliferation, or
embedded in cicatricial tissue. It may also be assumed that these conditions
are even more frequent than the records show since in the protocols of the
earlier observers, adhesions and peritoneal remains have often been reported
as present in the surroundings of the adrenals without the sympathetic plexus
being mentioned.
In other cases it is stated that in spite of the connective tissue embedding,
normal nerve elements have been demonstrated in the plexus; yet it remains
questionable whether these findings included all areas of the nervous organs,
and also whether nerve elements pressed upon by tissue of this kind may be
looked upon as functionally normal. Such connective tissue proliferation is
closely analogous to a compression of the sympathetic plexus by tumors (tuber-
culous, carcinomatous, or leukemic) or by aneurism of the aorta.
With or without such disease of the surrounding tissue, the semilunar
ganglia have shown many macroscopic and microscopic changes. The macro-
scopic alterations have been noted either as. enlargement, thickening and
swelling (and at this not always of the ganglia themselves but frequently
also of the nerve bundles extending from them to the adrenals) with hyper-
216 ADDISON’S DISEASE
emia and abnormal succulence; also decrease in size, atrophy and induration.
In some cases the ganglia have been implicated in a process of caseation
(tumor formation is also mentioned). Histologic investigations have shown
the signs of fresh or older inflammation and degeneration with their conse-
quences, particularly interstitial connective tissue proliferation, cellular infil-
tration and thickening of the capsules of the ganglion cells and nerve sheaths;
moreover, abnormal pigmentation of many tissue elements, fatty degeneration
and pigment atrophy of the ganglion cells (occasionally reaching a very high
grade). Finally there are observations of various forms of neuritis, atrophy
and degeneration of the nerve fibers traversing the ganglia and proceeding
from them. Conspicuous vascular changes (thickening and hyaline degenera-
tion of the walls of the vessels, accumulation of cells and hemorrhages in the
adventitia) have also been noted, particularly in the areas near the adrenals
(v. Kahlden).
The same changes (thickening, contraction, degeneration of ganglion cells
and nerve fibers) have also been frequently found in other parts of the
solar plexus.
Various observers note far-reaching degeneration of the splanchnic nerve,
partly in the form of fresh or older neuritis, partly as gray degeneration of
the medullary fibers, the latter sometimes as consequences of compression ;
for example, by an aneurism of the aorta (Jitirgens).
Similar neuritic disease has been found in the sympathetic system, some-
what removed from the adrenals, particularly in the boundary column of the
sympathetic and in its cervical ganglia. The former has often been found
conspicuously thickened and indurated, the latter decidedly swollen, and show-
ing inflammatory changes. Fleiner was able to follow similar processes of
the disease through a large part of the sympathetic nervous system, and also
in two cases in the central nervous system. These findings are the more
convincing as in both cases they were quite similar, while the nature of the
disease differed decidedly (one was dependent upon tuberculosis of both adre-
nals, and the other upon sarcomatosis of an adrenal and its surroundings).
In both instances a chronic process of inflammation could be demonstrated
which extended from the diseased adrenals through the semilunar ganglion
to the boundary column of the sympathetic with its thoracic and cervical
ganglia into the pneumogastric, and was particularly well developed in the
intervertebral ganglia of the posterior thoracic and upper lumbar portions of
the vertebral column. In all of these areas there was found diffuse connective
tissue proliferation, or focal accumulation of round cells in the neighborhood
of vessels; besides this markedly intense pigment atrophy of the ganglion
cells, and extensive degeneration of medullary fibers in the sympathetic, the
splanchnics and also in the vagus. In the spinal ganglia the nerve fibers
showed advanced degeneration, most markedly in the nerve branches leading
to the sympathetic, less so in those leading to the posterior roots of the spinal
cord. Finally, the same degenerative processes were found in a number of
peripheral nerves, chiefly in the sensory cutaneous branches.
In the spinal cord the same observer found no important changes, but such
have repeatedly been described by others (Burresi, Babes and Kalindero, etc.),
PATHOLOGICO-ANATOMICAL CHANGES OF THE NERVOUS SYSTEM 217
and especially in the dorsal cord. The changes consist partly of hyperemia
and round cell accumulation, partly of sclerosis with thickening of the neu-
roglia and of the walls of the vessels, also atrophy of the ganglion cells and
neuritic processes in the spinal roots (particularly the posterior ones).
It must also be mentioned that by some authors special stress is laid upon
disease of the small pericapsular adrenal ganglia which are frequently impli-
cated by the local process.
Many of these reports have been met by the criticism that the importance.
of the pathologico-anatomical changes has been exaggerated, and that many
of them do not go beyond what we have learned to recognize by more recent
investigations as the consequence of general nutritive disturbances produced
by many forms of anemia, cachexia and the like in the elements of the nervous
system. This criticism can only refer to the mild degrees of such changes,
as the atrophy of the ganglion cells and nerve fibers, the pigmentation of
tissue elements, etc.; and I do not intimate that the importance of changes
such as these is to be denied. It is, however, different with the severer findings
reviewed above, in which, as a rule, advanced degenerative conditions of the
cellular elements are combined with conspicuous inflammatory processes of
the interstitial tissue. Such changes must be counted among the characteristic
findings of the disease in question, and must be considered in judging of its
pathogenesis.
It is true that our limited knowledge makes it difficult to estimate the
relatwe frequency of such pathologic nerve findings. Judging from the mate-
rial at hand, we cannot look upon them as constant. For quite a number of
reports are diametrically opposed to those just mentioned, and show that,
in the investigation of certain areas of the nervous system, no abnormality
had been found. It is true a large number of these communications are far
removed from being susceptible of general proof. First, there are some of
them, particularly dating from earlier periods, in which the anatomical inves-
tigation regarding the more minute relation of the nerve elements was insuffi-
cient. It need only be mentioned here that in many of the earlier cases it
was decided macroscopically whether, for example, the semilunar ganglia
were of normal size, color, consistence and the like. Then the majority of
these investigations refer only to small areas of the nervous system; few
among them follow completely the important central parts of the sympathetic
system, and investigate whether the neighboring areas of the central nervous
system are also implicated. In the overwhelming majority of cases only the
semilunar ganglion and solar plexus have been examined; much more rarely
the splanchnics and the boundary column between the dorsal ganglion and the
cervical ganglion of the sympathetic have been examined. The intervertebral
ganglia, upon which lately special stress has been laid, as well as upon the
spinal roots and the spinal cord, have been but very rarely investigated except
in the few cases mentioned above. It may be added that these negative
reports (as well as the positive nerve findings) occurred usually in cases in
which the adrenals showed no conspicuous change.
‘Here, therefore, are flaws and doubts which can be removed only by con-
tinued and thorough histologic investigations of a large number of additional
218 ADDISON’S DISEASE
cases. Nevertheless, in judging these cases impartially, the impression is
received from the reports which have been published regarding the condition
of the nervous system, especially of the sympathetic, in Addison’s disease,
that there is decidedly more in favor than against the presence of important
disease of these tissues. This opinion coincides with the results of a later
English compilation (Thompson) ; here among 77 records which included
minute histologic investigations of sympathetic nerve areas, important changes
were noted in 60.
The question must now be propounded whether, by the aid of these anom-
alies of the nervous system, determined in a large series of cases, we can better
explain the atypical cases, in which, with true Addison’s disease (clinically),
no demonstrable adrenal affection is found to correspond. This question must
without doubt be answered in the affirmative. As regards the bronzing of
the skin it has already been indicated that for its development we must assume
an implication of the nervous system, especially vasomotor and trophic func-
tions, even in the cases with typical pathologico-anatomical findings. A
disease of the essential parts of the abdominal sympathetic and neighboring
nerve areas, and particularly changes in these processes with increased forma-
tion and transportation of pigment into the region of the cutis layers, may
be very readily conceived. In this connection we may point especially to the
spinal ganglion, whose influence in producing trophic changes of the skin,
according to clinical and experimental investigations, has at various times
been especially noted.
If then no additional knowledge concerning the connection of the adrenals
with pigment formation in the body is obtained by further investigations, the
pigmentation of the skin in typical Addison’s disease (as well as in cases with-
out demonstrable adrenal affection) will therefore probably be found related
to changes in the nerve areas in question. What then is the relation of the
other symptoms of the disease to the lesions of the nervous system? May they
also under these circumstances be referred to nervous disturbance? Up to a
certain point such an explanation does not appear unlikely: the characteris-
tic lumbar and epigastric pains of Addison’s disease are almost the same as
those which have long been referred to irritation of the abdominal sympathetic
ganglion. Furthermore the intestinal symptoms may be explained by irrita-
tion or paralyses of the abdominal nervous system, particularly of the splanch-
nic nerve, and the cachexia and other general symptoms may be in part
referred to nutritive disturbance due to changed gastric and intestinal func-
tions. Naturally the picture of this general disturbance (even without con-
sidering the pigmentation) remains a peculiar one, such as we are not accus-
tomed to see in most cachexias. And if we look upon the symptoms of the
disease as a result of disturbed suprarenal function (particularly the charac-
teristic muscular weakness), there would be no barrier for the assumption in
these cases of a functional disturbance of the adrenals as a consequence of
disease of the nervous areas which influence glandular activity.
That such a disease of the nervous system, without (or only with a sec-
ondary) implication of the adrenals, is capable under certain circumstances
PATHOLOGICO-ANATOMICAL CHANGES OF THE NERVOUS SYSTEM 219
of producing the picture of the disease, is evident from the rare cases which
have been cited in which compression of the solar plexus, of the splanchnic
nerves, etc., by tumors (aneurisms and the like) has been the basis of Addi-
son’s disease. But how often a similar affection of the nervous system is also
present (perhaps late, perhaps from the outset) in the cases running their
course with adrenal affection, cannot be decided at this time on account of our
insufficient knowledge regarding the nervous findings. The usual course of
the common affection will probably be this, that the affection, mostly inflam-
matory, starting from the adrenal attacks the surroundings; that is, first, the
semilunar ganglion, later, the other parts of the sympathetic, eventually, the
cerebrospinal nervous system. The frequency of this course of the disease
is suggested also by the fact that those adrenal lesions in which there is an
insidious inflammation or some similar process which attacks the adjacent
areas are especially apt to cause Addison’s disease. To this category belong
especially the tuberculous affections of the adrenals, most of which probably
depend upon atrophies due to older inflammatory processes; also certain
tumors which cause metastases. With the majority of single tumors of the
adrenal glands, therefore, there is no Addison’s disease, and in the rare cases
of adrenal tuberculosis without Addison’s symptoms, disease in the surround-
ings of the organs has, as a rule, been absent.
Whether, however, the form of disease with the characteristics of Addi-
son’s disease, which, starting from the adrenal attacks the surrounding areas,
does not also perhaps cause certain changes within the affected nerve areas
so that they may develop independently, we cannot say on account of our lack
of pathologico-anatomical knowledge. It must be assumed that under some
circumstances an analogous but independent disease of the nervous system may
take the place of adrenal disease and produce the same clinical picture entirely
without implication of the adrenals or with only a late involvement of the
glands.
Physiologic experiments have failed to determine the matter in question.
It is true that repeated experiments by extirpation (also cauterization) of the
semilunar ganglia have been attempted without, however, furnishing definite
conclusions: Previous experiments of this kind (Foa) have been entirely with-
out result; and in a more recent series of investigations (Lewin and Boer)
in animals which lived thirty days or longer after the operation, only paresis
of the intestines, usually with diarrhea, but with no pigmentation or other
characteristic changes, was noted.
The researches next to be mentioned relate chiefly to cases of Addison’s
disease (with autopsy) in which the adrenals were not implicated, but, on
the other hand, certain nerve areas were attacked. A few other cases remain
in which the autopsy shows no important changes in the adrenals and none
in the nervous system. The number of such cases is small, and from this
group many must be excluded in which the diagnosis is questionable. Of
those remaining it is not quite certain from the reports that all of the nerve
areas were considered in the investigation and that it was sufficient to exclude
any disease. Whether, and how often, cases of this kind exist, minute histo-
logic examination of similar doubtful cases must in the future decide. If we
220 ADDISON’S DISEASE
admit their occurrence, they cause great difficulty in explanation; for to
assume a functional disturbance of the affected nerve areas, and perhaps also
of the adrenals, without any anatomical substratum, would be very unsatis-
factory. It may be assumed, however, that cases of this kind will always
remain rare exceptions. ; :
The group of cases in which adrenal disease is present without Addison’s
symptoms, particularly without bronzing of the skin, does not belong, as has
already been stated, to the disease we are considering. Nor does it offer im-
portant reasons to vitiate the views which have been expressed above. In the
first place, we usually find in such cases affections of the adrenals which are
in marked contrast to typical cases of Addison’s disease: The majority of
them are tumors of the adrenal glands and the absence of Addison’s symptoms
is here the rule; thus a recent compilation of 26 cases of primary malignant
tumors of the adrenals showed that the clinical picture of Addison’s disease
was invariably absent. In most of the other cases of this group it remains
uncertain whether by tumor formation or other disease of the parenchyma of
the adrenals the destruction is as marked as is the rule in most cases of tuber-
culosis; the areas surrounding the glands also appear to remain comparatively
free. Finally, in explanation of these cases, an abnormally great development
of the accessory adrenals may be thought of.
I believe the considerations above adduced will suffice to make it obvious
that, according to the pathological and clinical material at our disposal, the
clinical picture of Addison’s disease does not depend exclusively upon a grad-
ual destruction of the adrenals, nor exclusively upon a disease of the nervous
system (i.e., the abdominal sympathetic and other nerve areas intimately
associated with it), but that both these factors are simultaneously active in
the development of the symptom-complex—a view in which I coincide with a
number of earlier as well as more recent investigators (Fleiner, Neusser and
others). How these forms of the disease merge into each other is very difficult
to determine, and varies evidently to an extreme degree. A particularly fre-
quent connection, according to the views mentioned above, appears to be a
kind of ascending disease, which spreads from the adrenals to the neighboring,
and, eventually also, to the more distant nerve tracts; that, however, opposite
(descending) processes are also at work is at least likely, and has been men-
tioned previously. Moreover, there need be no parallelism between these
pathologic processes; on the contrary, in well advanced changes of the adrenals
very slight implication of the nerves may be found, and vice versa; in quite
a number of cases according to present experience, the disease of one or both
parts may be entirely absent. By this variation in the relations of the diseased
areas, we may very readily explain the great variation in the intensity of indi-
vidual symptoms and in the time of their appearance, so that, for example,
the bronzing of the skin may occur years before the general symptoms, or,
rela the general disturbance may exist for a long time without pigmen-
ation.
If a definition of the pathologico-anatomical basis of Addison’s disease is
desired it may be given in the following form: The disease depends upon an
insidious, partly inflammatory, partly degenerative affection (most frequently
PATHOLOGICO-ANATOMICAL CHANGES OF THE NERVOUS SYSTEM 22]
dependent upon tuberculosis), which implicates first the parenchyma of the
adrenals and, secondarily, certain nerve areas which are in intimate relation
to the adrenals (particularly the abdominal sympathetic and some nerve areas
connected with it, perhaps also certain portions of the spinal cord). Since
disease of both of these regions may be combined in various ways, and may
also compensate for one another, the peculiar general affection develops which
represents what is characteristic of Addison’s disease.
I believe it is impossible to explain in a more definite manner the nature
of this general disturbance on account of the missing links in our present
knowledge. From experimental investigations, and also from the clinical
observations which have been outlined, it is evident that from disease of the
adrenals a deleterious element appears in the organism, and many theories
have been offered to explain the nature of Addison’s disease. Almost every
one of these is plausible up to a certain degree, but not proven; and almost
all explain only a few of the important phases of the clinical picture. Which
of these is to be accepted as the most reasonable is merely a matter of
opinion in the present status of our knowledge. I need indicate only a few
of these: They may be divided in general into. the “toxic” and “nervous”
theories, according to whether the changes in the adrenals or those in the nerv-
ous system have been assumed to be the more important. Of the first group,
recent experiments have made it seem probable that after extirpation of the
adrenals the development of substances resembling muscle poisons takes place
in the organism. They assume accordingly that the normal “ antitoxic action,”
which is said to be a function of the adrenals, declines or is entirely absent ;
hence the poisons circulating in the muscles and tissues are able to exert their
harmful influence. According to the views of others, the diseased adrenal
itself is supposed to furnish the toxins which, by their circulation in the fluids
of the body, produce the general affection. Other theories which consider a
regulation of cell nutrition to be the normal function of the adrenals ascribe
the disease to the development of toxic products by an abnormal activity of
the tissue cells which thus leads to the picture of a general intoxication. The
theory is plausible that, in consequence of the absence of the normal function
of the adrenals, a substance is missing in the fluids which should give to the
muscular fibers and other tissue elements the tonus necessary for their normal
functions. Opposed to this are the theories that the disease is one of the
nervous system, especially of the sympathetic, and that Addison’s disease
arises as part of a general trophoneurosis. Such views emphasize vasomotor
disturbances and an unequal distribution of blood in the body, whereby there
occurs a hyperemia in the area of the splanchnic nerve with anemia of the
peripheral parts; but these views are opposed by the absence in many cases
of well developed anemia. Between these groups of opinions are earlier views
according to which nothing but a general cachexia (which by some is desig-
nated as a tubercular cachexia) is said to be the basis of the clinical picture.
The disease is sometimes designated as an “ anematosis ” (Pepper) depending
upon a profound disturbance of blood production, but this view cannot be
accepted because of the small number of cases which show blood changes.
Many other theories might be mentioned.
222 ADDISON’S DISEASE
But I must repeat that the endeavor to propound such theories is, for the
present, not worth the labor. On account of the uncertainty which still exists
regarding the function, not only of the adrenals but also of individual areas of
the sympathetic nervous system, there is but little hope of following the
complicated pathologico-anatomical changes which produce the symptoms of
the disease. I believe it, therefore, to be correct to adhere to this view in the
explanation of the pathologic process: That the disease depends upon a patho-
logic modification or cessation of the normal relation to the organism of the
necessary functions of the adrenals and of the nerve areas which are inti-
mately connected with these structures.
The scant investigations at hand are naturally still open to doubt, and may
be modified or rejected after later researches. Whether, in the future, we
must be content with an explanation such as has just been given, or whether
we shall be able to determine the more minute pathogenetic processes in Addi-
son’s disease depends upon the results of continued investigations. In my
opinion, judging by what has preceded, these researches must be based
less upon physiological experiment than upon increased and minute histologic
investigation, especially in the areas of the nervous system that are implicated ;
we also need research in the field of the chemistry of the adrenals, of the blood,
and of metabolism. By histological study the question of the constancy of
a lesion of the nerves in Addison’s disease will be solved; by chemical research
the probable implication of the adrenals in pigmentation of the skin will have
to be decided. For histological investigation, the atypical cases without dis-
ease of the adrenals will be of the greatest importance. As such cases are
particularly rare, these advances in our knowledge will be very gradual, and
it will be all the more necessary, therefore, for us minutely to investigate each
available case in the future. ,
DIAGNOSIS
A few words regarding the diagnosis of Addison’s disease may be added,
particularly as the view has lately been expressed that diagnosis is not possible
during the life of the patient. Such a view refers of course only to the deter-
mination during life of the pathologico-anatomical changes which are ex-
pected in the adrenals, or (and this we must emphasize according to our
experience) in their surrounding areas, especially in the sympathetic nervous
system. The clinical picture of the disease in question, even when it does
not present itself in typical form, is usually not difficult to recognize. It has
previously been stated that this affection is very similar to many other discol-
orations of the skin combined with cachexia, for instance, to certain forms of
tuberculosis, carcinosis, malaria, pellagra, vagabond’s disease, and the like.
These affections, under some circumstances, may show similarity to the Addi-
son symptom-complex. But a longer clinical observation of most of them
will lead to a correct conclusion, since in these diseases (as has been mentioned
above) the pigmentation differs by certain irregularities, and by the absence . - -
of implication of the mucous membranes, from true bronzing of the skin,
and, further, because the symptoms directly referable to the suprarenal region
THERAPY 993
are absent. Above all, the correct. etiology may usually be recognized in the
other clifiical conditions. If, however, these pseudo-Addisonian affections can
be excluded, and if the true Addison symptom-complex is present, we must
remember the presence of changes which, according to experience, are fre-
quently present; viz., caseation of the adrenals, a presumption which may be
confirmed by the determination of tuberculous disease in other organs, par-
ticularly a moderately advanced pulmonary tuberculosis. In a similar man-
ner, in a small number of cases, secondary symptoms which favor carcinosis
or kindred affections may, perhaps, be combined with a palpable tumor in the
adrenal region, this directing the diagnosis to a malignant growth of the
adrenals. Only where both these forms of adrenal disease are unlikely will
the assumption of any other and rarer form of adrenal disturbance be justi-
fied. In all cases it must be remembered that, besides disease of the adrenals,
an affection of the surrounding nerve areas, particularly of the abdominal
sympathetic plexus, with a greater or less distribution to the central nervous
system, may be present; that moreover under some circumstances, these dis-
eases of the nervous system may take the place of the affection of the adrenals;
and that, finally, in rare exceptional cases, both may be absent. That the
finding of the latter cases, however, is not opposed to the clinical diagnosis,
“ Addison’s disease,’ I need not reiterate.
On the other hand, the cases of profound adrenal degeneration without
the symptoms of Addison’s disease, particularly without bronzing of the skin
(which are not very rare), will generally be impossible of diagnosis, That
these do not belong to Addison’s disease, in the strict sense of the term, I
have already stated. Lately it has been proposed to differentiate them by
the term “adrenal insufficiency.” Only in instances in which the disturb-
ances point definitely to the adrenal region, and particularly where palpation
shows a tumor or other abnormal condition in this area, can this type of
disease of the adrenals be suspected. Where this is not the case, the picture
of a general cachexia is present, a picture which, as a rule, is not characteristic
enough to separate it from other constitutional disturbances.
THERAPY
The doubts which envelop the pathogenesis of Addison’s disease will natu-
rally also appear in the views which dominate the treatment of this affection.
Accordingly we note from the time at which the clinical picture became known
up to within the last few years but few endeavors to adopt a specific or method-
‘ical treatment of the affection, and these few have not been further developed.
Thus, by some observers, remedies such as faradization, hydrotherapy, amyl
nitrite, nitroglycerin (on account of its action in raising blood-pressure)
and transfusion have been employed and advised without having obtained
general recognition. In some of these instances, and by these methods of
treatment, a decided improvement is said to have resulted, and some cases
have been reported even as “almost cured,” and to have died only during a
relapse. There are intercurrent improvements to which I have already re-
ferred when discussing the spontaneous tendency of the disease to a fluctuat-
224 ADDISON’S DISEASE
ing course. In these remissions a cessation of all the clinical symptoms not
infrequently precedes the fatal terminal stage, but the improvement cannot be
looked upon as the effect of treatment. However, it is quite likely that such
spontaneous remissions may be favored and increased by active symptomatic
treatment and general hygiene.
That up to the present time no cure of a case of Addison’s disease has
been authenticated has already been remarked. The few cases which have
been assumed to be such by their observers are doubtful as regards the diag-
nosis. Under these circumstances, the opinion of Potain, who is said to have
seen a case cured and who believes that the disease in one-tenth of the cases
is curable, is incomprehensible. Similar doubts are expressed in regard to
a case recently reported (by Oestreich), which is looked upon as an “ operative
cure” of Addison’s disease, and which I shall briefly mention: In a woman
whose pulmonary apex showed the symptoms of an old focus of infiltration,
and who suffered from marked cachexia, there was difficulty in digestion, gas-
tric and lumbar pains, and a tumor the size of a small apple was found in the
gastric region. This was removed, and after a good recovery from the opera-
tion the symptoms of the patient disappeared, strength increased, and in the
following nine months she was looked upon as well. The tumor was found
to be a tuberculous, degenerative adrenal organ surrounded by a fibrinous cov-
ering; the medullary substance of the organ was almost entirely destroyed.
That in this case extirpation of the tuberculous adrenal led to recovery cannot
be doubted; but unilateral, adrenal tuberculosis with cachexia and gastric
disturbance is not Addison’s disease; and that the patient without an opera-
tion would have succumbed to Addison’s disease is open to doubt.
Thus, until recently, the symptomatic treatment of the clinical symptoms
has been the only therapeutic indication in Addison’s disease, and besides
observation of the gastric and intestinal symptoms (in which we were warned
quite properly against the use of extremely active or drastic remedies, as by
this means uncontrollable diarrhea may be produced), on account of the promi-
nence of the asthenic phenomena, the use of tonics was the main indication.
Iron and arsenic here played an important réle, and I must mention that in
the two cases observed by me the longest quiescence of the disease with transi-
tory improvement of all the symptoms, also of the discoloration of the skin,
occurred after the continued use of Fowler’s solution in large doses.
An advance occurred in the treatment of the affection when the study of
the internal secretion of certain organs, above all of the so-called blood-vessel
glands, was combined with an attempt to introduce organotherapy. In fact,
a malady such as Addison’s disease, in which evidently in the majority of
cases the main and occasionally the only known pathological basis consists in
the destruction and gradual functional deterioration of a blood-vessel gland
necessary to life, appeared to be particularly suitable for the modern therapy of
compensation. Theoretic and experimental investigations, above all the trials
with injections of suprarenal extract in animals, already mentioned and
described, show the conspicuous and important actions of this secretion. I
shall only add that in these animal researches the value of adrenal therapy
was in part directly confirmed: thus in experimental animals, after bilateral
THERAPY 925
renal extirpation, life could be prolonged for twenty-four hours by injections
of suprarenal extract (Andersson and Hultgren). Moreover, experience
proved that in disease of the thyreoid gland, which may be looked upon as an
analogous condition, by a simple substitution therapy, the deleterious conse-
quences of the absence of the thyreoid could be combated, and a fatal general
affection, such as myxedema, could thus be transformed into a harmless con-
dition. Therefore, it is not surprising that in the last eight or nine years,
following the English physicians, various investigators have attempted to
employ suprarenal therapy in Addison’s disease, in which either the gland in
substance or preparations obtained from the glands were introduced into the
body. Besides the amelioration or cure of the affection, they hoped in this
manner to demonstrate, more conclusively than by the animal experiments,
the direct dependence of the disease upon the disappearance of the adrenals,
and also to show that the physiology and the pathology of the adrenals were
directly analogous to the thyreoid gland and athyreoidism.
Unfortunately the results of suprarenal treatment in Addison’s disease
have not justified these hopes. No cure of the disease in this way has been
recorded up to the present time. Yet a certain number of cases have been
reported in which by this treatment transitory improvement followed, and was
so conspicuous that it could not be disregarded entirely. Among these cases,
perhaps the most convincing are those in which, after cessation of the specific
treatment, an aggravation of the general condition occurred, and, eventually,
pigmentation of the skin followed; of these, two are particularly worthy of
mention :
Thus Schilling (1897) reports the case of a boy, aged fifteen, who was
ill for two years ‘and showed quite decided bronzing. For three months raw
adrenal substance was administered to him (a fresh gland from a sheep or
lamb daily). During this time an almost complete disappearance of the
abnormal pigmentation occurred (only a slight discoloration upon the mucous
membrane of the mouth remaining) and an increase in strength and of weight
(33 pounds) so that he was looked upon as almost well. After a three months’
cessation of the treatment, and following sudden symptoms of intoxication,
death occurred (perhaps in consequence of a beginning pneumonia). The
adrenals were contracted almost to cicatrices, and permeated by caseous foci.
More striking, perhaps, is the case observed by Edel (1900): A locksmith,
aged thirty-three, in whom the symptoms of rapidly increasing weakness and
bronzing, particularly of the face, dorsum of the hands, and penis, had existed
for six months without showing any remission. Suprarenal tablets were
administered (one gram each, two given twice daily), and after only two to
three days his strength began to increase, so that after fourteen days he was
able to return to work; moreover, the bronzed areas of the skin began to
improve from the third day of treatment, and five weeks later hands, face
and penis, with the exception of isolated areas, were again of a normal color.
After a month and a half of improvement, tubercular meningitis set in and
caused death in seven days. From the beginning of this complication the
adrenal tablets had been stopped, the bronzing reappeared, and a short time
prior to death had almost completely returned. The autopsy showed, besides
16
226 ADDISON’S DISEASE
distributed caseation of the glands, a tuberculous nodule in only the right
adrenal, while the solar plexus and the semilunar ganglion were embedded in
callous connective tissue.
In the study of such examples the previously mentioned tendency of cer-
tain cases of Addison’s disease to spontaneous remission with consequent fatal
exacerbation is to be remembered. But it must be admitted that here the
rapidity and the complete amelioration of the symptoms appears to be out of
proportion with what is observed in the spontaneous course of the disease.
Particularly, in the second case, the complete recurrence in a few days of the
dark bronzing of the skin can only be understood by assuming a preceding
artificial modification of the pigment metabolism of the body. It appears
that these two cases, and a few similar ones, are sufficient to prove the possi-
bility of a favorable influence upon the principal symptoms of Addison’s dis-
ease by the artificial introduction of suprarenal substance.
It is true that we have records of quite a number of cases opposed to these—
cases in which suprarenal treatment had no influence upon bronzing of the
skin, nor upon the general symptoms. And from the reports at hand I believe
that the number of these negative cases is at least equal to those in which
positive results have been obtained. Sometimes indeed a direct aggravation
of the symptoms has been noted from the beginning of this treatment. Nor
has it been possible to prove by chemistry that metabolism in the organism
is decidedly influenced by the introduction of adrenal substance. For even
though one investigator (Pickardt), after a nine days’ research in metabo-
lism in a case of Addison’s disease, during which time suprarenal tablets
were administered, found an increase of albumin decomposition, in an analo-
gous research by another investigator (Senator), nothing abnormal could be
determined. In the case of two dogs who were fed with adrenals (with the
raw gland as well as with the glandular extract) similar experiments showed
no decided change of the nitrogen balance (Blum).
Perhaps the form and amount in which the adrenal substance is adminis-
tered is important for its supplementary action. Apart from a few unsuc-
cessful or disastrous investigations with the implantation of animal adrenals
under the skin, the glands have been administered in a natural condition (as
fresh as possible), usually chopped up with necessary additions. They have
been occasionally given in q dry condition, as adrenal powder, but in most
cases they have been used as extract, which in rare cases has been subcutane-
ously injected, but has generally been given internally in the form of adrenal
tablets (particularly in England, but also in Germany and other countries).
The doses administered varied. according to the reports, with the fresh adrenal
gland, from one to two glands daily; with the extracts, an amount corre-
sponding to 0.2—4.0 of the dried glandular substance. It will be noted that
the best method of introducing the glandular substance has not been definitely
determined. Many further observations will be necessary to decide this.
The opinion expressed by some authors (for example, by Lewandowsky) that
the administration of the raw glandular substance is more effective than the
exhibition of the extract appears to be confirmed by a number of clinical
histories. But it must be pointed out that in the second of the cases men-
THERAPY 227
tioned above the conspicuous intercurrent improvement occurred after the use
of adrenal tablets. Whether an intravenous injection in man of suprarenal
extract, which has been advised, will produce a more intense action than other
methods, and whether it will not also produce dangerous symptoms, appears
to be questionable.
That the results by means of adrenal treatment in Addison’s disease are
no more definite and gratifying than those mentioned above is not surprising,
nor can they be looked upon as final. For, in the first place, the number of
investigations is much too small to determine this therapeutic question. I
estimate the number of cases that have been accurately reported as much less
than 100; and in most of these it must be remembered that there was oppor-
tunity for suprarenal treatment only for a short time, or only very late in the
course of the disease, so that the condition was an unfavorable one for therapeu-
tic results. Therefore a long continuance of observations will be necessary
before a definite opinion can be given regarding the value of organotherapy in
Addison’s disease, and to decide whether the apparent favorable results in
individual cases will be guaranteed by further observation.
But even if organo-therapeutic results should not improve with increasing
experience, this circumstance cannot be used to nullify the importance of
the adrenal function in the pathogenesis of Addison’s disease. The thera-
peutic introduction of adrenals from animals, or of extracts obtained from
these, can only substitute in a very feeble way for the secretion furnished by
the living gland in the human organism. Action similar to that which is
exerted directly by the adrenals upon the fluids of the body can hardly be
expected from the peripheral absorption (through stomach, skin, etc.) of the
finished products, especially since the latter, as all physiologico-chemical inves-
tigations have shown, are subject to great destruction in the tissues of the
body. Comparison with the remarkable action of the extract of thyreoid
gland which, even in the first investigations of substitution therapy was shown
to cure myxedema, should not lead us to expect similarly easy and surprising
results in all analogous investigations (even although they appear to be patho-
genetically well founded), since the physiologic and pathologie conditions in
many other organs are certainly much more complicated than in the case of
the thyreoid gland and its functions.
As regards the influence of organotherapy in Addison’s disease, we must
content ourselves for the present with stating that the experiences which have
been gathered are not sufficient to permit a conclusion. They are also insuffi-
cient to determine the likelihood of improvement or cure, or to decide theo-
retically whether or not the artificial introduction of adrenal secretion is a
proof of the adrenal theory in Addison’s disease. But neither do the reports
at hand require that we should cease to hope that further and more exact
therapeutic investigations will furnish better results.
From this, future observers may learn the practical lesson to test the
adrenal treatment of Addison’s disease upon every opportunity. If we begin
the treatment in individual cases as early as possible, and compare the influ-
ence of the various modes of administration, we shall gradually be able to
determine what to expect from this method of treatment, and to recognize
228 ADDISON’S DISEASE
whether there is any well founded hope of successful substitution therapy in
Addison’s disease. As in the pursuit of pathologico-anatomical knowledge
of the disease, so here a long time may elapse, as cases of the disease which
are especially suitable for favorable treatment are very rare almost all
countries.
Thus we see that in the realm of practical therapy in Addison’s disease
much is still obscure and much must be left for further investigation.
If we now return to the question at the beginning of this article, whether
according to present knowledge we may declare that Addison’s disease may be
explained by an absence of the adrenal function, we must give the answer
already indicated more than once, that for several reasons this is impossible.
The numerous experiments which have been carried out in clinical, anatomical,
physiological, chemical and therapeutic realms in the last half century to
determine the basis of the disease have given us much knowledge regarding the
clinical picture as well as in regard to many properties of the adrenals. But,
as we have seen, important links are absent for the explanation of Addison’s
disease as an affection of the adrenals alone. Hence, in disease of the gland
in combination with that of other organs, particularly of parts of the nervous
system, it now appears impossible to find this explanation without separating
the réles of these parts in the development of the definite clinical symptoms.
This conception will not appear strange to those who have endeavored to
explain the disease as a physiologico-chemical consequence of adrenal disease ;
and I believe it to be more satisfactory than the subjugation of the pathologic
process to a restricted theory which, at least for the present, leaves several
phases unexplained. Whether this view will be accepted in the future, or
whether the adrenal theory in a purer form will be found sufficient for the
explanation of the disease, will depend upon the results of future experience
and investigation. That these researches, together with our therapeutic en-
deavors, will in my opinion aid in the further explanation of the disease upon
a pathologico-anatomical and also upon a chemical basis has already been
indicated. Thus continued investigations in the interesting clinical picture
of Addison’s disease, and the elaboration of the previous observations, are
ties to the next decades of the new century as an object worthy of their
abors.
ACROMEGALIA
By C. BENDA, Beruin
THE erroneous idea that the gigantic is to be looked upon as an expression
of prehistoric times—primordial—is firmly rooted in the human mind.
When we think of the seas and forests primeval as inhabited by monsters
like the plesiosaurus and the megatherium we readily conclude that a primor-
dial race of gigantic people must have represented the survivors of the animal
kingdom who vanquished these leviathans. We are content with the réle of
dwarfed epigones, and in the specimens of unusual size occasionally seen we
acclaim the revival of this primordial power. Science has proven these fan-
tasies to be incorrect. We can prove, or at least infer, that prior to these
giant beasts, as well as to-day, there existed prolific races of smaller beings.
Prominent scientists assume that the original forms of the vertebrate animals
were dwarfed forms. Nothing conflicts with this hypothesis, and much
favors the probability that the apelike proanthropos also, and some at least
of the earliest races of man, were dwarfs, even though other primordial races
may have early attained a larger structural development. Thus our views
regarding giants have been fundamentally changed, since it is unlikely that
giants are to be considered as atavistic or primordial types. In the year 1872,
Carl v. Langer first proved by careful studies that besides a normal form of
giant skulls a pathologic one may be distinguished. To-day the opinion is
expressed that giant growth is commonly the result of a pathologic process.
This change of conception is intimately associated with our increasing
knowledge of that process of pathologic growth which is the subject of
this article—acromegalia. The investigations of Pierre Marie in the year
1886 are to be regarded as the foundation for this knowledge. Although cases
of the disease had been observed prior to this time and to some extent well
described, for instance, by the Italian Verga, it was, as Sternberg says, the
labors of the French investigator that introduced the disease into the clinic
from medical monstrosity and curio cabinets. Marie characterized the affec-
tion by means of the peculiar symptoms which had also been noted by other
observers, and of which now one, now another, proved most interesting. He
also worked out the principal clues for the differentiation of this process from
other affections which had some symptoms in common with it. Marie deserves
still further credit for giving to the disease its characteristic, euphonious, and
easily remembered name, for we must remember how readily the human mind
adheres to a scheme, and by adopting a distinctive name grasps the
conception which the name embodies. Nevertheless there = an impor-
2
230 ACROMEGALIA
tant point, not brought out in the name, which must be borne in mind
if the pathologic process and the autopsy finding are to be accurately remem-
bered: It is not the size of the extremities which represents the most striking
symptom of the disease, as might be concluded from the name; it is the
enlargement, the abnormal, disproportionate growth of these parts. If
Cyrano de Bergerac, besides his celebrated nose, had had large hands and
feet, regarding which history probably gives no reliable reports, this would
not have been a sufficient reason for calling him acromegalic, provided he had
had these deformities from birth, or by heredity. In contradistinction to some
descriptions (even very recent ones) of “unquestioned” acromegalic symp-
toms in the bony skeleton, it must again be pointed out that the characteristic
symptom of the disease is not the unusual form of certain parts but their
advancing change, and that in any case in which anamnestic and clinical
data in regard to this symptom were absent only the existence of all the other
factors and the resemblance to the picture of acromegalia can be considered
presumptive evidence. This is a concession to clinical medicine which re-
quires a certain amount of self-denial on the part of the pathological anato-
mist, but the ‘historical honor must in this case be accorded to the clinician
who founded the conception of the disease.
By Pierre Marie’s pioneer labors, by the long series of his thorough in-
vestigations and by those of his pupils, as well as by a great number of clinical
and pathological researches in which the most prominent scientists have taken
part, such an exhaustive description of the disease has been given that it
may almost be regarded as complete. Excellent comprehensive treatises,
among which those of M. Sternberg are to placed in the front rank, have dis-
seminated this knowledge throughout the medical profession.
ETIOLOGY
The tendency to this disease is an unfortunate prerogative of early matur-
ity; one-half of all the known cases develop in the third decade of life. Less.
frequently cases occur between the thirtieth and fortieth years, and a few
begin later; rarely has an onset before the twentieth year been observed.
Special stress must be laid upon the point that the disease, although usually
beginning after the body has attained its normal growth, nevertheless occurs
at a time of life when there is still decided plasticity of the body, and the
form thus presented must be separated from that of the true senile period.
Both sexes are affected to the same extent, but in the cases that begin late
a decided predominance of women has been noted. The disease is quite rare.
I believe that, including the four typical cases upon which I held an autopsy,
I have had more cases than any other pathologist. These are included in
about 8,000 autopsies which I have seen in a service of eight years in the
Urban Berlin Hospital; curiously, three of these cases occurred in a period of
thirteen months from March, 1896, to April, 1897, and only one occurred
before or after this period.
As may be seen from the previously mentioned observations of v. Langer,
there are obvious relations between acromegalia and giant growth since it
ce mae Ie eee ee
SYMPTOMS 231
appears that acromegalia most frequently attacks individuals characterized
already by great bodily size. According to Sternberg 20 per cent. of the
“ giants” are attacked by acromegalia. Among my four cases two were above
medium size. But, as is noticeable from the figures, the relation is not a
necessary one. At this point I should like to call attention to the fact that
in the skeleton of a dwarf which is in the Berlin Pathological Museum, and
which I had an opportunilty of-examining through the kindness of Professor
Waldeyer, I found suspicious acromegalic stigmata, so that, with all due regard
to what has been expressed above, I may presume that even dwarfs are not
exempt from the disease.
The cause of the disease is enveloped in obscurity. Of course trauma and
psychical emotion, as in all diseases which involve the nervous system, are
mentioned as starting points by the patients and their relatives, and are sug-
gested as causes of the affection.
SYMPTOMS
The onset of the disease is accompanied by very various neuropathic phe-
nomena. There are reports of extreme lassitude, of drawing pains and pares-
thesia in the head and in the extremities; in short, mild symptoms such as
almost every patient, whatever his disease, will admit if they are suggested to
him, such also as almost any healthy person will also acknowledge. Of impor-
tance in women is the invariable cessation of menstruation, and in some males
the appearance of impotence.
The peculiar changes, as a rule, are first noticeable in the face. A distor-
tion of the features occurs which renders the patient unrecognizable to his
nearest relatives, and this in a few cases can also be objectively shown by
photographs taken prior to the disease if the pictures and the patient are
brought together for comparison. I must further take this opportunity to
warn physicians against photographs of acromegalic patients. I regret that
I must sow the seeds of doubt in what the laity believe to be the absolute art
of photography, but I am a photographer myself, and I know how the products
of this art are attained. Besides pathologic acromegalia, there is also (as I
must reveal) an artificial one, which in portraits by novices in photography
is almost epidemic. This always occurs when a picture is taken of the entire
sitting figure, full face, with arms and legs extended. This depends upon a
simple perspective effect due to the use of photographic objectives of short
focus, and to our habit of placing the object at a very short distance from
the camera as is necessary to obtain large pictures. The first cause of this
faulty perspective is the misplacement of the object, which is seen in almost all
pictures of acromegalics that are known to me. In such pictures full face
reproduction, similar to that of the statues of Egyptian kings, has almost
become typical. How far the other effects of this faulty perspective extend
can only be determined by pictures in which the distortion, even of a single
extremity, is recognizable at once, as in a picture in my possession, in which
the extended great toes are almost as broad as all the rest of the foot. The
photographer has unconsciously intensified the impression of the abnormal-
232 ACROMEGALIA
ity that is to be depicted; if he had used a normal hand as a comparison for
the pathologic condition he would have perceived that the former, to make
the comparison possible, would have to be brought the same distance from
his apparatus as the latter, and not be left perhaps half a yard behind, as was
the case in the picture portraying the condition of the feet.
But, to return from this digression, aside from this little photographic
trick, a practised eye is not necessary to note in the advanced stages of the
disease the very characteristic condition of the face. The prominent super-
ciliary ridge, with the bushy eyebrows which occasionally almost meet in the
median line, gives the face a threatening expression; the swollen lips, the
very prominent zygomatic arch and the lower jaw give a somewhat bestial ex-
pression, and the enormous nose with its grim humor forms the only redeem-
ing feature.
A similar and progressive deformity in the extremities gradually becomes
noticeable. The feet become plump, larger, and broader, and the hand which
is deformed till it is like a bear’s paw appears especially conspicuous. This
impression is further increased by the comparative slenderness of the lower
arm. The X-ray picture shows that the bones are covered with exostoses;
these are particularly noticeable at the end phalanges of the fingers and toes.
According to Pierre Marie two forms of alteration of the hand are to be
differentiated, one of which consists in a general enlargement, the other in a
thickening of the bones of the hand. In the latter the exostoses are more
prominent.
Regarding the enlargement of the internal organs, one above all others
becomes clinically conspicuous, and must be counted among the most impor-
tant and constant symptoms of the disease—I mean the tongue, which
may assume extraordinary dimensions. In some cases closing of the mouth
is no longer possible. Enlargement of the thyreoid gland is often rec-
ognizable.
Of great importance, but not always present, are the symptoms which
point to a tumor-like enlargement of the hypophysis. These symptoms are
principally those of a basal cerebral tumor, but from the description of the
autopsy finding we shall readily understand that these symptoms need not
occur, even in very large tumors of the hypophysis, so long as the tumor does
not invade the cavity of the skull. In many cases the symptoms in question
are, however, well developed. They consist, first, in severe headache which
occurs in paroxysms, vertigo, vomiting, decrease of intelligence and, in par-
ticular, somnolence. The direct pressure of the tumor of the hypophysis acts
most constantly upon the optic nerves, or upon the optic chiasm, and shows
itself in hemianopsia, amblyopia even to amaurosis, due to atrophy. of the
stretched and compressed optic neryes. More rarely the muscles of the eye
are implicated, especially those supplied by the oculomotor nerve. At this
point I must also mention exophthalmos which has been observed in many
cases, and which is usually referred partly to the change in the bones of
the orbit, and partly to enlargement of the bulbus oculi. I believe, how-
ever, that the fact that acromegalic exophthalmos occurs periodically may best
be explained by the assumption that it is not due to organic changes in the
SYMPTOMS 233
cavity of the eye, but to stasis in the sinus cavernosus, as might readily occur
from the pressure of a hypophyseal tumor.
How many of the general nervous disturbances are to be referred to the
tumor, and how many to an independent disease of the nerves cannot be accu-
tately determined. But among other symptoms I must here refer to the
prominence of general nervous phenomena, such as pains, weakness, sensa-
tions of heat and the like. An important réle is played by increased secre-
tion of sweat, polydipsia, and polyuria, which in many cases are probably
the sign of a co-existing diabetes. Occasionally, however, they certainly
occur without this condition. In the further course of the disease a conspicu-
ous loss of strength is observed, and nephritis and myocarditis often super-
vene, so that we find the picture of a severe general intoxication. Death results
in such cases either from paralysis of the heart or from bronchopneumonia.
A remarkable and frequent complication of the disease is diabetes, which,
for example, occurred in two of the four cases observed in the Urban Hos-
pital, and in one of the patients was the cause of death by coma. It is ques-
tionable whether the diabetes of acromegalics is to be ascribed to the pre-
viously mentioned symptoms of intoxication, or whether it is directly due to
the tumor of the hypophysis. I incline to the latter view, for in the two
cases in which the largest tumors of the hypophysis were found by us it was
present, and disease of the pancreas was absent. Not infrequently the tumor
of the hypophysis causes death by edema of the brain. Finally, in a disease
which runs such a slow course it is not remarkable that intercurrent affec-
tions in no way related to the main disease frequently cause death. For
example, in one of our cases a perforating peritonitis, complicating cancer of
the stomach, led to the fatal issue.
The symptoms most dangerous to life are the immediate effects of pres-
sure from the tumor of the hypophysis, and those which present the general
symptoms of intoxication. This is favored, as J may mention here, from
a clinical standpoint, by the great importance of disease of the pituitary
body, and also by the fact that in all the cases mentioned in literature in
which death occurred in a short time without any intercurrent affections,
the phenomena of the tumor of the hypophysis were most prominent in the
clinical picture, and the autopsy always showed an extremely large tumor.
Even though one may not agree with Sternberg’s view that these cases are due
to a special type of tumor (see below in the account of investigations by
Hanau and myself), the claim of Sternberg must be recognized that these
cases are to be differentiated as a “ malignant ” form of acromegalia. My only
objection is that Sternberg defines this differentiation by such an arbitrary
mark—the duration of the disease for four years. I do not doubt that at
least one of our cases, the case of A. Frankel, who after six years succumbed to
the disease without complications, must also be included in this “ malignant “s
group. Another of our cases of the same duration would also be included
here if we assume the fatal diabetes which existed in this case to be a symptom
of the tumor of the hypophysis, as I unquestionably do. It is somewhat arbi-
trary, therefore, to divide the other cases, as proposed by Sternberg, into an
“ordinary” and a “benign” form, as they may last thirty, or even up to
234 ACROMEGALIA
fifty, years. It appears to me more rational to regard as malignant or acute
all cases which pursue an uncomplicated and progressive course leading to
death. In this type of disease the cases on record show that a duration of
about six years is the rule. It is best to regard as benign or chronic all cases
in which death is probably caused not by the acromegalia but by complications
which are not connected, or but slightly connected with the main disease.
PATHOLOGY
A somewhat wider, but by no means complete knowledge of the nature of
this remarkable disease has been obtained by autopsies and microscopic investi-
gations, of which quite a number are already at hand. Beginning with the
skeleton, we shall first direct our attention to the bones of the hands and feet,
which form the nucleus of the astonishing anomalies of growth that appear
during life. It is unquestionable that the bones in many of the cases that
have been described showed great enlargement. A case lately reported by
O. Israel is a prominent example of this kind. I believe, however, that in
most cases a sensation of slight disappointment cannot be suppressed when
the skeleton of the hand or foot is compared with our recollection, or, better,
with a plaster cast of the fleshy member. Above all we are then convinced
that the most prominent disturbance of proportions in many cases has almost
disappeared, and only minute comparison with normal skeletons will enable
us to note the abnormalities. The flattening and irregularities of the end
phalanges, which at the onset attract attention, as Sternberg correctly states,
are but slightly different from the normal skeleton, but it appears to me that
in acromegalia, they are found somewhat more constantly than in normal
skeletons. In a foot in our collection the second phalanx of all the toes from
the second to the fifth is somewhat elongated. Otherwise, however, only the
insertions of the muscles and tendons are roughened, thickened and covered
with osseous proliferations. It is these which at first sight give the impres-
sion of gross deformity. Upon minute investigation we discover smaller exos-
toses, irregular porosities of the cortical layer, bony outgrowths upon the ends
of the joints and the like, but we must admit that even all of these collectively
cannot produce the picture of the “bear’s paw,” as we see it in life. The
same impression is conveyed on examining the long tubular bones of the ex-
tremities, as well as those of the trunk. Everywhere the important point is
the decided roughness of the insertion of muscles which have proliferated;
otherwise the bones show only moderate change in form. As an exception I
must mention the clavicle, which in most cases of acromegalia shows a decided
increase in bulk. But we must not permit ourselves to be led astray by occa-
sional investigations of individual bones. One femur in our collection shows
enormous thickness, but it belongs to Stadelmann’s case, and must be correctly
looked upon as a combination of acromegalia with gigantism, and may be
entirely independent of the former disease.
The vertebral column occasionally shows ankylosis of the vertebral bodies
by bony bridges, but the commonest lesions are the hyperostoses and exostoses
of the vertebral processes, which perhaps form the main substratum of the
PATHOLOGY 235
frequently observed kyphosis of acromegalics, unless, as Arnold supposes, it is
habitual and due to the weight of the head.
The lesions in the bony skull are of quite different significance. The roof
of the skull shows no gross changes except early obliteration of the sutures
and flat exostoses. Upon the base of the skull the sphenoid bone is of chief
interest, and always shows more or less deformity due to the tumor of the
hypophysis. Its upper surface almost always shows a widening of the fovea
hypophyseos, with disappearance of the dorsum selle. In other cases the
floor is decidedly deepened and eroded, so that the sinus of the sphenoid
bone is laid bare above. In several cases reported in literature, and in one
of our collection, the usure also involves the partition and the floor of the
sphenoid cavities so that a continuous bony defect is seen at the base of the
skull. Otherwise the inner surface of the cavity of the skull shows no con-
stant changes. The lower surface of the occipital bone is usually markedly
deformed by exostoses at the insertion of the muscles. In the skull in our
collection just mentioned, the external occipital protuberance hangs like a
bent plug. The frontal bone is greatly thickened, particularly at the squamous
base, so that the superciliary ridges stand out prominently. This thickening,
however, is not solid. It is combined with a widening of the air spaces which
may spread to such an extent that the frontal sinus extends throughout the
greater part of the squamous portion of the frontal bone. In the bones of
the face it is particularly the increase in size of the zygomatic arch and the
lower jaw which, corresponding to the deformities determined during life,
appears in the bony skeleton. Besides the gradual thickening and elongation
of the lower jaw anteriorly, exostoses at the insertions of the muscles are
noted. The upper jaw is much less often involved in this elongation; hence
the lower jaw protrudes. These changes which are clearly noted only in the
skeleton show that the shape of the living acromegalic’s skull must not he
called recedent and prognathous, as was common before Sternberg corrected
the view. In a skull in my possession the alveolar process of the incisor teeth
is implicated so that by an anterior curvature of the lower teeth it is opposed
to the projecting lower jaw.
The microscopic examination of the diseased bones shows only that we
are not dealing with a specific process, but with a deposit and absorption of
osseous substance occurring in the same manner as in normal development.
In this connection it may also be pointed out that according to the results
of Langer, Klebs, and Sternberg, the mysterious influence of the disease upon
certain portions of the osseous system may at least be in part understood
when we recognize that some of the changes are secondary to other and more
prominent alterations. This may be most clearly recognized upon the head.
“The marked development of the apparatus of mastication requires a strong -
foundation upon the head. This may be furnished through thickening of
the solid supports, or by dilatation of the hollow supports, or by an extension
of the weight over a larger surface. The first requirements are fulfilled by
the hypertrophied zygomatic arches, the second by the widened air spaces,
and the third by the general increase in the size of the bones of the skull”
(Sternberg).
236 . ACROMEGALIA
This author also attributes the changes in the vertebral column, in the
clavicle, in the muscular and ligamentous insertions upon the occiput to one
predominating factor, the increase in weight of the head. This view is more
reasonable than that which explains the pathologic process as due to a gen-
eral irritative growth of bony tissue. There is another beautiful proof of
Sternberg’s theory which, so far as I know, has not been noticed by former
investigators. The pneumatic spaces in the bones of the skull are produced
by an absorption of the bony substance. The bone is of the same type as that
found in the so-called “ functional ” bony structures which are best recognized
in the spongiosa, and which become modified by the slightest pressure or the
slightest added weight of the bones so as to produce a structure suited to the
mechanical necessities of the situation. Since the functional structures in
acromegalia (the frontal sinuses) develop so enormously, we may look upon
this as a proof that the new formation of bone in these cases, unlike that in
leontiasis ossea, or in general hyperostosis, is not due to a pathologie osteo-
plastic activity, but is an adjustment to special requirements of the bone.
If, then, we accept Sternberg’s view, and suppose that such a secondary
bony proliferation accounts for the hypertrophy of the zygomatic arches, at
the base of the skull, in the vertebral column, etc., then the hyperplasia of the
apparatus of mastication, especially of the lower jaw, would have to be
assumed as the primary change. I, however, see no reason to stop here; I
think we may assume that the hyperplasia of the lower jaw is itself sec-
ondary, since this bone, too, shows throughout a uniform extension, so that
its deformities may be explained as chiefly the effect of an increased strain
on the insertions of the muscles and ligaments.
In this case the actual primary change would consist in an enlargement
of the soft parts, and especially of the tongue, which may be considered respon-
sible for the position of the jaws from the fact that by its increased volume,
for which the oral cavity is no longer adequate, it exerts pressure upon the
jaws. In fact the macroglossia is a characteristic feature of the clinical pic-
ture, and to this I should like to ascribe a dominant réle in producing the
change in the face, including the soft parts, namely, the lips and the nose.
The tongue has repeatedly been examined microscopically by others as well as
by myself. A prominent part in the hyperplasia is made up by the mucous
membrane, which is completely covered with wart-like proliferations of the
papille which are also distributed in the sub-papillary layers. Within the
muscular strata broad, abnormal, connective tissue strands appear. Whether
the musculature itself is increased cannot be decided. From the examination
of my preparations I do not, however, concur in the view sometimes expressed
that degeneration of the muscular fibers is present. I was able, by new stain-
ing methods, to show the transverse striation with such clearness that I have
utilized the preparations of acromegalic tongues as objects with which to
demonstrate transverse striped muscles. I must assume, therefore, that de-
generation of the tongue muscles, like that more frequently mentioned in
the muscles of the body, must be accounted for as one of the late marantic
phenomena of the affection.
With Striimpell I shall mention the changes in the soft parts of the ex-
PATHOLOGICAL ANATOMY 237
tremities, as well as in the face, which have also been noted by previous inves-
tigators, and shall regard them as a feature more prominent than disease of
the bones. I have already mentioned how slightly in some cases the bones
take part in the enlargement. The principal mass of the so-called “ bear’s
paw” is formed by the soft parts, so that here the conviction is almost forced
upon us that the enlargement of the bones, the thickening as well as the
elongation, arises only secondarily as a support for the increased mass of
the soft parts, and that in the exostoses at the insertions of the ligaments and
muscles we may also recognize the reaction of the enormous increase in weight
which is to move the extremities. The hypertrophy of the soft parts, as we
may convince ourselves both macroscopically and microscopically, is due to
extremely tense connective tissue strands richly permeated with elastic fibers.
These first thicken from the cutis itself downward. Afterward, enlarge-
ment of the papille and thickening of the epidermis become visible. The
connective tissue proliferation is most massive in the subcutis, next in the
deep fatty layers of the hands and feet. Each fat globule appears to be sur-
rounded by its own thick connective tissue capsule, and connective tissue
forces its way also between the fat-cells in thick layers, although we cannot
recognize any decided atrophy of the fat-cells. In one of my cases I found
the fat globules permeated in many places by a loose fibrous connective tissue
rich in mucin. Nevertheless, by their outlines and by isolated, well preserved
fat-cells, the distribution of the lobules is still easily recognizable, also their
sharp line of demarcation from the tense connective tissue of the surroundings.
This remarkable condition of the fatty tissue accounts for the fact that, in
fresh sections, it exudes like a compressed filling, and gives the impression,
described by several authors, that the skin is too scant for its contents. The
sweat-glands and nerve trunks of the cutis and of the subcutis have their own
special thickened layers of connective tissue, and we may note in the cutaneous
nerves, what Arnold first described, viz.: that connective tissue forms between
the individual fibers. The degeneration particularly described by P. Marie
and Marinescu, I could find in only one of the cases investigated by me, but
I do not doubt that it is frequently a natural consequence of the previously
described alterations. The same may also be said of the muscles, in which
also the hypertrophy of connective tissue is probably the primary factor and
degeneration the occasional consequence. Besides these diffuse changes, fibro-
mata mollusca, papillomata, and abnormal pigmentation are also observed.
The sebaceous glands and the hair remain quite normal, nor was I able to find
any decided abnormalities in the vessels.
PATHOLOGICAL ANATOMY
Of the pathological findings in internal organs I shall first briefly men-
tion a number of the less constant ones. The internal organs may be impli-
cated in the hypertrophy so that splanchnomegalia has been spoken of. We
cannot, however, determine in these findings in how far the observers were
dealing with simple gigantism, and how far it was a progressive enlargement
caused by acromegalia. This doubt applies to the large kidneys and livers
238 ACROMEGALIA
of many acromegalics. In other organs, as in the heart and the spleen,
pathologic enlargements occur, yet they must not be looked upon as conse-
quences of the acromegalic process, but as independent diseases.
Corresponding to the clinical symptoms, the frequently determined hyper-
plasias or degenerations of the internal female genitalia and of the testicles
are perhaps in intimate relation to the pathologic process, while the cutaneous
parts of the external genitalia are frequently implicated in the acromegalic
enlargements.
In the pancreas, connective tissue hyperplasia has been described several
times. On account of the frequent complication of acromegalia with dia-
betes, we might easily interpret this as a result of the acromegalic process.
But in the cases investigated by me, particularly in the one combined with
diabetes, the pancreas was perfectly normal, while, in another case in which
connective tissue increase was present, diabetes did not exist.
The central nervous system, i.e., the base of the brain, may be involved
directly and to a marked extent by the tumor of the hypophysis, particularly
the infundibular region, the pons, and the optic chiasm. All other findings,
such as column degeneration of the spinal cord, represent only accidental
complications. In the cervical sympathetic, Marie and Marinescu found con-
nective tissue increase and ganglion degeneration, and this was several times
confirmed by other observers. In my cases I was unable to recognize decided
changes in this region. :
The chief interest of pathological researches has been concentrated for a
long time upon the so-called “blood-vessel glands.” Of these the thymus
gland first attracted attention for a short time after Klebs had ascribed to
it a predominant réle in the disease. The enlargement of the thymus gland
is, in fact, a very frequent finding. The gland may extend into the anterior
mediastinum, so as to correspond with that of the new-born, though in com-
parison it is actually larger. The adrenals are large but normal. The thy-
reoid gland may develop into a massive goiter, or may be decidedly atrophic.
The enlargement may be of any of the types usually found in goiters, without
any predominant specific form being recognizable. The degenerative forms evi-
dently have nothing in common with those characteristic of myxedema. In my
case the glomus carotideum was examined, and found to be small and normal.
In the pathology of acromegalia our greatest interest is in the hypophysis.
Since the first undoubted autopsy findings of Verga in a case of acromegalia,
the characteristic findings in the skeleton by v. Langer, and the observation
of tumors of the mucous gland (pituitary body), the autopsies in acromegalia
have been more numerous. In accordance with the size and character of the
tumor, the description of the findings varies. There are extant descriptions
of the pituitary gland which show that the authors did not consider this to be
at all enlarged, and we can only base our assumption of an enlargement upon
the fact that masses were mentioned as present. In other cases the enlarge-
ments are distinct, but only of moderate degree. Thus, in two cases, I have
found tumors about the size of a cherry, one of which eroded the groove of
the pituitary body and the other the dorsum sella. The enlargements are of
every degree up to the size of a goose’s egg or even an apple. These either
PATHOLOGICAL ANATOMY 239
develop downward and penetrate the entire sphenoid bone to the pharynx, as
in a case of Hansemann and in one of my cases, or develop upward and com-
press and displace the organs at the base of the brain, as well as the nerves
and venous sinuses situated upon both sides of the sella turcica. This has
been variously described; in one of my cases the development was upward and
also, to a slight degree, downward. The tumor invariably develops from the
anterior lobe of the gland, and in a few cases has been described as simple
hyperplasia of the gland. In other instances, adenoma or struma hyperplastica
of the gland is directly mentioned. Besides these, in still other cases, prolif-
eration, softening, cysts or connective tissue hyperplasia have been found.
Finally, in a great number of cases the tumors have been regarded as malig-
nant. Among these, isolated cases of gliomata have been mentioned. Claus
and van der Stricht found a lymphadenoma. The majority of malignant
tumors of the pituitary gland have been found to be sarcomata. Sternberg
has laid particular stress upon the fact that in the six cases of malignant
acromegalia which were known up to the time of the publication of his mono-
graph, the tumors were all sarcomata. In the meantime Gubler, in a case
of malignant acromegalia histologically investigated by Hanau, and I myself
in at least two cases, found tumors of the hypophysis which were similar to
the malignant variety, and which upon superficial examination might also
have been looked upon as sarcomatous. But we recognized the tumor cells
as originating from the epithelium of the hypophysis, and designated these
tumors as hyperplastic, and eventually as malignant adenomata. Hanau ex-
pressed the suspicion that in the cases described as sarcomata the same ade-
nomatous form of tumor was really present. I was able to demonstrate in
my four cases that the character of the tumor was in the main the same, and
that its origin could be found in the glandular epithelium of the anterior lobe
of the pituitary body. I wish to lay special stress upon a fact (also noted
by Tamburini) that in at least three of my cases, a large part of the tumor
consisted of a very peculiar form of epithelium, the “ granular cells,” which
correspond to the so-called chromophilic cells of Flesch. These are the cells
which are looked upon as the essential functionating cells of the normal gland.
I presume that in every case of hypophysial tumor the hyperplastic prolifera-
tion of the cells is the basis for a neoplasm, and that, in the further course, a
malignant degeneration of the tumor starts in these cells; or a malignant pro-
liferation of other tissue elements may replace this primary new formation
and so destroy it.
When we consider the supposed importance of the hypophysial tumor in
the clinical picture of acromegalia, we must admit that it is by no means
free from objections. Several hypotheses in marked contrast to each other
may be mentioned. The most extreme (in one direction) assumes that the
tumor of the hypophysis is only a symptomatic enlargement of the organ
which may be markedly developed, slightly developed, or entirely absent. In
opposition to this is the conception that an abnormal function of the hypophy-
sis is the sole cause of the disease. A more conservative view ascribes the
disease to a primary anomaly of the “ blood-vessel glands,” among which the
hypophysis is to some extent implicated.
240 ACROMEGALIA
The question cannot now be determined with absolute certainty because
we must admit that it is not yet fully recognized that the hypophysis is dis-
eased in all cases of acromegalia. No less an authority than R. Virchow has
maintained from the beginning that the changes in the hypophysis are a sec-
ondary finding and were absent in some of his characteristic cases. A case
from Virchow’s Institute has lately been published by O. Israel, which appar-
ently proves this. These extraordinary differences in opinion can only be
reconciled by the fact that the differential diagnosis of the disease is by no
means so exact as might appear from the publications of P. Marie and Stern-
berg. It must be borne in mind that any of the individual symptoms of the
disease, the peculiar osseous growth, the changes in the soft parts, the macro-
glossia, and even the tumor of the hypophysis may occur independently.
Hence in many cases a difference of opinion may arise as to what symptom-
complex justifies the diagnosis of acromegalia. Virchow lays great stress
upon the changes in the bones of the extremities, and undoubtedly has fur-
nished incontestable proof, which is confirmed by the case of O. Israel, that
they also occur without a tumor of the hypophysis. This was also recognized
by Pierre Marie who diagnosticated a similar disease of the extremities as
hypertrophic osteoarthropathy.
T believe, however, that if we adhere to the name acromegalia for the
classical, clinical and anatomical symptom-complex of P. Marie alone, we
must admit that the changes in the soft parts and in the bones of the face have
‘at least as much importance as those of the bones of the extremities. In the
case of Israel clinical observation together with the autopsy findings in the
bone reveal, as the celebrated author himself emphasized, that other impor-
tant symptoms of acromegalia besides the tumor of the hypophysis were absent.
It appears to me most important that there was no record of the acromegalic
macroglossia and the corresponding deformity of the lower jaw. We may,
therefore, safely deny that this case is acromegalia, and must agree with the
author that it is inadvisable to deduce from it any far-reaching conclusions
as to the nature of acromegalia.
The fact is much more important that in literature quite a number of cases
are mentioned in which true adenomata of the hypophysis were found with-
out acromegalia. I still entertain the hope that by careful investigation with
the most approved methods we may find these tumors to deviate from the type
of those occurring in acromegalia. In a case recently examined by me, the
question arises whether the age of the patient, sixty years, might not explain
the absence of corresponding general symptoms. Opposed to the view that
the tumor of the hypophysis is a symptom and not the cause of acromegalia
is the fact that the common type of hypophysial tumors differs from the normal
structure of the gland (as was especially apparent in all of my four cases which
were minutely investigated) as well as from the other acromegalic hyper-
plasias, which in the main are composed of connective tissue.
The opinion that disease of the hypophysis produces the symptoms of
acromegalia only by co-operation with the other blood-vessel glands is not in
accordance with the fact that no other blood-vessel gland is so constantly
involved in the disease as the pituitary body. Indeed this is not even approxi-
PATHOLOGICAL ANATOMY 241
mately the case. The symptoms which have been recognized as consequences
of diseases of the other blood-vessel glands are generally absent in the clinical
picture of acromegalia; or, if they do occur, they represent distinct compli-
cations, and the characteristic changes of acromegalia are not produced by
disease of any of them. Finally, the especial, peculiar, histological structure
of the hypophysial disease favors the opinion that this plays a réle entirely
different from that of the other blood-vessel glands,
In so far as we can arrive at logical conclusions by exclusion and without
experiment, we may maintain the view which was first expressed by Pierre
Marie that disease of the hypophysis is the etiologic factor in acromegalia.
We will now consider in what manner the hypophysis causes the disease.
The original view of Pierre Marie that the changes are due to an absence
of function of the degenerated hypophysis—as in myxedema by an absence of
function of the thyreoid—is not substantiated by our more exact knowledge of
the character of the glandular proliferation. Somewhat more reasonable and
better founded are the hypotheses of Hansemann and Uthoff, who hold that
the relation between the enlargement of the hypophysis and the affected parts
is an altruistic hyperplasia. In whatever way the progressive development of
the hypophysis is produced, in that way the progressive development of other
parts (extremities, bones of the face and internal organs) is also brought
about. According to Hansemann, altruistic hyperplasia may occur with organs
that have an embryologic connection, as between the anterior lobe of the hypoph-
ysis and the tongue, but we can hardly say that there is any such relation
between the gland and the extremities. This view becomes even less tenable
when it is clearly demonstrated that neither the changes of the hypophysis
nor those of the extremity represent simple progessive hyperplasia, and that
in both we are dealing with new tumor-like formations of entirely atypical
nature.
In my previously published articles, I have accepted the view of Tamburini,
as do also Hanau and Woods Hutchinson, that the pathologic development of
the hypophysis is due to a hyperactivity and over-production of the secre-
tion which is to be utilized internally. Tamburini, at any rate, attributes
the phenomena of growth to these causes, while the cachexia observed in the
later stages of the disease is regarded as a consequence of the adenomatous
and cystic degeneration of the gland. For several reasons this theory must
now be somewhat modified. First, in its original form, the division of the
disease into two phases is impossible. On the contrary, in the purest type
of acromegalia, Sternberg’s malignant form, the development of the tumor
of the hypophysis is unquestionably combined with symptoms of peripheral
hyperplasia and the injurious effects of this upon the entire organism. Tam-
burini’s theory is also difficult of acceptance because its adherents, as well
as its opponents, have been forced to the conclusion that if his views are cor-
rect, the secretion of the hypophysis must also influence the normal growth
of the body; Woods Hutchinson has gone so far as to declare that the hypophy-
sis is the center for body growth.
These difficulties lessen when the processes of peripheral growth are recog-
nized as constant but less important consequences of acromegalia (which is
17
242 ACROMEGALIA
clear to me), and the true nature of the disease is conceived as a tumor-like
formation in the connective tissue which, as Erb and Ponfick have already
pointed out, resembles that of elephantiasis and also myxedema. It might
be more easy to ascribe the symptoms of the disease to the action of a specific
toxic secretion which, under normal circumstances, possesses an unknown
function, and which is present in the circulation in such slight amounts that
no deleterious effect is produced. I refer to the zymogen-like granules secreted
in the chromophilic cells which, in at least three of my cases, I found enor-
mously increased, while in the normal gland their action appeared of less
importance. I believe it may be strictly maintained that if there is a lessen-
ing of the normal supply of the bodies to the circulation they may affect the
activity of digestion as profoundly as the blood plasma as shown by recent
investigations. Hence an over-production of them may cause severe damage
to the tissues of the body.
TREATMENT
In conclusion I shall refer briefly to the therapy of the affection. I have
only negative points to report, since, up to the present time, it has been abso-
lutely without effect. Yet a knowledge of the pathology of the disease may
prevent error in the choice of therapeutic measures. The uncritical way in
which organotherapeutic “curative” results have been published led, as a
matter of course, to the production of hypophysis tablets and their admin-
istration to acromegalics as soon as it became known that in acromegalia the
hypophysis appeared to be affected. Fortunately, it has been demonstrated
both by the use of these and by animal experiment that the administration of
the pituitary gland by mouth is quite harmless; we may assume that its
active constituents are rendered inert by the digestive fluids. Otherwise, we
would realize the unpleasant truth that this therapy must aggravate the dis-
ease by increasing the materia peccans. Until a hypophysis antitoxin is pro-
duced, the only rational treatment, based on the pathology of the disease,
must be the extirpation of the hypophysial tumor. We cannot understand
why the hand of the fearless surgeon who has dared to attack the neighboring
Gasserian ganglion should halt at this operation.
ran
? COP hs
%
CHRONIC ARTICULAR RHEUMATISM
By W. HIS, Base.
In attempting to describe a disease so familiar and commonplace as chronic
articular rheumatism (this appears to be the prevalent opinion in regard to
it), it is almost necessary to begin with a captatio benevolentiw. A few years
ago, when J began to study this disease somewhat in detail, I learned that it
had long attracted the attention of many scientists. The last of the greater
compilations, that by Pribram, although by no means exhaustive, contains
notes of over 500 investigations which refer to chronic articular rheumatism,
and among the authors are found the most prominent names in medical sci-
ence, of whom I shall mention Charcot, Bouchard, Lancereaux, Pierre Marie
in France, the Garrods, father and son, in England, Richard Volkmann,
Senator, Baumler, and Albin Hoffmann in Germany.
The disease is by no means a new one; it was familiar to the ancients
who confounded it with gout and designated it by the collective term arthritis.
It was not until the year 1800 that Landré-Beauvais expressly pointed out
that the disease was a distinct entity. Alfred Garrod in his celebrated book
on gout proved that the deposit of urate salts which is the materia peccans
in the joints affected by gout never occurs in chronic articular rheumatism.
Nevertheless, there are still some authors who, even in recent years, have
endeavored to merge the two diseases, believing them to be one. This attempt
is due to the fact that certain phenomena in the joints, and many of the
accompanying and subsequent symptoms in both diseases, may be the same;
we shall refer later to this point more in detail.
The manifestations of chronic articular rheumatism are very various, and
if the descriptions of different authors are compared with one another, it is
often difficult to believe that they are portraying the same disease. What
one experienced observer describes as a frequent finding, another, no less
experienced, has scarcely ever seen. Similar to this is the variety of opinions
in regard to the etiology; greater diversity of views can scarcely be conceived.
According to some authors, for instance, M. Schiiller and Bannatyne, chronic
rheumatism is an infectious disease in which there can be invariably demon-
strated certain microdrganisms; to others (Bouchard, Lancereaux) the disease
is the expression of a constitutional anomaly which is markedly hereditary,
running in families, and showing itself by numerous other symptoms. Other
writers believe that the affection is in the main a local process confined to the
joints and periarticular tissues. Finally, there are some who consider it a
disease of the central nervous system.
248
244 CHRONIC ARTICULAR RHEUMATISM
Just as diverse is the nomenclature. Almost every author has attempted
to arrange the varying pathological pictures in distinct groups (all mentioned
by Pribram), and of the names that have been chosen some refer to the clinical
course (for instance, Charcot’s rheumatisme articulaire chronique progressif).
some to the shapes assumed by the joint (arthritis deformans of Virchow and
R. Volkmann, rheumatisme noueuxz of Trousseau), some to the anatomical
findings (M. Schiiller’s polyarthritis villosa) and some to their authors’ etiolo-
gic views, for example, rheumatisme goutteux, diathésique (Pierre Marie) and -
infectieux (Teissier and Roque).
This confusion is increased by the fact that the same title is applied to
quite opposite pathological conditions. Thus, the rheumatisme déformant of
the French, with effusion, proliferation of the capsule, and ‘spindle-shaped
swelling of the joint, is identical with what the German surgeons and clin-
iclans (following R. Volkmann) call chronic rheumatism in contrast with
arthritis deformans, which is characterized by atrophy of the capsule and
proliferation of the bone, in many joints or in one alone (for example, the
malum senile cox).
This confusion can only be cleared up by describing briefly all the principal
types of joint disease.
1. When a young person, after brief prodromal symptoms or a tonsilitis
with fever, is attacked with painful swelling of the joints, the inflammation
spreading from one joint to another, affecting large and small joints alike,
and without predilection for any—when the endocardium, the myocardium,
the pericardium, the pleure, perhaps even the meninges are involved—we
recognize in this picture an infectious disease, acute articular rheumatism,
and we know that, as a rule, it runs its course without leaving permanent
changes in the joints. Exceptionally, however, swelling of one or more joints
and moderate pain and stiffness remain. After weeks or months the joint
function is more or less completely restored or the diseased condition becomes
permanent. This is chronic arthritis, resulting from an attack of typical
acute articular rheumatism.
Now as the primary forms of chronic arthritis may begin with acute
febrile attacks, their differentiation is often difficult. Davaine closely studied
the disease, and laid especial stress upon possible prodromes, splenic tumor,
visceral complications, the ease with which the effusion in the joint may be
displaced, the absence of trophic disturbances (atrophy of the muscles), and the
absence of family predisposition to acute articular rheumatism. Unquestion-
ably Davaine has arranged this in too schematic a manner, and, therefore,
in any individual case we may waver for a time in our decision; the occur-
rence qf secondary chronic rheumatism is, however, recognized by all later
authors.
2. The second form is prone to attack persons between thirty and forty
years of age. The disease is ushered in with fever and pains in the joints,
which are swollen but not to the same extent as in acute rheumatism. They
have an elastic, tense feeling, but fluctuation is obtained with difficulty; the
skin is slightly reddened, and is edematous above and below the joint so that
the affected joint shows a spindle-shaped swelling. Gradually new joints are
CHRONIC ARTICULAR RHEUMATISM 245
attacked or those affected improve, but a number of those first attacked always
remain permanently diseased.
The joints exhibit conspicuous regularity in the order of their involve-
ment. First, the smaller joints of the body are attacked; the phalangeal and
interphalangeal joints of the fingers with the exception of the thumb, the
corresponding joints of the toes, then those of the hands, of the elbows and
knees; the shoulder and hip are almost always exempt. The disease, how-
ever, shows a preference for certain joints which are usually spared by acute
polyarthritis, such as the jaw, the sternoclavicular joint and the sternocostal
joints. Secondly the affection is conspicuously symmetrical: Almost always
both hands, both feet, both knees are attacked; only the joints mentioned
above are, as a rule, attacked unilaterally. The further course of the disease
varies. Hither the joints return more or less to the normal, to be similarly
attacked after months or years (often acutely and with fever) or the affection
is “chronic from the onset,” and in time changes occur in the joints which
prefigure the third form now about to be described.
3. The third form generally attacks elderly persons, particularly women
during the menopause; the disease begins with indistinct nervous symptoms,
drawing or tearing pains, furry sensations or formication, sensations of cold,
etc., in the hands and feet. The patients notice that the motility of the
fingers gradually decreases. Fine movements such as sewing, knitting, writ-
ing, become difficult, particularly in the morning and during cold weather.
Careful observers note that the ends of the joints and the basic and inter-
phalangeal joints are slightly thickened; they feel hard and are not very
tender on pressure. The fingers gradually deflect toward the ulnar side, and
this is first noticeable in the proximal! joint with the extended interphalangeal
joints; finally complete subluxation results in the basic joint, though in this,
as well as the other changes, the thumb is rarely implicated. The inter-
osseous spaces show deep grooves; the ball of the thumb and little finger are
atrophied. The same changes take place in the toes. Muscular contractures
appear early and cause abnormal positions of the extremities. Charcot, with
his artistic mind, attempted to arrange these positions according to a system:
A flexion and an extension type (more correctly a hyper-extension type) each
type with several sub-varieties. If, with Vidal, we accept also an extension
type (straight line) every imaginable form results, and if we reflect that the
fingers of the same hand may present various types side by side, the value
of this schematic division will not appear great. Besides the muscular con-
tracture, changes in the joints add to the immobility; the capsule shrinks to
fibrinous strands, the surfaces of the joints coalesce by connective tissue liga-
ments, exostoses and ecchondroses appear: The final result in well marked
cases is complete immobility of the joints in abnormal positions; the unfor-
tunates are condemned to permanent invalidism, and fill a large part of our
almshouses and homes for incurables.
This form differs from the two first mentioned by its gradual and afebrile
1 These, however, although rarely, are sometimes attacked in acute polyarthritis ;
indeed, the jaw may be the only joint attacked (Hamm, Manasse),
246 CHRONIC ARTICULAR RHEUMATISM
onset, its slow course, the absence of effusion into the joints, cutaneous edema
and capsular swelling. It resembles them in a preference for the small joints
and in the conspicuous symmetry; moreover, every possible transitional form
occurs, so that they can only arbitrarily be differentiated. More correctly,
perhaps, we may call them different developments of the same disease. There-
fore I have not yet accepted the division which is often made (lately by
Curschmann) into chronic articular rheumatism and arthritis deformans, I
agree with Charcot, who designates the two as the exudative and the dry
form of primary chronic progressive polyarthritis.
4. The fourth form is characterized by appearing in elderly persons and
in the aged, by a markedly chronic course, by invariable limitation to one
or more large joints, and frequently, although not always, by its connection
with trauma. This is the arthritis deformans of R. Volkmann, the rheuma-
tisme chronique partiel of Charcot, the best known type of which is the malum
senile coxe. But this affection is not infrequently noted in the fourth and
fifth decades of life, most often, perhaps, in the shoulder after a fall or
contusion.
Effusion is almost always absent. When the patient is at rest the pains
are moderate or cease entirely; movement is limited to a great extent, muscle
contractions or, at least, constrained positions, generally occur and atrophy
is frequent (in the shoulder, mostly of the deltoid and triceps). Upon move-
ment, friction and cracking are heard and felt in the ends of the joints. After
the disease has lasted a long time deformities due to exostoses and ecchon-
droses invariably appear. These will be described below.
5. The fifth form includes the chronic, deforming and ankylosing dis-
eases of the vertebral column (Pribram). Julius Braun, in 1875, was the
first to collect a large number of cases. Striimpell described the implication
of the hip-joint in arthritis of the vertebral column. Pierre Marie in 1898
worked out the symptomatology of “ spondylose rhizomélique ” which appears
in men immediately after the completion of their growth, and consists in com-
plete adhesion of all vertebre, scoliosis and kyphosis of the shoulder- and hip-
joints, but with intact extremities. Another form was described by Bechterew
in 1892: Limited movement in the vertebral column with anterior curvature,
particularly of the upper parts; associated with this pareses of the muscula-
ture of the neck, trunk and extremities, and atrophy of the muscles of the
back and scapula. Common to both of these forms are nervous disturbances
—anesthesia and paresthesia, neuralgia, paralyses and muscular atrophies in
varying form and extent. The Striimpell-Marie form distributes itself from
below upward ; Bechterew’s variety from the shoulder to the hip.
In the meantime, in a large number of observations, particularly those
compiled by W. Anschiitz, it was noted that a sharp differentiation of these
forms is impracticable, that, on the contrary, numerous transitional stages
are observed. Some of these begin at the upper or lower end of the vertebral
column, with or without involvement of the joints of the trunk, or, finally,
in combination with chronic arthritis of the extremities in one or another
order. Joh. Miiller described a case with extreme stiffness of the articulations
of the ribs, respiration being maintained entirely by the diaphragm and the
CHRONIC ARTICULAR RHEUMATISM 247
abdominal muscles; Clarke described a disease confined to the costovertebral
joints of the twelfth pair of ribs. Anatomically the process produces changes
in the ligaments of the intervertebral sheaths and of the vertebral joints in
varying combinations (Schlesinger) ; the nervous disturbances are partly due
to compression of the nerve roots, partly to chronic meningitis (Bechterew).
Etiologically we must consider primary and secondary chronic arthritis, arthri-
tis deformans, gonorrhea, syphilis and other infections. Whether the affections
confined to the ligamentous apparatus and intervertebral sheaths are to be
classed as chronic arthritis may be questionable. Biumler calls attention to
the fact that stiffness of the hip-joints and lower vertebral articulations in
consequence of the patient’s increased weight may lead to disease of the upper
vertebre. R. Bennecke lays stress upon the action of frequent, though insig-
nificant, trauma upon the vertebral sheaths and bony structures. In conclu-
sion, similar clinical pictures are presented by contracture of the lumbar
Fic, 4.—Rinteen Picrurr Suowinc Heserpen’s Noprs upon THE INDEX AND LitTLE
FINGER, WITH ExosTOsES OF THE SECOND AND THIRD PHALANGES,
248 CHRONIC ARTICULAR RHEUMATISM
muscles and those of the back. Beer, Zenner, and lately Cassirer and Senator
have described such “ myogenous” vertebral stiffness, some of which may be
due to hysteria and some to acute fibrous myositis.
These conditions indicate that chronic rigidity of the vertebra may be
due to very different causes, but we may be certain that those forms which
occur in connection with acute or chronic articular rheumatism or with disease
of the joints of the extremities should be classed as chronic arthritis.
6. As the sixth and last type, I must mention those almost painless or
only temporarily painful nodes which occur in the terminal joint of the three-
jointed fingers, appearing upon their posterior surface, giving them an oval
shape, hard to the touch, and gradually, from rigidity of the joint, fixing the
fingers in a position of flexion or abduction. They are often looked upon as
the signs of uric acid gout; E. Pfeiffer believes them to be a certain guide
in diagnosis even in the absence of other gouty symptoms.
Heberden, who discovered them, did not attribute them exclusively to
gout, and I coincide in the opinion of the majority of later authors who find
these Heberden’s nodes occasionally in gout, occasionally in chronic arthritis,
but most often as the only arthritic symptom in otherwise healthy individuals.
The Réntgen picture shows them to be exostoses, and they form a connecting
link between chronic rheumatism and arthritis deformans; with the former
they have in common symmetry and multiplicity, with the latter, the bony,
marginal proliferations, and the usually painful and chronic course. It is
well to follow Charcot and to separate them as special forms of disease.
This finishes the description of the most common types; but it must be
added that in individual cases transitional stages occur which tend to merge
the types into each other. For this reason clinical findings do not permit a
fine differentiation, and an attempt has been made to found a classification
upon the anatomical changes.
PATHOLOGY
The anatomical changes extend to all parts of the joint, cartilage, bone
and capsule, and frequently also to the adjoining muscles, tendons and tendon
sheaths. In the earlier stages these changes are relatively but little known;
they are found as accidental lesions, and often run their course during the
life of the patient without symptoms. Thus, the patient from whom illustra-
tion 5 was taken was a chorus girl and dancer until a few weeks before her
death. Moderate changes are noted by surgeons, who look upon chronic
rheumatism as a border-land which should be gradually brought under their
dominion. The later changes are well known anatomically, but they illumi-
nate the problem of their origin as poorly as ulcerative phthisis explains the
onset of pulmonary tuberculosis.
Even to-day it is not quite clear whether the affection begins in the car-
tilage of the joint or in the synovial membrane. Sometimes the one, some-
times the other, appears to be the case; nevertheless both are early attacked.
In the cartilage the basic substance appears completely detached, the cartilage
cells proliferated, and sometimes discharged from their capsules into the
joint fluid.
PATHOLOGY 249
In some forms the amount of synovial fluid is increased. occasionally
turbid but—and this is characteristic of chronic arthritis—never purulent.
The villi of the synovial membrane are hyperemic (violet red), showing
Tic. 5. —METATARSO-PHALANGEAL ARTICULATION OF A CHorRus GiRL, AGED Forty-l'ive, witH
Becinnina CHronic ARTHRITIS WITHOUT Symptoms; DEATH FROM CONTRACTED KIDNEY.
Fibrillation of the cartilaginous basic substance, proliferation of the cartilage cells, the
capsules of which partially open into the joint cavity. The capsule of the joint is intact.
marked proliferation; occasionally fatty degeneration is noted (lipoma arbo-
rescens), and in well developed cases present the appearance of sheep’s wool;
the capsule and its surroundings show edematous infiltration. The bone
appears unchanged in the early stages of the disease.
In later stages the smooth surfaces are denuded of cartilage, the bone is
bare, and, if joint movements have still been performed, shows grooves, re-
sembling the crevasses of a glacier. Often the bared surface is dense and
ivory-like, or it is covered by connective tissue which extends from the borders
of the synovial membrane, from transformed cartilage cells, or even from
the surfaces bare of cartilage. This connective tissue covers the joint surface
(Kachel), and frequently adheres to the opposing joint ends (fibrous anky-
losis). These connective tissue strie may calcify and finally ossify (bony
ankylosis). Upon the border of the cartilage, wherever it is covered by
synovial membrane, ecchondroses develop which are transformed into osteoids
and finally into bony tissue. By these exostotic marginal proliferations, the
joint end attains a mushroom form and resembles the crown of the antler
of a deer.
250 CHRONIC ARTICULAR RHEUMATISM
The bony substance becomes rarefied and fragile, the capsule, which was
at first flaccid, proliferated, and infiltrated with serum, is transformed into
fibrous tissue which cicatrizes around the ends of the joint and limits motion.
In the proliferated villi, islands of cartilage or bony tissue form, and these
may be thrown off as free joint bodies. The final stage is complete osseous or
fibrous ankylosis of the joint which is fixed in more or less unnatural position
and greatly deformed.
All these processes are common to the various forms of chronic arthritis;
at one time one, at another time another, becomes prominent. Thus, in the
exudative form of progressive chronic polyarthritis, proliferation and edema-
tous infiltration of the synovial membrane and its surroundings dominate
the situation, hence the spindle-shaped form of the joints. The cartilage
often appears to be secondarily implicated.
In, polyarthritis “ sicca” which has a chronic beginning, the proliferation
of the joint is not as marked as the fibrous transformation of the cartilage.
The outlines of the joint ends as a consequence of this become prominent,
and exostoses, if present, may be felt through the tense skin as hard, prom-
inent nodules which may sometimes be seen. This form also shows a tendency
to fibrous ankylosis. In senile deforming monoarthritis these osseous border
proliferations with disappearance of cartilage play the main réle in the limita-
tion of movement; the capsule forms no essential part of the clinical picture.
Finally, Heberden’s nodes are exostoses which at first slightly limit motion.
If the anatomical descriptions of later authors are compared (particularly
Schuchardt and Weichselbaum) we are forced to agree with Charcot who
declines sharply to separate the forms according to the anatomical findings.
He regards them as in some sense branches of the same trunk,
CLINICAL SYMPTOMS
The clinical picture would be incomplete if only the joint lesions were
considered. Very frequently there is early impairment of the general health.
The cases occurring in young persons with fever are particularly apt to show
from the onset emaciation and conspicuous cachexia. This can hardly be
attributed to the fever. Occasionally the fever lasts for weeks and reaches
102° F. and higher, but there is no proportion between the height or duration
of the fever and the emaciation. Indeed even after the temperature falls the
patients remain weak. The inactivity of the patient, the want of fresh air,
and the constant pain have been urged in explanation. But if we bear in mind
that patients with disease of the spinal cord become abnormally fat despite
the fact of constant pain and immobility, we cannot concur in this view,
but must look upon these forms of arthritis as conspicuous instances of
wasting disease. Amyloid degeneration (Roese) which frequently appears
confirms this. It is true other cases of arthritis belong to the fat plethoric
type and here also transitional cases are recorded. Frequently, particularly
in the young, there is moderate anemia and oligocythemia.
Most of the muscles of the body take part in the emaciation ; in some cases
the entire musculature suffers but almost invariably the muscles in the neigh-
CLINICAL SYMPTOMS 251
borhood of the joints are involved, and among these the extensors are most
seriously affected.” If rheumatism attacks the hand the intérossei atrophy very
early, often before the patients notice any hindrance in movement. This
occurs in the exudative as well as in the dry form. In the latter we find a
very characteristic ulnar abduction of the basic joint of the fingers from the
first to the fourth. An attempt has been made to explain this by contractures
of the muscles or from the flaccid condition of the capsule; this, however, I
believe to be incorrect. For in older persons this is frequently the first symp-
tom noted, even before there is any abnormal distention of the capsule or any
muscular contractions. It is more reasonable to assume that the lumbricales
atrophy simultaneously with the interossei, which normally have the property
of adduction, besides that of extension of the basal phalanx. Later this devia-
tion terminates in well marked subluxation. That the bones take part in the
atrophy is well known; in the senile monoarthritic deforming variety this
begins in the end of the joint; but in the juvenile polyarthritic form the
Réntgen picture often shows a conspicuous coalescence and disappearance of
the spongiosa in the neighborhood of the affected joint. Perhaps this is the
effect of immobilization. But since Sudeck has shown that in every form of
arthritic inflammation, distortion or trauma may produce within a few weeks
decided atrophy of the bones, transient or permanent, similar conditions should
also be looked for in chronic arthritis. The skin and its structures take part
in the process, and Herz has described a case in which, with every new attack,
a glove-like desquamation of the skin of the hand and shedding of the nails
occurred; such cases are rare. The changes resembling scleroderma are more
frequent; the shining ivory-like skin adheres to the deformed joint, smooth
and immovable. In the juvenile cases there is frequently an excessive func-
tional hyperhidrosis, The contractures which occur particularly in the flexor
muscles of the fingers and toes are important, but these may also be noted
in the extensor groups which are to a high degree responsible for the terrible
and incurable deformities in some of which the knees are drawn up to the chin.
Frequently the tendons and tendon sheaths are involved in the process and
along these structures tough subcutaneous nodules occasionally appear which
may be temporary or permanent; these are also noted in acute rheumatism
(see a dissertation by Rabinowitsch). Pribram asserts that he has only ob-
served them in acute rheumatism; Fig. 6, however, is an example of such
nodules in a case of undoubted chronic polyarticular arthritis.
In conclusion, I must mention intermuscular or intramuscular, dense, cal-
lous infiltrations which are rarely alluded to in literature, but are well known
to orthopedists and masseurs, and are skilfully treated by them.
The visceral complications are especially interesting on account of their
importance in the conception of the disease. That the endocardium may be
attacked has been admitted, and the frequency with which this happens varies
in different reports from 4 per cent. to 80 per cent. of the cases. The second-
ary and the senile deforming varieties do not attack the heart. In the statis-
ties of primary chronic polyarthritis there are differences of opinion as to
whether functional heart murmurs or only the genuine valvular affections have
been included, Pribram, who was the first to call attention to this variation,
252 CHRONIC ARTICULAR RHEUMATISM
gives the following statistics of his cases. In the forms beginning acutely,
there were 53.4 per cent. of heart murmurs and 20 per cent. of valvular
disease ; in cases chronic from the outset only 13.5 per cent. of heart murmurs
and 4 per cent. of valvular disease.
Chronic nephritis of benign character and showing but slight tendency to
uremia is not infrequently observed.
Among other complications those affecting the eye, such as iritis, iridocy-
clitis and episcleritis, and the skin (various forms of erythema, eczema, urti-
caria and psoriasis) are to be mentioned. The occurrence of multiple sym-
metric lipomata has frequently been observed in connection with chronic
arthritis, as well as bronchial asthma, dyspepsia, hemorrhoids and numerous
nervous disturbances, and this gives rise to some confusion. These affections
are spoken of particularly by authors who look upon chronic arthritis as an
expression of a general constitutional anomaly.
Lancereaux, in 1870, divided rheumatism into two classes, of which one,
“qui ne laisse jamais des traces sur son passage ” corresponds to acute articular
rheumatism; the other he said was: “pas une maladie, mais un syndréme,
4
Fic. 6.—Suscutanzous Nopuuus SITUATED UPON THE Dorsat TENDON SHEATHS IN A CASE
or Curonic ExupativeE PoLyartTuritis In A Younc Girt.
une manifestation d’un état constitutionel,” “le branche d’un grande famille
pathologique,” “herpétisme,” a vasomotor trophic neurosis, expressing itself
: in dynamic (migraine, epistaxis, neuralgias) and material disturbances in the
skin and of the tissues deficient in blood-vessels, In this group is also included
the triad of diabetes, obesity, and gout. Bouchard gives a similar definition
of “arthritisme”; both authors emphasize its conspicuous family and hered-
CLINICAL SYMPTOMS
bo
53
itary character, and even so careful an observer as Potain believes: “ Ce n’est
pas telle ou telle forme de rheumatisme qui se transmet, mais une prédisposi-
tion générale exposant 4 un groupe commun d’affections dans laquelle il faut
méme ranger la goutte.”’
On this point it is difficult to arrive at a definite conclusion. When we
read the clinical reports of German, French, English and American authors
Fic. 7.—PaTELLAR CARTILAGE oF A YouNG MAN wuHo, AFTER Passinc THRouGH AN ATTACK
or Gout, SuccuMBED To Croupous PNEumontia. The cartilage shows a velvety fibrilla-
tion of the matrix similar to the condition in chronic arthritis. The joints contained no
deposits of urate salts.
we receive the impression that certain forms of chronic polyarthritis frequently
attack debilitated persons. One author has, however, gathered his clinical
material in the hospital, among feeble, anemic, poorly nourished patients,
cases of true arthritis pauperum, whereas the cases of others were among those
living in affluence, the portion of the population debilitated by luxury and
close intermarriage.
Under such conditions we cannot regard the simultaneous appearance of
two or more diseases as a proof of their identity, and since decisive statistics
are not to be had, the critical skepticism of A. Hoffmann and other German
authors is certainly justified.
Yet the relation of arthritis to apparently dissimilar affections—and here
I must mention psoriasis—becomes constantly more obvious. Adrian has re-
cently reported 94 cases of this combination, which has been known in France
for some time. Gerhardt was the first to observe the condition in Germany,
Fic. 8.—Rapiocrapy or tum Hanp or a Goury Parimnr. At the point marked by the
asterisk, gouty tophi are seen as translucent foci; at the dagger, exostoses similar to Heb-
erden’s nodes; at the double dagger, subluxation in the basal joint of the little finger.
CLINICAL SYMPTOMS 255
and after a critical analysis he came to the conclusion that coincidence can
be wholly excluded, since in his and other cases the affections show simul-
taneous exacerbations and improvement.
Here, also, the relation existing between chronic arthritis and gout must
be considered. This much is certain: 1. That after gout has existed for a
long time in a joint, proliferation of the cartilage, exostoses and disappear-
ance of the capsules are found; 2. That atypical gout may give rise to poly-
articular swelling, resembling the exudative form of arthritis; 3. That in gouty
families, individuals may present symptoms resembling chronic arthritis.
But if we do not wish to lose ourselves in a realm of unfruitful speculation,
we must adhere to the belief that gout is an affection characterized by a
deposit of uric acid salts in the body and by the presence of uric acid in the
blood. The latter point will decide the differential diagnosis of doubtful
cases, in which we should place our dependence not upon the uncertain thread
test of Garrod, but upon the more difficult chemical analysis.
We may, therefore, look upon gout as one of the causes of chronic arthritic
changes, while recognizing that the two diseases are by no means identical.
The constitutional predisposition appears to be of especial importance in
one form of chronic arthritis, namely, that marked by Heberden’s nodes.
They are found isolated, especially in the aged, and then are frequently hered-
itary; very often they are associated with asthma, migraine, neuralgia, sciatica
and muscular rheumatism and particularly with gout. Bouchard was the first
to describe nodosities of the middle joints of the fingers due to swelling of
the second phalanx and occurring in cases of gastric dilatation; he gave them
the name of “ comptodactylie,’ and showed that this swelling disappeared
with improvement in the gastric affection. Pribram also observed one case
of this malady.
I do not believe that it will be possible hereafter to deny the existence
of a constitutional arthritis; but it is not necessary to adopt the scheme of
the French, who look upon every non-infectious arthritis as an expression of
an “herpétisme or arthritisme.” In the future accurate weighing of all the
circumstances will show whether definite anatomical lesions exist or an arthritis
runs a particular course in persons with a predisposition of the type described
by the French.
The infectious theory of arthritis has many more supporters than has
dyscrasia. The febrile form which comes in paroxysms with a relatively
frequent endocarditis and severe general disturbances gives strong support to
this view, and on several occasions microérganisms have been cultivated (by
M. Schiiller, Bannatyne, Blaxall and Wohlmann) from the contents of the
joint and their pathogenicity has been proven by animal experiment. Un-
fortunately, the microorganisms described are not all the same, and so careful
an investigator as Pribram found it impossible to detect any of them in the
cases he examined. The pathogenic agent, therefore, as in the case of articular
rheumatism, is not yet determined and the infectious nature of the disease
is only a hypothesis, although a very probable one.
As a third possibility, disease of the central nervous system has been con-
sidered. This is suggested by the symmetry of the affection, the atrophy and
256 CHRONIC ARTICULAR RHEUMATISM
contractures of the muscles, the trophic cutaneous disturbances, and the simi-
larity of the chronic rheumatic joint changes to unmistakable nervous arthrop-
athies occurring in tabes, syringomyelia, progressive muscular atrophy, hemi-
plegia, progressive paralysis and also in peripheral neuritis. In the latter
disease rarefaction of the bony substance with swelling of the distal ends of
the extremities and the formation of club finger tips is observed (pulmonary
osteoarthropathy of P. Marie, see the compilation of W. Berent). In diseases
of the central nervous system disfiguring deformities appear with atrophy and
proliferation of the bones and cartilage, and these show a great resemblance
to senile monoarthritis, differing, however, by their more rapid course, absence
of pain, fissures in the capsule, and extra-capsular, osseous and cartilaginous
proliferations.
To explain the muscular atrophy the assumption of a primary nervous
affection is quite unnecessary, since Charrier has shown that this atrophy
accompanies all joint inflammations, especially when they run their course
with effusion (Kremer). Hoffa proved that they do not occur when the
centrifugal nerves are severed; they are, therefore, trophoneuroses which are
produced by reflex action initiated by the diseased joint surfaces.
As anatomical investigation of the spinal cord has given positive results
only in rare, exceptional cases (R. Wichmann) the neurotic explanation seems
scarcely probable. Under certain circumstances, some forms of arthritis might
be looked upon as infectious trophoneuroses, following Teissier and Roque.
It is, however, quite unlikely that the various forms of chronic articular
rheumatism are due to any single cause. In the first place, we may exclude
monoarthritis deformans, which is so closely allied to other senile changes
(Weichselbaum) and which is so frequently produced by trauma. But it is
also unlikely that there is any one cause for all cases of chronic polyarthritis,
if we bear in mind the forms which are similar in all these symptoms, and
yet are produced by various well known and quite distinct infectious diseases.
Gerhardt in 1896 originated the term acute rheumatoid or pseudo-articular
rheumatism, and defined it as follows: “ Pseudo-articular rheumatism is that
form of disease in which it may be proven, or where it is very likely, from
its external appearance, that it is produced by the special pathogenic organ-
isms of a definite infectious disease; the remaining cases are included under
true articular rheumatism.” These pseudo-rheumatisms have in common that
they occur only in a minority of the individuals who are attacked by the
infection in question and that the same organism which produces the infectious
disease also produces joint pain, arthritic swelling or suppuration of the joint.
In this sense we may speak of chronic rheumatoid (“ pseudo-rheumatism ” of
Pribram) as an arthritis in which the exciting cause is one of the acute
exanthemata, influenza, or pneumococcus infection, particularly gonorrhea,
syphilis and tuberculosis. Gonorrhea is a clear example of the fact that the
same microérganism, according to its virulence and the individual constitu-
tion of the affected person, may cause any grade of the disease from a transi-
tory arthritic pain and serous effusion to an incurable, chronic deforming
arthritis and spondylitis. I should like to call particular attention to rheu-
matic tuberculoid or tuberculous rheumatoid, a condition which lately has been
es a
eT
TREATMENT 257
frequently described (Poncet, Maillard, H. Strauss, Barjon, Roma, Potal).
The usual course of such cases is this: the disease begins as a subchronic or
chronic articular rheumatism which finally becomes localized to one or more
joints, and there develops typical tuberculous changes. This course resembles
osteomyelitis, of which we observed a case in the clinic at Basel in an indi-
vidual aged seventeen, in whom, after a fever lasting several months, accom-
panied with wandering multiple joint swellings, muscular contractures, and
exostoses, the epiphyses became loosened from the neck of the left femur,
thus confirming the diagnosis.
True chronic polyarthritis may owe its origin to various infections, or to
constitutional causes of the type suggested by Lancereaux and Bouchard.
Perhaps in some cases nervous disturbances may play a réle. These cases
cannot be diagnosed by rules, no matter how skilful the reasoning processes,
but only by following the advice given by Archibald Garrod, to inquire into
the family history of each individual case, its nervous disturbances, etc., and
by carefully investigating the bacteria present. Perhaps in this manner a
rational differentiation of the varying forms, which to-day is impossible, may
in time be attained.
TREATMENT
As in all chronic diseases for which we have no specific, the number of
remedies is legion. But, in giving a synopsis, I shall divide them into
groups.
First, internal remedies, I take for granted the knowledge that the anti-
theumatics, the salicylates, antipyrin and allied remedies often diminish pain,
but never have the specific action which is the case in acute articular rheuma-
tism. The salts of iodin are very useful, not only in gonorrheic and syphilitic
theumatoid, but also in the exudative polyarthritic form. Tonics are advised
by the best authorities, and since experience has shown that in these affections
the local difficulties are closely related to the general health of the patient,
cod liver oil, iron, arsenic, quinin and strychnin preparations are of decided
benefit in anemic, feeble, emaciated individuals, especially after febrile parox-
ysms or after active treatment. The salts of lithia, and mineral waters
containing lithia, have been advised on account of their action in gout, but
there is no rational indication here for their use. In fact, in a disease in
which excessively chronic and decided yet spontaneous changes occur, the
value of any curative agent is always very uncertain.
Menzer’s successful trials of streptococcus serum, which were based upon
the theory of an infectious etiology, are interesting but by no means con-
clusive.
The principal réle in therapy is played by external physical remedies.
Water must be mentioned first. That energetic applications of cold water
are harmful in the first stages of inflammation is a common experience.
Only after acute exacerbations have run their course, and after long continued
sweating procedures, may cold douches, needle baths, and affusions be made use
of by an experienced and careful hand, and then serve a useful purpose as a
hardening process.
18
258 CHRONIC ARTICULAR RHEUMATISM
Warm water in all forms is frequently employed, from the Priessnitz pack
to a hot bath. The latter are used particularly in the form of natural springs,
which are of ancient repute. Their effect is to be ascribed more to the tem-
perature of the water and the duration of the bath than to the chemical
constituents of the water (hydrogen sulphid, alkaline sulphates, calcium, gyp-
sum, sodium chlorid, ete.). In rheumatism, the unaccountable experience is,
that natural mineral waters may bring about improvement after the effect
of hot water baths in the home has been exhausted. This effect is chiefly due
to the cutaneous irritation of mineral waters rich in carbonic acid, such as
those of Nauheim and Oeynhausen, or of mud baths combined with the thermic
effect of the water. To these must be added the effect of applications of peat-
soil, fango, natural sulphur, ete., and heat applied in various ways, sweat
procedures, hot air and steam douches (the latter often producing a relaxa-
tion of muscle contractures and stiffness), sand baths, local and general hot
air baths and, finally, local inflammatory applications; painting with tincture
of iodin or ichthyol, compresses with iodin—potassium iodid salve (1:10: 100),
vesication, etc.
All these applications have in common a tendency to produce hyperemia,
and August Bier has contributed other original therapeutic methods. The
irritating or anodyne effect of derivatives and counterirritants has always
been explained on the hypothesis that the blood is drawn from the distant
diseased parts to the surface. Bier has shown that this is incorrect; that, on
the contrary, the deeper parts partake in the hyperemia, and that this produces
the anodyne and absorbent effect. Bier stimulates this action still further by
hot air and stasis. The former produces an intense, highly active, i.e,
arterial, hyperemia, which is greater the higher the temperature of the agent.
A simple apparatus, a wooden box with two openings to permit the en-
trance and the exit of the hot air, and bandages on which to rest the affected
member are sufficient for the purpose; the hot air is produced by a Quincke
sweat tube, or a phénix a air chaud, the tube being introduced into the open-
ing of the box. Similar apparatus has been employed by Tallermann, and
Lindemann has used electric heat; the effect of the electric light baths now
in vogue, in which the electric bulbs radiate not only light but. heat, is the
same. For institutions these are very serviceable, as they are not dangerous
and are easy to regulate. Bier’s apparatus, however, has the enormous advan-
tage that it may be constructed by a carpenter, at very slight cost, in the
house of the patient, and be employed at the bedside. The effect of this remedy
is excellent, as I am able to testify.
The value of passive hyperemia attracted the attention of Bier on account
of the rarity with which tuberculosis of the lungs is found associated with
valvular disease of the heart. He attempted artificial blood stasis in tubercu-
losis of the joints, and was so gratified with the success attained that he
employed this method also in other joint diseases. Above the diseased area
an elastic (rubber) bandage is applied so tightly that the extremity becomes
edematous.
However, the pressure must not be so great as to compress the arteries;
the member must be warm, and the stasis must not produce the slightest pain.
LITERATURE 959
The compression may be continued for a long time. I have carried on this
treatment for several months at a time. Bier has lately, however, advised
us to use the method for only one or two hours daily.
The effect is at first to decrease the pain to such a degree that, for example,
the tearing pains of gonorrheal arthritis soon cease, giving way to a feeling
of well-being.
The rule which Bier has expressly emphasized is this, that the stasis itself
must never produce pain; as soon as this appears, the bandage must be
loosened or removed.
The further effect of stasis is to increase absorption. It is evident at
once that joint effusion, edematous infiltrations of the capsule, and prolifera-
tion of the joint villi are more amenable to some treatment than are ecchon-
droses and osteophytes, that, therefore, the dry atrophic form of chronic
arthritis is less susceptible to treatment than the hypertrophic proliferating
forms with their spindle-shaped joints. Bier’s hot air and stasis treatment,
judged by the results, is by no means a panacea. The physician treating a
ease of chronic rheumatism must decide which symptoms most urgently call
for relief. Fresh joint and capsule swellings require rest, the alleviation of
pain, and the application of remedies which increase absorption, such as the
salicylates, iodin, and heat. Older capsular contractures, in which immobility
and fibrous ankylosis have occurred, require active and passive movements and
the condition is often felieved by stasis. Muscular atrophy is benefited by
faradic treatment and, above all, by massage. Contractures require applica-
tions of heat, prolonged baths, hot air or steam douches, peat or fango poul-
tices, and protection from cold.
The earlier the treatment is begun, the better the result.
Firm ankyloses and hyperostoses, particularly of the larger joints, require
surgical and orthopedic treatment; practice with suitable apparatus may im-
prove the gait, and prevent the bad consequences of too great weight upon
the vertebral column. The operative treatment of mono- and polyarthritis,
according to the few results reported by W. Miiller and his pupil Elter,
deserves further trial.
LITERATURE
A very complete compilation has recently been given by Pribram in Nothnagel’s
Handbuch, vii, 2.
C. Adrian, “Ueber Arthropathia psoriatica.” Grenzgebiete der Medicin, 1903, xi,
p. 237.
W. Anschiitz, “Ueber die Versteifung der Wirbelgelenke.” Grenzgebiete der Medicin,
viii, p. 461.
Bannatyne, Wohlmann and Blaxall, Lancet, 25, April, 1896. ;
Barjon, “Radiographie appliquée 4 l’étude des arthropathies déformantes,” Paris,
1897.
Bechterew, “Steifigkeit der Wirbelsiule.” N eurologisches Centralbl., 1893, und
Zettschr. f. Naturheilkunde, 1899, xv.
Beer, “ Rigiditat der Wirbelsiule.” Wiener med. Blatter, 1897, Nr. 8 u. 9.
260 CHRONIC ARTICULAR RHEUMATISM
W. Berent, “Zur Aetiologie osteoarthropathischer Verainderungen.” Berliner klin.
Wochenschr., 1903, Nr. 4.
A. Bier, “Hyperimie als Heilmittel,” Leipzig, 1903; ferner 19. Congress fiir innere
Medicin in Berlin, 1901; Miinchener med. Wochenschr., 1898 und 1901, Nr. 48.
Bouchard, ‘ Lecons sur les autointoxications,” 1887.
I. Braun, “Klinische und anatomische Beitrige zur Kenntnis der Spondylitis de-
formans,” Hannover, 1875.
R. Cassirer, ‘Ueber myogene Wirbelsteifigkeit.” Berliner klin. Wochenschr., 1902,
Nr. 10 u. 11.
Charrin, “Progrés Méd.,” 1894.
I. I. Clarke, “Note of a Painful Condition of the Twelfth Pair of Ribs.” Clinical Soc.
of London, October 11, 1902.
H. Curschmann, “Berichte der med. Gesellschaft zu Leipzig.” Schmidt's Jahrbiicher,
1895.
G. Davaine, “Etude comparée du rheum. art. aigu. et des poussées aigues du rheum.
chronique.” Thése, Paris, 1897.
J. Elter, “Weitere Beitrige zur chirurgischen Behandlung der Arthritis deformans.”
Zeitschr. }. Chirurgie, 1903, 66, p. 387.
Sir Alfred Garrod, “Natur und Behandlung der Gicht.” German by Eisenmann.
Wirzburg, 1861.
Archibald Garrod, ‘Clinical and Pathological Relations of the Chronic Rheumatic
Affections.” Lancet, March 16, 1901.
C. Gerhardt, “Ueber Rheumatoidkrankheiten.” 14. Congress fiir innere Medicin in
Wiesbaden, 1896, p. 169. “ Verhaltnis der Schuppenflechte zu Gelenkerkrankun-
gen.” Berliner klin. Wochenschr., 1894, Nr. 38.
A. Hoffman, “ Lehrbuch der Constitutionskrankheiten,” Stuttgart, 1893.
Herz, ‘Ueber das gleichzeitige Vorkommen von chronischen Haut- und Gelenker-
krankungen.” Wiener klin. Wochenschr., 1896, Nr. 26.
Hoffa, “ Zar Pathogenese der arthritischen Muskelatrophien.” Volkmann’s Sammlung
klin. Vortrdge, 1892, N. F., Nr. 50.
M. Kachel, “Untersuchungen tber Polyarthritis chronica adhxsiva.” Ziegler’s
Beitréige, 1903, xxxiii, p. 327.
O. Kremer, “ Pathogenese der arthritischen Amyotrophien.” IJnaug.-Diss., Greifswald,
1902.
Lancereauz, “ Atlas d’anatomie pathologique,” Paris, 1871. “Traité de ’herpétisme,”
Paris, 1883; ‘‘ Lecons de Clinique médicale,” 1892, I.
Landré-Beauvais, “ Doit-on admettre une nouvelle espéce de goutte sous le nom de
goutte asthénique primitive?”” Thése, Paris, an viii (1800).
Lindemann, “Locale Behandlung von Gelenkrheumatismus, etc., mit elektrischen
Heissluftapparaten.” Therapeut. Monatshefte, Mirz, 1900.
L. Maillard, “ Rheumatisme tuberculeux.” Gazette hebdomad., 1900, No. 88.
K. Manasse, “Zwei Falle von isolirter rheumat. Erkrankung der Kiefergelenke.””
Miinchener med. Wochenschr., 1902, Nr. 20.
Menzer, Deutsche med. Wochenschr., 1903, Nr. 67 und Zeitschr. f. klin. Medicin, 47,
~p. 109.
Joh, Miiller, “ Beobachtung tiber reine Zwerchfell-Bauchathmung bei ankylosirender
Wirbelgelenkentziindung.” Verhandlungen der Wiirzburger phys.-med. Gesell-
schaft, 1901, p. 41.
W. Miller, “Zur Frage der operativen Behandlung der Arthritis deformans.” Archiv
j. klin, Chirurgie, 47, 1894.
LITERATURE 261
Pribram, “Chronischer Gelenkrheumatismus und Osteoarthritis deformans.” Noth-
nagel’s Handbuch der spec. Pathologie und Therapie, vii, 2.
E. Pfeiffer, “Ueber Gichtfinger.” Berliner klin. Wochenschr., 1891, Nr. 15.
Potain, Semaine méd., 20. Mai, 1891, p. 210.
A. Poncet, “Rheumatisme tuberc. abarticulaire.” Lyon méd., 1902, No. 29; Gazette
hebdomad., 1902, Nr. 58.
Potal, “Rheum. artic. tub. chronique.” Gazette hebdomad., 1902, No. 10.
H. Rabinowitsch, “ Beitrige zur Kenntnis des Gelenkrheumatismus mit Knoétchen-
bildung.” Jnaug.-Diss., Berlin, 1899.
Roma, ‘‘Rheumat. tuberculeux.” Gazette hebdomad., 1902, No. 93.
Roese, ‘Ueber amyloidentartung bei chronischer Arthritis.” Inaug.-Diss., Leipzig,
1897.
Schuchardt, ‘“Krankheiten der Knochen und Gelenke.” Deutsche Chirurgie, 28.
Lieferung. ,
M. Schiller, Berliner klin. Wochenschr., 1893, Nr. 36, 1900, Nr. 5 bis 7; 15. Congress
fiir innere Medicin, Berlin, 1897.
Schlesinger, ‘‘Chronische Steifigkeit der Wirbelsiule.”” Grenzgebiete der Medicin, 1900.
Senator, “Krankheiten der Bewegungsorgane.” Ziemssen’s Handbuch der spec.
Pathologie, xiii.
Sudeck, “Acute (trophoneurotische) Knochenatrophie nach Entztindungen und
Traumen der Extremitaten.”’ Deutsche med. Wochenschr., 1902, Nr. 19.
H. Strauss, ‘‘ Acute Miliartuberculose unter dem Bild einer Polyarthritis.” Charité-
Annalen, xxiv.
Tallermann und Mendelsohn, “Behandlung des chronischen Gelenkrheumatismus.”
Deutsche med. Wochenschr., 1898, Nr. 11.
Teissier et. Roque, “ Rheumatisme chronique.” Traité de méd. de Brouardel. Gilbert
et Girode.
Trousseau, “Clinique médicale.”
R. v. Volkmann, ‘‘Krankheiten der Gelenke.” “Pitha-Billroth’sche Chirurgie.”
Vidal, “Considérations sur le rheum. chron. primitiv.” Thése, Paris, 1855.
Weichselbaum, Virchow’s Archiv, lv.
Wohlmann, Brit. Med. Jour., November 11, 1900.
PENTOSURIA
By F. BLUMENTHAL, Bertin
Prior to the last few years all urine which gave a distinct and unquestion-
able reduction test was considered to contain sugar, and permitted us to con-
clude the presence of grape sugar; this view is no longer tenable. We know
now that a variety of sugars are found in human urine all of which react to
the recognized sugar tests (Trommer’s, Nylander’s, the phenylhydrazin test).
Besides grape sugar we find milk sugar, which appears during the puerperal
period in a woman who has an abundant secretion of milk yet does not nurse
her child; this substance may persist in the urine for months post partum,
in fact as long as the secretion of milk continues. Here the differential diag-
nosis from grape sugar is accomplished very simply by the fermentation test ;
milk sugar docs not ferment with yeast, while grape sugar does. Robinson
and Lépine, and also Rosin and Laband, have lately described cases of levulo-
suria which is characterized by its independence of the ingestion of carbo-
hydrates, and this condition may be recognized by the decided levorotatory
power developed during the fermentation test of the urine. Of less impor-
tance is the occurrence of maltosc, which occasionally appears in the urine in
diseases of the pancreas, and the presence of which can scarcely be detected
even by the most delicate chemical methods. Of more importance are the con-
bined glycuronic acids and the pentoses.
We refer here to the former substances because the combined glycuronic
acids may be considered as pentose-carbonic acids, C;H,,0,CO,. Combined
glycuronic acids are found in the urine after the administration of numer-
ous drugs, especially such as contain the aldchyd and ketone groups (Neu-
bauer), and these may then be excreted in the urine in combination with gly-
curonic acid. Among the best known of these drugs are: morphin, chloral,
turpentine, menthol, antipyrin, ete. Glycuronic acid is also found in the
urine combined with indoxyl and with phenol. As some of the combined
glycuronic acids respond to the Trommer and Nylander tests, it may be of
importance in such cases—particularly with doubtful tests—to search for the
cause, and it is then not infrequently found that, at least in human urine, we
are dealing with a very decided indicanuria. If the patient who voids this
reducing urine has taken any drug, the supposition is natural that it has been
excreted as glycuronic acid and has thus caused the reduction.
The urine coming from a case of pentosuria gives a distinct but somewhat
delayed reaction with Trommer’s test, and usually (as E. Salkowski first
262
PENTOSURIA 263
noted) the reduction with Trommer’s test only takes place upon cooling, but
then quite suddenly.
The phenylhydrazin test is also positive with pentose; Nylander’s test, is
not quite so distinct, and thus it happens that a person applying for life
insurance is sometimes rejected on the ground that he is supposed to be a dia-
etic. ‘This happened in the case of a patient, aged thirty, who had been mar-
ried for but a short time, and who, on account of his rejection for life insur-
ance, was very unhappy. In great excitement he consulted a physician for a
probable diabetes. Upon examination of the urine the physician at once be-
came suspicious, for the urine was optically inactive in the polariscope and
did not ferment with yeast. When the urine was examined more accurately
(Prof. Salkowski) it was found that the sugar it contained was pentose.
Here was a case in which the examination of a urine having reducing
properties but optically inactive and non-fermentative led to the discovery
of pentose; the question may quite properly be asked, “ How can such a diag-
nosis be confirmed with certainty? ”
A urine that contains pentose, and only such a one, gives the ORCIN TEST.
This is done in the following manner: 3 c.c. of urine are decomposed with
about 6 ¢.c. of fuming hydrochloric acid; to this is added a few granules of
orcin and the mixture is then heated to the boiling point. As soon as the
mixture begins to boil, a bluish green color appears which is proof positive of
pentose. Urine containing grape sugar or milk sugar does not give this reac-
tion; urine containing glycuronic acid gives the test only upon prolonged boil-
ing, and then the precipitate is never greenish blue but more of a violet
color.
Before the orcin test was introduced into the chemistry of urine, the
phioroglucin test was used but it was much less positive. According to E.
Salkowski, this test may be carried out in the following manner: 3 c.c. of
urine are decomposed with 3 c.c. of hydrochloric acid of a specific gravity of
1.019, to which a few granules of phloroglucin are added and the mixture is
heated to the boiling point. Even after slight heating a cherry red color
develops which gradually becomes more distinct, and finally (a point that is
characteristic) turns greenish black. If amyl alcohol is then added, and the
mixture shaken, the coloring matter is dissolved, and shows an absorption
band between D and E, i. e., between yellow and green. Urines which contain
large amounts of glycuronic acid show a brownish black color, but present
the same absorption lines; urines which contain only traces of glycuronic
acid show no absorption lines nor the characteristic colors indicative of
pentose,
I believe that the orcin test is more reliable than the phloroglucin test,
as most of the glycuronic acids yield no reaction with the latter; at least, not
if the test is done in the manner I have indicated. In using the orcin test,
one or two drops of liq. ferri sesquichlor. may be added, according to Bial ;
this produces a beautiful blue color. Or Bial’s reagent may be used (acid.
muriat. cone. 250.0; orcin 0.5; liq. ferri sesquichlor. 10 drops). Confusion
with pentose, provided the urine is examined twenty-four hours after it has
been voided, is only possible with two of the glycuronic acids at present known,
264 PENTOSURIA
namely, with mentholglycuronic acid and turpentinglycuronic acid. Both of
these glycuronic acids have the property of decomposing spontaneously, and as
free glycuronic acid also reacts to the orcin test, they may be confounded. We
are prevented from making this mistake, first, by the history, as mentholgly-
curonic acid and turpentinglycuronic acid are only excreted after the inges-
tion of menthol and turpentine; secondly, by the odor of the urine; menthol
urine smells of peppermint, turpentine urine of violets. Therefore, in human
urine, since the introduction of the orcin test, there can scarcely be any diffi-
culty in the recognition of pentose. The circumstances are different in the
urine of the herbivora. They frequently take up with their food a mass of
pentosan, that is, the anhydrid of pentose. The pentosans have the same rela-
tion to pentose that glycogen has to grape sugar. These pentosans are in part
excreted as such and give the orcin test, as does pentose, for by heating with
hydrochloric acid pentose is developed from pentosan.
As the urine of the herbivora very frequently has reducing properties and
therefore gives a more or less distinct orcin test, confusion with pentose is not
impossible. In these cases the phenylhydrazin test must be employed; if this
is positive while the fermentation test is negative, pentose is present. If the
fermentation test is positive, after fermentation has ceased the phenylhydrazin
test must also be positive if pentose is present.
After this slight digression, we return to the chemical analysis of the
urine. If we have under consideration a urine that gives a positive reaction
with Trommer’s test, the phenylhydrazin test, the orcin and phloroglucin tests
for pentose, if the urine is optically inactive and does not ferment, then the
patient excreting such a urine has pentosuria. The question now arises, What
does this condition indicate? As it is certain that he is excreting sugar, i.e.,
pentose, there is unquestionably a disturbance in sugar metabolism. We are
then confronted with another question, whether we are dealing with a variety
of diabetes mellitus, a pentose diabetes, or something else. If we are dealing
with a variety of diabetes mellitus, the combustion of carbohydrates must be
diminished, as in the case of diabetes. Such a connection must be thought of,
all the more so as Ruff has produced pentose from derivatives of grape sugar
by oxidation with potassium permanganate and hydrogen peroxid, and it is
possible that the human organism may also carry on this process of oxidation.
Further, as it is known that the pentose which occurs in nature and enters the
body with the food, such as the l-arabinose and 1-xylose, undergoes only partial
combustion even in the healthy, it is not unnatural to explain pentosuria by
conceiving that the patient, from the forms of sugar with six carbon atoms,
forms pentose. This he incompletely oxidizes, and hence excretes a portion
of it. If this view were correct, with the withdrawal of starch from the food
pentosuria should disappear or at least lessen, and, on the other hand, with
the profuse administration of starch or grape sugar the pentosuria should
increase.
, But when we withdraw carbohydrates from patients who excrete pentose,
: a at oe that the pentosuria continues, and apparently in the same
es - as formerly, while the administration of even 100 grams of grape sugar
a strict diet free from sugar does not lead to a decided increase of the
ae
PENTOSURIA 265
pentosuria. From these results it is obvious that pentose in the animal organ-
ism is not formed by the oxidation of hexose, i.e., the varieties of sugar with
six atoms of carbon or their multiples.
This to some extent also answers the question whether pentosuria is a
variety of diabetes mellitus. The latter disease is characterized by the fact
that the power to burn starches and hexoses is diminished. That this is not
true of pentosuria, at least not of all cases of pentosuria, was shown by Bial
and myself, for the administration at once of 100 grams of grape sugar caused
no glycosuria. The combustion of d-galactose in our case of pentosuria was
also entirely normal. It follows from this that the patient with pentosuria
has no greater tendency to alimentary glycosuria than the healthy; hence if
we look upon alimentary glycosuria as a proof of the existence of diabetes
mellitus, the urine of the pentosuric is in this respect also entirely negative.
There is good ground for the supposition that pentosuria is a pentose diabetes,
in which metabolism for sugar with six atoms of carbon is normal, while the
property of combustion for pentose 1s diminished or has entirely ceased. With
food in the form of grain and fruit, and in beer and tea we ingest a certain
amount of pentosans; it is quite possible that pentosans are changed into
pentose in the stomach by the action of hydrochloric acid; but the organism
is incapable of oxidizing them and they are therefore excreted. This hypoth-
esis is accepted by Naunyn and Liithje, and by others. Can this view be
possible ?
The pentose which we ingest with our food is the dextro-rotary l-arabinose,
while, as we know from the investigations of Carl Neuberg, inactive arabinose
also occurs in the urine. Since inactive arabinose, as the researches of Emil
Fischer have shown, can only occur by the combination of d-arabinose and
l-arabinose, the organism must, in addition to l-arabinose, also furnish d-arabi-
nose; so that i-arabinose may be formed.
The question whether the organism contains pentose groups has been dis-
cussed for a long time. As is well known, Hammarsten found in the nucleo-
proteid of the pancreas a reducing substance which he assumed to be pentose.
K. Salkowski has produced phenylosazone, and, upon the basis of an analysis
of the same, has determined with certainty that the reducing substance is pen-
tose. On account of the abundant furfurol formation which is said to be char-
acteristic of pentose, and which upon decomposition was shown to be present
in the nucleo-proteids from various animal organs, and on account of the
production of phenylosazones at the melting point of pentosazone, 157° to
160° C., I have maintained that all animal nucleins contain a pentose group,
and that the pentose group is characteristic of nucleins just as is the group of
xanthin bases, for I found no proteids which contain pentose except nucleins.
I have also held that when an albumin body gives the phloroglucin test for
pentose we are justified in declaring it to contain nuclein. This view at the
time appeared to be decidedly opposed to the prevailing opinion. A. Kossel
and Neumann had, two years previously, found no pentose group in nucleinic
acid of the thymus gland. The former denied absolutely the presence of a
carbohydrate group in the spermatic nucleinic acid. Noll, the pupil of A.
Kossel, forbore entering into this discussion. He believes that we must dis-
266 PENTOSURIA
criminate sharply two reducing carbohydrates. One is loosely combined with
the nucleins, and in the formation of nucleinic acid separates from nuclein ;
the second, a firmly combined atomic group with a molecule of nucleinic acid,
causes the production of levulinic acid and formic acid, the latter of which
does not form a reducing carbohydrate. In view of this, Kossel’s adherents
admitted the presence of a reducing carbohydrate in animal nuclein, but
refrained from any expression regarding the nature of the reducing substance.
Later, Friedrich Miiller questioned the opinion, then prevalent, that pentose
was the sugar of the vegetable kingdom and did not occur in the animal king-
dom. He believed there was often a confusion of pentose with glycuronic
acid, a confusion which was by no means impossible on account of the test
then in vogue. This diversity of views led Bergell and myself to make further
researches in regard to pentosuria. From a urine supposed to contain pentose,
he and I obtained a barium combination of the questionable sugar, the analysis
of which showed we were, in fact, dealing with pentose. By this means, the
presence of pentose in the urine of animals was further confirmed by Jastro-
witz and Salkowski, and the production by Carl Neuberg of pure r-arabinose
from so-called pentose urine furnished proof incontestable in every respect.
Furthermore, Wohlgemuth, who at my suggestion examined the nucleo-proteid
of the liver, produced from this a chemically pure phenylosazone which by
analysis proved to be phenylpentosazone. The presence of pentose in animal
organs was later confirmed by other competent observers. Thus Neumann,
the former co-worker of Kossel, found that, with an improved technic, nucleinic
acid obtained from the thymus gland gave a decided pentose reaction. The
labors of Bang, Jacob, and Bergell, Friedenthal, Umber, Grund and others,
proved the correctness of the theory first suggested by me that not only all
vegetables but also all animal nucleo-proteids contained carbohydrates belong-
ing to the pentose group.
The question now arises, How was it possible that these-groups were so long
overlooked in the nucleins by prominent investigators, and that my earlier
results were so long unconfirmed? This must be ascribed to the fact that in
the nucleo-proteid of the thymus, as Umber and I determined in the pancreas
proteid, the pentose group is very loosely combined. ‘T'o obtain the nucleo-
proteid of the thymus a solution of the same in an alkali and precipitation with
acetic acid are sufficient to separate the greater portion of the pentose and
to obtain a phosphorus-containing albumin body that no longer shows pentose
but still contains some xanthin bases. And for the nucleo-proteid of the pan-
creas Umber has shown that the pentose group is one of the first products of
pepsin digestion which enters solution. This view might very readily coincide
with that of Kossel’s adherents who believe that the reducing carbohydrate
is very loosely attached to the nucleo-proteid, for on the solution of thymus-
nuclein in alkali a phosphorus-containing albumin body which still contains
xanthin bases, i.e., a nuclein, is retained. I believe, therefore, that such a
body free from pentose should, at most, be designated an atypical nuclein.
That the pentose group is but loosely combined with the nucleins is cer-
tainly not true of the pancreas nuclein, for Bang has obtained pentose from
its nucleinic acid.
PENTOSURIA " 267
According to recent investigations of Neumann, pentose is present in the
nucleinic acid of the thymus; hence it follows that the pentose group is an
integral constituent of at least some of the nucleinic acids, if not of all.
Of the pentoses which occur in animal nucleins, that of the pancreas has
been most minutely investigated. Bang supposed it to be dextro-rotary, and
Neuberg has lately arrived at the surprising conclusion that the pancreatic
pentose is I-xylose. This latter theory is of great importance as bearing on
the origin of pentose in chronic pentosuria. For, if on other grounds we were
inclined to believe that the pentose of urine originates from the pancreatic
nuclein such an opinion would by this result be proven to be erroneous. It is
impossible to understand how xylose could be changed into arabinose. It is
true that we have only proven for pancreatic nuclein that its pentose is l-xylose ;
the other nucleins have not been investigated in this respect.
The researches in metabolism by Bial and myself have also made it appear
unlikely that pentoses are formed in the pentosuric patient by an imperfect
nuclein decomposition, since the metabolism of the pentosuric shows no such
increased destruction of nucleins. Neither the excretion of uric acid nor the
excretion of phosphoric acid is increased in pentosuria. It also appears to be
impossible that the inactive arabinose in pentosuria originates from other
nucleins, and not alone from the pancreas nucleins, and we must search else-
where for an explanation of the origin of pentose.
Carl Neuberg has given us important and interesting conclusions in this
field. He demonstrated that the l-xylose which is found in pancreatic nuclein
originates from grape sugar; now we have assumed for a long time that glu-
cose is partly oxidized from glycuronic acid. If we consider glycuronic acid
as pentose carbonic acid, C,H,,0,CO,, it need only give off its carbo-xylose
group to produce dextro-rotary l-xylose. This the organism requires for the
construction of nucleins. On the other hand, in his opinion, the r-arabinose,
the urinary sugar of pentosuria, originates in a very different manner.
As is well known, milk sugar is split wp in the intestine into dextrose and
galactose; a portion of the galactose is certainly utilized for glycogen pro-
duction. Another portion enters into cerebrin, for Thierfelder was able to
demonstrate the presence in cerebrin of galactose. The galactose contained
in cerebrin, however, is dextro-rotary, like the galactose contained in food.
But it is very easy to change this d-galactose to its inactive form, and then
from the inactive galactose inactive arabinose may readily be produced by
oxidation. Carl Neuberg is therefore of the opinion that inactive arabinose
originates from derivatives of galactose. How far this view is correct is still
uncertain, for the behavior of i-galactose must be tested in the organism of
a pentosuric patient. The behavior of the ordinary d-galactose has been stud-
ied by Bial and myself, but we were unable to determine an increase of pentose
excretion. '
It is evident from these considerations regarding pentosuria that prior
to its discovery by E. Salkowski we had but slight understanding of the sugar
metabolism of the human organism, and that in pentosuria we are dealing with
an anomaly of sugar metabolism which must be assumed to be an independent
one. It has nothing in common with diabetes, and is also net to be regarded
ae
268 PENTOSURIA
as a pentose diabetes, for the property of combustion of the pentoses of the
food is nowise altered. The same conditions are present here as in levulosuria,
which Rosin and Laband have lately determined represents an anomaly in
the production of levulose, not, however, dependent upon a disturbance of its
combustion. I do not believe it can be doubted that in true diabetes we shall
ultimately reach the point of separating a group of cases in which the forma-
tion of grape sugar in the organism is disturbed; while there is no anomaly
of combustion. I mean the cases with slight excretion of sugar (1 per cent. or
less) and this almost entirely independent of the carbohydrate constituents of
the food. Perhaps, also, in many severe cases such a disturbance in the syn-
thesis of sugar may be found.
Pentosuria is therefore an independent disturbance of metabolism, which
is characterized by the fact that in this condition an inactive sugar has
been found in nature for the first time. Thereby the law that the animal
organism and plants can produce only active varieties of sugar has been
proven erroneous. A second law, which for a long time was considered
incontestable, namely, that the pentoses are the sugar of the vegetable king-
dom only, and do not occur at all in the animal kingdom, has also been
nullified.
We must separate true chronic pentosuria from alimentary pentosuria.
A large number of individuals do not possess the property of oxidizing large
amounts of pentosan introduced with the food, but excrete a portion of these
pentosans as pentose. This is alimentary pentosuria. The amount of pentose
excreted is about 0.2 to 0.5 per cent. This pentose always arises from the
pentosans which are taken up with the food, for the most part in the dextro-
rotary l-arabinose contained in fruits. This phenomenon we generally see
in the summer when fruit is freely eaten (cherries, strawberries, whortleber-
ries, plums).
This alimentary pentosuria has nothing in common with chronic pento-
suria, in which arabinose also occurs; here not the dextro-rotary but the inac-
tive appears in the urine. We now find, however, that besides chronic pen-
tosuria the alimentary type may also exist, and I am in possession of records
of cases in which both the inactive arabinose and the dextro-rotary appear in
the urine. The proof of this has been deduced as follows: first, the urine
without fermenting was dextro-rotary; secondly, only pentosazone could be
produced from it; and thirdly, according to Neuberg, a solution of the osazone
in pyridin alcohol proved dextro-rotary.
True chronic pentosuria, as we have seen, is characterized by the fact that,
independently of food, inactive arabinose is excreted continuously. The
amount of inactive arabinose varies in this condition between 0.3 and 1 per
cent. by Knapp’s method of titration.
We find, however, cases also of chronic diabetes that are complicated by
pentosuria, i. e., showing a slight excretion of pentose. To this group belong
a number of diabetics in whose urine very small amounts of pentose have been
demonstrated, as shown by Kiilz and Vogel. In these cases the pentose has
not the slightest clinical importance so far as can be determined at this time.
It occurs in such minute traces that its presence cannot be detected by our
PENTOSURIA 269
common tests, and the utilization of several liters of urine is necessary to find
the substance at all. We have no knowledge as to which pentose appears in
the urine in diabetes (whether pentose of the food, or inactive arabinose, or
pancreas pentose, i. e., l-xylose), nor do we know whether it is particularly in
the severe cases of diabetes that pentose is excreted.
To quite a different group belong those cases of pentosuria in which, besides
pentose, glycose appears transitorily in the urine. In this instance the gly-
cosuria may have an accidental cause (morphin), as in the case of Jastrowitz
and Salkowski which led to the discovery of pentosuria. We may, however,
encounter the combination of true pentosuria with mild diabetes. I have
seen such a case. The quantity of grape sugar amounted to 0.6 to 1 per
cent., the amount of pentose was 0.3 to 0.5 per cent. As the urine was
sent to me for investigation only a few times, I can say nothing further
about the course of the case. Only this much could be determined, that
the pentose found in the urine was inactive, therefore probably an inactive
arabinose.
The second group of chronic cases of pentosuria includes the pure cases,
in which no other sugar than pentose is found. Up to this time the following
cases are reported in literature: first, the case of Jastrowitz and E. Salkowski
in which the glycosuria disappeared after morphin was stopped, while the
pentosuria proved chronic; secondly, the two cases described by Salkowski and
myself. The first of these occurred in a merchant, thirty-six years of age,
and always healthy, who was married and had four living children. The
amount of pentose he excreted varied between 0.7 and 1 per cent., with an
average amount of urine of a liter to a liter and a half per day. This case
occurred in 1895 in the practice of Dr. L. Feilchenfeld who still has the
patient under observation. Up to this time the pentosuria has never been
associated with any serious symptoms. The patient repeatedly suffered from
hydrocele, and the fluid obtained by puncture was examined by me and found
to contain grape sugar but no pentose. The urine has also been utilized by
C. Neuberg for the preparation of r-arabinose. The patient was decidedly
thin.
The third case occurred in a banker, aged sixty-five. This patient (ac-
cording to the report of Dr. Blumenthal, who treated him for over twenty years
before the pentosuria was discovered) is said to have repeatedly had reducing
substances in his urine, but grape sugar was never found until 1895, when the
pentosuria was discovered. This case is especially interesting as, in the
family of the patient, numerous chronic diseases occur, particularly diabetes
and nervous diseases. Up to two years before death (which occurred in 1900)
the urine in this case constantly showed about one per cent. of pentose. For
some time before death he was treated by another physician; his death was
due to arteriosclerosis. The autopsy showed calcification of the coronary
arteries; the pathologist told me that nothing of special interest was found
in the pancreas, but unfortunately he had not been informed of the existence
of pentosuria.
The fourth and fifth cases were published by Dr. Bial. The fourth was
that of a merchant from Warsaw, aged thirty-seven, who suffered from mild
270 PENTOSURIA
gastric and intestinal symptoms and supposed himself to be a diabetic. Small
amounts of sugar had been frequently found in his urine, and a suitable diet
had been advised. The report from a Warsaw chemical laboratory shows
slight quantities of sugar found by Trommer’s test and a positive reaction to
phenylhydrazin. This patient was also conspicuously thin. Bial determined
that pentose was present in the urine in July, 1898, as well as constantly for
twenty days in July, 1899, but no grape sugar could be found.
Case V (Bial). A druggist, twenty-eight years old, perfectly well. The
amount of pentose in Case IV amounted to 0.3 per cent., in Case V, 0.35 per
cent.
Case VI. Reported by Dr. Fritz Meyer. A merchant, aged thirty-nine,
never previously ill, was rejected by a life insurance company six years ago,
and before the discovery of pentosuria, on account of diabetes. He was treated
in Carlsbad, was on a strict diet, and was declared to be cured as the examina-
tion of his urine by the polariscope showed optical inactivity. Five years ago
he married, and is now the father of a healthy child. His health, with the
exception of a mild attack of perityphlitis, has always been good. In April,
1900, symptoms appeared which gave rise to the suspicion of a constitutional
disease; his weight is said to have decreased decidedly; it amounted to 150
pounds. He complained of headache, lumbar pains, lassitude, vertigo, and
severe neuralgia, particularly in the region of the sciatics. The urine
amounted to 1,800 c.c.; it was clear, contained no formed elements, and was
without albumin. The urine reacted positively to Trommer’s and Moore’s
tests; being optically inactive it was examined for pentose, and pentosuria was
determined.
In the seventh case, the patient was an American lady, who had been several
times under treatment in Carlsbad on account of supposed diabetes. Her case
was always considered to be a severe one, for, in spite of the strictest diet, it
was never possible to render the urine aglycosuric. In this case quite a
decided amount.of pentose was found, over 1 per cent., but not the slightest
trace of grape sugar.
The eighth case (Dr. Brat) occurred in a lady, aged sixty-two, who for
several years was under professional treatment on account. of a presumably
mild diabetes. She had a slight degree of fatty heart, otherwise, however,
she was quite well. This lady has been under my observation for more than
a year, and in this entire time has never excreted grape sugar. In her case,
however, the urine was somewhat dextro-rotary, 0.2 per cent., and I believe it
therefore not unlikely that, besides inactive pentose, a dextro-rotary pentose
was present in slight degree.
Case IX. The brother of the patient just described (Case VIII), aged
about fifty, perfectly well. His urine showed about 75 per cent. of pentose.
According to analyses made by several chemists since 1892, 0.2 to 2 per cent. of
sugar was determined. One found only a reducing property in the urine but
no sugar. There is no question in my mind that the gentleman was not dia-
betic, for a breakfast containing large amounts of sugar gave no results. The
case is otherwise of no clinical interest; the other brothers and sisters present
neither diabetes nor pentosuria. ,
PENTOSURIA 271
Additional cases of pentosuria have been described by Colombini in mor-
phin habitués; by Caporelli in xanthoma, others by Reale and Romme, and a
case of alimentary pentosuria with glycosuria by Barszewsky.
It is not remarkable that so many cases of pentosuria have been confounded
with diabetes, for the qualitative tests are the same. The important ques-
tion is, and remains: Has pentosuria anything in common with diabetes? Have
pentosurics on account of their pentosuria a special liability to become diabet-
ics? On account of what has been above stated these questions must be
answered negatively.
Pentosuria is a disturbance of metabolism which is connected perhaps with
cerebrin metabolism, perhaps with the formation of galactose. Negatively the
principal point is that there is no evidence of insufficiency in the utilization of
the carbohydrates consumed with the food.
Another question now arises: What is the prognosis of pentosuria? It is
unwise to express a dogmatic opinion on this point since we have known
the disease for only a decade. Notwithstanding this, it may be said that the
prognosis is probably much more favorable than in mild diabetes, for the pen-
tosuric utilizes fully the starches and other carbohydrates which are adminis-
tered with the food, and the amount of pentose which he forms and excretes
is small, at most from 15 to 20 grams per day. This, therefore, represents
no more serious prognosis than the mildest cases of diabetes. Upon the other
hand it must not be forgotten that sugar is circulating in the blood. That
this is true is obvious from the investigations conducted by Bial and myself,
as we have proven the presence of arabinose in the blood. But the presence
of a large quantity of sugar in the blood leads to arteriosclerosis, and may
give rise to other changes.
Whether the pentosuric is more susceptible to infections than a healthy
person, as is the case with diabetics, is very difficult to say, for up to the pres-
ent time the data are very scanty. Upon the whole, and in the majority of
cases, the prognosis of pentosuria can certainly not be termed very serious.
Regarding therapy, such treatment as we employ in diabetes is out of place
in pentosuria, as is obvious from all that has been stated. In general only
this much is to be said: (1) A pure meat diet, according to the experience
of Fritz Meyer and myself, is not well borne by pentosurics, for neuralgic
symptoms, if present, are increased. (2) A milk diet is found to be particu-
larly advantageous.
In conclusion, a word regarding the frequency of the disease. Although
it may be assumed from the, as yet, scant publications that pentosuria is a
rare affection, I cannot admit that it is to be regarded as a curiosity like
maltosuria. Such a comparison is incorrect, for pentosuria, in the first place,
gives us a very interesting insight into disturbances of metabolism ; and sec-
ondly, it cannot be considered immaterial that a person, as in almost all of the
cases that have been cited here, should be supposed for years to be a diabetic,
and subjected to dietetic and mineral spring treatment which is absolutely
out of place. In life insurance the decision is of the greatest importance. The
pentosurics must at least be admitted to have as favorable a prognosis as the
mild cases of diabetes.
272 PENTOSURIA
If it be further remembered that nine cases have been detected in Sal-
kowski’s laboratory and in the First Medical Clinic of Berlin, the affection
cannot be so rare as many believe. Hence a knowledge of this disturbance and
of the means to its diagnosis is an absolute necessity for every physician.
Briefly the most important diagnostic factors are as follows: Positive
orcin test with negative fermentation test proves pure pentosuria; positive
orcin test and positive fermentation test denote pentosuria and glycosuria.
A turning to the right of the polariscope does not prove the non-existence
of pentosuria, for dextro-rotary pentose also occurs in the urine.
19
DISEASES OF THE BLOOD
BLOOD AND BLOOD EXAMINATION
By A. LAZARUS, Cuartorrensure (Brrzin)
THE examination of the blood, in comparison with other clinical investi-
gations, has very slowly forced its way into practice. While the conscientious
physician rarely fails to make an examination of the urine or of the sputum
in cases in which it seems necessary or at all useful, examinations of the blood,
even the simplest, have up to the present been resorted to by a very small
number of practitioners.
The object of this article is to call attention to the necessity of clinical
blood investigation, and to describe the simplest methods. It will then become
a matter of routine to examine the blood no less frequently than the various
other secretions, excretions, or inflammatory products.
Of course, the importance of the results of blood investigation in different
diseases of the blood is not always equally great. In the cases in which a dis-
ease of the blood or of the blood-producing organs comes into question, an
examination of the blood is more important than any other clinical research,
and often this alone will guide us to a definite opinion. This is true of the
various forms of anemia, of leukocytosis and leukemia, of many diseases of the
bone-marrow, and in certain parasitic diseases of the blood. [There can
hardly be said to be “ many diseases of the bone-marrow ” recognized to-day,
and the blood has never yet helped much to advance our knowledge in this
direction. .
Parasitic diseases of the intestine and other internal organs should be men-
tioned here among those in which blood examination is of great diagnostic
value.—ED. ]
The number of cases is, however, disproportionately greater in which an
examination of the blood, although actively complementing other methods, is
alone not decisive. It may be of value in the differential diagnosis between
various acute infectious diseases; it may make clear the nature of many cases
of poisoning ; in the prognosis of many bacterial diseases we may under some
circumstances find points of support in the condition of the blood ; the prophy-
laxis and therapy of malaria, according to Robert Koch’s investigations, can
only be made certain by regular examinations of the blood, and to these many
other examples might be added [e.g., trichiniasis, filariasis, uncinariasis,
trypanosomiasis.—ED. ]. ;
That the history under some circumstances may become enriched by an
examination of the blood is obvious if we remember that after recovery from
275
276 BLOOD AND BLOOD EXAMINATION
certain infectious diseases protective bodies may be demonstrated in the blood
serum.
After these brief indications it will be seen that we have quite a large field
of activity, even if we limit ourselves to such an investigation of the blood
as is of immediate clinical importance. It is impossible, however, to omit a
brief explanation of the normal physiology and anatomy of the blood, as this
enables us to measure the degree of pathological change liable to occur.
We must first decide upon the best method of obtaining the amount of
blood necessary for investigation. Of course for clinical purposes only those
methods of examination are valuable which need no more than one or two
c.c., or—if there be a necessity for frequent repetition—a few drops of blood.
Consequently, many clinical methods, compared with strict physiological
processes, suffer more or less in reliability. This fact has lately given rise to
an endeavor to modify certain physiological methods which hitherto have
necessitated large quantities of blood. The results have, in the main, been
rather unsatisfactory. This is true, for example, of the “clinical” estima-
tion of the alkalinity of the blood, and of the iron and phosphorus in the blood.
If large quantities of blood cannot be obtained, it is better to refrain entirely
from such estimations than, by an appearance of exactness, to produce figures
of questionable value.
Fortunately, however, for many important clinical investigations, only a
few drops of blood are necessary, and these are best obtained under aseptic
precautions by a simple prick of the finger, of the toe, or of the lobe of the ear.
[In America the finger is rarely used, as the pain of puncture is much greater
than in the ear. An ordinary glover’s needle (bayonet-pointed) is convenient,
cheap and efficient. A sewing needle can be used but does not answer nearly
as well—Ep.] By friction or by active muscular movement these portions of
the body may previously be made somewhat hyperemic. In general the choice
of the place is immaterial; for smear preparations the finger is preferred.
In very sensitive patients, provided the investigation is to be repeated fre-
quently, the ear is chosen. The prick is made with half of a steel pen or with
a Soennecken’s lancet; but we may also use the so-called “ pistol knife” in
which the needle-shaped knife may be adjusted, and, by pressure of the spring,
inserted to an exact depth.
If larger quantities of blood, i.e., a few cubic centimeters or more, are
necessary it is advisable, provided there is no contra-indication, to obtain the
material by wet cups; in which proceeding it must of course be remembered
that blood thus obtained is more or less admixed with lymph. Finally punc-
ture of a dilated vein of the arm by the aid of a Pravaz syringe, which is very
readily performed, or an ordinary venesection may be resorted to.
The withdrawal of blood, if performed aseptically, is entirely without dan-
ger and, as a rule, does not disturb the patient in the least. We should never
forget, before proceeding, to assure ourselves that we are not dealing with a
hemophilic. In such persons, even with a simple puncture of the finger, there
may be great difficulty in stopping the flow of blood. [In such cases a mere
touch of the needle point to the skin will give us all the blood needed without
producing any troublesome hemorrhage.—Ep. ]
HEMOGLOBIN 277
I. HEMOGLOBIN
The exuding drop of blood shows even to the naked eye a number of prop-
erties. The redder it is, the richer it is in oxyhemoglobin; the darker, the
greater the amount of reduced hemoglobin. Accordingly, it is at once recog-
nized from these properties whether the blood originates from the arterial and
capillary vessels or from the venous system. In carbonic acid poisoning the
color of the blood is particularly bright and, as a rule, is designated as
cherry-red.
In the red oxygen-containing blood differences in the intensity of the color-
ing are readily determined, but these are frequently not easy of recognition
in very dark venous blood. Such differences become more noticeable if the
drop of blood is caught and spread out upon white linen or upon white blot-
ting paper; the greater or lesser staining power of different drops of blood is
very well demonstrated in this simple manner, and, with some practice, from
the color of the stain a conclusion may be drawn as to the AMOUNT OF HEMO-
GLoBIN in the blood. Following this principle, Tallqvist has described a
“hemoglobin scale” by the aid of which gross differences in the amount of
hemoglobin may be quite accurately estimated. [The Tallqvist scale gives us
not ideal accuracy but all the accuracy that we can use in diagnosis, prognosis
and treatment. Its errors rarely exceed 10 per cent., and in the hands of the
unskilled other and more “ accurate ” instruments often show more errors than
this. The cheapness of the scale and the ease and quickness of using it are
also important recommendations.—ED. |
Accuracy is greater with apparatus especially constructed for the estima-
tion of the coloring power of the blood, the so-called hemoglobinometer. This
apparatus is quite properly named ; for, in the main, it is the amount of hemo-
globin contained which determines the coloring property of the blood; the
importance of a few other coloring substances contained in the blood is in
comparison quite insignificant.
For clinical purposes a large number of blood colorimeters have heen de-
scribed; on account of their simplicity Gowers’s hemoglobinometer and
Fleischl’s hemometer are most used, and will now be described (Dare and
Oliver).
The principle of the Fleisch] hemometer, as modified by Miescher, is the
following: By the aid of a pipette which is furnished with the apparatus (Fig. 9
Mel.) an exactly determined amount of blood is dissolved in a measured quan-
tity of distilled water; the color of this solution is compared with that of a
colored glass wedge which, by its gradually increasing thickness, represents a
scale of blood concentrations. The point in the wedge is now searched for
which is just as intensely colored as the solution of blood that is to be exam-
ined, and the number is read off which is found at this point of the glass
wedge. If, for example, the color of the blood solution is equal to that desig-
nated as 75 in the glass wedge, it means that the examined blood contains
75 per cent. of the normal amount of hemoglobin. Besides the estimation
of the percentage of hemoglobin, this apparatus also makes it possible to
278 BLOOD AND BLOOD EXAMINATION
reckon the absolute amount of hemoglobin in milligrams in 1 c.mm. of blood.
[It is essential to remember that percentage readings are very misleading when
applied to children, since their normal is about 75 per cent. of the normal of
adult men. Women’s blood contains 10-15 per cent. less coloring matter than
men’s. All hemoglobin instruments should be graduated in milligrams per
c.mm. of blood instead of in percentages of a supposed “ normal.”—Ep.] The
investigation is rather laborious because it can only be carried out with arti-
ficial illumination. The apparatus is quite expensive on account of the diffi-
culty in manufacturing the glass wedge. Its use, however, is valuable, for
an investigator in constant practice is able to reduce the errors to 5 per cent.
and less.
The little apparatus of Gowers works on the following principle: A tube
contains a standard color solution which possesses the tint of a diluted watery
ICHERT, WIEN
Fic. 9—Hemometer. (After v. Fleischl-Miescher.)
hemoglobin solution. In a graduated glass tube of the same size a small but
accurately determined amount of blood is diluted with water until it is the
same color as the color in the test-tube; naturally this occurs the sooner the
thinner the blood is at the beginning. If, for example, an equalization of
color is reached at 60, this indicates that the blood only contains 60 per cent.
of hemoglobin in comparison to normal blood.
This test is quite simple and it may be completed in a few minutes during
the office hour; the apparatus is very cheap. With a well made instrument
the errors may be reduced to from 10 to 5 per cent. I must call attention to
the fact that the manufacture of this apparatus is carried on by some quite
unreliable manufacturers, so that, for example, test solutions are furnished in
HEMOGLOBIN 279
color tints such as thin watery blood solutions never show. Probably because
of these poor instruments, there has been a partial opposition to the use of the
Gowers apparatus.
A short time ago Sahli made a change in the Gowers hemoglobinometer,
which appears to have added greatly to the value of the apparatus. For this
purpose the measured quan-
tity of blood is first placed
in a slightly diluted hydro-
chloric acid solution which
produces a dark brown so-
lution of hydrochlorate of
Fie. 10.—Hemomerer. (After Sahli.) Fig. 11.—Hremometer. (After Sahli.)
hematin. This mixture is then diluted with water until it corresponds ex-
actly in color to a test solution which is furnished with the apparatus, which
also consists of hydrochlorate of hematin in a definite dilution. From the
amount of water necessary to produce this correspondence in color, we may
estimate the amount of hemoglobin in the drop of blood that has been
tested. In its mechanism the apparatus is much superior to the original,
as may be seen in the two illustrations which are placed side by side (Figs.
10 and 11).
Among other instruments (of which there is a great number, each investi-
gator having his favorite one) I should like to mention one of the latest, the
practical importance of which upon a large scale must still be proven, and the
use of which is somewhat more difficult than of those previously depicted H the
principle, however, is interesting, and differs greatly from that of the colorime-
tric ones that have been described ; for this reason it is necessary to compare its
results with those obtained by the aid of other instruments. I refer to the
hemophotograph of Gaertner (see Figs. 12 and 13). Gaertner started
the observation that the permeability of a diluted watery blood solution for the
photographic rays of sunlight was in inverse proportion to its hemoglobin con-
tent. For this reason he spreads the blood solution to be examined in a layer
of definite and uniform thickness, lays photographic paper under it, and per-
280 BLOOD AND BLOOD EXAMINATION
mits the sunlight to penetrate this for a definite time. The degree of black-
ening which the paper shows under the blood layer is compared with a stand-
ard scale, and then the hemoglobin is read from a table which has been obtained
empirically.
In quite a series of investigations I have compared
the results obtained with the apparatus of Gowers and
Gaertner and have found reasonable uniformity.
-_—)
a
ARNO
huss
Fic. 12.—Hemornorocraru. (After Gaertner.) Fig. 13.—HEMOPHOTOGRAPH.
(After Gaertner.)
When by the aid of some of these instruments a result has been obtained,
it must always be borne in mind that no exact test has been made, that, on the
contrary, all sorts of errors may be present. Those which are due to the
imperfections of the instrument I have already pointed out; and we must
always assume 5 to 10 per cent. of errors in the examination of a definite drop
of blood, even although we are quite expert in the examination; with the
novice this percentage may be much greater. Unfortunately, it is impos-
sible by the use of more exact so-called physiologic methods to avoid these
errors in the estimation of hemoglobin, partly because the methods are com-
plicated, and partly because they require too large amounts of blood, and,
therefore, cannot be utilized in practice.
To these errors, which are, however, due to the methods or instruments,
still others must be added which are due to a certain changeability in the
blood itself. It is well known that the most varied influences may change
the caliber of the blood-vessels, by stimulating the vaso-dilators or the vaso-
constrictors; for example, light, heat, cold, muscular activity, etc. Accord-
ing to the caliber of the vessels—of course within certain narrow limits—
the number of corpuscles in the capillary blood will vary, and with this the
amount of hemoglobin, the specific gravity, the total solids and the albumin
contents of the blood. Moreover, if the blood to be examined is not obtained
by puncture or incision of the blood-vessel directly, but, as in the great major-
ity of cases, by a prick in the finger or by wet cups, the unavoidable admixture
COUNTING THE BLOOD-CORPUSCLES 281
of tissue lymph to the blood means another source of error, although in itself
not a great one.
In spite of all these objections, which should be constantly borne in mind,
the clinical estimation of hemoglobin is of great value; in practice it is un-
questionably more important than all other methods of blood examination.
The decision of the most important question, whether the patient be anemic
or not, can only be made positively by a hemoglobin test. The physician
should accustom himself to look upon an examination of a patient as com-
plete only after the blood has been examined by the aid of a hemoglobinometer ;
then a surprisingly large number of persons will be found whose blood will
show quite a different condition from what might have been expected before
the examination from their general appearance. My estimation is rather too
low than too high when I say that fully one-half of those who are pale, who
have pale mucous membranes and cool extremities, and for this reason usually
designate themselves as “anemic,” show a perfectly normal amount of hemo-
globin. Such persons do not suffer from an abnormal composition of the
blood, but: from its abnormal distribution. That the- greatest differences in
regard to treatment will result from this in individual cases certainly requires
no further demonstration. I shall only point to the futility of many a treat-
ment by iron; due to the fact that the treatment was begun without any indi-
cation for it, i. e., without proof of a diminution in the amount of hemoglobin.
A careful test of the amount of hemoglobin in the blood would in many cases
cause us to relinquish the iron treatment and lead to the use of other cura-
tive methods.
In conclusion I must add that a diminution in hemoglobin may occasion-
ally be discovered where the external appearances by no means indicate anemia ;
of course a correct estimate of the degree of anemia in such cases must depend
upon a test of the hemoglobin.
The chief value of the clinical investigation of hemoglobin depends upon
the fact that it soon informs us whether and to what degree the blood may be
looked upon as anemic; from this we can determine whether to investigate
the blood for other changes or not.
II, COUNTING THE BLOOD-CORPUSCLES
For this purpose we use exclusively the Thoma-Zeiss counting apparatus
(Fig. 14). This consists of a pipette G with a mixing chamber #, in which
the one or ten per cent. blood dilutions are made; and of a counting chamber
D and ¢ in which under the microscope 400 divisions may be recognized, each
containing z255 cmm. In counting the red blood-corpuscles the following
method is pursued: The blood is sucked up to a definite mark in the capillary
tube, and then diluted with a preserving fluid. We use exclusively Hayem’s
solution, the composition of which is the following:
Mercurie ehlorid, ..cc4c6¢sas Sew deraeee eek Heesus 0.5
Sodium sulphate ...... cc. sees eee eee eee eee .. =—5.0
Soditin Chlorid, sess eee ele aed y aah eee ca oe 1.0
Rife Desbe aay das dees te ern seo 40s Kura ee CORRE IRE RK 200.0
282 BLOOD AND BLOOD EXAMINATION
A drop of the diluted solution is allowed to fall upon the counting cham-
ber, the cover-glass is placed over it, and this is permitted to sediment for a
short time. [Tiirck’s emendation of this step in technic is of value. Before
sap
yseensiiy
r fi i ina vi Omm. a
Cf ne
EEE EEE | omm.
XC tt r00 I
Fic. 14.—HemocytometTer. (After Thoma.)
blowing out a drop of diluted blood upon the counting-dise, he puts on 2
corners of the shelf (W, Fig. 14), that is, to support the cover-glass, a minute
drop of water. The diluted blood drop is then adjusted on the counting dise
and as rapidly as possible the cover-glass is let down and pressed firmly into
position by strong pressure with the thumbs.
Newton’s rings are then visible at once, and the
cover-glass is sealed firmly in position.—Ep.]
After which (using about 300 diameters magnifi-
cation) as many as possible of the squares in view
should be counted. If, for example, we have
diluted the blood 1:100 and then count in 32
squares (Fig. 15) 300 red blood-corpuscles, the
following calculation is made (we must multiply
with 100 to compensate for the blood dilution) :
300 xX 4000 x 100
Fie. 15.— Tse Microscopic 32
PictuRE witH Bioop-Cor- Za! We
pusctes. (After Landois.) This is the number of red blood-corpuscles con-
tained in a ¢.mm.
Any one in constant practice with this instrument possesses an exact meas-
uring apparatus in which the danger of error is very slight; naturally, the
aggregate of inaccuracies is less when more squares are counted. [Of course
the amount of error depends on the number of squares counted. With men
properly trained no constant practice is needed. My own practice is to count
100 squares. The error is then negligible—Eb. ]
It must be noted that, particularly in extreme anemia, the number of
blood-corpuscles may easily be reckoned as too low, since the microcytes which
occur here are apt to be missed if we are using a low power. Obviously the
observations we have made in regard to the variation in the composition of
= 3: 750,000;
COUNTING THE LEUKOCYTES 283
the blood, in speaking of the hemoglobin test, are also true as regards the
blood-count.
In practice the value of the determination of the number of red blood-
corpuscles is not very great, but it is important in any careful study of cases.
This is obvious if we realize that the amount of hemoglobin and the number
of blood-corpuscles are not always exactly proportional; that, for example, a
diminution in the hemoglobin contents to 50 per cent. does not necessarily
imply a diminution of erythrocytes from 5,000,000 to 2,500,000 ; they may be
above or below this. We designate as the average “value” (V) of the indi-
vidual corpuscle a i.e., the division of the percental hemoglobin figure by
the percental diminution or increase of the erythrocytes. [“ Color-index” is
the word generally used in America instead of “value.”—Ep.] If, for exam-
ple, the amount of hemoglobin has been reduced to 50 per cent., the erythro-
cytes being 2,500,000 to the cmm., the average “value” has remained 1; if,
however, with 50 per cent. hemoglobin only 200,000 red blood-corpuscles are
present, the V has even risen to 1.25 ($9). On the other hand, the
“value” is only 0.8 if we have only 40 per cent. hemoglobin and 2,500,000
red blood-corpuscles. This “value-estimation” is of importance for the rea-
son that the various types of anemic conditions are distinguished by the
“value” [or color-index] of the blood; for example, in chlorosis or in post-
hemorrhagic anemia [or, in fact, in any well-marked secondary or symp-
tomatic anemia.—Ep.], V is often decidedly below 1, while in progressive
pernicious anemia it is frequently decidedly above 1.
The number of red blood-corpuscles to the c.mm. upon the average amounts
in men to 5,000,000, in women to 4,500,000. [Hewes and other Americans
have noted that in healthy American adults the number of red cells is usually
near 6,000,000, often above that figure—Ep.] In most anemic conditions
this is reduced, and values below 1,000,000, even as low as 300,000, have been
seen without absolutely precluding the recovery of the patient. On the other
hand it must be emphasized that a normal number of erythrocytes is not
proof against the presence of anemia, unless the amount of hemoglobin is
also normal.
Under certain circumstances, some of which have not yet been sufficiently
explained, a decided increase of red blood-corpuscles occurs, a hyperglobulia.
This is, for example, the case in the various forms of stasis of the circulation,
but it is also the expression of an actual increase of blood formation. Under
such circumstances, Tiirk, for instance, found 9,150,000 erythrocytes.
[Cases of this type were first described by Cabot in 1899, later by Osler who
noted particularly the enlargement of the spleen associated with the poly-
cythemia.— Eb. ]
Ill. COUNTING THE LEUKOCYTES
To count the white blood-corpuscles we use a dilution of only 1 to 10,
which may be done in the large-bore mixing pipette in the Thoma apparatus.
In order that counting may be facilitated the red blood-corpuscles are
284 BLOOD AND BLOOD EXAMINATION
destroyed, and for this purpose the blood is diluted with 0.5 per cent,
acetic acid solution. This process has only one disadvantage, viz., that the
nuclei of erythroblasts which may be present cannot be differentiated from
white blood-corpuscles. In general, however, this error is quite without im-
portance.
The normal number of white blood-corpuscles in a c.mm. of blood varies
between 5,000 and 10,000.
By an estimation of the absolute number of white and red blood-corpuscles
we simultaneously learn their proportion to each other, the importance of
which we shall describe somewhat more minutely at another place.
IV. SPECIFIC GRAVITY
The most exact method, one easily ‘carried out with some practice, is that
of Schmaltz. For this purpose we require one or more drops of blood, about
0.1 to 0.2 «ce. This is sucked up into small glass capillaries that have been
previously weighed upon an accurate chemical scale, noting how much they
weigh when empty, and how much after having been filled with distilled
water at a temperature of 15° C. Then the weight of the tube filled
with blood is determined, and the specific gavity of the blood is cal-
culated by dividing its weight by the weight of the same amount of distilled
water.
Hammerschlag’s method has been the most extensively used from the fact
that it does not necessitate an expensive scale, but only a simple aérometer
with divisions from 1.010 to 1.070.
This process is based upon the physical law: “A body floats in a fluid
of the same specific gravity.” According to Hammerschlag a medium-sized
drop of fresh blood is permitted to fall into a benzol chloroform mixture; if
the blood after being dropped into the fluid sinks still lower, it is heavier
than the mixture, and by the addition of a corresponding amount of chloro-
form an attempt is made to compensate for this. If the drop of blood remains
upon the surface it is lighter than its menstruum, which is now made lighter
by the addition of more benzol. If, finally, the blood drop remains at the
height at which it is first dropped, it possesses the specific gravity of the
benzol chloroform mixture, which may easily be read off by the aid of the
aérometer. As the blood drop under the influence of the fluid surrounding it
readily changes its weight, splitting into many small particles, this process
must be catried on very rapidly or fresh drops must be constantly made use of.
The benzol chloroform mixture can always be utilized for new estimations, as
it is readily freed from blood by filtration.
In exactness, Schmaltz’s pyenometer is decidedly superior to Hammer-
schlag’s method.
In normal males the specifie gravity of the total blood is 1.059, in normal
women 1.056 upon the average.
In general, the estimation of the specific gravity only complements or con-
firms the results obtained by hemoglobin estimation. According to minute
exact investigations the amount of hemoglobin and of the specific gravity
SPECIFIC GRAVITY 285
are equal to one another, so that by this somewhat more complicated method
of examination we learn no more than may be more simply determined.
There are also tables from which we may read off directly the specific gravity
of the blood with a definite amount of hemoglobin, and vice versa. This
intimate dependence is clear without further explanation: The hemoglobin,
as the principal constituent of the red blood-cell, determines the greatest
fluctuation in the gravity of the total blood, especially since the fluid of the
blood is of an extraordinary constancy in its composition. Only when the
specific gravity of the blood serum becomes decidedly lighter than the normal
will the parallelism between hemoglobin and specific gravity of the total blood
be destroyed.
Closely related to the estimation of the specific gravity are the quantitative
estimation of the total solids and the estimation of the amount of albumin
’ or nitrogen of the blood. Neither method has as yet been adopted in practice,
partly because they are much too difficult, and partly because they do not
enable us to form any opinion which we cannot otherwise arrive at much
more readily. It must be added that the result of the estimation of nitrogen
in some cases cannot be utilized at all, for, besides the hemoglobin and the
white blood-corpuscles, other nitrogen-containing substances, of other origin,
may be present in the blood and in an indefinite amount. In reviewing what
has been written in special works upon the subject regarding these methods
of investigation, we must say that they have added nothing distinctly new
to hematology.
The investigations which have been made with the total blood have been
extended for scientific purposes to the individual constituent parts, also par-
ticularly to the estimation of the amount of albumin and of the specific
gravity. The separation of the two integral parts, BLOOD-CORPUSCLES AND
SERUM, may be made in a simple manner either by sedimentation or centrifu-
gation. Material for investigation may be procured even from a few drops
of blood; it is sucked up into small glass tubes in which the serum, at the
latest in twenty-four hours, may be spontaneously expressed.
As the most important result of these researches, it must be emphasized
that the serum in some pathologic conditions does not take part in the
changes of the total blood but retains its composition. Thus, according to
Grawitz, the serum in chlorosis and in progressive pernicious anemia does not
fake part, or to a very slight extent, in the hydremia of the total blood, and
invariably shows normal quantities of total solids. In chronic nephritis, the
hydremia of the total blood is chiefly attributed to the decided increase of
water in the serum.
I shall mention still other methods of blood examination, although they
have not as yet been considered of importance in practice; because it seems
advisable briefly to describe some conditions of which mention is occasionally
made, For, since the purpose of this article is the stimulation of more
frequent hematologic investigation in practice, we must consider not only
those methods which have heen found of practical value, but those with which,
in spite of great efforts, little or nothing has been demonstrated either theoret-
ically or practically.
, 286 BLOOD AND BLOOD EXAMINATION
V. ALKALINITY
The estimation of the ALKALINITY of the blood must be first mentioned.
That fresh blood has an alkaline reaction cannot be directly determined by
the use of litmus paper on account of the color of the blood, but a particularly
sensitive red litmus paper must be moistened with a dilute sodium chlorid
solution, then the blood to be tested must be dropped upon it and the paper
be rinsed again with a sodium chlorid solution. It is very difficult to deter-
mine the degree of alkalinity with any accuracy. In the newer methods the
blood to be used is made of a lacquer color, and this is titrated against a
normal tartaric acid solution with lacmoid paper. For this purpose we usually
require somewhat larger quantities of blood, 5 to 8 cc.; C. S. Engel has,
however, constructed an “alkalimeter ” which makes it possible to carry out
the test with zy ¢.c. of blood.
How slight is the importance of these investigations, even to-day, is shown
by the reports of various authors that even the normal values vary within
wide limits; for instance, from 203 (Canard) to 508 (Loewy) mgm. NaOH
in 100 cc. of blood. With such differences in the normal value, it is not
surprising that results obtained under pathologic conditions give rise to con-
clusions still less definite. Thus, one author found increased alkalinity in
certain diseases in which another found decided diminution.
In the present status of the question, we must be cautious in introducing
such an uncertain method of investigation into practice; for, since the result
is finally expressed in figures which have a deceptive appearance of exact-
ness, it is much more misleading than the most subjective method of exami-
nation.
We are by no means convinced of the biologic importance of the alkaline
reaction of the blood. Many authors are inclined to look upon the bactericidal
properties of the blood as bearing a certain parallel relation to the alkaline
reaction of the blood, but are unable to prove the correctness of this view.
Even with such a proof little appears to be gained. For it is self-evident
that a definite degree of alkalinity means a relative optimum for bacteria,
since the increase of alkalinity at once produces for them unfavorable
conditions.
I must call attention to the fact that Brandenburg may perhaps have
opened a way out of these uncertainties by his recent investigations. Bran-
denburg demonstrated that we must differentiate between the alkali combined
with albumin and that combined with carbonic acid. These elements can
be separated from one another since the latter is capable of diffusion, while
the alkali combined with albumin is not. Thus it was shown that the
diffusible part of alkali represents a very constant value corresponding to
about 60 mgm. NaOH—while the non-diffusible part is exposed to the
greatest variations. It is now conclusively shown that under pathological
conditions even when there is great variation of the total alkalinity from
the normal, the amount of diffusible alkali—* the alkali tension ”—remains
almost unchanged.
SPECTROSCOPIC EXAMINATION 287
VI. VOLUME OF RED CELLS
Some authors attach a certain value to the determination of the volume
of the red blood-cells in a definite amount of blood. For the correct estima-
tion of this various instruments have been invented, and either those in which
the blood-corpuscles are separated from the serum by centrifugation (“hema-
tokrit”) or those in which this occurs by spontaneous sedimentation, can be
employed. Every method should be rejected in which salt or a salt solution
is used to prevent the coagulation of the blood. For the volume of red
corpuscles remains uninfluenced only when it comes in contact with an isotonic
salt solution; as, however, particularly in pathological conditions, a special
concentration is isotonic for each kind of blood in each individual case, the
estimation of the volume would first depend upon a previous determination
of the isotonic salt solution; and such a difficult process can be of no use
in practice.
The method which we owe to Koppe is very valuable because coagulation
is prevented in the centrifugal tubes of his hematokrit by the absolutely
smooth walls of the tubes. As the blood, therefore, remains unmixed we may
perhaps assume that, after complete centrifugation, the proper proportion of
plasma and cells as it exists in the blood-vessels is shown.
If, however, the pathology of the blood is investigated by estimations of
volume, the figures obtained by these instruments show nothing that may be
looked upon as enriching our knowledge or promoting our understanding
of diseases of the blood; and I only refer to this method for the sake of
completeness, with the express statement that at present it cannot be consid-
ered a clinical method of investigation.
VII. SPECTROSCOPIC EXAMINATION
For certain methods of examination of the blood the use of the sprcTRo-
SCOPE must be understood, for in the recognition of various hemoglobin com-
binations which are characteristic of certain conditions, particularly of poison-
ing, the spectroscopic investigation of the blood is absolutely necessary and
enables us to reach conclusions not to be arrived at by the microscope or any
other methods. The principle of this method must be considered as under-
stood; but it may be mentioned that in qualitative investigations, as a rule,
a so-called pocket spectroscope is sufficient, and that it is well to place the
blood for examination in watery solutions of varying concentrations between
two plane parallel glasses.
The determination of CO-Hb and of methemoglobin, the former occurring
in carbonic acid poisoning, the second in various forms of intoxication, par-
ticularly with potassium chlorate, is of the greatest practical importance. The
spectroscopic determination of methemoglobin, as may be noted from the
adjoining table, is possible by characteristic absorption lines (Fig. 16). (The
determination of CO-Hb is difficult on account of the similarity of the spec-
trum with that of O-Hb. The differentiation is only certain when we observe
288 BLOOD AND BLOOD EXAMINATION
that the line of CO-Hb does not disappear upon addition of reduction agents,
for example, ammonium sulphate, because CO is firmly combined with hemo-
globin; while the spectrum of O-Hb is changed by the same agent to that of
reduced hemoglobin.
Aa BE D
4o 50 bo
rill il obubiitben wt
| TT
| oe |
i)
a nh
‘LLL ‘a
ns |
a ir eu ey a TEC
50 100 io
be et D E F
Fig. 16.—Tue Various AssorpTion Specrra or Hemoctosin. In all of the spectra the
various Fraunhofer lines and a scale in millimeters are drawn. (After Landois.)
Finally, the slightest degree of hemoglobinemia may be demonstrated with
certainty by the spectroscope in those cases in which ocular examination
leaves a doubt as to whether or not the serum contains hemoglobin.
VIII. AGGLUTINATIVE REACTIONS
To the law of immunity which has made us acquainted with the vital
importance of functional changes in the blood we owe a valuable diagnostic
method. We know that in the natural infections of man, as well as in
animal experiment, peculiar changes occur in the blood serum, under the
AGGLUTINATIVE REACTIONS 289
influence of specific bacteria or bacterial toxins. Among these we may differ-
entiate two classes: The antitoxic sera and the bactericidal sera; the first
variety is represented by the serum containing diphtheria antitoxin, the second
by the energetic bacteriolytic action of the blood serum in convalescence from
cholera.
As a variety related to the last group the agglutinating scrum may be
included, which occurs during the course of, and after recovery from, many
infections. We are most familiar with this condition in enteric fever, in
which it first led to valuable and practical diagnostic results.
The essential part of the phenomenon is that, in a mixture of such serum
with typhoid bacilli in a culture medium, they are deprived of their motility
and clump, i.e., “ agglutinate.” To determine this fact a few drops of serum,
1 to 2 cc., are sufficient, and these may be most easily obtained by centrifuga-
tion or sedimentation in thin glass tubes. The phenomenon may be demon-
strated macroscopically as well as microscopically (Gruber-Widal reaction).
In the former case, with nutritive bouillon after the addition of the serum,
we see how a profuse uniform turbid accumulation of typhoid bacilli clears
completely in from twelve to twenty-four hours, and a delicate flocculent
precipitate forms which, even by powerful shaking of the test-tube, can no
longer be disseminated.
The microscopic test is carried out in the following manner: A drop of
the typhoid culture which is to be utilized for the test is arranged as a hanging
drop, so that we may convince ourselves of the active motility of the bacilli.
If serum in an exact proportion is then carefully added to the collection of
bacilli, and one drop is placed under the microscope in a positive reaction,
we notice even after a few minutes, at latest after a quarter of an hour, a
complete cessation of movement, a clumping of bacteria in large groups, as
well as an indistinctness in their outlines.
[Another method is the following: A 3-inch test-tube of small caliber
is carried to the bedside of the patient together with a clean medicine dropper.
Ten drops of water are allowed to fall from this dropper into the test-tube.
The patient’s ear is then punctured in the ordinary way and a full drop of
blood is sucked into the dropper and then expelled into the water in the
test-tube. The test-tube is then corked and carried to the laboratory where
the culture is kept, and one drop of the blood and water mixture is mixed
with one drop of the culture and examined between slide and cover. There
is no need of separating serum and corpuscles in this test; the whole blood is
equally serviceable. : : :
For public health work the blood may be dried on tin foil, folded in, and
mailed to the State Laboratory where dilution is made by weight. This
method is extensively and most successfully used by the State Board of Health
in Michigan.—Eb. ] . aap
The value of this reaction test can only be properly appreciated if it 1s
carried out with certain precautions. First, we must assure ourselves of the
proper composition of the typhoid culture to be used in testing, and must be
sure that it is a fresh one, not older than a day. The serum requires, as
already stated, a corresponding dilution, because even normal serum if undi-
20
290 BLOOD AND BLOOD EXAMINATION
luted may cause agglutination; on the other hand, the dilution should not
be too weak, as the agglutinating substances in some cases of enteric fever
are not present in very large amounts, and if the serum be too greatly diluted
they are inactive. It is best to begin with a dilution of one part of serum
to thirty parts of bouillon, and, if a positive reaction be obtained, it should
then be determined with how weak a dilution we can still secure a reaction.
In some cases, a positive reaction has been obtained even after concentrations
of 1-5,000. If the test gives a positive result with a high dilution, the
diagnosis of enteric fever is thereby assured, with the one limitation that the
serum may perhaps have received its agglutinating properties from a typhoid
fever some time previously, even several years before.
If, however, the result of the test is negative with a dilution of 1: 30, it is
well to repeat it in the course of the disease, daily if possible. Frequently
it is noted that in the early course of the disease the serum, which at first
showed no reaction while diluted, gradually in slighter concentration betrays
the presence of agglutinating substance. But the diagnosis of enteric fever
cannot be excluded with certainty even in case of a continued negative result
of the reaction. The appearance of the reaction may be expected at the
earliest upon the eighth day of the disease.1_ [Since it is impossible to fix in
any way—except arbitrarily—the first day of the disease, it is hard to make
any accurate statement about the earliest appearance of Widal’s reaction.
At the time when patients first consult a physician, two-thirds of them show
a positive agglutination reaction in the blood, but in a few it is delayed as
late as the fifth or sixth week, or it may never appear. Over 95 per cent. of
cases, however, show a reaction at some time in the course of the disease.
Different epidemics vary greatly in these points, some showing a large pro-
portion of early reactions, while in others physicians complain of the high
percentage of negative reactions in the earlier weeks of the disease——Ep. |
In view of the very valuable diagnostic success of serum diagnosis in
enteric fever, it may be readily understood that an attempt would be made
to reach the same results in other diseases, but, unfortunately, there has been
as yet no practical success. Endeavors specially directed to the recognition
of tuberculosis by its specific agglutinating reaction may be looked upon as
futile, since Robert Koch reached entirely negative results in this direction.
IX. BACTERIOLOGICAL EXAMINATION
The diagnosis and also the prognosis may, under some circumstances, be
helped by the bacteriological investigation of the blood. There are quite a
* Lately Proscher (Centralbl. f. Bakteriologie, xxxi) has proposed a modification
which indicates a decided practical improvement. According to this it is particularly
valuable that a typhoid bouillon may be utilized in which the bacilli have been killed
by the addition of one part of a forty per cent. formalin to 100 parts of bouillon. This
bouillon may be used for weeks without losing its agglutinating property. For the
action of the serum upon the baci!li Préscher allows from one to two hours at blood
heat; for viewing the serum bouillon mixture which is kept in a bowl we employ a
low power dry lens (about 3, enlargement)
BACTERIOLOGICAL EXAMINATION 291
number of diseases in which, particularly in especially severe cases, the
pathogenic agents enter the blood. Formerly we contented ourselves with a
microscopic investigation of fresh or stained blood to determine the presence
of bacteria. But this process should only be resorted to for the determination
of the spirilli of relapsing fever, or, perhaps, of the bacilli of anthrax. In
other cases it may lead to errors, first because of the small number of germs
that may be present, and, secondly, because confusion with accidental bacterial
contaminations may readily occur. It is therefore advisable to puncture a
vein of the arm under strict antiseptic precautions, to withdraw 1 to 2 c.c.
of blood, and to prepare cultures, best in bouillon, or to determine by animal
experiments the probable presence of pathogenic bacteria.
In this manner we are able to determine with certainty in the circulating
blood the presence of streptococci, staphylococci, pneumococci, the bacilli of
enteric fever, of the plague, of tuberculosis and others. [Typhoid bacilli have
repeatedly been cultivated from the blood of doubtful febrile cases before
the Widal reaction had appeared. Hence this procedure may be of great
value in obscure cases. The same is true of the cultivation of pneumo-
cocci from the blood in obscure pneumococcus infections and “central pneu-
monias.”—Eb. |
The determination of the pathogenic agents just mentioned can only be
designated as an auxiliary factor in diagnosis, but the recognition of spirilli
in the blood is the only means for a positive diagno- O O
sis of relapsing fever. As a rule this determina- Cs ©
tion is very easy, for the peculiar curved form of ae
the spirilli (see Fig. 17) precludes confusion with —
other organisms. Their number is usually very O
large; our detection of them is greatly facilitated © , y Cj?
by their motility, and, finally, they stain readily (ae
with various anilin colors, for example, intensely ‘sca ee. QO
with fuchsin, so that they may be easily found ina © . Oy O
dry preparation even if present in the blood in 0 SS O wY
very eroal numbers. shire 5 ‘ Fic. 17.—Retapsinc FEvER
Probably in no other disease is the practical “geiniis, (After v. Jaksch.)
importance of blood examination greater than in
malaria. This is naturally not the place in which to describe the entire devel-
opment of the malarial parasite, nor even to mention all of the varieties which
occur in the blood, as a special article has been devoted to this important sub-
ject.1 Here it need only be mentioned that, in many cases, we should look
for the plasmodia in the blood, and should familiarize ourselves with the most
important points in the technic of examination.
In the investigation of the blood for malarial parasites for diagnostic
purposes, the stained dry specimen is unquestionably the most suitable, and
we shall explicitly describe its preparation in another place. For when very
few parasites are in the blood, this method alone assures their detection, and
©
O
1 Compare the article by Loeffler in the volume on “ Infectious Diseases.”
292 BLOOD AND BLOOD EXAMINATION
with very little practice it protects us more fully from error than an investi-
gation of the fresh blood.
The withdrawal of blood had best be made in the afebrile period; and
even here it must be borne in mind that, for as long a time as possible prior
to this, no quinin should be administered.
Fixing the preparation is best accomplished by the use of absolute alcohol
for five minutes. [It seems likely that all the fixing methods described in
this article will soon be replaced by the fixation produced by methylic alcohol
which is the menstruum in which the various “ Romanowsky ” stains are dis-
solved. Using Leishman’s or Wright’s modification of the Romanowsky
method we fix the specimen in the same fluid which later (when water has been
added) stains the specimen. This saves much time, trouble, the apparatus
and expense. The technic is given in detail below.—Ep.] Staining is best
done either by a one per cent. methylene-blue solution, or by the Chenzinsky
methylene-blue eosin mixture mentioned in another place, or after the method
especially proposed for the study of malaria by Romanowsky-Ziemann.
With an enlargement of about 500 and the use of an oil immersion, it is
not difficult even for the novice to recognize the fully developed plasmodium
within the red blood-corpuscles. First, the blue tint which they acquire from
the methylene-blue readily distinguishes them from the nucleus of the cell;
this is an uncommonly delicate sky-blue in contrast with the darker blue of
the nucleus, which more closely resembles the actual color of the material used
in staining. [With the Romanowsky stain which is now widely used in this
country for all blood-specimens, the nucleus is colored crimson and its con-
trast both with the blue of the parasite and the yellow of the surrounding
corpuscle forms thus one of the most recognizable features of the organism.
—Ep.] By the amount of pigment the recognition of the plasmodium is
also decidedly facilitated.
It is more difficult if only the very young forms of the plasmodia are
present, those which are still very small, and have not as yet formed pigment.
Occasionally the characteristic seal-ring shape facilitates their recognition;
frequently, however, the apparently structureless forms may be confused with
the nuclei or the fragments of a nucleus of the erythrocytes, or with the dots
of “stippled” erythrocytes. Here the character of the staining in particular
gives a point of support for their recognition. Observations made at a more
favorable time, and eventually an examination of the fresh blood to determine
the motility of these bodies, furnish convincing proof.
How important it is to carry out an examination for plasmodia is shown
by the fact that, according to Robert Koch, the prophylaxis as well as the
therapy of malaria is intimately connected with the results of the blood
findings.
The investigation itself, however, is so simple that it should never be
omitted in any case in which long protracted, perplexing fever is present, or
in which the history, or the condition of the spleen, or other clinical phenom-
ena point to the possibility of a malarial infection. Especially in regions
in which malaria is quite rare valuable time for the patient is frequently lost,
because the physician has neglected the examination of the blood, supposing
BACTERIOLOGICAL EXAMINATION 293
a septic disease or a tuberculosis, etc., to be present, and malaria has not been
recognized as the true cause of the morbid phenomena. [In this country the
opposite mistake is more common. Many cases of tuberculosis are miscalled
malaria because they have chills, and no proper examination of the chest or
of the blood is made.—Ep. ]
Among all the methods of blood examination used in the last decade un-
questionably the most far-reaching results have been attained by the investi-
gation of the NORMAL AND PATHOLOGICAL HIsToLocy of the blood; this was
particularly fostered by the technic of the dried preparation and the differ-
ential stains introduced by Ehrlich.
If a drop of fresh blood is placed under the microscope, enlarged about
500 times and examined with an oil immersion a number of important points
may be observed. There will first be noted, provided the layer of blood is
thin enough, the shape of the red blood-corpuscles, their depression, their
hemoglobin staining ; by this method also the rouleaux formation of the blood
discs becomes plain. The structure of the white corpuscles may be recognized
by this simple process, and various forms may be differentiated from one
another.
Thus the lymphocytes are perceived as cells about the size of a normal
red blood-corpuscle, though some attain double or even three times this size;
their nucleus is circular, takes up the greater part of the cell, and is sharply
demarcated from the narrow protoplasmic border surrounding it.
The majority of the leukocytes are conspicuous by their dense, decidedly
refractive, fine granulations; one, two, or three faint nuclei deposited in them
may be recognized. These cells are twice or three times as large as the
erythrocytes. In a few of the leukocytes present (eosinophiles) the granula-
tions are much more decidedly refractive, and the individual granules are
much coarser. These two last named forms are alike in size, as well as in the
conditions and the number and shape of their nuclei.
The blood-plaques are most easily recognized by their agglutination in
clumps and slight refractive power.
Studies of the more minute structure of the leukocytes can only be made
with difficulty by this simple method, as the forms not yet described are
usually only present in very small numbers. Moreover, in a prolonged exam-
ination, the blood soon suffers changes which produce disturbance. In con-
sequence of this the investigation of the fresh blood is of very little service,
and we are usually compelled to preserve the blood by a proper method and
to stain it. For these purposes there is no better process than the DRIED
STAINING PRocrss after Ehrlich [except the methylic alcohol fixation described
below.—Ep.], and this is as simple in its operation as it is serviceable. It
has the practical advantage that it allows the investigator to work quite inde-
pendently of the presence of the patient, to choose the time and place of
examination, and permits at any time a repetition of the investigation and
a demonstration of the result obtained.
The specimen is made as follows: Cover-glasses of about 18 mm., having
a quadrangular shape and of special thinness (0.1 to 0.08 mm.) are used;
294 BLOOD AND BLOOD EXAMINATION
these are carefully cleansed in ether and alcohol so that fat, fiber and all parti-
cles of dust are removed. [Water is sufficient for cleansing cover-glasses pro-
vided they are properly polished with silk or tissue paper afterwards.—Bb. |
On a cover-glass of this kind a small drop of blood which has exuded from a
prick of the finger is collected; this glass is dropped, blood side downward,
upon a second glass, with the result that the blood soon spreads out spon-
taneously in a thin film between the two very flexible glasses to about three-
quarters of their extent, as if in a capillary space. After a complete distribu-
tion of the drop of blood, the glasses are removed from one another [by
sliding off the upper of the two covers without any lifting or tilting, but
strictly in the plane of their surfaces—Eb.], and the blood is seen distributed
upon each in a uniform
layer. If the drop taken was
small enough, the blood cells
are found in an even layer
side by side without over-
lapping each other. In view
of the fact that the red
blood-corpuscles are dam-
‘aged with extraordinary ease,
especially by moisture, this
maneuver should not be at-
tempted with the unaided hand; for the moisture of the tip of the fingers is
capable of changing the outlines of the red blood-corpuscles and of extracting
their hemoglobin. For this reason, in the preparation of these specimens two
forceps should be used in the manner
depicted in Fig. 18. [For any one whose
fingers are not habitually and obviously
damp the use of forceps is unnecessary.
—Eb. |
When the blood films have dried,
which usually happens within twenty to
thirty seconds, it is necessary before
subjecting them to the stain to fix the
blood in a suitable manner. For practi-
cal purposes it is sufficient usually if the
specimens are placed for five minutes in
a solution of 1.0 formol in 100 parts of
absolute aleohol. After this method of
fixation almost all the stains which need
practically be considered may be em-
ployed. If we intend, however, to pre-
pare especially beautiful specimens, or
to make investigations for scientific pur-
poses, then Ehrlich’s old method—fxation by heat alone—had better be
utilized. Most serviceable for this purpose is a small copper kettle (Fig.
19) inside of which a small quantity of toluol is brought to the boiling point.
Fic. 19.
BACTERIOLOGICAL EXAMINATION 295
The thin copper lid of the kettle will, a few minutes after the toluol has begun
to boil, reach the temperature of the boiling point of toluol (111° C.). Upon
the plate heated in this manner the cover-glasses with the dried blood are
placed for thirty to sixty seconds, and this fixation is quite sufficient for most
of the staining methods.
Among the methods of staining the blood those of Ehrlich have shown
themselves to be the most successful. In particular his triacid solution, which
in its application is quite simple, brings out a great many points, and fur-
nishes reliable conclusions. The formula for its preparation is the following:
The three stains, orange G, acid fuchsin and methylene green, are prepared
in saturated aqueous solutions, and are mixed in the following amounts and
order (with thorough shaking during the process) :
Orange Gases or. eas aay eee Teles 13-14 ce.
CIC: TUCHSIN 6 4 cede de Mou ew dpa e SP eES oes 6- 7 “
AQyidest, 4.sirs Funstiet cag Sade ein care waa 15 a
Alcon Ol) Gaccitetns cy anty vitae hl Aone Rae n Stanek 15 a
Methyl greens. sesnsee ei uiu sinew ee us 25.5 “
AIGOKO) wayiainway ware eae eae eae 10 SS
GIVCOMMY wicca ewes eew eevee aueweoseanae 10 i
If the fixed blood preparation is allowed to float for about five minutes
upon a few drops of this staining solution, the staining is finished. There
is no danger of over-staining, even in a decidedly longer duration of staining.
The cover-glass is then thoroughly rinsed in water, carefully dried between
blotting papers and mounted in Canada balsam. ;
For certain purposes, as we shall see later on, this triacid solution is not
suitable, and we are compelled occasionally to use complementary stainings
with methylene-blue, or with methylenc-blue eosin mixtures. Formule for
such stains are the following:
Very instructive pictures are obtained if we stain for half a minute with
a solution of 0.5 eosin to 100 c.c. of a 60 per cent. alcohol, rinse in water,
and subsequently stain for two minutes with a watery methylene-blue solution
of 1-250.
Specimens of great clearness and elegance are obtained by a careful appli-
cation of the Chenzinsky’s methylene-blue eosin mixture:
Concentrated watery methylene-blue solution......... 40 ec.
0.5 per cent. eosin solution in 70 per cent. of alcohol... 20 “
Distilled Waters: ic cuv cusses wen cee eae ee ea RRS 40 “
This solution must be filtered each time prior to use; the staining requires
from six to twenty-four hours and, to prevent evaporation and the precipita-
tion of the staining material, must be carried out in air-tight closed cups.
By the aid of these staining methods we are enabled to recognize a number
of the peculiarities of the blood cells, which are indistinct or entirely unrecog-
nizable in fresh blood. Some of the newer, particularly the so-called “ uni-
versal,” stains have such glaring faults that,’ at least for the present, they
296 BLOOD AND BLOOD EXAMINATION
appear to be unsuitable for practice. [After using and teaching Ehrlich’s
method as just described for eight years, I have recently discarded it in favor
of one of the “ universal ” stains which our author here condemns. Leishman’s
“ Romanowsky ” stain made up by Wright’s method (see Journal of Med.
Research, 1902, vol. vii) is much quicker and easier to use, needs no fixing
fluid or heating apparatus, and gives pictures which in 99 cases out of 100
are superior to those obtained by Ehrlich’s method.
The technic is as follows: Adjust the cover-glass film in Cornet’s forceps,
Flood it with the stain, using a medicine dropper and keeping the bottle
tightly corked when not in use. After one minute add water drop by drop
until a greenish iridescent scum appears on the surface. About 7 drops are
needed with a % inch cover-glass. Allow the stain, so diluted, to act two
minutes. Wash in water, and allow the preparation to stand one minute more
in water. Dry in blotting paper and mount in Canada balsam.
This stain brings out all that Ehrlich’s method does and, besides this, stains
the blood-plates, the granules of mast-cells, the chromatin of malarial parasites
and the basophilic granules in abnormal red cells—all points of value.
The only weak point of the Romanowsky stains is the deceptive resemblance
between certain megaloblasts, certain lymphocytes, and certain myelocytes.
In perhaps 1 case in 100 this troubles a beginner; in perhaps 1 in 1,000
it troubles an expert; but in no case. does this difficulty affect the essentials
—the diagnosis, prognosis, or treatment of the case.—Ep. |
In examining normal blood which has been stained according to these
methods we note the following important peculiarities: The red blood-
corpuscles have been wholly stained with orange, that is, with eosin, and this
causes the unstained depression which is free from hemoglobin to stand out
prominently.
Among the white blood-corpuscles the lymphocytes must be first mentioned
(see colored plate, Row VII, a and b). Their nuclei show the above described
configuration, and on staining with a triacid ‘solution they are moderately
well stained with methylene green, the protoplasm, however, being of a very
pale yellowish color. [The nuclei are often so faintly stained as to be nearly
invisible. The protoplasm frequently remains unstained or shows a faint gray
color.—Ep.]_ In methylene-blue eosin ‘preparations the nucleus is deeply
stained with the blue stain, which is very frequently, however, found to be
more marked in the blue color of the rim of the protoplasm. This is an
expression of the fact that the protoplasm of the lymphocytes is more baso-
philic than its nucleus. In the not infrequent cases in which it is difficult to
determine the relation of a white blood-corpuscle to a definite cell group, this
condition is always a positive sign that the cell must be looked upon as a
lymphocyte; however, the absence of this reaction is not absolute proof that
the cell is not related to the lymphocytes, for, as may be noted from the
colored plate, the protoplasm occasionally shows a weaker stain with the
basic staining material than the nucleus.
The cells which, in fresh blood, we have recognized as finely granular and
polynuclear, are shown, in staining with the triacid stain (IX, 6) to have
pale green colored nuclei and very fine, almost dust-like granulations of a
BACTERIOLOGICAL EXAMINATION 297
reddish violet color, filling the entire protoplasm. The granulation owes this
color to the chemical action of a combination of the acid fuchsin and the
methylene-green produced by a “neutral” stain; for this reason these granu-
lations are designated as neutrophilic, and this variety of cells as polynuclear
neutrophilic leukocytes. As this granulation only stains in “neutral” dyes,
it remains unstained in the methylene-blue eosin mixtures that do not contain
a “neutral” dye stuff, and we therefore find in the polynuclear leukocytes
in this stain an entirely unstained protoplasm, while the nucleus shows an
intense blue (IX, a).
A small number of white blood-corpuscles by their staining and mor-
phology show a close relationship to the group described above; they only
differ in that the granulation is much more sparse, and that instead of a
polymorphic and intensely stained nucleus a larger, less indented, quite faintly
stained nucleus is present. These cells we designate as transitional forms
(see colored plate VIII, c). They are the stages immediately prior to the
polynuclear neutrophilic leukocytes which in part are formed from the fol-
lowing groups:
Large mononuclear leukocytes. This cell form is one which is most dif-
cult to differentiate from the lymphocytes; nevertheless this differentiation
is absolutely necessary. In the triacid stain they are remarkable for their
size, being three times as large as a normal red blood-corpuscle. Their
nucleus is large, comprising about one-third of the cell, usually eccentrically
placed, round, of a pale green stain; their protoplasm is almost unstained and
free of granulations (VIII, b). The cells stained in methylene-blue (VIII, a)
are often decidedly more characteristic. We have one prominent sign which
greatly facilitates the differentiation of this variety of cells from the larger
forms of the lymph-cells; namely, that while (as has been mentioned above,
and as may be noted from the colored plate) in the lymphocytes the boundary
between the nucleus and the protoplasm is sharply marked, in the large mono-
nuclear leukocytes the dividing line is indistinct, so that frequently we cannot
determine where the nucleus begins and the protoplasm ends. The proto-
plasm of this cell variety is apparently never more decidedly basophilic than
its nucleus.
The three last named cell forms constitute an intimately connected group,
that is, links in a chain of development the beginning series of which are the
large mononuclear leukocytes, and from these, by transformation and division
of the nucleus as well as by the extension of granulations, the transitional
forms and, later, the polynuclear neutrophilic leukocytes, arise.
The cell forms which in fresh blood are conspicuous by their coarse granu-
lations may also be readily differentiated from the others in the stained
preparation. Their nuclei stain with nuclear stains with medium intensity;
the granulations which almost completely fill the protoplasm. in the triacid
solution are orange or copper color (X, }), and in eosin-containing solutions
they are stained a brilliant red (X, a); unfortunately, in the reproduction
they are not very well depicted. On account of this property of acid dyes
(especially eosin) to attract these granulations, the entire cell is called
oxyphilic, acidophilic or eosinophilic.
298 BLOOD AND BLOOD EXAMINATION
Another variety of the white blood-corpuscles is the mast-cell (XI, a, 8, c),
the peculiarities of which cannot be recognized in fresh blood, but only upon
the use of very definite methods of staining. [Mast-cells are beautifully
stained by the Romanowsky method mentioned above——Ep.] These cells are
characterized by a quite coarse, often irregular, granulation which as a rule
only partly fills up the protoplasm. Their distinctive feature, however, is
the basophilic reaction of the granulations and their power to modify ‘the
color tone of most of the substances that stain them (“ metachromasia”), so
that, for example, with kresyl-violet R they stain almost pure brown, They
also differ from other granulations by their ready solubility in water, so that
they can only be stained in alcoholic, not in watery, stain solutions, There-
fore, the two staining mixtures mentioned above which are in most common
use are not suitable for staining the granulations of the mast-cells, but we
can best use for this purpose alcoholic solutions of methylene-blue, dahlia, or
kresyl-violet R. [See last note—Ep.] In the preparations stained with
triacid the mast-cells are recognizable, since the insufficient staining of the
granulation causes the cell to appear as if permeated by vacuoles (XI, c).
They are frequently so sparse in normal blood that they can only be discov-
ered by examining several preparations.
These various cell forms may be determined in all normal blood by the
aid of different stains, and in the adult they are found in about the propor-
tion shown in the last division of Tasue A, where the large mononuclear
leukocytes and the transitional forms, on account of their close relationship,
are included in one group.
In the arrangement of Taniz A the fact is disclosed that the lymphocytes
occupy a unique position among all the white blood-corpuscles. This is
mainly due to their origin: They originate in the lymphatic tissue of the
body, the principal mass of which consists of the lymph-glands; lesser amounts
of this variety of tissue are, however, also present in the bone-marrow, and it
therefore, perhaps, contributes a small portion of the lymphocytes of the blood.
The groups from the second to the fifth, however, originate exclusively in the
bone-marrow; only under definite pathological conditions does the production
of these varieties of cells also occur in other regions. The point of origin
of the mast-cells, which is chiefly in the bone-marrow, must also be the con-
nective tissue where they are formed in large quantities, particularly in certain
pathological conditions,
A second comprehensive difference between the lymphocytes and the five
other varieties of cells consists in the fact that the latter have the property
of active movement which the lymphocytes do not possess; we shall see later
that this difference is of great importance for the conception of pathological
processes. [It has been conclusively shown, I think, that lymphocytes do
possess the power of ameboid movement.—Ep. ]
BACTERIOLOGICAL EXAMINATION 299
TaBLe A
THE WHITE BLOOD-CORPUSCLES OF THE NORMAL BLOOD
Per cent.
3 Tee aes I. Lymphocytes (large and small) 22-25
E 3a a. II. Large mononuclear leukocytes
2 bo ae ee 2-4
BS] 8g B 5 III. Transitional forms
a Ee 3™ | IV. Polynuclear neutrophilic leukocytes 70-72 1
g ae V. Eosinophilic leukocytes 2-4
5 VI. Mast-cells 0.01-0.5
The blood-plaques are recognizable in fresh blood by their lesser size
(1-3 »), their clump formation, and their slight refractive power; they stain
a pale blue in methylene-blue solutions, and in the triacid stain from gray
to grayish brown. [In most triacid preparations the blood-plates are invisible.
With Romanowsky stains they are dark plum color and are easily seen.—Eb. |
Before entering upon the physiologic and pathologic importance of individ-
ual cell forms we must first describe a few cell anomalies. In different patho-
logical conditions decided changes in the shape and size of the red blood-corpus-
cles are noted, and these we designate by the term potkilocytosis (Plate, Row
III). The average normal size of the red blood-corpuscle is from 8-9»; in
some conditions of the blood, besides these “ normocytes ” there are also very
small forms which may be only 2 to 3» in size (“ microcytes”) ; on the other
hand we may observe large forms which are frequently from 14-15 p, in rarer
cases may even reach 18, 20 and 22 » (macrocytes, megalocytes, gigantocytes).
Besides the changes in size, the manifold changes in the shape of the blood-
corpuscles are important, and may be looked upon as an expression of seg-
mentation and decomposition.
Occasionally combined with these pure morphologic changes, but quite as
frequently entirely independent of them, we note in the erythrocytes deviations
from normal conditions which are shown by a diminution of their hemoglobin
contents. For example, forms of various size are noted in which the central
depression is very markedly extended so that only a comparatively small part
of the disc, often only a quite narrow rim, appears to contain hemoglobin;
i.e., to stain in the corresponding solution (see colored Plate, Row IIT).
A diminution in the amount of hemoglobin of the individual blood-corpus-
cle is also occasionally shown by a generally weaker power of staining.
Besides these slight deviations in tinctorial properties, the red blood discs
frequently show marked qualitative anomalies; for instance, we note very
frequently blood dises which do not take a pure stain with eosin or orange,
but a mixed one, so that in staining with the triacid stain they are more or
less grayish brown, in methylene-blue eosin solution from bluish red to lilac,
and occasionally they may appear pure blue. This behavior, which now is
generally designated as “ polychromatophilic degeneration,” may be explained
by the fact that foreign substances which stain with the nuclear colors have
(1 60-72 per cent. are normal limits, in my opinion.—Ep. ]
300 BLOOD AND BLOOD EXAMINATION
been deposited in the plasma of the red blood-corpuscle (see Plate, Row IT).
[There are many, and on the whole convincing, reasons for regarding these
granules as evidence of regeneration or of unripeness, but controversy is still
active on the subject, and it seems best for the time to use some neutral term
such as “basophilic stippling.”—Eb. ]
Such a deposit’ of substances which, for example, stain in methylene-blue
but not, however, in the triacid solution, is found in a granular or dust-like ,
form in the protoplasm of the red blood-cells, whether this is normally stained
or degenerated in the manner above described (polychromatophilia) (see
Plate, Row VI). We should be cautious in assuming the identity of these
deposits with the granules of the white blood-corpuscles; therefore we should
also avoid the designations granular, granulation, granulated erythrocytes,
etc., and choose the non-implicating designation “ stippled erythrocytes.”
Much less frequent than these staining anomalies of the red blood-corpus-
cles is an additional one, the appearance in the circulating blood of nucleated
red blood-corpuscles, “ erythroblasts.’ It is well known that normally in
the red bone-marrow nucleated red blood-corpuscles appear. These are about
the. size of the normal non-nucleated blood discs, but contain a nucleus of an
extraordinarily intense stain and a protoplasm that usually appears in the
color of the stains that color hemoglobin, more rarely in that of polychromato-
philic degeneration. They are unquestionably the early stages of the normal .
erythrocytes, and for this reason are designated as normoblasts (see Plate,
Row IV). On the other hand, only under pathological conditions in the
adult do we find another form of erythroblasts which are decidedly larger
than the normal red blood dises, and have a diameter of 14, 16, even 20 » and
more. ‘Their nucleus, as a rule, is but feebly stained by nuclear dyes, their
protoplasm almost invariably shows the condition of polychromatophilic degen-
eration. We designate this variety of cells as megaloblasts, or gigantoblasts
(see Plate V, a, b), and recognize in them the embryonic stages of megalo-
cytes and gigantocytes.
In the white blood-corpuscles changes in form or in staining property are
of slight importance. It should be mentioned that very frequently the proto-
plasm of the lymphocytes at its border shows proliferation and segmentation,
processes which indicate a degenerative condition without our being able to
assign to them definite pathologic importance.
Much more interesting is the appearance in the circulating blood of a cell
form which, under normal conditions, is met with only in the bone-marrow.
This is a mononuclear leukocyte of varying size (8 to 20 in diameter) (see
Plate, Row XII), the protoplasm of which is filled by a dense neutrophilic
granulation; Ehrlich has given this corpuscle the name “ myelocyte.”
The white blood-corpuscles show variations of great importance in their
number, both as regards their total number per cubic millimeter and in their
proportion to the red blood-corpuscles (32) and particularly, in the propor-
tion of the individual forms of the white blood-corpuscles to one another. The
estimation of the proportion of we is possible by the aid of Thoma’s appa-
tatus for counting the absolute numbers; this may also be accomplished with
BACTERIOLOGICAL EXAMINATION 301
the stained dry preparation. For this purpose we use the movable quadratic
Ehrlich eye-piece (see Fig. 20). The principle of this diaphragm depends
upon its making it possible to count the red and white blood-corpuscles in
different large divisions of the field of view, so that, for example, the leuko-
cytes are counted in 4 field six or nine times as large as the field in which the
Fie. 20.—Euruicu’s Eyr-precr witu Iris DiaPpHRaGM.
reds are counted. The total number determined after counting a larger series
of fields of the red is then directly compared with the sum of the white by
multiplying by six or nine. A prerequisite for a correct result by this method
of estimation is an absolutely uniform layer of blood upon the cover-glass.
The proportional relation of the individual varieties of blood-corpuscles
to one another may be determined by a simple calculation of the cells when
examining a dry preparation.
We have described the fundamental characteristics of the blood cells in
their normal and pathological condition, omitting everything that depends
upon purely theoretic investigation and which has not yet been directly applied
to practice, as well as that which is still being debated, and concerning which
the views of competent observers are still at variance. How has it been possi-
ble to utilize this material in general and special pathology?
In the article upon Anemia (see this volume) due stress has been laid upon
the pathological changes which the red blood-corpuscles undergo in the various
anemias, and we may now limit ourselves to a description of the changes in the
white blood cells in the same diseases.
In the first place, as regards the appearance of pathological cell forms,
for the reasons indicated we have included only the myelocytes in our descrip-
tion. But the circumstances under which these are found in the circulating
blood agree in so many points with the circumstances under which the num-
ber of white blood-corpuscles increases or decreases that they require no
special elucidation.
Consequently, the most important chapter in the pathology of the white
blood-corpuscles is that which treats of the changes in their total number and
the relative proportions of the individual leukocyte forms. Since, in general,
we refer to the presence of leukocytes as leukocytosis, an increase of their
302 BLOOD AND BLOOD EXAMINATION
total number we speak of as hyperieukocytosis, and a diminution, as hypoleu-
kocytosis. [1 prefer the term “leukocytosis” for an increase, and the term
“leukopenia” for a decrease, in the circulating leukocytes——Ep.] Even at
the normal, the absolute number of white blood-corpuscles and the propor-
tion of their different varieties show distinct variation; in different pathologic
conditions, however, and especially in infectious diseases, the deviation of these
conditions from normal becomes more marked. We find the explanation for
this in the principle of chemotaxis, according to which bacteria and their
products of metabolism, as well as numerous other toxic substances, are capa-
ble of attracting by chemical irritation the cells which have accumulated in
the blood-forming organs, a condition which we designate as positive chemo-
taxis; on the other hand under quite similar circumstances the leukocytes are
repelled by the previously mentioned poisons, so that the number in the cir-
culating blood is decreased, and this process we call negative chemotaczis.
The self-evident presupposition for this attraction and repulsion of the leu-
kocytes (since the condition is a notable example of action at a distance) is the
property of the leukocytes to show active movement. For this reason we give
to this state the name active leukocytosis.
Active leukocytosis furnishes the most varied pictures, not only quantita-
tively but qualitatively, because of the fact that the chemotaxic irritability of
the different leukocyte varieties shows specific differences. Thus there are
substances which only influence one variety of cell in a positive chemotaxic
manner, being inert toward all others. This shows itself most frequently in
a decided increase of the polynuclear neutrophilic leukocytes alone in numer-
ous infectious conditions, as in septic diseases, diphtheria, and articular rheu-
matism; other infections have a negative chemotaxic property for this -cell
form so that, for example, in enteric fever, we often find them decidedly
diminished. On the other hand the eosinophilic leukocytes show marked
power of attraction for the blood in bronchial asthma, in pemphigus, in trichi-
nosis, and in several varieties of helminthiasis. More rare, but nevertheless cer-
tain, is a chemotaxis of the mast-cells exhibited according to this principle.
It is a peculiarity of the chemotaxic reaction that all leukocytes endowed
with one type of granulations are attracted simultaneously even if the com-
position of the nucleus varies; for example, the myelocytes react im the same
way as the polynuclear neutrophilic leukocytes. For this reason, in accord-
ance with the variety of the cell that is influenced, we speak of neutrophilic
hyperleukocytosis or hypoleukocytosis of eosinophilic or mast-cell leukocytosis.
Besides these specific leukocytoses, we diagnosticate another form of hyper-
leukocytosis which we designate as a mixed form, because in this all cells that
are capable of chemotaxic reaction are increased in the blood. This is
myclogenous leukemia; we therefore arrive at the hypothesis, no matter how
obscure to us the etiology and pathogenesis of myelogenous leukemia may
still be, that in this disease a toxic substance is active which has the property
of influencing all myelogenous cell varieties in a positive, chemotaxic manner.
A form of white blood-corpuscles must still be mentioned which does not
possess the active property of locomotion: these are the lymphocytes. [See
note at foot of p. 298.] It is therefore evident that this form is not subject to
EXPLANATION OF THE COLORED PLATE
e cells drawn with Leitz one-twelfth oil immersion.) iene
I. Erythrocytes, stained with triacid and with the Chenzinsky stains.
II. Polyehromatophilic’“ degeneration.”
eat
III. Poikilocytosis; pessary forms.
IV. (a) Normoblasts.
(8) Free normoblast nucleus.
V @) Megaloblast.
(b) Gigantoblast.
VI. “Stippled”’ erythrocytes.
otic
VIL... Lymphocytes.
VIII. Large mononuclear leukocytes:
(a) with Chenzinsky.
(0) with triacid.
(c) transitional form.
IX. Polynuclear neutrophilic leukocytes.
X. Eosinophilic leukocytes:
(a) with Chenzinsky.
(6) with triacid.
XI. Mast-cells:
e (a) with methylene-blue.
(b) with dahlia. -
(c) with triacid.
XII. Myelocytes.
BLOOD AND Blin: beavis. +
ATAIY GAM0100 ABT TO VOILAYAIZA
(.srorerssntsers Seo s{¥Soust-osro stsad sisus ssormtb 23$e0 SUA),
ciate YAecixaed) ods dtiv bas biosiit dtivw boaiste zotyoordtyid .1
“ noitstaaegeb ™ silidqotamoidovloT IL
2entot iszeog ;2i20syoolidioT -TII
etesldonri0¥%. (xy .VI
eveloua Jesldonrion 9911 (8)
- terldolsgoM (») .7
stesidotaosgin (4)
zolyooults “ balqqit#" IV
was qoodgaryd ATT
ea ‘reebpodnel ielsysn0gom sgis] .1IV
; : solenisnad) diiw (9)
i are 2 sbivgint. tiv (5)
-arto4 [gnoitiene3d (9)
eo tyood al otlidqortaron rssisyavioL .XI
7“ ™ dy ‘oat oilidqoitizol De
El heieeans iste (9)
eS ac ON Bib Red ditiw (6)
ueynotaxie reat 4
Since. ‘alloo- jeslt IX
ne auld ci d3iva (9)
7 : eile ettive (8)
SE Ubpogitt dive (9)
’ a + “eotroolorl Ze
ams lh wy Nope a
SEY pease ae lig moet:
frate as a mixed form,
reaction are inerens .
we Therefore arrive at the
and pathogenesis af 1
wt toxic substance is ac,
verenots eell varieties a a pecs
riod -COTPUBE Tow Yt ust i 4 fue Hreaet«
i wot :
voaf locomotion: these are the ps.
{tts therapy: Gvudheot that this for |
La Tg
inher
* ckopors
mreeatted
hen.
BACTERIOLOGICAL EXAMINATION 303
the laws of chemotaxis. Since, in spite of this, there are often transitory or
permanent variations in the number of lymphocytes found in the blood, these
require another explanation. We find this either (a) in the increased pro-
duction of lymph-cells, due to hyperplasia or inflammation of the lymphatic
tissue, or (b) in an influx of this variety of cells by increased lymph circula-
tion. The lymphocytes themselves are entirely passive in these processes, and
for this reason we designate their increase as passive leukocytosis. Extreme
degrees of this condition we designate as lymphatic leukemia. (A special de-
scription of the various forms of leukemia will be found in this volume, the
article being by Professor v. Leube.)
I cannot close this article without showing by a few examples that the
researches described here are of importance in the diagnosis of diseases other
than the actual blood diseases. .
The number of the leukocytes, for instance, is decidedly important in the
differential diagnosis of the infectious diseases. If we remember how diffi-
cult the differentiation of enteric fever from other affections occasionally is,
any sign which facilitates the diagnosis will be a great help. The affections
which may be confounded with enteric fever, such as osteomyelitis, general
sepsis, pneumonia, etc., are characterized by a decided increase of the neutro-
philic leukocytes, while in uncomplicated typhoid fever this variety of cell is
decidedly diminished or is at most present in only normal numbers.
In the differentiation of inflammations of the cerebral meninges, an ex-
amination of the blood may often be of benefit; and if, in a case of undoubted
meningitis, we find a normal relation of the leukocytes, the assumption of the
tubercular form instead of a purulent one is justified.
The occasionally extremely difficult differentiation between scarlatina and
measles may often be facilitated by a blood examination owing to the fact that
a distinct diminution of the polynuclear leukocytes, or an almost normal con-
dition of the same, is quite characteristic of measles, while in scarlatina a
decided polynuclear neutrophilic hyperleukocytosis is the rule.
Lately Curschmann and subsequent investigators have reported that in
numerous cases of perityphlitis, the diagnosis of an abscess which could not
be determined by palpation was made from an increase of leukocytes to 20,000
and more, and this prevented all necessity for exploratory incision. [“ Lately”
the Germans have wakened up to these facts which have been known and used
in America since described by me in 1894.—Ep.] The subsequent surgical
operation absolutely confirmed the reliability of this symptom. On the other
hand, clinicians have in numerous cases discountenanced a surgical operation
on account of an almost normal leukocyte finding. Here, also, the further
development of the disease justified the diagnosis. Almost as much impor-
tance may be ascribed to the phenomenon of leukocytosis in the diagnosis of
abscesses localized elsewhere, which otherwise could not be determined with
certainty.
In a case in which the diagnosis was otherwise obscure, Brown concluded
from a decidedly marked eosinophilic hyperleukocytosis that the underlying
condition was trichinosis; the further course of the disease justified this
opinion.
THE ANEMIAS
By P. EHRLICH anp A. LAZARUS
FRANKFoRT-oN-MAaIN CHARLOTTENBURG (BERLIN)
In reviewing the earlier literature of anemia, very exact descriptions of
the general clinical symptoms may be found, while the changes in the blood
seem to have been somewhat overlooked. The object of this article is to
acquaint physicians with the advance in knowledge along these lines; points
which have long been established facts will be passed over rapidly, and the
special consideration of hematology will be our aim.
Easy as it may be to distinguish the different forms of anemia, mistakes
in their recognition have sometimes occurred, and do still occur, chiefly through
a disregard of hematology. The fact that there can be no anemia without
changes in the blood seems to have been long ignored. Disturbances in the
circulation of the blood, especially, lead to incorrect diagnoses, because these
disturbances cause important clinical symptoms common also in anomalies in
the composition of the blood. Such symptoms are: Intense pallor of the skin
and mucous membranes, small pulse and its increased frequency, and among
subjective phenomena weakness and vertigo. These acute symptoms appear,
for instance, under such psychical influences as fear, terror, etc., or in acute
somatic disorders such as affections of the stomach, or from fatigue, or from
excesses in “‘ Baccho et Venere.” They may also be present in chronic condi-
tions, especially in neurasthenia, in gastric affections, and in heart disease.
Mistakes are therefore prone to occur, because in a few instances the symptoms
mentioned are also present in true anemia.
The presence of anemia is, therefore, only positively established after
blood-changes have been proven. We never find that the blood deviates from
the normal in one respect only; in every case thorough examination shows a
group of changes. Still, a determination of the hemoglobin alone is sufficient
to demonstrate the existence or non-existence of an anemia. We say a person
is anemic if on testing his blood an amount of hemoglobin smaller than normal
is found, and we adhere to this designation even if other important properties
of the blood and the clinical symptoms appear entirely normal. On the con-
trary, when a patient has the general clinical symptoms of anemia while his
blood shows a normal percentage of hemoglobin, we do not call him anemic.
In practice, every case of anemia is identical with oligochromemia.
The reduction of hemoglobin may be due to the fact either that too little
is formed or too much consumed. A formation of hemoglobin that does not
keep pace with the normal consumption may be either the expression of an
304
SIMPLE ANEMIA 305
affection of the hematopoietic organs, or in consequence of the fact that too
little material, or an inferior material, is at the disposal of these organs.
An exaggerated consumption of hemoglobin takes place in hemorrhages
and, indirectly, also in wasting processes of all kinds. The processes of blood
regeneration and blood consumption are so intimately related that a disturb-
ance of one of these processes is likely to bring about a disturbance of the other.
Often the blood regeneration is only relatively insufficient; that is, the
blood-forming organs, especially the bone-marrow, furnish less blood than is
required for the momentarily and abnormally increased demand. In these
cases it often occurs that the hematopoiesis is more considerable and more
energetic than in health, entire portions of the bone-marrow, physiologically
passive, now becoming active; the consumption of blood may, however, re-
main so great that even an increased production does not maintain the balance.
In these cases, whether the work of the blood-making organs is absolutely
increased or diminished, the amount only, not the manner, of blood formation
is changed.
On the contrary, we see conditions in which the type of blood-formation
in larger or smaller regions of the bone-marrow has changed, and hemato-
poiesis has assumed a type which is abnormal in the adult organism.
Those anemic conditions in which blood restitution takes place according
to a normal type are called SIMPLE ANEMIAS; and those in which the process
is partially or wholly different from the normal type which will be considered
more in detail later, are called PROGRESSIVE PERNICIOUS ANEMIAS. [The old
term, “simple anemia,” to which Ehrlich here reverts, does not seem to me
likely to come back into use. It seems most reasonable to retain our present
current term, “ secondary or symptomatic anemia,” for trouble of this type,
and to use the terms, “ pernicious anemia” and “ chlorosis,’ with the con-
sciousness that they, too, are secondary, but secondary to a cause which in most
cases is wholly unknown.—ED. |
SIMPLE ANEMIA
As a result of extensive observations of the blood changes, and of supple-
mentary studies of the changes in the bone-marrow, we know that in by far
the larger number of cases of anemia the normal mode of blood regeneration
is preserved ; hence, these are classed as SIMPLE ANEMIAS.
The causes of simple anemia are, first of all, acute, subacute, and chronic
posthemorrhagic conditions. The supervention of anemia in these instances
from the loss of considerable blood is readily understood.
Many constitutional or organic diseases lead to simple anemia, either by
reducing the appetite, or by the loss of blood and tissue-juices, but especially
through suppuration and albuminuria. Poisons also play an important réle.
Here the large group of autointoxications play a part and another damage is
done by toxic substances developed by bacteria and other parasites. We may
explain in two ways the effect which brings about the anemia without being
able, in the special instance, to determine with certainty which of the two
active causes, or whether, perhaps, both together, have been operative. Some
21
306 THE ANEMIAS
of the poisons appear to destroy the blood directly; others to diminish or to
change the function of the hematopoietic organs.
Excluding the diseases accompanied by suppuration, bleeding, and gan-
grene, a few others deserve especial mention as producing simple anemia.
Such, for instance, are chronic digestive disorders, malignant tumors, scrofu-
losis, syphilis, malaria, and the different forms of helminthiasis.
In addition to the symptoms of the diseases which, according to the old
terminology, were called “ secondary anemia,” the symptoms of sirnple anemia
may be found in cases which are apparently “idiopathic.” They are the con-
sequence of faulty hygienic conditions, among which unsatisfactory nutrition
plays the greatest réle, and it may here be remarked that food which leads
to a reduction in the percentage of hemoglobin need not necessarily be insuffi-
cient in quantity but it is lacking in iron and albuminous substances. [That
faulty nutrition is a cause of anemia seems, of course, most plausible, but
definite evidence for it is so far wanting —Eb. |
But, whatever the cause of the anemia in individual cases may be, no dif-
ference is to be noted in its essential results, the changes in the blood, or in
their main clinical symptoms.
The most important symptom is the REDUCTION IN HEMOGLOBIN; this not
only characterizes the disease as anemia, but also gives us information as to
the degree of the morbid changes. Cases vary greatly in this respect, and vary
without any apparent relation to the etiology. We meet with cases of “simple
anemia” in which the values are but slightly below the normal. To this
class belong also cases which show 20, 15 and even only 10 per cent. of the
normal amount of hemoglobin.
In the mild cases of simple anemia, the red blood-corpuscles differ little
from those of normal blood. In cases somewhat more serious, deviations
from the normal number and morphological changes are observed. In ex-
treme cases the number of red cells may amount to less than 10 per cent. of
the normal; 50 per cent. is by no means rare.
For the numerical relation between the percentage of hemoglobin and the
blood-corpuscles in simple anemia, the etiology seems to be, to some extent, a
determinative factor. Parallel deviations of both values from the normal are
often seen; for instance, a reduction of 30 per cent. in the amount of hemo-
globin corresponds to a reduction of 30 per cent. in the number of red corpus-
cles. After hemorrhages, however, we find that the amount of hemoglobin is
considerably less than the corresponding red corpuscle count; and in cases of
uncomplicated chlorosis, the parallel is disturbed in the sense that the number
of red corpuscles is often nearer the normal than the hemoglobin value.
The morphological changes of the erythrocytes in simple anemia affect
their size and their shape. We find that the individual red corpuscles show
considerable difference in size; being mostly smaller than normal. Increase
in size is rare, and is then but slight. The.shape of the red corpuscles is fre-
quently more or less distorted and deformed. These conditions of deviation in
size and shape are designated “ poikilocytosis.” Milder degrees of simple
anemia do not show it, but the degree of poikilocytosis corresponds to the
severity of the anemia.
SIMPLE ANEMIA 307
The reduction in the hemoglobin value of the individual corpuscle is, in
some cases of simple anemia, very striking. This can be seen in fresh blood,
but better in the dry stained preparation, from the fact that a larger area
of the center remains unstained than would correspond to the physiological
depression of the corpuscle. In some forms only a ring of stained portion
may be seen (pessary forms).
Furthermore, the red corpuscles often manifest under the microscope a
change in reaction to the usual stains. This change is known as “ anemic
or polychromatophilic degeneration.” + It may be recognized from the fact
that the hemoglobin of the corpuscles does not assume the-pure color of the
stain (eosin, orange), but a mixed color (blue-red in the methylene-blue eosin
solutions, grayish-yellow with the triacid solutions). These changes are often
very pronounced even in the mildest degrees of simple anemia.
A rare occurrence, which is probably characteristic only in especial forms
of simple anemia, is the presence of granular or punctiform deposits in the
protoplasm of the erythrocytes (“stippled erythrocytes”); these are most
apparent when stained with methylene-blue. They are found especially in
lead anemias, even in the mild grades, and also in malarial anemias. In
simple anemias of other etiology, even in very grave cases, they are commonly
absent, so that to a certain extent specific significance may be attached to
them. [The universally applicable Romanowsky stains, described and recom-
mended above, bring out the stippling beautifully.—Eb. ]
Of great importance in the diagnosis of the different kinds of anemia is
the fact that in the circulating blood nucleated red corpuscles of the same
kind as those found in the normal red marrow (“normoblasts”) sometimes
appear. Such cells are noted in comparatively few cases of simple anemia.
We find normoblasts with fair regularity, though usually only transitorily, in
post-hemorrhagic conditions, and sometimes, in these cases, in quite large
numbers. Their appearance proves an increase in intensity of the activity of
the bone-marrow, and in extent of marrow which is active; for the clinical
phenomenon corresponds anatomically to a more or less decided transformation
of quiescent fat marrow into functioning red marrow, and an especially marked
richness of these portions in normoblasts. We must emphasize the fact that
the appearance of normoblasts in the blood is in no relation to the severity
of the anemia; sometimes they are found in the mildest conditions, and are
often looked for in vain in the severest. Except in acute post-hemorrhagic
anemia their number is always small—so that only one nucleated corpuscle is
found to one thousand and more non-nucleated red blood-corpuscles.
Besides the presence of normoblasts microblasts are sometimes noted.
Other alterations in the properties of the blood are also found in simple
anemia, always in the direction of a reduction in the values. This is true of
the SPECIFIC GRAVITY OF THE BLOOD, its total solids, and the amount of albu-
min it contains; the reduction is the more pronounced the greater the devia-
tion of the hemoglobin from the normal.
The WHITE CORPUSCLES in simple anemia present nothing that is charac-
1See article, “ Blood and Blood Examination.”
308 THE ANEMIAS
teristic. In one case we may find a normal number of their different varieties,
in another case a marked neutrophilic hyperleukocytosis may be present, in a
third a hypoleukocytosis, or an increase in the number of lymph-cells, ete. So
many factors influence the condition of the leukocytes, that in the multitu-
dinous cases of simple anemia due to causes or complications differing from
one another, no uniform picture can be described.
Summarizing, we may say that the most important and essential symptoms
of the blood-changes in simple anemia are a diminution in the hemoglobin
percentage and in the number of red blood-corpuscles, poikilocytosis, and the
changes in the staining reaction. By attending to these factors in each indi-
vidual case we can decide whether or not it belongs to the simple anemias,
and how grave the prognosis is.
The general clinical symptomatology of anemic conditions exhibits a few
traits so characteristic as to make them in most cases readily recognizable even
without an examination of the blood. Owing to their wide distribution, they
are so well known to physicians that a brief reference to them will suffice.
The pallor of the skin and of the mucous membranes is an obvious conse-
quence of the diminished hemoglobin percentage of the blood. It is often
intensified by a permanent constriction of the peripheral blood-vessels. The
same causes lead to a lessened capacity for muscular work, and readily produce
sensations of weakness and fatigue. The most vital internal organs must also
suffer in consequence of a reduction in the value of the nutrition; and, in
severe cases, all physical and psychical functions are below par.
It is surprising that, in anemic people, THE GENERAL METABOLISM, even
the interchange of gases, is not, as a rule, reduced; whereby we may conclude
that if, in some cases, these functions are abnormal, it is due not to the anemia,
but to some special cause or complication.
Even in severe cases, the adipose tissue is well preserved unless a loss of
flesh follows in consequence of some special circumstances (as severe nutri-
tive disturbances). This is a striking phenomenon for which no satisfactory
explanation has been given; it was formerly attributed to a reduction in the
oxidation processes, but this is usually not present at all; and the reduction
in muscular activity and other functions is not sufficient cause.
Related to this phenomenon is FATTY DEGENERATION of some of the organs,
especially of the muscles and the circulatory system. Fatty degeneration and
fatty infiltration are chiefly found in the muscles of the heart, in the muscles
of the eye, and the intima of the blood-vessels.
To the fatty degeneration of the endothelial cells of the blood-vessels may
be attributed the fact that in many anemic conditions a general HEMORRHAGIC
DIATHESIS develops, which not infrequently combines with the primary dis-
ease to form a vicious circle. By their localization in the organs of special
sense, hemorrhages of the eye and the ear are especially alarming, and lasting
injury with total destruction of sight and hearing has been observed in severe
cases of simple anemia. On this occasion we consider it our duty to differ
with the widespread opinion that the symptom of retinal hemorrhage in anemic
conditions belongs exclusively to progressive pernicious anemia.
SIMPLE ANEMIA 309
The diagnosis of simple anemia, therefore, is often easily made from its
most manifest features. The careful physician will, however, make a blood ex-
amination, or at least a test for hemoglobin, even in cases where a glance is suf-
ficient to show that he is dealing with anemia. In this way alone can we
determine with certainty what part vasomotor influences play in shaping the
disease. This alone will assure us that the supposition of anemia is not un-
founded ; and if the test shows a reduction we have then positive information
regarding the degree of ancmia. Moreover, in every case of severe anemia, a
microscopic examination of a stained specimen of the blood is absolutely neces-
sary in order to make the important differential diagnosis between simple and
progressive pernicious anemia.
The prognosis depends, in the first place, upon the cause of the disease.
If this can be removed there is a good prospect of a cure. Under such cir-
cumstances, even in the severest cases in which the hemoglobin and the number
of red corpuscles amount to only 10 per cent. of the normal, we have known
cases of simple anemia to terminate in complete recovery.
The treatment of simple anemia must in the first place be directed to the
cause. In numerous cases in which the cause is found and removed, as, for
instance, continually recurring hemorrhages in the intestinal tract, worms,
improper hygienic conditions, etc., no special treatment of the anemia is neces-
sary after the removal of the cause; for spontaneously the blood returns to its
normal state.
When causal treatment is impossible, or when it fails to influence the
anemia beneficially, attention must be paid to the symptoms of anemia as such.
In the great majority of cases, medication is far superior to any other mode
of treatment. Jron and arsenic, separately or combined, lend a powerful
stimulus to blood production, and after their rational administration, often
even in a few weeks, the morbid changes in the blood and in the general con-
dition disappear, and make way for a restoration to health. The choice of
the special preparation is essentially unimportant; the main point is to con-
tinue the treatment long enough, and to administer sufficiently large doses.
The general rule that 0.1 gram of iron is to be given pro die may serve as
a criterion for the administration of special iron preparations, organic or
inorganic. The dose of arsenic varies widely, and it must be determined by
the individual tolerance. Usually we succeed hest if we administer 3 to 5 milli-
grams of arsenious acid, divided into several doses, properly diluted and given
ona full stomach. The drug should be continued for a long while, even after
the normal status has been reached. a
But there are other anemic conditions in which iron and arsenic give unsat-
isfactory results, or are of no use whatever. Here dietetic and physical therapy
must be resorted to. As the metabolism of anemia does not deviate from the
normal, the normal diet of healthy people may be allowed. Theoretically, pref-
erence has been given to food rich in iron (meat, yolk of egg, spinach, apples,
etc.). Often, however, owing to the special peculiarities of a given case (for
instance, in cases complicated with gastro-intestinal affections) special modifi-
cations of the diet must be made which cannot be here considered.
Among the general auxiliary measures in the treatment of anemics, rest—
310 THE ANEMIAS
physical, mental and psychical—must be accorded the first place. In this con-
nection, certainty in diagnosis will aid materially in the choice of treatment;
for instance, the pale neurasthenic, not really anemic, needs considerable phys-
ical exercise; while the muscular activity of a true anemic must be limited
as much as possible.
Modern hydrotherapy has gradually acquired a prominent place in the
treatment of anemia; but we must always bear in mind that the withdrawal
of too much bodily heat is to be avoided, because all anemics are sensitive to
cold. Cold applications, such as cold ablutions with friction, or partial
douches of short duration, are best given in the morning immediately on ris-
ing—for then the redilatation of the cutaneous blood-vessels takes place pleas-
antly and actively after the patient returns to his bed. Here, too, we must
remember the distinction between the treatment of anemics and of pseudo-
anemics; the latter have a perfectly normal composition of the blood, and
only suffer from an abnormal contraction of the peripheral blood-vessels.
In protracted cases, a change of climate is frequently very beneficial, and,
particularly in excessive anemia, a sojourn in the mountains of medium allti-
tude. More robust patients may be sent with advantage even to high moun-
tainous regions, which often powerfully stimulates the regeneration of the
blood.
In most cases of severe anemia, a sojourn at the seashore is not to be
advised; in moderately severe cases it is to be recommended. Great caution
must be exercised in the use of sea-baths, as they sometimes aggravate anemia.
PROGRESSIVE PERNICIOUS ANEMIA
PROGRESSIVE PERNICIOUS ANEMIA must be distinguished from other anemic
conditions because in blood-regeneration it presents a most striking peculiar-
ity. In opposition to the process in simple anemia, in progressive pernicious
anemia blood-regeneration in larger or smaller regions of the bone-marrow
takes place in a manner different from the physiological. In the blood-form-
ing organs and in the circulating blood cells we note cells which are never
found in the healthy adult organism. Since these cells are found physio-
logically in the embryonal life of man, we speak of a “reversion of blood-
formation to the embryonal type.”
Before accurate study of the changes in the blood and in the bone-marrow
had been made possible, the consideration of this particular form of anemia
as a special type was based upon a more negative foundation. If the symp-
toms of severe anemia were found without a distinctly palpable cause, the
disease was considered idiopathic, and was designated progressive pernicious
anemia. Almost always in such cases we observed in the blood the changes
alluded to, which are to be accurately described later on, and thus these posi-
tive signs, particularly as they are regarded as the expression of marked trans-
formation in the body, are almost universally recognized as the important
differential diagnostic points.
The theory of the “ primary” nature of progressive pernicious anemia was
shattered in the course of time by numerous experiences, and this aided us
PROGRESSIVE PERNICIOUS ANEMIA 311
in arriving at our present standpoint. To-day we know that progressive per-
nicious anemia may undoubtedly often follow other diseases, and not as an
independent disease, but only as a symptom; as, for instance, in the case of
diabetes. We shall now briefly describe what has been demonstrated with
certainty.
The best illustration of severe anemia which we possess is the case of
individuals who-harbor the bothriocephalus latus in their intestines. Not-
withstanding all the controversies on this subject, there can be no doubt that
this worm, living or dead, may produce the most severe anemic conditions, and
that this bothriocephalus anemia is a true progressive pernicious anemia. We
understand fully the mode of action of this parasite, and may regard it as
proven that the disease is due to toxic substances that have a hemolytic effect,
and thus cause anemia. Further it may also be assumed as likely that the
parasite changes the activity of the bone-marrow in a peculiar way. The in-
contestable fact that a very large number of people are afflicted with bothrio-
cephalide without becoming anemic may be explained in different ways. In the
first place, there may be a difference in the degree of virulence of the toxins;
or, again, a difference in the susceptibility of the host. For there is no doubt
that individuals of one species may possess a very different susceptibility to
the same poison; for example, the susceptibility of rabbits to crotin has lately
been proven to show enormous variations. Finally, the explanation of a grad-
ual autoimmunization to the toxin is quite reasonable.
Leaving now the consideration of bothriocephalus anemia, which is at pres-
ent understood, we may say that all that is known of the presumable causes
of progressive pernicious anemia may thus be summarized: “The same dele-
terious agents which are capable of producing a ‘simple’ anemia may also
develop the progressive pernicious form.” Why apparently identical causes
may in some instances produce the common simple anemia and in others the
comparatively rare progressive pernicious anemia we do not as yet know.
In considering the symptoms of progressive pernicious anemia, CHANGES
OF THE BLOOD, especially morphological alterations, claim our closest at-
tention.
In a typical, well-defined case of progressive pernicious anemia, the first
glance at a good stained preparation is sufficient to distinguish it from simple
anemia. We find that the majority of erythrocytes, or at least a large number
of them, have a diameter largely above the normal, 15 to 18 » (megalocytes)
and, by their stain, these cells disclose to us a great richness in hemoglobin.
On repeated examination, we almost always find some megaloblasts, 1. e.,
erythrocytes with nuclei, the predecessors of the megalocytes. Except in the
worst stages of the disease, the number of megaloblasts is always very scant.
[The number of megaloblasts usually exceeds the number of other erythroblasts,
but presents no close parallelism with the severity of the clinical manifesta-
tions or with the intensity of the anemia. It is true that in most cases the
number of megaloblasts increases as the symptoms are aggravated, and dimin-
ishes in the remissions of the disease. But to this rule there are many excep-
tions—Ep.] Besides megaloblasts, normoblasts and microblasts are also to
be found. Of non-nucleated red corpuscles, besides megalocytes, we also see
312 THE ANEMIAS
célls of normal size or smaller; the smallest forms, the microcytes, are fre-
quently observed.
All other peculiarities of simple anemia are to be found in progressive
pernicious anemia: Poikilocytosis, polychromatophilic degeneration, and
“ stippled” erythrocytes; contrary to the rule in simple anemia stippled eryth-
rocytes are found with great regularity in progressive pernicious anemia.
The red corpuscles are always noticeably reduced, often to the low figure
of 20 per cent. to 10 per cent. of the normal.
The leukocytes are often absolutely reduced, but not always; moreover, a
neutrophilic hypoleukocytosis is often found. [Especially in the remissions
of the disease when the number of red cells is rapidly increasing and the mar-
row is very active—Eb. |
The other blood values differ little from those of severe cases of simple
anemia. The hemoglobin percentage, the specific gravity, the amount of sol-
ids, and the amount of albwmin show a diminution of their values correspond-
ing with the grade of the disease. [Why the authors do not mention at this
point the high color-index, i.e., the relatively increased hemoglobin which is
so characteristic (though not invariable) in the disease, I do not under-
stand.—Ep. |
According to this, of all the changes in the blood, only the changes in the
size of the erythrocytes, and the formation of the nuclei of the erythroblasts
denote the variety of anemia. The appearance of megalocytes and megalo-
blasts is characteristic of progressive pernicious anemia, while their permanent
absence is indicative of the simple form. For megaloblasts and megalocytes
appear in the blood only when some region of the bone-marrow shows a megalo-
blastic degeneration. The simultaneous occurrence of normoblasts, normo-
cytes, and smaller forms, as well as a temporary predominance of one or the
other of these forms, is not at all surprising when we consider that the trans-
formation of the bone-marrow is always only partial, and is often limited to
very small areas, while in the other regions of the bone-marrow the blood ele-
ments are produced physiologically.
The other properties of the blood can only be looked upon as denoting the
DEGREE of the disease, as in simple anemia. We must expressly state that
in undoubted cases of progressive pernicious anemia moderate values of the
hemoglobin, a moderate number of red blood-corpuscles, a moderate specific
gravity, etc., may be found; while, on the other hand, minimal values are met
with in positive cases of simple anemia. It follows that the degree of anemia
is, to a certain extent, independent of its type.
In the CLINICAL PICTURE of progressive pernicious anemia marked charac-
teristics are a peculiar pallor and a slight puffiness of the skin, which may
enable the physician to guess the diagnosis at the first glance. No word will
exactly describe the color of the skin; the designation “ faded-yellow ” perhaps
best portrays the real condition, but no description can take the place of per-
sonal observation.
Moderate jaundice is frequently present, and slight edema may be almost
always noticed in the face, in the abdomen, and in the legs.
The contrast between the severity of the constitutional symptoms and the
PROGRESSIVE PERNICIOUS ANEMIA 313
well-nourished appearance of the patient is still more striking here than in
chlorosis and other simple anemias. There is hardly a disease in which, with
so great a cachexia, the adipose tissue is so well preserved.
Concerning the METABOLISM in progressive pernicious anemia we have
little knowledge. The increase of proteid decomposition, which has been
observed in some cases, must be due to some inconstant factor, for in other
cases there is no increase at all. The same is true of the oxidation processes.
Fever is present in almost all cases, if only transitorily, but it is by no
means characteristic, and bears no relation to the intensity of the disease. Its
origin is probably a ferment intoxication from the destruction of red blood-
corpuscles.
The CARDIAC SYMPTOMS are prominent. For a long time the disease was
considered to be merely a symptom of severe cardiac degeneration. The sub-
jective disturbances which are very often troublesome to the patient consist of
(a) palpitation, brought about by the least exertion, which often leads to (b)
true precordial distress and (c) severe dyspnea. Auscultation of the heart
reveals over all the valve-areas a clear, soft, usually systolic, rarely diastolic
murmur. Percussion as a rule is normal. The heart symptoms are often so
intense that during life it is impossible to distinguish the condition from
genuine endocarditis.
Nevertheless, we must state with emphasis that well-defined severe cases
of progressive pernicious anemia have been observed in which the heart showed
neither subjective nor objective morbid phenomena.
The weakness of the heart action is best indicated by the character of the
PULSE, which usually is of low tension, small, and frequent. [Very frequent
and very interesting in this disease is the violent pulsation of the elastic
peripheral arteries which often equals that seen in aortic regurgitation.
Edwards? has recently reported a case of pernicious anemia in which the
abdominal aorta. was so expansile and pulsated so forcibly that aneurism
seemed the only explanation. The carotids flap loosely.—E. ]
On the part of the DIGESTIVE oRGANS, marked anorexia, persistent nausea,
belching and vomiting, and also unconquerable repugnance to certain foods,
for instance, meat, are often noticed. Examination of the gastric contents
in the living has not infrequently revealed a complete suspension of the gastric
secretion—* achylia gastrica.” The abdomen, as a rule, is everywhere soft
and not sensitive upon pressure.
The motor capacity of the intestine, the power of absorption, and the
secretion of the intestinal glands seem, as a rule, normal. oe
The sPLEEN is generally normal or only slightly decreased in size, but
there are positive cases recorded in which extraordinarily large splenic tumors
complicated the clinical picture. ;
Some disturbances of the CENTRAL NERVOUS SYSTEM may be noticed,
though in comparatively rare instances. The mind may be in a condition of
deep depression or marked exaltation, and the one may repeatedly alternate
with the other. Toward the end, disturbances of consciousness and deep coma
1 Trans. of the Assn. of American Physicians, 1903.
314 THE ANEMIAS
appear. In a number of cases, failure of the memory and lasting impairment
of intelligence have been noticed.
In the reports of the last decade, numerous disturbances of the sPinaL
corp—in fact, a symptom-complex—have been observed corresponding exactly
to the picture of a genuine tabes dorsalis; namely, pupillary rigidity, loss of
knee-jerks, ataxia of the limbs, incontinence of the bladder and rectum,
lancinating pains, disturbances of sensation, anesthesia, and paresthesia. In
some cases one or another classical symptom of tabes is missing and those
of the clinical counter-picture, spastic spinal paralysis, are found. [Occa-
sionally intense neuralgic pains in the extremities occur when locomotion
is attempted. These cases are doubtless akin to those of intermittent claudi-
cation.— ED. |
It has already been remarked that these affections of the nervous system
are not regular accompaniments of progressive pernicious anemia; and it
must be added that in all probability they are usually independent of the
severity of the anemia, but due, as we suppose, to some special etiology. In
any case, we are not justified in regarding these symptoms as consequences
of the anemia, but they are presumably co-ordinated consequences of the
same cause—the effect of toxins. [Three groups of cases should be here. dis-
tinguished :
(a) Those in which the nerve symptoms appear late in the course of a case
of obvious pernicious anemia.
(b) Those in which there are no nerve symptoms (except peripheral pares-
thesia) during life, but obvious sclerotic changes in the cord post mortem.
(c) Those in which the cord symptoms precede and overshadow the mani-
festations of anemia. This most interesting group of cases has been studied
especially by James J. Putnam of Boston —Eb. ]
More exact clinical knowledge of progressive pernicious anemia has led
us to give special consideration to the changes in the eye, particularly to the
RETINAL HEMORRHAGES and their consequences. It cannot be denied that
these changes are usually found in progressive pernicious anemia, but isolated
cases have been met with in which the eyes were quite normal; and besides, in
undoubted cases of simple anemia as already mentioned, profuse retinal hemor-
rhages may occur. Consequently this symptom may be considered as a sign
of the degree, and not of the variety, of the anemia.
Disorders of the sense of hearing and of smell are of slight importance and
exceedingly uncommon ; hut these may, under some circumstances, proceed to
complete suppression of these functions.
The POST MORTEM FINDINGS in progressive pernicious anemia are of espe-
cial interest because in some respects they give important information regard-
ing the nature of the disease.
Besides the extreme anemia of all the organs and the hemorrhages that
are always present, though these vary in amount and localization, sIDEROSIS
is always found, that is, an abnormally increased amount of iron in the inter-
nal organs, especially in the liver, in the spleen, in the bone-marrow, and in
the lymph-glands. [Neither the hemorrhage nor the siderosis is invariable,
though in the majority of cases they are found.—Ep.] This increase of iron
PROGRESSIVE PERNICIOUS ANEMIA 315
in progressive pernicious anemia may be considered a proof of the invariably
concomitant increased destruction of red corpuscles.
FATTY DEGENERATION, the clinical consequences of which have already
been alluded to, is found quite often in the muscles of the extremities, of the
trunk, and conspicuously in the muscles of the eye. Almost always we find
the fatty degeneration of the heart muscle which is such a well-known charac-
teristic of the disease. The fatty degeneration of the arterioles and capillaries
is interesting because it occasions hemorrhages in the internal organs.
Attention must be devoted to the picusTive TRACT, because the achylia
gastrica sometimes present leads us to expect definite anatomical changes. In
fact a more or less marked atrophy of the gastric and intestinal glands has
been found repeatedly, yet the pathologico-anatomical changes at the autopsy
by no means always coincide with the symptoms during life; quite marked
degenerative changes have been found in cases where the functions of the
stomach and intestines had apparently been perfectly normal, while, on the
other hand, in cases in which achylia gastrica undoubtedly had been present
no anatomical changes were found. The relations of the gastro-intestinal
atrophy to progressive pernicious anemia have not as yet been sufficiently
demonstrated. It must be remembered that only comparatively few cases of
anemia, and those not always the most severe, show these changes; and fur-
thermore, that in a series of other changes nowise related to progressive per-
nicious anemia, atrophy of the gastro-intestinal glands has been found. The
supposition is reasonable that this atrophy and anemia have no causal relation
to each other, but that they represent the effects of a common cause.
A few instances of progressive pernicious anemia have been reported in
which carcinoma of the stomach, in extent about the size of a hazel-nut, and
without ulceration or metastases, has been found. The small size of these
tumors prevents our recognizing in them the cause of the anemia; but if one
is not content to call it “coincidence” the supposition that progressive per-
nicious anemia has prepared the way for the formation of the tumors is not
altogether unreasonable. Of course, the cases in which advanced carcinosis is
found combined with progressive pernicious anemia must be judged quite dif-
ferently ; here it is probable that the carcinoma is the cause of the anemia.
On account of the symptoms suggesting tabes and other diseases the cEN-
TRAL NERVOUS SYSTEM has been made the subject of especially thorough re-
searches. Besides the hemorrhages which are most apt to occur in the brain
and spinal cord, we find focal and also diffuse degenerations of the nerve
fibers in the white substance of the spinal cord, with consecutive prolif-
eration of the connective tissue. These changes, which occur particularly in
the posterior columns, are without doubt the cause of the severe clinical
symptoms. :
The changes in the BoNE-MaARROW, especially those revealed by the micro-
scopical examination of the organ, are the most important of all, because we
find in them convincing proof of the necessity of classifying anemic conditions
according to the mode of blood-regeneration. If we consider only the macro-
scopical evidences, the classification of anemia appears impossible ; for in
almost all cases we find a transformation of the yellow fat marrow into red
316 THE ANEMIAS
lymphoid marrow, these changes including sometimes smaller, sometimes
larger, portions of the bone-marrow. If, in a case of simple anemia, we were
to examine such a portion microscopically, an exact picture of the normal
lymphoid marrow would be seen, such as is always found in the ribs, the verte-
bre, the sternum, and is besides characterized by the presence of white cells
(which we do not take into consideration), and by red blood-corpuscles of the
same size as the erythrocytes of normal blood, some without, some with, nuclei.
But the picture we obtain in cases of progressive pernicious anemia of all,
or of many, of these transformed red bone-marrow regions is entirely differ-
ent. The nucleated, as well as the non-nucleated, red blood-corpuscles are of
such a size, and contain such a rich quantity of hemoglobin, as is never ob-
served in the bone-marrow of the normal adult but only in the embryo. These
differences seem to be so essential as to necessitate a special classification of the
anemias, even if they did not bear out what we should expect from the clinical
symptoms and the condition of the blood.
In progressive pernicious anemia the whole fat marrow very rarely degen-
erates into lymphoid megaloblastic marrow, and this is a factor which enables
us the better to comprehend certain variations in the blood findings, and is of
the greatest importance in practical diagnosis. Often only a portion of the
lymphoid marrow shows a megaloblastic structure, while the other regions are
lympho-normoblastic. Moreover, only a part of the fat marrow is diseased
in most cases. Of course, the number of megaloblasts and megalocytes con-
tained in the circulating blood depends upon the size of the megaloblastic por-
tion of the bone-marrow, and other temporary variations in the composition
of the blood may be thus explained.
It is our purpose to discuss in this article only points of practical impor-
tance. But we must not forget that a series of questions most intimately
related to the changes in the bone-marrow are still awaiting solution. For
bothriocephalus anemia, the correct explanation has probably been given, and
most authors of the present day maintain the view that the toxin of the bothrio-
cephalus causes the specific megaloblastic changes of the bone-marrow. This
gives us a hint as to the etiology of other types of progressive pernicious ane-
mia, and inclines us to the general supposition of a specific toxic influence.
It is more difficult to answer the question as to what particular circumstances
transform a simple anemia into the megaloblastic form, an occurrence which
must certainly be considered infrequent considering the prevalence of simple
anemia. At present, the toxin hypothesis does not sufficiently explain the
extraordinarily rare cases in which progressive pernicious anemia develops as
the consequence of a simple posthemorrhagic anemia.
But it cannot be disputed that progressive pernicious anemia may develop
from a simple anemia, and this confirms the view that there must be transi-
tional stages in which it is exceedingly difficult, and often even impossible, to
determine to which class of anemias a given case belongs. Still, we meet with
such transitions and intermediate stages within the whole domain of pathol-
ogy, in fact in all departments of natural science; they must not, therefore,
be an obstacle to the differentiation of the fully developed forms, nor are they
proofs of the non-existence of special types of the disease.
PROGRESSIVE PERNICIOUS ANEMIA 317
Therefore, in spite of many uncertainties, we are warranted in stating that
the condition which most distinctively stamps progressive pernicious anemia
may be described as follows: PRoGRESSIVE PERNICIOUS ANEMIA IS NOT AN EX-
TREMELY MARKED DEGREE OF ANEMIA, BUT A DISTINCTIVE TYPE OF THE DISEASE
CHARACTERIZED BY A PECULIAR MODE OF BLOOD-FORMATION.
THE COURSE OF THE DISEASE
The course of progressive pernicious anemia presents some remarkable and
characteristic features, which are more pronounced than in any other disease.
Only occasionally does the disease run a continuously progressive and fatal
course; usually the morbid condition is relieved once or several times by a
state lasting for weeks or months that may simulate almost perfect health.
These “ remissions” often follow stages of the disease so severe that they seem
to be the immediate precursors of death; during extreme prostration, a change
suddenly sets in—spontaneously or under the influence of medication—a
change that within a few weeks often leads to apparently perfect recovery.
Remissions such as these, as many as five or more, have repeatedly been noticed
in the same individual.
The duration of the disease varies from a few weeks to five or ten years;
but by far the majority of patients succumb in a year or a year and a half
after the symptoms have distinctly developed.
The prognosis of the disease is exceedingly grave; the so-called recoveries
have probably been only the beginning of the remissions, which delay, but
cannot avert, the fatal issue. According to our present knowledge, the disease
must be considered incurable and fatal. [In the vast majority of cases, in-
cluding most of those published as “ cures,” death follows within three years,
but there are a few well-authenticated cases still alive at the end of ten years.
Perhaps 1 in 100 may recover.—ED. |
Bothriocephalus anemia is a striking exception to this rule. This form of
the affection is often entirely cured by the expulsion of the worm, even though
symptoms of progressive pernicious anemia have already developed to the full-
est extent, and the anemia has attained a high degree. We recognize from
this that the mere presence in the blood of megaloblasts and megalocytes—i. e.,
the megaloblastic degeneration of the bone-marrow—does not in itself make
the prognosis absolutely unfavorable, but that even with this the disease may
lose its progressive character if we can succeed in removing its cause from the
organism. So long as we are ignorant of the origin of progressive pernicious
anemia, so long are the prospects of a cure decidedly unfavorable.
The most important point in the diagnosis is the differentiation between
simple and progressive pernicious anemia. In well-marked cases of the latter,
the general clinical picture enables us to make the diagnosis. The peculiar
pallor, the extreme weakness, the tired expression, the marked development
of heart symptoms, the retinal hemorrhages, the striking contrast between the
asthenia and the well-preserved adipose tissue—all these combine to form a
picture that clearly stamps the disease after a merely superficial examination.
318 THE ANEMIAS
If the patient is under observation for a longer time, the appearance of a
remission is a remarkable aid to the diagnosis. Even in such characteristic
cases, besides the clinical examination, we must not omit an examination of
the blood as a control test; if the general clinical picture of the disease is not
perfectly developed, blood examination is even more essential.
If we find in the blood undoubted megaloblasts besides genuine megalocytes,
the diagnosis of progressive pernicious anemia is established beyond doubt.
[This statement is certainly too strong. Undoubted megaloblasts with a
majority of normoblasts occur in some perfectly curable post-malarial anemias.
It is the predominance, not the presence, of megaloblasts and megalocytes
that is most significant—Ep.] If we do not find them it is more difficult
to reach a conclusion. Whoever is careful to bear in mind the above-mentioned
changes in the bone-marrow will exclude pernicious anemia in doubtful cases
only after repeated examinations of the blood have shown it to be entirely
free from these characteristic elements.
We must always remember that the megaloblasts usually pass only in small
numbers from the bone-marrow into the blood. Hence we must examine
thoroughly several technically perfect preparations before we can positively
say that this variety of cell is absent. If the blood is of a pronounced megalo-
eytic character, then the diagnosis of progressive pernicious anemia may be
made even though megaloblasts are absent, because the appearance in the blood
of large numbers of megalocytes cannot occur without a previous megaloblastic
transformation of the bone-marrow.
Another diagnostic difficulty is the fact that there are undoubtedly cell
forms which morphologically represent a transitional stage between normo-
blasts and megaloblasts. If these are sparse, they may be left entirely out of
consideration; if they appear in great numbers, they are indicative of pro-
gressive pernicious anemia.
To determine the cause of progressive pernicious anemia, an examination
of the feces for tape-worm ova is necessarily important; the presence of the
bothriocephalus ova or links will aid materially in the prognosis and treat-
ment. [Uncinaria eggs should also be looked for, though the type of anemia
produced by uncinariasis is usually somewhat different from that described
here.—Ep. |
From the standpoint of differential diagnosis we must bear in mind endo-
carditis, carcinoma of the gastro-intestinal tract, tabes dorsalis, and Addi-
son’s disease, and, during the comatose terminal stages of the malady, other
affections in the course of which severe disturbances of consciousness occur.
In these cases, the verdict depends mainly upon the blood examination.
THERAPY
Treatment offers hope of success only in the bothriocephalus anemia.
After the anthelmintic (extr. filix mas) has produced its effect, if the anemia
is not too far advanced a definite cure will shortly follow. These results
encourage us to try the filix mas even in cases in which the bothriocephalus
has not been found.
THERAPY 319
Marked improvement and even apparent cure has heen repeatedly noticed
after the stomach and intestines had been thoroughly cleansed by laxatives
and irrigations. In such cases we are warranted in the interpretation of the
a aia pernicious anemia as an autointoxication from the gastro-intestinal
tract.
Organotherapy, the treatment of the disease with bone-marrow, has thus
far given no results.
On the contrary, some very surprising, though not always accountable,
results have been attained by the transfusion of small quantities (40-100
ec.) of defibrinated human blood. In several cases transfusion has been
followed immediately by the onset of a complete remission of the disease and
life was prolonged for months, though when transfusion was again performed,
after a relapse, it was ineffectual. But if the patient’s life is endangered,
and if coma has already set in, this operation is our last hope and resource,
and should at least be attempted.
The most important and successful treatment is by arsenic. To this
remedy we are indebted for an extraordinarily large number of apparent cures,
and by its aid in some cases we succeed in bringing about remissions and in
delaying the imminent outbreak of a relapse.
Nevertheless there can be no lasting cure, even with the aid of arsenic.
This remedy is administered according to the generally observed rules:
Small doses in the beginning and gradually increased, long-continued use,
and a gradual decrease. The doses should be adapted to the individual sus-
ceptibility and reaction; as a rule, even during the acme of the treatment,
we find doses smaller than the maximal to be sufficient. During the remission,
when no symptoms are present, it is well to give the remedy from time to
time for several weeks. The best indication for a renewal of the treatment
is afforded by regular examinations of the blood, which may give warning of
a new outbreak before the clinical symptoms suggest it.
An unfortunate idiosynerasy for arsenic not infrequently develops in the
course of treatment, and may prove disastrous for the patient, inasmuch as the
proposed substitutes for this remedy have not yet borne the test of experience.
As for general treatment, rest and comfort are of paramount importance.
The diet must be adapted to the individual susceptibility of the stomach and
intestine, as well as to the sometimes insurmountable repugnance of the
patient for meat. In view of the debility of the patient, hydrotherapeutic
treatment is not advisable, but sponge baths may be given without danger.
General massage is preferable to bathing. A change of climate may he indi-
cated during the remissions, and a sojourn in a mountainous region of mod-
erate altitude is more likely to prove beneficial than any other climatic change.
LITERATURE
The earlier literature of this subject, in all its details, is given by Ehrlich-Lazarus,
“ Anemia,” “ Nothnagel’s Handbuch,” viii, Wien, 1900. More comprehensive works
which have appeared are: Strauss and Rohnstein, “The Composition of the Blood in
Different Anemias,” Berlin, 1901; Schaumann, “ Pernicious Anemia in the Light of
the Modern Toxin Hypothesis,” Volkmann’s Clinical Lectures, New Series, No. 287.
CHLOROSIS
By E. GRAWITZ, Cuar.orrensure (BERLIN)
Amone the numerous cases of anemia constantly coming under observa-
tion in the hospital, one group stands out prominently, which, in regard to the
origin as well as the symptomatology, and the entire course of the affection,
occupies a distinctive position, and, since the time of Hippocrates, has been
considered to indicate an impoverished condition of the blood. [As Stengel
has recently remarked, there seem to be fewer cases diagnosticated as chlorosis
in the clinics of the larger American cities than was the case some years ago.
Whether there are, in fact, fewer cases or whether better technic makes us
reject many that were supposedly, but not actually, chlorotic, I do not
know.—Eb. |
SYMPTOMS
This group consists almost exclusively of young girls and young women,
in whom the anemia betrays itself by a conspicuous pallor of the skin and the
mucous membrane. [I have never seen in adolescent boys any cases of anemia
at all resembling those which in girls we call chlorosis, and those reported in
literature are mostly a good many years back and vaguely reported.—EDb. |
In many cases there is also a> decided yellowish tinge which may sometimes
verge upon green, and, as frequently happens in pathology, from this by no
means significant nor even very frequent green color, a term has originated
which has long encompassed the entire symptom-complex, and has become
current in the language of all countries; namely, the designation “ chlorosis”
(from yAopés, greenish).
Besides this pale or pale yellow discoloration of the skin, there are in
many cases dark gray rings around the eyes; it is especially worthy of note
that there is no sign of loss of the subcutaneous adipose tissue; on the con-
trary, many of these patients have a plentiful layer of fat.
It may be seen, therefore, that this form of anemia is not due to a general
cachexia, but occurs in well-nourished persons, a fact which is confirmed by
an examination of other organs.
Besides the peculiar color of the skin, the majority of chlorotics show a
more or less pronounced edematous infiltration of this tissue, so that, for
instance, the lower eyelids often seem swollen, and imprints of the examining
fingers on the back and at the ankles of the patient are distinctly persistent.
These signs lend to the patient a peculiar doughy appearance, which, at
320
SYMPTOMS 321
the first glance, vividly recalls that of persons affected with acute nephritis,
yet this, of course, is not due to the yellowish discoloration.
The circulatory apparatus presents numerous and striking symptoms. In
the heart there is almost always an increase of the area of dulness, to the right
and to the left. The hand may feel a distinct systolic thrill, especially over
the pulmonary artery, and on auscultation systolic murmurs, which commonly
have a peculiar blowing character, are very distinctly heard.
These cardiac murmurs have been recognized for a long time, and, in spite
of careful study, are still subjects of dispute. The murmurs are usually loud-
est over the pulmonary artery, and an attempt has been made to explain them
by the fact that there is a relaxation of the heart muscle owing to insufficiency
of the blood-supply, that the papillary muscles do not contract with sufficient
power, that, therefore, during systole there is a relative insufficiency of the
auriculoventricular valves which causes a regurgitation of the blood to the
auricles during systole in the same manner as in cases of organic mitral insuf-
ficiency.
This much is certain; that these systolic murmurs are intimately related
with the anemic condition of the blood, that they appear when the disease
develops, and disappear when the general clinical picture shows improvement.
Therefore, they have been properly called “anemic murmurs,” in contra-
distinction to heart murmurs produced by valvular lesions which are desig-
nated “organic murmurs,” and an exact knowledge of these conditions is the
more important as it is frequently the duty of the physician to decide whether
changes and murmurs in the heart, especially in young persons, are to be
attributed to a valvular lesion or whether they are only accompanying symp-
toms of anemia. [The term, “anemic” or “hemic” murmurs, is not well
chosen, for the majority of such murmurs occur not in anemic cases but in
fevers, in neurotic or excited conditions, in growing children and after any
violent exertion (boat-races, etc.). On the other hand, cases of marked
anemia without any murmurs are not very uncommon. I prefer the term
“functional murmur.”—Ep.] As an instance of the importance of this dif-
ferential-diagnostic distinction, we may mention the requirements for enlist-
ment in military service, in which this question is of momentous importance.
As a criterion in practice the following important points favor anemic
murmurs:
1. The existence of distinct anemia.
2. The simultaneous presence of the systolic murmur over all the valves.
3. Especial loudness in the pulmonary area.
4. Absence of that accentuation of the pulmonic second sound which con-
stantly accompanies insufficiency of the mitral valve.
It must, however, be stated with emphasis that simple as this appears in
theory it is often difficult in practice to arrive at a decision; for, in the first
place, training is necessary to make these examinations correctly, and, further,
prolonged observation of the patient is the only decisive criterion, for, as has
been stated, anemic murmurs are transitory while organic heart murmurs are
permanent. ; eet
Neither does the character of the pulse give reliable information in regard
22
322 CHLOROSIS
to this question. The pulse of anemics is for the most part simply accelerated,
of varying strength, and often slightly dicrotic; in some cases a crural mur-
mur has been noted. Obviously, then, the pulse of chlorotics presents no char-
acteristic changes.
The acceleration of the heart beat and of the pulse is explained by a diminu-
tion of hemoglobin, as the blood, in order to accomplish the required oxida-
tion of the whole organism, must circulate more rapidly than when it contains
anormal amount of hemoglobin. As a result of this, acceleration of the heart’s
action is one of the common symptoms of chlorosis as well as of other forms
of anemia.
Subjectively, the patients are often vividly conscious of this acceleration,
so that a troublesome sensation of cardiac palpitation develops, a point which
has been noted in the earliest literature as a prominent symptom of chlorosis.
This sensation becomes aggravated upon exertion as when they attend to their
housework, ascend stairs, etc. Asa result they readily become short of breath,
and the rapid beating of the heart which appears after these slight exertions
often persists afterward as a subjective but very disagreeable symptom.
In these cases it is surprising to note that some chlorotics, who during the
day become dyspneic on the slightest exertion, are able in the evening to
attend a ball and indulge most immoderately in dancing, and even to con-
tinue this exercise for hours without any difficulty in breathing approaching
that which occurs during the day, when, for instance, they ascend only one
flight of stairs. Of course, upon the following morning, a particularly great
prostration is discernible.
Similar to the murmurs in the heart, in such patients “ venous murmurs”
have for a long time been recognized which are designated “nun’s murmurs”
or also “ bruit de diable.”” These are best auscultated over the sterno-clavicu-
lar articulation ; care must, however, be exercised that the neck of the person
is not turned too much to one side, for, in this case, the murmur may also be
noted in normal subjects. This murmur is due to the circumstance that the
jugular vein is held by tense bands situated behind the articulation just men-
tioned, so that in this region it cannot expand and contract with facility, as
it does, for instance, higher up in the neck. Now, since in anemics the lumen
of the vein is lessened—being less full—when the blood enters from the nar-
rowed portions into the easily dilatable parts previously mentioned, differences
in the blood current arise which give rise to these murmurs. This is the usual
explanation of these conspicuous venous murmurs, but it is unsatisfactory,
inasmuch as in other anemic conditions in which the blood reveals much
greater deterioration than in chlorosis—therefore a more favorable condition
for the production of the murmurs—no adventitious bruits are discernible.
[It should be mentioned at.this point that violent pulsations of the peripheral
arteries, especially the carotids, are noticeable and sometimes troublesome in
cases of severe anemia of any type. The arteries flap and jump so violently
as to remind one of the conditions seen in aortic regurgitation.
Dilatation of the heart is not uncommon and may be demonstrated by
radioscopy or by percussion. A beautiful picture of a heart dilated in the
course of a case of chlorosis is included in the v. Ziemssen-Rieder Atlas.—ED. ]
SYMPTOMS 323
The respiratory apparatus in chlorotics shows few deviations from the
normal. A symptom noticeable in many of the patients is an accelerated res-
piration rate, which is to be explained, like the acceleration of the heart’s
action, by a relative deficiency of the blood in oxygen. This, however, is not
characteristic of chlorosis, but is also met with in other affections accompanied
by deficiency in hemoglobin.
Much more numerous are the symptoms on the part of the digestive appa-
ratus. First of all, as an almost invariable symptom, there is found anorezia
and repugnance for certain kinds of food, for instance, meat; and, on the
other hand, and this is a characteristic symptom of the disease, a morbid desire
for food difficult to digest or wholly indigestible. Thus, many of these patients
have an especial liking for sour foods, vinegar, pickled products, ete., and
furthermore, for lime, chalk, slate pencils and the like; longings which remind
one forcibly of similar cravings in pregnancy.
Atony of the muscular wall of the stomach is often found, which not infre-
quently leads to dilatation and displacements of this organ. Still, I cannot
coincide in the opinion of Meinert, who considers gastroptosis, that is, the
pathological descent of the fundus of the stomach, a constant symptom of
chlorosis, and even makes it responsible for the origin of the whole disease.
As a matter of fact, there is often found in young girls a displacement of
the stomach from its normal limits, the result of tight lacing and the wearing
of corsets; and, as general weakness of the muscles exists on account of the
anemia, conditions are very favorable for the development of gastroptosis and
dilatation in consequence of the stagnation of food and tight lacing.
In many cases the secretory activity of the stomach is quite normal; in
others an excessive production of hydrochloric acid is met with; and in still
others acidity is decreased. These, however, are facts that must be ascer-
tained by direct examination of the gastric contents, and should never be
guessed at from the subjective complaints, as, for instance, from the inclina-
tion to eat chalk.
The activity of the intestines is usually disturbed, and constipation is
one of the commonest symptoms; indeed, as will be seen later, theories
have been developed which ascribe the origin of the whole disease to this
phenomenon.
Concerning the metabolism of chlorotics, exact researches have been made,
especially by v. Noorden and his pupils, from which it is ascertained that in
these patients no especially increased waste of albumin occurs, that the absorp-
tion of oxygen is within normal limits, and that the excretion of urea shows
no noteworthy change.
The body temperature is neither increased nor diminished. The appear-
ance of fever is probably to be explained for the most part by the presence of
complications. Slight transitory rises of temperature without demonstrable
organic changes occur in some cases; but we must consider the close relation-
ship between chlorosis and hysteria—a fact which we shall consider frequently
later on—in which fever of like character also is noted, and has thus far not
been satisfactorily explained.
In chlorotics the sexual functions are disturbed in various ways; and here
324 CHLOROSIS
again the attempt has been made to refer the development of the disease to
these disturbances.
Menstruation in chlorotic girls is delayed, or if it has already appeared it
becomes scanty or ceases when the chlorosis develops. In contrast to this, other
chlorotics suffer from remarkably profuse menstruation, which sometimes may
be normal for a few months; at the same time, there is considerable suffering
at the onset, such as headache, general nausea, indisposition, pain in the abdo-
men, ete.
In opposition, however, to the opinion that the menstrual anomalies are
the actual cause of the disease, it must be maintained that many chlorotics
menstruate in a perfectly normal manner until the onset of the disease, so
that, logically, these anomalies which develop during the course of the chloro-
sis must undoubtedly be considered as secondary conditions. Leukorrhea is
also very frequent in chlorotics.
The symptoms referable to the nervous system are numerous, and here
we must differentiate two groups, one of which may be easily recognized as
solely a consequence of the anemic condition of the blood, while the other has
an independent character and is specially significant. To the first group belong
vertigo, specks before the eyes, syncope, which can be easily explained as due
to a deficient supply of blood to the brain, all the more so as the symptoms
ameliorate when the patients are kept in a recumbent posture, so that the
access of blood to the brain is facilitated, while they become most prominent
as soon as the patients assume the erect position or attempt to walk. These
symptoms of anemia of the brain, resulting from unsatisfactory circulation
of the blood—at the same time poor in oxygen—become manifest in a similar
manner also in other forms of anemia.
In the second group (nervous symptoms independent of anemia) belong
especially psychical anomalies, which manifest themselves by a change in the
disposition, and a dislike for mental and physical exertion; on the other hand,
when it is specially interesting to the patient, she can endure a considerable
amount of exertion, as, for instance, in dancing, as has been previously men-
tioned. [Insomnia at night and a heavy sleepy condition in the daytime are
often seen in chlorosis, but some patients sleep excessively.—Ep. ]
As regards sensibility, we often find anesthesia of different parts of the
skin as well as of the mucous membranes, for example, of the pharynx; in
other cases there is hyperesthesia, and especially newralgic phenomena in the
distribution of different nerves. Intercostal neuralgia is quite common, and,
if it occur on the left side, is often incorrectly referred to the spleen as the
so-called “ splenalgia,” of which the patients complain.
Motor disturbances, also, are often accompanying symptoms. Paresis of
ve various muscles of the larynx and also of those of the extremities is often
ound.
The condition of the reflexes varies; they are frequently normal, some-
times diminished, in other cases exaggerated. ;
Moreover, disturbances of the sympathetic system manifesting themselves
by an abnormal innervation of the blood-vessels are very important. Thus
we may observe in these patients an abnormal facility for blushing followed
THE BLOOD 325
by a rapidly succeeding pallor. The appearance of erythematous areas upon
the trunk may also be grouped with these.
Disturbances of the organs of special sense, particularly often that of
vision, manifesting itself by the fact that the patients soon tire in reading,
sewing, etc., in most cases are caused by weakness of the eye-muscles and of
the mechanism of accommodation.
Besides this, in many instances, serous infiltrations of the retina are found,
which then appears strikingly pale, and, especially about the papilla, lacks
distinct contour, and looks as if loosened.
Now and then attacks of transitory blindness or partial deficiencies in
vision are noticeable, which, although they greatly alarm the patient, offer a
good prognosis and disappear completely.
Anomalies of taste have already been mentioned. We also find abnormal-
ities of smell; the same as in hysteria.
THE BLOOD
THE BLOOD OF CHLOROTICS has, for a very long time, been the subject of
thorough and extensive researches, and even with the naked eye the watery
appearance and the marked pallor of the blood, which flows freely from the
slightest puncture, is conspicuous. If blood of this kind is diluted with a
definite quantity of water, and this mixture is compared with a similar dilu-
tion of a like quantity of normal blood, the difference in color is very decided;
this is also shown by all the various instruments which are constructed for
the same purpose, i.e., for comparison, by means of transmitted light, of the
color of the blood with a standard color, the so-called hemoglobinometer, so
as to determine a decided reduction of the coloring matter of the blood.
The exact estimation of the amount of hemoglobin from the amount of
iron contained in the blood also shows a considerable reduction of the iron
and hemoglobin values, so that there can be no doubt that in chlorosis there
is a considerable reduction of the hemoglobin percentage.
In opposition to this, it is of special interest that the count of red blood
cells, which in the course of time has been made in many cases and from
different standpoints, shows in the majority of cases of uncomplicated chlorosis
no considerable reduction in the number of these cells, which are the carriers
of the hemoglobin, and it can be stated positively to-day that a reduction in
the number’ of these cells, an “ oligocythemia,” is not present in chlorosis.
The normal number of red corpuscles in a cubic millimeter of woman’s blood
is about 4,500,000; in chlorotics we find an average of from 3,800,000 to
4,000,000, and in some cases even an almost normal number; while a marked
reduction in the number of red blood cells is found only in such chlorotics
as are debilitated in consequence of a prolonged duration of the disease, insuffi-
cient nutrition and complications of some kind.
These two important facts, that, on the one hand, the amount of hemo-
globin is always considerably reduced, sometimes to a third of the normal,
while the number of red blood cells is changed but very little, allow us to
conclude positively, that some individual red blood cells must be poorer in
326 CHLOROSIS
hemoglobin. Therefore, we designate this peculiar form of anemia in chloro-
sis as an “oligochromemia,” that is, a deficiency in the. hemoglobin of the
blood. This symptom forms one of the most important characteristics of the
blood of chlorotics, and is only seldom found so pronounced in the other
anemias. [In my experience “chlorotic blood ”—excessively low color-index
—is not at all uncommon in other forms of anemia, e. g., in “ splenic anemia,”
malarial anemia, cancerous anemia, post-hemorrhagic anemia, etc. Chlorotic
blood is in no way peculiar.—Ep. ]
If attention be directed to the cells of the blood themselves, we find the
view corroborated, even on examination of the unstained preparation; each
individual red cell has sustained a considerable loss in its hemoglobin. The
majority of these cells appear strikingly pale, and absorb stains very imper-
fectly, a sign that the quantity of coloring hemoglobin in the cells has been
considerably reduced.
Morphologically we find striking differences in the size of the red blood
cells. Many of them appear remarkably large (macrocytes) and at the same
time quite pale, without a distinctly pronounced central umbilication—as
though swollen. These large, pale discs have been designated, quite appro-
priately, “ chlorotic” blood-corpuscles. Still other cells, on the contrary, are
distinguished by their diminutive size (microcytes). [Finnish observers have
proved that the average diameter of the red corpuscles in chlorosis is often
diminished. The cells grow smaller as the disease is aggravated, and return
gradually to their normal size in convalescence.—Ep. |
The stained cells show very distinctly the anomaly designated polychro-
matophiha; that is, they partially take up the basic stains instead of acid
stains; and, therefore, the stained preparation has a peculiar appearance
characterized by the fact that many large cells, very faintly stained erythro-
cytes, alternate with many small intensely stained cells, and with cells showing
polychromatophilia.
On the other hand, genuine phenomena of degeneration, such as potkilo-
cytosis and granular “ degeneration” (the presence in the red cells of numer-
ous, very small, basophilic granules), do not belong to the blood picture of
chlorosis, but occur only in very far advanced cases of this kind when decided
disturbances of nutrition are present, or complications which lead to cachexia;
as, for instance, habitual constipation with increased intestinal decomposition.
In the same manner, nucleated red blood cells are not, as a rule, present
in chlorosis, hut occur only in the extreme grades of the disease when intense
ae of the hematopoietic organs, i.e., of the bone-marrow, has taken
place. :
The condition of the Tewkocytes in chlorosis is not uniform. It may be
stated positively that these cells do not show any characteristic change in this
disease. Very often their number is increased ; especially during those stages
of the disease in which regenerative processes in blood production are mani-
fested by other signs as well as, for instance, by the appearance of nucleated
erythrocytes.
In the experience of the author, no new cell forms appear in this variety
of leukocytosis; but we have rather to deal with an increase in number of
THE BLOOD 327
the normal forms of leukocytes, and by preference with an increase in the
number of polynuclear neutrophilic forms and of the lymphocytes, while ab-
normal forms, as, for instance, the myelocytes (large leukocytes, with one
nucleus and with neutrophilic granules) belong to the exceptions.
To sum up, we may say that the leukocytes do not play a role of any
importance in the blood changes of chlorosis.
The third formed constituents of the blood, the so-called “ blood plaques,”
‘attract especial attention in chlorosis because here they appear in remarkably
increased numbers, sd that large groups of these small colorless structures
may often be seen in each field of the fresh preparation.
We are still uncertain as to their significance. Some authors, for instance,
the pupils of Arnold, consider them as a segmentation product of the red
blood cells, while others believe them to be fragments of disintegrated nuclear
substance.
Since these small bodies, as I have repeatedly noted in many examinations,
may be partially stained with basic stains, especially well with methylene-
blue, and partially with certain nuclear stains, for instance, with Ziemann’s
[or Leishman’s] eosin methylene-blue mixture, I believe that, at least in the
majority of cases, they may be considered fragments of nuclear substance, and
at best only a small number of them may have originated from red blood cells.
In any case, our knowledge concerning these small structures is so indefi-
nite that from their appearance in increased numbers in the circulating blood
we cannot draw any conclusion, either general or special, in regard to chlorosis.
In uncomplicated cases of chlorosis, the blood serum shows, as a rule, no
noteworthy reduction in the percentage of albumin. The specific gravity of
the serum is on the average 1.028, which corresponds perfectly with the com-
position of normal serum, and the total solids appear to be normal in amount,
averaging about 10 per cent. [The greatest menace to the life of the chlorotic
is thrombosis of the cerebral sinuses. Venous thrombosis of the extremities
is also much commoner than in any other form of anemia. As a rule, throm-
bosis occurs in the severest and most chronic cases. It is very possibly con-
nected with the excess of platelets in the blood.—Ep. |
Taking into consideration all these changes, it follows that the blood in
chlorosis is of a peculiar composition, and characterized by the fact that the
normal number of blood celis is only very slightly reduced while the amount
of hemoglobin of the individual cell is considerably diminished, and thus a
peculiar relationship between the fluid constituents of the blood and the blood
cells develops, which is surprisingly manifest if we puncture a vein in the
arm, permit a few cubic centimeters of blood to flow into a tube, and centrifu-
gate it before it coagulates. In doing this we notice (as also when we allow
the blood to coagulate spontaneously or to form a sediment) that the mass
of the red cells, in toto, is extraordinarily reduced, often to only 25 per cent.
of the whole blood mass, compared with 75 per cent. of the blood fluid, while
in normal blood both components are present in about equal proportions.
It is obvious from the above mentioned examinations that the blood cells,
although present in about normal numbers, are markedly deficient in hemo-
globin, while the chief bulk of the blood is formed by plasma, so that this
328 CHLOROSIS
condition of the blood has been properly designated “ polyplasmia,” that is,
an increase of the total amount of plasma in contrast with other changes of
the blood, such as are found, for instance, in chronic circulatory disturbances
in consequence of heart or lung diseases, in which the volume of the blood
cells exceeds by far that of the plasma, and in which, therefore, a condition
of “oligoplasmia” is present. [The researches of Haldane and Smith re-
garding the total volume of the blood in chlorosis as measured by capacity
to absorb CO gas point to the same polyplasmia referred to by Grawitz.—Eb. ]
All these changes must be carefully considered, as they point the way to
a more thorough understanding of the pathologic process in chlorosis, as we
shall see later. However, the circumstances in all cases are by no means so
simple and so distinctly pronounced that we are able to make the diagnosis
of chlorosis from the blood changes alone. We must emphasize explicitly
that in general practice the blood examination can only confirm the diagnosis ;
the disease itself can only be diagnosticated by taking into consideration all the
previously described symptoms.
In conclusion let us review the entire symptomatology of chlorosis, and
compare it with that of simple anemia, for example—to choose the simplest
form—post-hemorrhagic anemia, such as develops after repeated hemorrhages
from the stomach or the uterus.
In simple anemia we find general pallor, extension of the cardiac dulness,
systolic murmurs and also venous murmurs as in chlorotics; in addition the
signs of anemia of the brain are found, specks before the eyes, vertigo and
syncope. On the other hand, if there are no complications, the entire group
of nervous symptoms are lacking in simple anemia, especially anomalies in
the psychical sphere and of the appetite; in spite of the increased frequency
of the pulse, as the result of anemia, the troublesome cardiac palpitations are
absent, as are also the symptoms referable to the sensory sphere and the
vasomotor tissue which give to chlorotics their peculiar puffy appearance.
The changes in the blood, too, are essentially different, for in simple anemia
following hemorrhage we always find a considerable reduction in the number
of cells, while the amount of hemoglobin in the individual cell is only slightly
or not at all decreased. [This is true immediately after the bleeding. Later,
the amount of hemoglobin becomes relatively diminished, and the blood may
simulate closely the conditions found in chlorosis——Ep.] On the other hand,
the serum in these anemias always shows a more or less considerable diminu-
tion in the percentage of albumin, so that these two main factors, the blood
cells and the blood serum, are entirely different from those of chlorosis.
Moreover, in anemias following severe hemorrhage we find nucleated red
corpuscles and an increase in the number of leukocytes. [Post-hemorrhagic
leukocytosis is a curiously inconstant phenomenon. As a rule it occurs, not
immediately after the hemorrhage, but some days later, and its duration is
very variable. Unless frequent examinations are made the wave of increase
is often missed altogether.
The same is true of the “shower” of normoblasts which usually occurs
after hemorrhage, but may be very brief.— Ep. |
PATHOLOGICAL ANATOMY 329
PATHOLOGICAL ANATOMY
The anatomical lesions of this disease have by no means been determined
with certainty. The great difficulty in making positive statements regarding
organic changes in chlorosis lies in the fact that in uncomplicated chlorosis
fatal cases are exceedingly rare, and we are consequently dependent upon the
scant observations obtained when chlorotics have perished from an intercur-
rent disease, and in these cases we are compelled to decide which among the
organic changes are to be referred to chlorosis and which are to be attributed
to the affection causing the fatal issue.
In these cases, changes in the hematopoietic apparatus of chlorotics, that
is, in the marrow of the long, tubular bones, which might be held responsible
for the origin of the blood changes, are as yet not understood. The author
himself examined thoroughly the tibiee of two chlorotic girls, and was unable
to find any disease changes, macroscopically or microscopically, in the distri-
bution of the red and fat marrows.
Best known are the changes in the circulatory apparatus, presented by
Virchow as the anatomical foundation of chlorosis, and which for a long
time were interpreted in this sense by clinicians. According to Virchow, we
are dealing in these cases with a defective development of the heart and of
the large arterial vessels, with a hypoplasia or dwarfed state in which the
changes in the vessels become manifest by abnormal narrowing, thinness, and
elasticity of the arteries, and also by irregular ramifications of the vessels.
This hypoplasia of the heart and vascular system, as Virchow teaches,
favors the assumption of a predisposition, either congenital or acquired in early
youth, which, as a rule, causes actual disturbances having pathological im-
portance only at puberty, and that chlorosis itself, though incurable, may, by
proper treatment, particularly by dietetic measures, be kept in a state of
latency.
These hypoplasias of the heart and valvular system subsequently became
matters of great importance, and the narrow, thin-walled and enormously
elastic aorta has briefly been designated “aorta chlorotica,’ without at all
explaining how a diminished amount of hemoglobin in the blood can result
from narrowness of the vascular system, secondly, why the chlorotic symp-
tom-complex can in many cases be so readily and permanently overcome, and,
finally, the important question why men who, according to Virchow, also
frequently suffer from hypoplasia of the heart and of the arteries, are so
rarely attacked by chlorosis. In regard to this latter point particularly, i.e.,
the rare occurrence of chlorosis in men, it is remarkable that Virchow disre-
garded this in his hypothesis, in spite of frequent anatomically recognizable
changes in the vascular system.
As a matter of fact, in many chlorotics, hypoplasia of the heart and of
the vessels certainly plays an important réle, but only in so far as it represents
an irreparable and, therefore, very unfavorable complication of chlorosis; for
in this condition we are dealing with a faulty structure of the vascular system
which is acquired in early youth, which cannot of itself lead to chlorotic
330 CHLOROSIS
blood changes, i.e., decrease in the amount of hemoglobin, but which in all
likelihood brings with it another pathological condition of the blood which
we must designate as oligemia vera, i.e., a decrease in the total mass of
the blood. .
Such persons with lessened capacity of the heart and of the vessels and
probably of a lessened total quantity of blood, may, provided they do not
over-exert themselves, appear to be quite healthy; and, as a matter of fact,
we are very frequently surprised to find this state of affairs in a well developed
form at the autopsy of persons in whom we could not suspect an anomaly of
the vascular system.
In itself it is quite unlikely that hypoplasia of the vascular system 1s capa-
ble of producing chlorosis, It can at most be looked upon as a predisposing
factor; aside from this it certainly plays an important réle in those chlorotics
who show an abnormal tendency to relapses, characterized by very slight
inclination to improvement, so that such cases have also been designated as
“habitual” and “ persistent ” chlorosis.
At the present time it may be maintained with certainty, that the severe
anatomical changes of the vascular system are not characteristic, nor are they
even the specific anatomical foundation of chlorosis. In our further discus-
sion, we shall have to consider their effect as factors in prognosis and treat-
ment.
Similar hypoplastic changes have also been found in the genital organs,
and these changes have also been considered to bear a causal relation to
chlorosis. Yet here we may hold the same view as in the hypoplasia of the
vascular system, that these anomalies are to be looked upon only as predis-
posing factors, and that they cannot be regarded as an explanation of the
entire symptom-complex, especially of the blood changes.
All other changes, such as degeneration of the heart muscle, parenchyma-
tous inflammation of the kidneys, and other anatomical alterations, are to be
considered as secondary. Hence it must be admitted that at the present time
a definite anatomical cause of this disease is absolutely unknown.
FREQUENCY OF CHLOROSIS WITH REGARD TO
SEX, AGE AND LOCALITY
It has been noticed for many years that chlorosis affects preferably the
female sex. There are, however, undoubtedly cases of genuine chlorosis in
young men, all the symptoms of the disease most distinctly presenting them-
selves, in the blood as well as in the other organs. As Wunderlich has
observed, the symptom-complex is noted usually in young men of poor
physique and of sedentary occupation—tailor-apprentices, office clerks, etc.
[See Editorial Note II on p. 320.—Ep.] We do not as yet know whether or
not the above mentioned changes in the heart and vascular system are already
existent in these cases and predispose to the outbreak of the disease.
The age at which chlorosis appears in the great majority of cases is that
of puberty, from the twelfth or fourteenth year to the twentieth. [From
eighteen to twenty-three is, in my experience, the period in which the great
PREDISPOSING INFLUENCES 331
majority of cases occur. Immediately after the establishment of menstruation
chlorosis is rare. An interval of five, or even ten, years often follows.—Ep. ]
The disease does appear, however, in young children, or, on the other hand,
and this is not infrequent, may occur in the twenties; after the thirtieth year
chlorosis is exceedingly rare, either as a primary or recurrent attack.
Concerning the constitution it may be said that young, delicately built
girls, weak in muscle, but comparatively fat, are most likely to be affected
with chlorosis; on the other hand, the robust constitution of a girl raised in
the country, for instance, a servant, offers no protection against the appear-
ance of this disease. It must be confessed, however, that when chlorosis
appears in girls of the latter type, as a rule it is milder, and can be remedied
sooner and more surely than in those with a delicate constitution.
Whether chlorosis occurs more often in certain localities than in others
is difficult to determine, for it is almost impossible to obtain positive statistics
of this disease, and especially because many physicians include under the
name of chlorosis all varieties of anemia in young girls. It is certain at any
trate that the disease is more frequent in large cities than in the country.
PREDISPOSING INFLUENCES
Many factors may be looked upon as predisposing causes of chlorosis, and
a knowledge of these is of the utmost importance for the thorough compre-
hension of the entire picture of the disease on the one hand, as well as for
the treatment on the other hand.
These deleterious predisposing influences are to be found, first, in the
domain of general hygiene, and, secondly, among certain organic diseases.
In the first group, i.e., the hygienic influences, we must include errors
in physical and mental training, which, especially among the higher classes,
are of great social importance.
Here, to cite a very frequent error, we observe a neglect of the physical
development of growing girls as compared with that of boys. Out of regard
for their dress, they are not permitted to romp freely, but are taken out to
walk by the side of a governess; they are not sufficiently in the fresh air, and
have no opportunity of enjoying a rapid, powerful and invigorating exercise
of the muscles.
When we consider the view of Virchow, previously referred to, that hypo-
plasia of the heart and of the vascular system is partially acquired in intra-
uterine life but is specially developed in extra-uterine existence, the thought
involuntarily arises that, in many cases, this lack of development of the heart
and vessels may be due to the fact that the normal stimulus for such a develop-
ment of the vascular system as is unquestionably necessary for free movement
of the muscle masses in the limbs and trunk is in these children not sufficiently
active, and that this faulty development of the circulatory apparatus may,
perhaps, be considered a form of inactivity hypoplasia. [If this be true, the
apparent diminution in the number of cases of chlorosis presenting themselves
at our clinics might be explained by the more active habits of life which are
certainly prevalent in America in the present decade.—Ep. ]
332 CHLOROSIS
As already remarked, although the whole complex of symptoms in chlorosis
cannot be explained by these anatomical changes, yet they surely form pre-
disposing factors, and moreover, as we shall observe later, chlorosis is undoubt-
edly more severe in these abnormally organized girls than in those with a
normal circulatory system.
Still more injurious is the pernicious habit of allowing young girls to wear
tightly laced corsets which compress the lower parts of the thorax, hinder
respiration and the circulation of the blood, and unquestionably, besides pro-
ducing the well-known changes in the liver, lead to alteration of position,
and prevent the motility, of the stomach. [That tight lacing has any definite
relation to chlorosis is, J think, quite unproved, though many writers refer
to it—Eb. ] /
Other injurious causes are to be found in the nutrition; these consist of
disturbances of digestion with a loss of appetite for wholesome food; instead
of nourishing the young girl with milk and other easily digested and nutri-
tious food, she is allowed to feed upon dainties.
Among the lower classes, unhygienic conditions of living are frequently
at fault; growing wp in damp, badly ventilated rooms into which the rays
of the sun rarely penetrate, eating insufficiently and of indigestible food, are
conditions potent as predisposing causes of chlorosis. [It has still to be
shown, I think, that bad hygiene can or does produce any type of anemia.
It is natural to expect that anemia would result from such conditions, but I
have never seen any good reason to believe that it does.—Ep. ]
In all classes, premature indulgence in alcohol must be considered ; this is
often permitted children through mistaken dietetic priuciples, but conduces
to the undermining of the health at an early age.
To these faults in training psychical factors are added, such as the prema-
ture awakening of sensuality by exciting literature, exaggerated novels and
the like, from which ideas of love develop entirely too early and, in many
cases, not only exert an unwholesome influence upon the psychical nature,
but upon the whole physical condition.
A peculiar predisposition favoring the development of chlorosis may be
observed daily in the life of a large city. This is manifested in young servant
girls, who, as a rule to-day, come from the country or from small towns to
the large cities in quest of higher wages, and often, after a brief residence,
suffer from well-developed chlorosis. This contingent of young girls forms
a large proportion of our hospital patients, and it is interesting to inquire
into their history. Usually we find that these girls, on the average from
eighteen to twenty-two years of age, were while at home always well, strong,
and able to work, as may also be inferred from their “service books.” After
arrival in the large city, a very brief period sometimes elapses before they
become ill and show the fully developed symptom-complex of chlorosis.
The author has taken special interest in these cases, and after careful
investigation has found that two to four weeks are often sufficient to transform
@ healthy and robust-looking girl into a patient with pronounced symptoms
of chiorosis. It is worthy of note that these patients manifest no anomalies
of the stomach or intestines except, perhaps, transitory constipation, nor any
THE GENESIS OF CHLOROSIS 333
disturbances of the sexual functions, a point which is important for the com-
prehension of the entire process.
As factors which favor the outbreak of the affection we may mention
the changes in the food and in the mode of life, particularly the late going
to bed and the hard work (the climbing of many flights of stairs). Other
causes which play an important role are the hurry of life, psychical exaltation,
especially nostalgia, and finally reduced consumption of fresh air.
Certainly, it is undeniable that the mere removal of a previously perfectly
healthy young girl from the country to a large city is sufficient to produce the
entire symptom-complex of chlorosis, and that the same girl, if sent back to
her former country home, will lose every trace of the disease; for this reason
the author suggests the name “ city chlorosis” for this variety of the affection.
Besides these factors, organic diseases may lead to the development of
chlorosis. As an instance, we may mention “ gastroptosis” with the digestive
disturbances that accompany it. Meinert, especially, has called the attention
of the profession to its frequent presence in chlorosis.
Menstrual abnormalities, too, particularly profuse menstruation, certainly
predispose to chlorosis, as also probably does an attack of an acute infectious
disease.
Reviewing at a glance all these predisposing factors, beginning with the
anatomical changes of the circulatory apparatus, then the unhygienic influ-
ences, and, finally, actual organic diseases, it is at once apparent that there
exists no specific factor nor one single factor which is found as the cause in
all cases, but, on the contrary, taking into consideration the great variety of
predisposing causes, we have reason to believe that the points of minor resist-
ance that favor the outbreak of this peculiar disease are manifold. The
question arises which, in this large number of diversified and detrimental
influences, is the connecting link that may satisfactorily explain the genesis
and the true nature of the disease.
THE GENESIS OF CHLOROSIS
The views that have been expressed with regard to the development and
the true nature of this disease vary greatly. First, the theory is to be consid-
ered which treats of chlorosis as an essential blood disease, in which all
organic changes or symptoms on the part of the organs are of a secondary
nature, and the blood itself is the primary seat of the disease. This view
is no longer tenable on account of the numerous and exact blood examina-
tions that have been made in the last few decades, the results of which have
been mentioned above. According to our present knowledge, a specific dis-
ease of the blood must of necessity be combined with changes of the blood
cells, and, as we have noted, there is absolutely no support for this view, since
the principal and most important morphological changes consist in a decrease
of the hemoglobin of the blood-corpuscles, while degenerative changes, as well
as characteristic pathological changes of the leukocytes, are entirely absent.
The absence of pathological changes of the bone-marrow, as we have al-
ready stated, is against the view of a substantive blood disease, and another
334 CHLOROSIS
point must be particularly emphasized to which Becquerel and Rodier, the
celebrated investigators in the realm of hematology, called attention about the
middle of the last century, namely, that the changes in the blood of chlorotics
do not correspond with the severity of the clinical picture; on the contrary,
particularly at the onset of the disease, when all of the other symptoms are
conspicuously developed, the blood changes are comparatively slight, and only
increase upon prolongation of the malady. This late deterioration of the
blood, according to our present knowledge, must be referred partly to an
insufficient ingestion of food, in some cases also to accompanying symptoms;
for example, to profuse menses, sometimes perhaps to autointoxication from
the intestines. Therefore, the assumption that in chlorosis the blood itself
is the tissue primarily diseased cannot be maintained.
The development of chlorosis has been also attributed to disturbances in
the sexual functions; for, as previously remarked, too slight or too profuse
menses are observed in most cases of chlorosis, and Trousseau actually refers
to menorrhagic chlorosis.
Anatomical anomalies of the sexual organs, which not infrequently appear
as hypoplasia of these organs, have, as we found to be the case in the circula-
tory apparatus, been looked upon as responsible for the development of the
disease. Nevertheless, these changes cannot all be looked upon as special
causes of chlorosis, but, at most, in many cases as predisposing causes. In
the majority of instances, however, they are certainly secondary conditions
in the chlorotic pathological picture.
That these anomalies have no general importance in the genesis of chlorosis
may be seen clearly from the fact that in numerous chlorotics neither abnor-
malitaes nor functional anomalies of the sexual organs can, at any period of
the disease, be discovered.
In accordance with modern pathological views, an attempt has lately been
made to attribute to the sexual organs the development of chlorosis in another
sense. It has been assumed that from these organs (as we know positively in
the case of the thyreoid gland) besides their well-known specific function,
still another internal secretory activity proceeds, by means of which materials
reach the circulation, and that this activity bears a certain relation to the
hematopoietic function.
This view is based mainly upon the fact that chlorosis is prone to appear
in that period of life in which the sexual organs mature. Yet it is indicative
of the uncertainty of these views that, while v. Noorden assumes that there is
an absence of the internal secretion in chlorotics, and that as the result of
this the material reaching the blood is insufficient to stimulate blood forma-
tion, in opposition to this Lloyd Jones holds the opinion that at the time of
sexual maturity internal secretions enter the blood in superfluous amounts,
and in some complicated manner bring about its chlorotic composition.
These modern views according to which chlorosis is attributed to the hypo-
thetical functional disturbances of the generative organs appear to me as
untenable as the earlier ones which were based upon anatomic and well-known
functional disturbances. I believe these views of chlorosis to be just as partial
as those concerning hysteria, in which the name at once shows that the origin
THE GENESIS OF CHLOROSIS 835
of this disease was formerly supposed to be in the uterine sphere, although
there can be no doubt that in this morbid state many hysterical women have
perfectly normal sexual organs and functions, so that to-day no physician
seriously refers the symptom-complex of hysteria to the uterus.
Another opinion which ‘was firmly maintained by Clark and Nothnagel is
that in chlorotics, who almost invariably suffer from constipation, there is an
abnormal process of decomposition in the intestines, and from the resorption
of products of this the disease originates.
This theory of autointoxication, however, cannot be considered to explain
the entire pathological picture; indeed it may be contidently asserted that
many chloroties never suifer from constipation—neither before nor after the
onset of the disease. Nevertheless, J am under the impression that in some
eases of chlorosis, autointoxication from the intestines may have an auxiliary
deleterious effect, and I believe that various degenerative signs in the erythro-
cytes which do not conform to the ordinary blood-picture of chlorosis may
often be attributed to these auxiliary causes.
Another theory as to the etiology of chlorosis has been proposed by Meinert,
who, as has been stated, lays special stress upon displacement and atony of the
stomach; this, in his opinion, develops a dragging of the abdominal sympa-
thetic, and is said to cause anemia, that is, chlorosis.
In reviewing these theories, of which I have indicated only the most impor-
tant, it may be noted that they are alike unsatisfactory from the circumstance
that they do not conform to a uniform principle, active and pathologic in all
cases, but, on the contrary, of all of them it may be said that the anatomical
or functional changes considered to be causative are in many cases certainly
not present.
When we consider the characteristic symptoms which distinguish chlorosis
from other simple conditions, and reflect that such symptoms can be produced
by the nervous system exclusively, and remember, on the other hand, the pecul-
iar blood finding which shows a conspicuous accumulation of plasma in the
blood and a decrease of hemoglobin in the cells without a diminution in the
number of the cells, the conviction forces itself upon us that the characteristic
changes found in this form of anemia must be referred to the nervous system.
In my opinion chlorosis depends more upon anomalies in the lymph-
formation than in the blood-formation; abnormal amounts of fluid accumulate
in the tissues as well as in the chlorotic blood, as was shown in the description
of the symptomatology, and in chlorosis it appears as though the blood-vessels
were disturbed in their function, and the systematic exchange of fluid between
blood and tissue altered; thus accumulations of fluid arise which, because of
disturbed secretory activity, are not excreted in sufficient amount, and in conse-
quence lead to stasis of the lymph.
These disturbances in the circulation of the blood and lymph are, in my
opinion, to be referred to anomalies in function of the vasomotor nerves, to
which also we may refer the pallor and blushing that in chlorotics appear and
disappear so rapidly. Abnormalities in the exchange of fluid between the
blood and the tissues of the body are especially dependent upon pathological
functioning of the vasomotor nervous system, as my former investigations
336 CHLOROSIS
have taught me. I believe, therefore, that in this direction, i.e, in some
neurosis of the vasomotors, we must search for the explanation of the peculiar
blood findings of chlorosis, for hereby the polyplasmia of the blood and of
the tissues may readily be explained, and it. is also perfectly comprehensible
that from a general accumulation of fluid in the tissues, particularly in the
bone-marrow, the supply of hemoglobin to the erythrocytes should be deficient.
Chlorosis, therefore, I consider to be a neurosis, which appears in young
adolescents, not exclusively, but usually, in girls and women; its development
being favored by various preceding, predisposing causes. The anemic compo-
sition of the blood is simply one symptom of this neurosis, even though it is
the most invariable and most prominent symptom. The origin of the anemia
may be also referred to a faulty function of the nerves, as also are all other
nervous symptoms which characterize chlorosis.
The symptomatology, as well as the views regarding the etiologic factors,
and also the therapeutic results which are to be later described, in my judg-
ment exclude a specific organic disease of the blood, as well as the idea of an
anemia dependent on the formerly mentioned functional and anatomical
anomalies; on the contrary, I believe chlorosis to be a link in a chain of neu-
roses particularly prevalent in females, and to represent a peculiar form of the
general hysteric symptom-complez.
DIAGNOSIS
In regard to the diagnosis of chlorosis, it must first be emphasized that
the blood finding alone is not decisive in the recognition of chlorosis, as the
blood condition above described occurs not only in chlorosis, but is occasion-
ally found in other anemias, and therefore cannot be looked upon as typical
or pathognomonic. In this disease, as well as in other anemias, the blood
finding may be utilized to confirm the diagnosis after a previous general ex-
amination of the organs, but, on the other hand, the diagnosis cannot be made
from the blood condition and the organic changes be, then made to conform to
this finding.
The diagnosis in well-developed cases may be readily made when the dis-
ease occurs in young, puffy-looking girls, with a yellowish-green color of the
skin, who present the manifold symptoms and anomalies on the part of vari-
ous organs which have been described. There are, however, some difficulties
here which not infrequently lead to error, and are therefore of importance in
practice.
It must be emphatically pointed out that it is a mistake to make a diagnosis
of chlorosis, without further consideration, when young girls showing general
pallor come under treatment; on the contrary, this peculiar disease must be
distinguished from the usual forms of anemia, and here we may consider par-
ticularly the anemia which is the result of internal hemorrhages, for example,
from the menses, or hemorrhage due to gastric ulcer which, under some cir-
cumstances, may produce even more serious changes in the composition of the
blood than chlorosis, but which, for obvious reasons, and chiefly from a thera-
peutic standpoint, must be differentiated from chlorosis.
COURSE OF THE DISEASE 337
The local examination of the genital organs in the one case, or of the
stomach, the vomit, the feces, etc., in the other, will guard us from error.
But even before these points are decided, chlorosis may usually be distin-
guished from simple anemias by the great number of pre-eminently nervous
and circulatory disturbances which distinctly separate the one clinical picture
from the other.
There are other organic diseases which often occur insidiously in young
girls and lead to anemia, so that difficulty in diagnosis may arise, especially in
family practice where the aids to diagnosis are not so easily obtained as in the
hospital, and where errors may more readily be made.
In the first place I shall name pulmonary tuberculosis, which, at the onset,
often causes but slight local disturbances, perhaps only a trifling cough of
which but little notice is taken. Nevertheless, the affection in these early
stages gives rise to a distinct anemia. [It is important, however, also
to recognize that intense pallor without any demonstrable anemia is very
prone to occur in tuberculosis—Ep.] And it becomes an imperative duty
most carefully to examine the lungs, especially at the apices, in any doubt-
ful case. .
Another organic affection, which in practice frequently resembles chloro-
sis, is chronic nephritis; this is prone to appear at puberty in those who, as
children, have passed through an infectious disease and recovered, especially
scearlatina which was later followed by a sequel—renal inflammation—the lat-
ter, however, not having been entirely cured but, on the contrary, continuing
to affect the patient in later life, although not infrequently the distinct signs,
particularly edema, appear first during puberty. It is therefore absolutely
necessary in doubtful cases to make a careful examination of the urine, both
chemically and microscopically.
COURSE OF THE DISEASE
The course of the disease in individual cases shows great variation, and
from the earliest periods cases of chlorosis have been observed in which there
was prompt improvement, whereas others manifested a tendency to relapses,
and others again were so stubborn as to appear incurable in spite of any form
of therapy. ‘
Therefore, various forms of chlorosis have been differentiated, such as
“ transitory,” “relapsing,” and “habitual.” These variations in the form of
the disease can rarely be recognized at the onset. The course is also dependent
on a variety of: factors so that these forms can only be differentiated from one
another after prolonged observation. The most common form is unquestion-
ably the benign and transitory, in which all of the symptoms and the blood
condition are relieved in the course of a few weeks.
The main contingent of this group is of course made up of girls and women
of strong constitution, who, before the development of chlorosis, were com-
paratively well and active. The favorable progress of the disease, as will be
more minutely demonstrated in the therapy, is due partly to the fact that the
patient is removed from her usual surroundings, and is treated under condi-
23
338 CHLOROSIS
tions which have a beneficial influence upon metabolism in general and upon
the nervous system.
The cases which run an unfavorable course, particularly those forms of
the malady which are looked upon as habitual, i.e., those not completely dis-
appearing, are unquestionably often complicated by anatomical abnormalities
such as have been described; for instance, by an abnormal smallness and nar-
rowness of the heart and vascular system, and, probably, by an unfavorable
predisposition of the hematopoietic apparatus, and a diminution in the amount
of blood. In these cases we are not dealing with pure chlorosis, but with a
complicated anemia due to anatomical and chlorotic changes, and in many
of these instances Virchow’s opinion must be regarded as correct; namely,
that the chlorotic symptoms may be suppressed by suitable therapy, but the
disease can never be entirely cured.
It is important to note that these very persons whose vascular system 1s
imperfectly developed offer very slight resistance to other morbific and dam-
aging influences, i.e., that they are usually predisposed to catarrhal affections
of the various organs, and that they are more subject to severe acute infectious
diseases, as, for example, pneumonia, etc., than persons with a normally devel-
oped vascular system. This fact explains the previously mentioned anatomical
anomalies found at the autopsy of anemic young girls.
Quite as obstinate as these mixed forms of oligemia and chlorosis due to
anatomical changes are the forms of the affection in early youth due to such
errors in bringing up as have been described—insufficient nutrition, deficient
stimulation of the circulation, and undue irritation of the nervous system—
so that these children from their earliest years have never, in fact, had a hale,
hearty, rosy-cheeked appearance, and have never shown the normal mental and
physical vigor and sprightliness characteristic of a well-developed child that
has received proper bringing up under good management.
We meet such girls chiefly in private practice among the better classes;
almost from infancy they are markedly languid, at school they are less capable
of application, and are easily fatigued; on the other hand, as they grow, they
develop a special liking for belles-lettres or for books which excite the imagi-
nation, and show but slight inclination to exert their physical powers. It is
therefore quite possible that in these girls, on account of insufficient muscular
exercise and stimulation, an undeveloped condition of the heart and vascular
system is induced, so that in some of them pure chlorotic symptoms no longer
appear, but mixed forms of general anemia (oligemia) and chlorosis.
It is interesting to observe these girls when they reach puberty, marry, and
attain a riper maturity. We usually find that the chlorotic symptoms, i.e.,
the puffy appearance and the numerous irregularities on the part of the vari-
ous organs, especially of the vascular system, disappear. Nevertheless, these
women remain pale, are inactive, easily irritated, and form a large proportion
of the widely distributed group of hysterics, so that, upon accurate investiga-
tion of the history of most hysterics, the report is obtained that in early youth
they had been anemic.
This fact bears further testimony, in my opinion, to the close relationship
of chlorosis and hysteria. Indeed it may be observed in various realms of
e
TREATMENT 339
hematology that diseases of the blood and of the nervous system present many
identical etiologic factors, and frequently show a certain parallelism in their
course.
Finally, the fact must be borne in mind that in many cases chlorosis appears
as a hereditary condition, and we may assume that both the debility of the
nervous system, and the anatomical incompleteness in the structure of the
vascular system are inherited. But the view may be just as well maintained
that errors in bringing up which favor the outbreak of chlorosis may be trans-
mitted from the mother to the daughter in consequence of the faulty manner
of life in some families just as a disease may be transmitted.
PROGNOSIS
The prognosis in general is that of other benign diseases which are readily
cured, and consequently it may in general be regarded as favorable from the
onset. It is especially so in the case of those girls in whom the symptoms have
appeared suddenly, and who previously neither were anemic nor showed other
pathological symptoms. Such cases occur in domestics who have grown up
in the country or in-a small town. More unfavorable are the conditions in
girls who from early youth have shown the signs of anemia, who are addicted
to all the previously mentioned errors of education and general hygiene, the
importance of which in the development of the disease has been indicated
above. Those cases are doubtless particularly unfavorable that are complicated
by the existence of anatomical anomalies of the heart and vascular system
such as were pointed out. These latter young girls, in consequence of their
generally lessened power of resistance, are in greater danger when acute dis-
eases such as pulmonary inflammations, influenza, enteric fever, etc., appear
intercurrently.
TREATMENT
Chlorosis is generally amenable to treatment, but from the onset we must
bear in mind the factors which favor the development of the disease, and as
every rational treatment must begin by an attempt to remove the cause of the
malady, or at least its predisposing elements, it becomes the duty of the physi-
cian to try to discover in the individual case what causes have favored the
development of chlorosis, a point that is of paramount importance in family
practice, where the error must be sought in the general mode of life of the
family and particularly in the bringing up of young girls. This is often a
difficult and delicate task, and requires great tact and judgment on the part
of the physician.
Particularly for this reason, i.e., because the development of the disease
is favored by the injudicious manner of life and habits of the family, it is
wise in many cases to remove the patient from her usual surroundings and
place her in a suitable sanatorium, preferably in a suitable health resort; in
many cases the results will prove that stubborn cases of chlorosis that have
resisted all the therapeutic efforts of home practice are speedily cured on
removal from their former surroundings. It may be maintained with cer-
340 CHLOROSIS
tainty to-day that there is no specific in the treatment of chlorosis, and that
even iron, which Felix Niemeyer declared in his time to be a specific, cannot
be looked upon as such nor infallible.
On the contrary, experience proves that some chlorotics, who have shown
no appreciable improvement under a plentiful iron treatment because their
general hygienic surroundings were unchanged, are restored to health in a
short time if they—as is frequently the case, for example, with the previously
mentioned domestics—are sent from their usual sphere of activity to the
country where fresh air and generally favorable hygienic conditions exert a
curative influence upon them without a drug therapy of any kind whatsoever.
In keeping with my view that chlorosis is a neurosis in which the blood
alteration is not the essential part of the disease, but usually forms the most
constant symptom, I have for some time attempted to influence this disease
without administering drugs that have a specific action upon the blood com-
position, and particularly without the employment of iron preparations, but
purely by the same dietetic and hydrotherapeutic measures which are em-
ployed in other neuroses, especially in hysteria. With this antinervous régime
I have completely cured a number of chlorotics in about the same time as with
the ordinary iron therapy, yet it is true that some individual cases were favor-
ably affected after an iron therapy had been instituted.
It is evident, at all events, that under hospital treatment with good nurs-
ing and proper nutrition, the use of sweat baths at the beginning, friction
with light massage later, and the internal administration of some nervines
such as bromide or valerian, but without any iron medication, the same favor-
able results can be obtained as are observed in girls who regain their health by
being sent back to their country homes.
This therapeutic experience strengthens my belief in the view that chloro-
sis is a peculiar neurosis going hand in hand with a damage in hemoglobin
formation, and, to my surprise, I recently found that Sydenham in his excel-
lent “Lectures upon Hysteria,” which even to-day are well worth reading,
particularly emphasizes this, that chlorosis is curable by the same remedies
which are effective in hysteria.
In spite of these experiences, I do not by any means intend to deny the
value of iron treatment in chlorosis. This has been demonstrated in prac-
tice, time and again, by numerous examples; I generally advise the adminis-
tration of iron in the treatment of chlorosis. I merely wish to point out that
in these cases iron is not to be looked upon as a specific, that we must not
commit the error of thinking that enough is done when we prescribe a good
tron preparation for a chlorotic girl, but that the main point in treatment
undoubtedly consists in good nursing and diet.
The treatment of chlorosis is best begun by ordering complete rest in bed,
a laxative to relieve the coprostasis, and something to stimulate the appetite.
It is well at the start to ascertain by an examination of the gastric contents
the state of the secretory and motor functions of the stomach; for, in somé
cases, as has been stated, hydrochloric acid is in excess, while in others it is
diminished, and in still other cases atony of the gastric walls exists which
prevents the timely expulsion of the ingesta. All of these morbid changes
TREATMENT 341
in the stomach must be relieved by a rational treatment before we proceed
with a special therapy; and, as a rule, it is comparatively easy to correct. these
anomalies of secretion.
The diet in the beginning must consist of easily digested food, of which
milk is of the greatest importance, and only in very stout girls is it necessary
to limit or entirely withhold this, the best nutritive measure. Easily digested
vegetables, especially the green vegetables, such as spinach, which, by the way,
contains a small amount of iron, green peas and beans, mashed potatoes, and
Tice are particularly advisable. Later on, finely scraped raw beef or scraped
ham may be allowed, while the use of eggs, at least in large amounts, is not
recommended on account of the intestinal decomposition which readily ensues.
Very frequently at the onset of treatment it is necessary to remove the
edematous swellings which appear in the face, giving the patient a peculiar
puffy appearance; these are also seen in the ankles and elsewhere. For this
purpose, venesection has lately been employed again, as it was by many physi-
cians at the beginning of the preceding century, though even then, when
venesection was in vogue, experienced physicians such as Becquerel and Rodier,
on the basis of their exact blood investigations, cautioned the profession against
the indiscriminate employment of venesection in chlorosis. To-day, with our
knowledge of the more minute constituents of the blood in chlorosis, vene-
section cannot be looked upon as a justifiable therapeutic measure; for the.
plethora, i.e., the excessive accumulation of fluid in the blood, the removal
of which was attempted by the exponents of the venesection therapy, is rather
increased by the loss of blood and by the consequent inflow of lymph, and in
my opinion the only favorable result of venesection is the reactive outbreak of
sweat to which these physicians attached great weight.
This effect of the outbreak of sweat upon the fluid accumulated in the
blood and in the tissues can, in my opinion, be brought about more effectively
and with less danger by a simple sweat bath. In puffy chlorotics, during the
first period of the treatment, I employ hot baths followed by sweating two or
three times a week, and I find that the subjective difficulties as well as the
objective findings are always favorably influenced thereby.
Massage, too, is effective, particularly as long as the patients remain in
bed; it acts very favorably in stimulating the circulation and the entire
metabolism.
Iron therapy, as already mentioned, forms an essential adjuvant in the
treatment of chlorosis, although to-day we no longer hold the old opinion that
iron is directly utilized in the formation of hemoglobin in the body, but it is
to be looked upon mainly as a stimulant for the hematopoietic organs. That
iron actually reaches the fluids of the body Ly absorption, a point that has been
questioned even very recently, has lately been positively proven chiefly by
the investigations of Quincke. ;
The number of iron preparations at our disposal for therapeutic purposes
is exceedingly large. Besides the inorganic compounds of iron such as ferrum
orydatum, ferrum sulphuricum, ferrum citricum, ferrum carbonicum, ferrum
chloratum, and ferrum sesquichloratum, we possess countless newer prepara-
tions which contain iron in albumin combinations, and to these lately have
342 CHLOROSIS
been added remedies which contain hemoglobin itself in different combina-
tions.
All of the last-named remedies are based upon the hypothesis that iron is
absorbed and assimilated more readily when combined with albumin products,
especially those prepared from blood itself in accordance with modern organo-
therapy; these give to the organism as directly as possible a compensation for
the loss of hemoglobin in the pathologically altered blood.
Of the organic iron preparations there are to be named ferratin, an arti-
ficially produced iron preparation (Schmiedeberg), which is said to be iden-
tical with the iron combinations present in the organism and in the food;
further, ferrum peptonatum and the various liquores ferrt albuminati. Of
iron-containing blood preparations new ones are combined and placed upon the
market almost daily, so that it is scarcely worth while to mention the names
of these, for the most part, ephemeral preparations. Especially fashionable
in practice are hematogen, hemaldumin, hemol,. sanguinal, etc. It must be
remembered in the employment of all these remedies that in all probability
the iron, whether given in an organic or inorganic combination, is primarily
attacked by the gastric juice and changed into a chlorid combination, and that
later it is absorbed in the bowel as an iron chlorid albuminate. It is therefore
quite unlikely that the artificial or natural iron albuminates are absorbed in
the form in which they are administered, and it may be assumed that, during
the time of their absorption into the fluids of the body, great labor is thrown
upon the stomach and intestine, much greater than in the administration of
inorganic preparations.
Regarding the special activity of these remedies in chlorosis, neither from
literature nor from my own experience are many observations of patients of
this sort known to me, from which it might be concluded with any certainty
that any one of the above-mentioned organic preparations produces a cure
more rapidly and with greater certainty than is observed upon the administra-
tion of the ordinary iron preparations.
What is particularly lauded by the manufacturers concerning these reme-
dies is the useful action of the albumin contained in them; but it must be
mentioned that these amounts of albumin are so small that they play-no réle
in the nutrition of the chlorotic, particularly as in this disease there is no
noteworthy deficiency in albumin metabolism.
Unquestionably the majority of these modern remedies act by suggestion,
and therefore in practice we can rarely do without them, as the laity nowadays
manifest the greatest interest in the products of pharmaceutical industry. In
cases, however, in which the therapy remains uninfluenced by these subjective
effects upon the patient, as in hospital treatment, there is absolutely no reason
for rejecting the old well-tried iron preparations in their various combinations ;
thus, for example, the excellent Blaud’s pills.
According to the suggestion of C. Gerhardt, for some years I employed
with success liquor ferri sesquichlorati, three to five drops three times daily,
diluted in water.
The numerous iron springs in Germany and neighboring countries contain
iron for the most part as a suboxid combined with carbonic acid, and the
PROPHYLAXIS 343
waters are, therefore, suitable for drinking at the spring; not, however, for
bottling, as carbonic acid readily passes off and the iron is then precipitated.
A few springs contain sulphate of iron, and still fewer, chlorid of iron.
The best-known German iron springs are in Pyrmont in the Duchy of
Waldeck, Langenschwalbach at the Taunus, Bocklet (near Kissingen), Char-
lottenbrunn, Cudowa and Flinsberg in Silesia, Driburg in the Teutoburger
Woods, Elster in Saxony, Franzensbad in Bohemia, Kohlgrub in Bavaria, 900
meters above the sea, Muskau in the Lausitz, Liebenstein in Meiningen, Freien-
walde on the Oder in Brandenburg, Pulzin in Pomerania, Reinerz, 500 meters
high, in the earldom of Glatz, Steben in Upper Franconia.
Of foreign iron springs there are particularly to be named: Farnbiihl in
Luzerne, St. Moritz in the Upper Engadine, 1,700 meters above the sea, and
Val Sinestra in the Lower Engadine; further, Haarlem in Holland, Szlidcz
in Hungary, Spa in Belgium.
Besides iron, in some cases arsenic is of use as in other anemias; and
therefore, besides the preparations of the pharmacopeia, arsenical spring-
waters must also be considered; the best known are those of Roncegno and
Levico in the Southern Tyrol as well as the Guber Spring in Srebrenica in
Bosnia.
The beneficial effect of all of these iron and iron-arsenic spring cures cer-
tainly does not consist only in their contents of iron and arsenic, but quite
as much in the stimulation to metabolism by change of climate and the con-
stant outdoor life, so that, in fact, many extremely chlorotic patients are seen
to recover in these regions who show but slight improvement while at home in
spite of any iron preparation.
Of other drugs quinin is chiefly to be mentioned, while remedies such as
phosphorus, manganese, and organopreparations, for example, bone-marrow,
thymus, etc., are of no importance.
PROPHYLAXIS
Although in the direct treatment of the chlorotic symptom-complex a great
variety of dietetic, physical and medicinal auxiliary remedies are at our dis-
posal, it must nevertheless be repeated that many cases of chlorosis belong to
the diseases which are readily preventable, and particularly where the social
position of young girls precludes the necessity of their earning their own live-
lihood, and the external conditions are favorable for healthy development.
Since, in spite of this, the disease is observed frequently in well-to-do
families, it must be attributed wholly to the utter ignorance even to-day in the
most highly cultured families regarding the fundamental principles of hyguene,
a deplorable condition which must be combated, on the one hand, by a greater
dissemination of the laws of hygiene among the people, and, on the other hand,
by the activity of each individual family physician.
It is sufficient here, to avoid repetition, simply to refer to the deleterious
factors which have been previously mentioned as predisposing, and which may
be removed in a large measure by hygienic regulation of the mode of life, by
bodily exercise, exercise in the open air, etc.
LEUKEMIA
By W. von LEUBE, Wirzsure
Since the discovery of leukemia by Virchow in 1845, we designate by this
term a disease characterized by an increase in the number of white cells in the
blood as the result of the morbid activity of the blood-forming organs, and in
which the blood alteration forms the essential feature of the progressive and
pernicious course of the disease. [The blood changes dominate the clinical
picture, and are manifest in many organs post mortem, but it is the belief of
most authorities that the heightened activity of glands and marrow to which
they are due is itself a result of some toxic (chemotactic) stimulus.—EDb. |
This definition is sufficient clearly to differentiate “leukocytosis” from
leukemia. In leukocytosis we are, in fact, also dealing with an increase of
the leukocytes in the circulating blood; but this is a transitory symptom in the
course of manifold diseases. At the same, leukocytosis is not, like leukemia,
a morbid condition of a progressive and pernicious nature; on the contrary
it is in a measure the expression of the self-protective power of the body
against the disease present.
COMPOSITION OF THE BLOOD
Without a thorough knowledge of the composition of the blood and of
the genesis of its different morphologic elements, an insight into the nature
of leukemia is impossible. We shall, therefore, describe briefly the normal
condition of the blood and of its cellular elements before we discuss leukemia
in detail.*
The three formed elements of the blood are, as is generally known, the
red blood cells, the white blood cells and the blood-plaques. These last have
thus far little, or no, importance in pathology.
The red blood cells, “erythrocytes,” are flat, circular, biconcave discs,
averaging 7.5 micromillimeters in diameter. Normally they do not contain
a nucleus, but consist of a protoplasmic stroma the gaps of which are filled with
hemoglobin. The formation of the red blood-corpuscles occurs in embryonic
as well as in post-fetal life from nucleus-containing, colored blood cells, the
1 This article relating to the diagnosis and pathogenesis of leukemia is based, in the
main, upon the complete and recently revised chapter on Leukemia in the sixth edition
of my “Special Diagnosis of Internal Diseases” (English edition, Leube-Salinger, D.
Appleton & Co., 1904.)
344
COMPOSITION OF THE BLOOD 345
hematoblasts. These cells are invariably present in the red bone-marrow of
the flat bones, of the sternum and of the ribs, the base of the skull and the
vertebre. The red blood cells which at first contain a nucleus, lose this later
by caryolysis,‘i.e., by dissolution of the nucleus (according to some investi-
gating authors by expulsion) and then enter the circulating blood as non-
nucleated red blood-dises. We must at present adhere to the view that in
post-fetal life the red (non-nucleated) blood cells are formed exclusively in
the red bone-marrow, namely, from the nucleus-containing, red blood cells
which are constantly present in these regions. The latter cells, the hemato-
blasts, appear, at least in embryonic life, to arise from lymphocytes by hemo-
globin production, first as megaloblasts, which perhaps are originally the
mother cells of the normoblasts. [Several authorities of the first rank take
exception to this account of the hematoblasts, and believe that red and white
cells arise from different stems.—Ep.| However, after the latter have been
formed, they increase by mitosis, constantly producing new normoblasts. Be-
sides the bone-marrow, in embryonic life the lymph-glands also probably have
an erythropoietic function [probably also the liver, and possibly the spleen.—
Ep.]; but in the adult organism blood-formation occurs only in the bone-
marrow, where also the transformation of normoblasts into non-nucleated blood
discs occurs (by caryolysis). Under normal conditions only non-nucleated
blood cells pass from the bone-marrow into the blood. Whenever an appre-
ciable quantity of nucleated red blood cells is found in the blood, pathological
conditions are present: Infections, intoxications, inanition. If large num-
bers of nucleated blood cells are in circulation, severe anemias, even of the
severest character, are present.
When the red blood cells die they are replaced by fresh material coming
from the bone-marrow, so that the number of erythrocytes remains at almost
a constant figure, namely, about 5,000,000 for men and about 4,500,000 for
women te the cubic millimeter, a proportion of about 600 to 1 of the white cells
[5,000,000 is too low for the average of healthy adult males in America. The
correct figure is much nearer 6,000,000.—Ep.] The majority of the blood
cells, unquestionably, disintegrate in the liver. We are justified in this as-
sumption for reasons which need not be here minutely considered, and of
which only one shall be mentioned, viz., that in the liver large amounts of
biliary coloring matter are daily produced. But bile, as its chemical compo-
sition proves (hematin C,,H,,N,O,Fe by taking up water and giving off iron—
+ 2H,0 — Fe—forms bilirubin C,,H,,N,0,), can only consist of hemoglobin
which has been given up from the stroma of the red blood cells. We can in
fact artificially increase at will the production of biliary coloring matter by
the injection of hemoglobin into the blood.
The white blood cells (leukocytes) represent colorless, membraneless cells
with one or more nuclei and a protoplasm variously constituted. Since the
introduction of new methods of staining in examining the blood, the first
application and completion of which we owe to P. Ehrlich’s excellent investi-
gations in the pathology of the blood, the fact has developed that normal blood
contains not only two varieties of leukocytes, as was assumed for a long time,
but many kinds, differing markedly from each other. It is best to differen-
346 LEUKEMIA
tiate two principal varieties, mononuclear and polynuclear (or polymorpho-
nuclear) cells, both of which show various subvarieties:
A. Mononvuctear Forms: Cells with one nucleus and varying amounts
of basophilic, non-granular protoplasm.
1. Lymphocytes, characterized by a large, round, centrally-placed nucleus
and a narrow protoplasmic ring. The latter, as well as the nucleus, reacts
basophilically, especially the protoplasm which shows no granulations. [No
granulations, that is, with Ehrlich’s stain. With the Romanowsky stain a
variety of pink, violet, and sometimes a few blue granules are seen in the
protoplasm of the lymphocytes. This is true of all sizes of lymphocytes,
though commoner in the large forms.——Ep.] The lymphocytes have no power
of ameboid movement. [I am convinced by the observations of several com-
petent men that lymphocytes (especially, but not only, the larger forms) do
have the power of ameboid movement.—Ep.] The majority of them scarcely
attain the size of the red blood discs; rarely are large lymphocytes found, espe-
cially in the blood of children. The number of lymphocytes amounts to about
25 per cent. of the white blood-corpuscles. Some individual examples, espe-
cially of the larger forms, show slight segmentation of protoplasm. 2. Large
mononuclear leukocytes, twice or three times larger than the lymphocytes,
differing markedly from the large lymphocytes, in that the large, usually oval
nucleus is generally eccentrically situated and that the non-granulated proto-
plasm is relatively well developed. This protoplasm and the nucleus have,
like the lymphocytes, a basophilic reaction, but, in contrast to the latter, the
protoplasm stains less readily than the nucleus. Transitional forms between
the first and second variety are not observed, and for this reason, according
to Ehrlich, the “large mononuclear” cells are strictly differentiated from the
lymphocytes, all the more so as “ transitional forms” from the large mono-
nuclear to the polynuclear are observed, i.e., large cells with neutrophilic
granulation and with indentations in the nucleus. [All recent and unpreju-
diced observers seem to me to agree that there are abundant transitional forms
between the “large lymphocyte” as here described and the “large mononu-
clear leukocyte” of the same text. A differentiation of these two varieties is
in my opinion impossible—Ep.] The number of the large mononuclears in
normal blood is always small (about one per cent.).
B. PoLtynuciear Forms: Cells with several small nuclei or usually with
a polymorphous nucleus, i. e., with marked indentations of the nucleus, so that
some of the nuclear segments are connected by thin chromatin threads. The
polymorphonuclear (“polynuclear”) leukocytes are further characterized by
ameboid movement. The protoplasm is granular and shows varying condi-
tions regarding staining which give rise to the differentiation into the three
following varieties:
1. Neutrophilic polynuclear leukocytes, usually designated as “ polynu-
clears,” characterized by the dense granulation of the protoplasm and the
affinity of the same to “neutral” staining material. They form in the nor-
mal blood about 70 per cent. of the white blood-corpuscles. [There are no
true neutral stains. A special differential acid stain like Ehrlich’s “ ériacid”
is what is here referred to.
COMPOSITION OF THE BLOOD 347
The normal percentage of polynuclear leukocytes is in this country more
often near 60 per cent. than near 70 per cent—Ep. ]
2. Hosinophile cells, characterized by their size and by the coarse granules
in their protoplasm which stain intensely by acid stains (eosin). ['The size of
eosinophiles is not characteristic. They are about the size of a polynuclear
cell or often a little smaller, but their irregular shape (as seen in thin smear
preparations) renders a definite statement as to their diameter difficult—
Ep.]_ They resemble the neutrophilic polynuclear cells and, like these, are
markedly contractile; their number amounts to about 3 per cent. of the white
blood-corpuscles.
3. Basophilic leukocytes, “ mast-cells” are scanty in normal blood (0.5
per cent. of the leukocytes). They are characterized by the intense basophilic
reaction of the granules in their protoplasm and by the very slight staining
affinities of the nucleus; the granulation does not color with the triacid stain,
hence mast-cells appear in triacid preparations as light, non-granular cells.
Opinions are more at variance concerning the origin of the white blood-
corpuscles than of the red, although a number of investigators (Virchow,
Kélliker, Max Schultze, Neumann, Heidenhain, Arnold, Mokoff, Rieder,
Engel and, above all, P. Ehrlich, and in late years Askanazy, Pappenheim and
Rubenstein) have closely studied this subject. At present, it is difficult, almost
impossible, to take a positive stand in the mooted question. The following
theory is probably more in accordance with present opinions than any other.
After the investigations of the last decade, and especially since the intro-
duction of tinctorial methods of examination by Ehrlich, Virchow’s view that
the lymphocytes are the young, the leukocytes the old, forms of the cells, the
latter arising from the former, can no longer be accepted in its simple, strict
conception. On the contrary, it is better to adhere to the view that the lympho-
cytes, the leukocytes and the hemaglobin-containing cells represent separate
stages of development of cells, which probably are only alike in their first
elements—namely, cells with non-granular, weakly basophilic protoplasm and
one round nucleus. From these the myelocytes develop in the bone-marrow,
the protoplasm becoming granular (neutrophilic or eosinophilic), while the
nucleus still retains its round form; in the later stages of development the
granulation becomes more marked, the nucleus flattened, sinuate and, finally,
pigmented (polymorphonuclear leukocytes with neutrophilic or eosinophilic
reaction). At this age the cells enter the circulating blood as “ polynuclear ”
leukocytes. A few immature cells, i. e., still basophilic, non-granular and sup-
plied with one nucleus, enter the blood as the so-called “ mononuclear ” leuko-
eytes, which then mature in the blood, becoming polynuclear leukocytes. The
cells which have begun to mature in the bone-marrow remain in the bone-
marrow until perfectly mature, becoming polynuclear leukocytes, so that the
blood does not normally contain myelocytes. The mature polynuclear cells,
however, enter the blood upon chemotactic, physiological irritation in rela-
tively small but usually quite constant numbers, under pathological condi-
tions frequently in very large numbers (“ leukocytosis ”) The loss of the
polynuclear cells which pass into the blood is compensated by the for-
mation of new primary stages of the same, the myelocytes, and by the fur-
348 LEUKEMIA
ther development of the latter into a correspondingly greater number of poly-
nuclear cells.
In the spieen and lymph-glands leukocytes are not produced, at least
not in noteworthy amounts (even in cases where they are much needed, as in
leukocytosis). On the other hand, the lymph-glands (the spleen only to a
slighter degree) are the points of origin for the formation of lymphocytes,
which, as is well known, represent one-fourth of the white blood cells in nor-
mal blood. Similarly to the myelocytes they are probably also formed in the
bone-marrow from large basophilic, mononuclear cells which are the early
stages of the leukocytes and generally do not enter the blood, or at most only
as “large lymphocytes” in children, and under pathologic conditions in
lymphatic leukemia (where they are met with in the blood in great numbers,
particularly in the acute form of the disease). Just as the myelocytes mature
(“age”) into polymorphonuclear leukocytes, so does the nucleus of the
lymphocytes pass through this aging process in that it later undergoes lobula-
tion and fragmentation (Rieder’s cells), without the protoplasm losing its
basophilic, non-granular character.
The nuclear changes—lobulation and segmentation into several nuclei—
therefore, indicate the physiological age of the cells; just so may we assume,
in general, that a slighter staining quality (amblychromasia), especially of
the cell nuclei, characterizes the cells as incomplete, undeveloped, in contrast
to the intensely staining (“ trachychromatic”) mature forms.
As already mentioned, the bone-marrow is almost exclusively the organ of
production of the myelocytes and polynuclear cells, although typical myelo-
cytes are found in the spleen and lymph-glands (without having been carried
in by the blood stream). On the other hand, the lymph-glands are to be con-
sidered the seat of production of the small lymphocytes. Of course, we find
lymphocytes in scant numbers in the bone-marrow too; of these it is probable
that a fair proportion have been carried in, a part, however, having been
formed in the marrow itself.
The origin of the very small number of mast-cells, which, under normal
conditions, are found in the blood, has not yet been determined with certainty.
Most investigators assume that they originate in the connective tissue; others
believe that they develop from lymphocytes.
SYMPTOMS AND BLOOD-CHANGES
Let us now return to the discussion of leukemia. Marked cases are mani-
fest at the first glance by the extreme pallor of the patient’s skin and mucous
membranes, and occasionally by the color of the blood as obtained by puncture
or incision of the finger tips which may be whitish red. [Cases are pale only
if anemia has developed, and this even in well-marked cases is often not nota-
ble. In the later stage of the disease, but not until then, anemia becomes
severe.—Ep.] The microscopic examination of the fresh blood in cases of
leukemia of high grade shows even without counting the abnormal increase
in the white blood-corpuscles. But a count and a comparison with the num-
ber of erythrocytes is absolutely necessary in the less marked cases. Whereas
SYMPTOMS AND BLOOD-CHANGES 349
normally we find an average of 8,000 leukocytes (in children somewhat more,
9,000 to 10,000) in a cubic millimeter of the blood taken from the veins, i. e.,
one white cell to 600 erythrocytes, the number of leukocytes may so increase
in leukemia that the proportion is 1 to 50, 1 to 10, or 1 to 2. In fact, the red
and white blood-corpuscles may even be present in similar amounts in the
blood. The count of white blood-corpuscles shows 100,000 and even 500,000
and more, to the cubic millimeter.
In some cases of leukemia, no noteworthy change in the erythrocytes, either
in number or appearance, occurs; as a rule, however, they are decreased in
numbers to about one-half of the normal or even less, just as in severe anemias.
In general the decrease of the erythrocytes is in proportion to the increase
in the number of white blood-corpuscles. But the numerical relation of the
erythrocytes in leukemia is a secondary consideration, and the diagnosis of
the affection depends primarily upon the white blood-corpuscles. There are
cases of simple anemia in which the number of red blood-corpuscles is mark-
edly diminished, but the production of white has remained normal; then the
proportion of the white to the red cells may become 1 to 25, etc., without
leukemia being present. For example, in pernicious anemia, with a diminu-
tion of the erythrocytes to 250,000 to the cubic millimeter, and a normal con-
dition of the white blood cells (8,000), the proportion would be about 1 to
30 and still no leukemia would be present. Leukemia is, however, to be as-
sumed under all circumstances if the proportion falls below 1 to 20, because
these figures can only occur when, besides the decrease in the number of the
red blood-corpuscles as a result of anemia (even in the most excessive diminu-
tion of the same that has been observed up to the present in cases of per-
nicious anemia), the number of leukocytes is absolutely increased at the
same time.
Besides the diminution in the number of red blood-corpuscles, the blood
also contains, as a rule, numerous nucleated red blood-corpuscles in the form
of normoblasts, more rarely megaloblasts, or transitional forms between these.
The amount of hemoglobin in the blood is diminished in leukemia but the
coloring of the individual corpuscles (abnormally decreased in numbers) need
not be diminished. An increase in the blood-plaques has also been observed
upon several occasions. ;
The diagnosis of leukemia can be made without further consideration in
cases which show an extraordinary increase of the white blood-corpuscles, but
in doubtful cases the presence of the disease can only be determined by an
exact microscopical examination of the morphology of the leukocytes.
Besides the increase in the white cells, what is particularly conspicuous in
the microscopic examination of leukemic blood is that in the majority of cases
the polynuclear cells are most numerous; in other cases, however, the lympho-
cytes form the greater number, and this type of blood alteration persists dur-
ing the entire course of the illness. [In 41 cases of myelogenous leukemia
studied by me the polynuclear cells average 47.5 per cent. It is the polymor-
phous condition of the blood, the endless variety among the leukocyte forms,
that most impresses one in this disease.—Ep.] We, therefore, quite properly
differentiate two different varieties of leukemia.
350 LEUKEMIA
1. Lymphocyte leukemia.
2. Leukocyte leukemia.
Since the source of the lymphocytes, as has been mentioned, is the spleen
and the lymph-glands, and that of the leukocytes is the bone-marrow, the
common designations of lymphatic leukemia (lymphemia) and myelogenous
leukemia (myelemia) may be selected for these two basic forms of leukemia.
As, however, the bone-marrow also normally produces typical lymphocytes,
and as it has been determined in rare cases that an over-flooding of the blood
with lymphocytes may occur by proliferative changes in the marrow without en-
largement of the spleen and lymph-glands (myelogenous lymphemia), I pre-
fer the less prejudicial division of the leukemic forms into “lymphocyte leu-
kemia ” and “ leukocyte leukemia.”
In the blood at the autopsy, or after prolonged standing of the blood of
leukemics, Charcot’s crystals are found, usually within the leukocytes, and par-
ticularly in the eosinophilic polynuclear cells. Their relation to the last-
named cells has lately been determined beyond doubt, so that we’ may say:
Wherever eosinophile cells are present in large numbers, Charcot’s crystals are
also found. This at once makes it clear that they are absent in lymphocyte
leukemia, and, on the other hand, that the crystals are not only found in leuko-
cyte leukemia but in all diseases in which eosinophiles occur in large numbers,
nasal polypi, bronchial asthma, etc. The demonstration of Charcot’s crystals
is, therefore, by no means pathognomonic of leukemia, the less so as they are
also found in normal bone-marrow, which is not to be wondered at.
In comparison with the results of the microscopic examination of the
blood, all the other morbid phenomena of leukemia are of decidedly subordi-
nate importance, even though in the individual case they greatly aid in the
diagnosis. There are cases of leukemia in which, besides the alteration in
the blood and the symptoms of anemia in connection therewith, all other
objectively demonstrable morbid phenomena are absent, and the diagnosis must
be made entirely from the blood findings! These are, however, under all
circumstances, as will be shown later, rare and exceptional cases; the rule is
that many organs, especially those connected with blood-formation, suffer
marked changes which may be demonstrated by physical examination.
In this connection we must mention particularly the enlargement of the
spleen which is present in the majority of cases of leukemia. The splenic
tumor is usually of considerable size; it extends to the median line or beyond
and downward to the hypogastric region. On account of its sharp indented
margin, the direction of the growth of the tumor, and especially its evident
origin from the left hypochondrium, there is rarely cause to doubt that we are
dealing with a tumor of the spleen. The diagnosis may be difficult if, as in
one of my cases, the large spleen turns so that the hilus appears at the top.
The consistence of the splenic tumor is hard; its circumference, after it has
attained a certain size, is usually constant. Rarely transient shrinkages are
noted, or, on the other hand, excessive swelling or rupture of the organ. As
a rule the swollen spleen is not sensitive to palpation, and the subjective diffi-
culties which the tumor causes are generally slight. At most the patients
complain of a feeling of fulness in the abdomen and slight difficulty in respira-
SYMPTOMS AND BLOOD-CHANGES 351
tion; less frequently pain occurs in the splenic region, or even inflammatory
phenomena which manifest themselves in peritoneal friction sounds in this area.
In some of the cases, most frequently in lymphocyte leukemia, /ymph-
gland enlargement occurs. [I have never seen lymph-gland enlargement ex-
cept in lymphocyte leukemia——Ep.] As a rule, the glands of the neck and
axillary region, more rarely those in other areas of the periphery or the inter-
nal lymph-glands, are affected. The glandular tumors are moderately hard,
the skin covering them is movable and not reddened. If the mesenteric and
retroperitoneal glands are hyperplastic, they may be occasionally felt through
the abdominal walls. In case the enlargement affects the tracheal and bron-
chial lymph-glands, at least a probable diagnosis of this result of the leukemia
may be made, provided the symptoms of tracheal or bronchial stenosis, of
paralysis of the vocal cords, the result of pressure upon the recurrent laryn-
geal nerve, or difficulty in deglutition, arise. In marked cases of swelling
of the tracheo-bronchial lymph-glands or of the persisting thymus gland, the
percussion note over the manubrium is dull and the bone is arched outward.
In the adenoid tissue of the tonsils and also in the adenoid follicles at the root
of the tongue hyperplasia and swelling may likewise be noted.
Besides the spleen, the various lymph-glands, and the other adenoid organs,
the bone-marrow is almost always affected by anatomical changes. Accord-
ing to the experiences gathered up to this time, changes in the bone-marrow
are invariably present in leukemia. In lymphocyte leukemia we find, espe-
cially in the lymph-glands, in the spleen and eventually in the liver, but
invariably also in the bone-marrow, proliferations of the lymphoid tissue,
which in these cases may become so plentiful that the production of the poly-
nuclear cells in the bone-marrow and the passage of the same into the blood
may be prevented by the overgrowth of the lymphocytes in the marrow. As
soon as the lymphocytes begin to enter the blood, floating in from the bone-
marrow, hyperplastic lymph-glands and spleen (quite passively as we must
assume from Ehrlich’s convincing deductions), the picture of lymphocyte leu-
kemia develops.
The implication of the bone-marrow in the leukemic processes can never
be determined with certainty intra vitam by the sensitiveness of the bone to
pressure, but only when the microscopic examination reveals in the circulating
blood mononuclear, granular marrow cells, the origin of which from the bone-
marrow is certain, and also large quantities of nucleated red blood cells.
Besides the three above-named organs which are particularly affected in
leukemia, other portions of the body, although less frequently, are involved in
changes which are in direct relation to leukemia. In the majority of cases
the liver, in consequence of leukemic-cell infiltration between the acini, is
enlarged. The surface is smooth, its consistence moderately hard. Marked
grades of ascites and jaundice are only to he expected if the periportal lymph-
glands are enlarged and press upon the portal vein and biliary passages. As-
cites, that is, the transudation of a large amount of fluid into the peritoneal
cavity, may also be caused by a leukemic nodular infiltration of the peritoneal
layers and of the omentum. This is, however, not frequent. ;
Leukemic infiltrations occur also in the stomach and intestine; they arise
352 LEUKEMIA
from adenoid tissue areas of the wall (i.e., the solitary follicles). Dyspeptic
phenomena and diarrhea point to this complication but do not permit cer-
tainty in diagnosis. In some patients a leukemic stomatitis and pharyngitis
develop.
It is noteworthy that, in spite of the diminution of the erythrocytes, nei-
ther dyspnea nor orthopnea occurs in leukemia, at ledst not according to my
experience (provided there are no complications on the part of the respiratory
organs). [I have repeatedly seen dyspnea and even orthopnea in leukemia as
goon as anemia became severe or circulatory stasis marked—Ep.] Petten-
kofer and Voit first demonstrated in one of their patients, who was suffering
from leukemia, the ability of the organism, during rest, regardless of the
diminution of the erythrocytes, to assimilate as much oxygen as a healthy
person with the same nourishment. Neither do marked disturbances of
metabolism occur in the course of leukemia, or, if they are now and then
noted, they are at least not dependent upon the leukemic processes as such.
The tendency of the leukemic to catarrhal affections of the respiratory passages
may favor the production of pulmonary inflammation in some cases; in other
cases lymphatic infiltrations form in the lungs. The development of lym-
phatie nodules has been noted in the epiglottis, in the larynx and in the
trachea, also upon the pleura; not rarely do transudates appear in the pleural
cavity.
Painful non-ulcerating nodes occasionally develop in the skin, and must
be looked upon as leukemic lymphoid formations. [Deafness was produced in
one of my cases by nodules in the ear——Ep.] A tendency to profuse sweat-
ing is not rare, and adds to the exhaustion of the patients.
The murmurs noted upon auscultation of the heart are of an accidental
nature, the result of the marked anemia which occurs in leukemia. [Late
in the course of the disease—Ep.] In consequence of poor nutrition and
exhaustion of the heart muscle such a dilatation of the heart may occur that
the valves though still normal in their length can no longer close. Thus rela-
tive mitral and tricuspid insufficiency may develop.
Not only such relative cardiac insufficiencies and accidental murmurs may
occur as a consequence of the anemia which develops in leukemia, but also
quite a number of other symptoms such as appear more or less regularly in
any anemia; e.g., palpitation, weakness and lassitude, vertigo, headache,
attacks of syncope, and edema; perhaps also fever which is irregular but may
be at times quite high (102° F. to 104° F.).
In the course of leukemia, in rare cases, long-continued priapism occurs,
due perhaps to a thrombosis in the corpora cavernosa. This symptom has
been observed a number of times, and occurs so rarely in other conditions
that its presence should be considered suggestive of leukemia.
Of special interest in the diagnosis of leukemia are the changes in the eye-
ground which occur in the course of the affection. In keeping with the in-
creased number of white-corpuscles and the anemia the fundus of the eye
has an unusual, pale, orange-yellow appearance. But this discoloration is not
conspicuous in all cases; it is always absent if the amount of hemoglobin has
not been materially decreased. The so-called retinitis leukemica is character-
SYMPTOMS AND BLOOD-CHANGES 353
ized by an extremely tortuous condition of the veins, a band-like opacity of
the retina, and hemorrhages into the same, as well as by opacity, indistinct
contours and bluish-yellow color of the optic nerve papilla. Not rarely the
veins are accompanied by white streaks, and white areas intermixed with hem-
orrhages are visible in the macula; the hemorrhages are circular in shape,
with a prominent yellowish-white center. Occasionally there is a tendency to
the development of numerous large hemorrhages which may also occur in the
vitreous body, so that the ophthalmoscopic picture may resemble that of
thrombosis of the central vein of the retina. Such a thrombosis may occur
simultaneously with hemorrhages around the optic nerve and in the latter
itself, and may also develop in the orbital portion of the optic nerve. Func-
tional disturbances are present to only a slight extent.
The changes in the urine observed in leukemia are of great importance
in diagnosis, as well as in the study of the disease.
Apart from the occasionally observed albuminuria, which is in part the
result of the anemia, in part the consequence of lymphomatous infiltration of
the renal substance (which is indicated by the presence of casts and of a large
number of leukocytes in the sediment of the urine), a change in the excretion
of the solid constituents of the urine is more or less frequently found in leu-
kemia. An absolute and relative increase of the excretion of uric acid (up to
8 grams per diem) has been almost invariably observed.
This increase of uric acid in leukemia is certainly not, as was formerly
supposed, the result of insufficient oxidation in the organism. This opinion
is contradicted not only by the results of the investigations of Pettenkofer and
Voit, but also by the fact determined by Stadthagen, that in the body of the
patient suffering from leukemia the sodium urate which has been administered
per os is capable of further oxidation. Neither can the excessive production
of uric acid be considered due to the enlargement of the spleen commonly
present in leukemia, as patients with chronic splenic tumor excrete uric acid
in normal amounts in contrast to leukemia with enlargement of the spleen,
in which the excretion of uric acid is markedly increased. As we know now
that uric acid originates from the nuclein which is liberated in the decompo-
sition of the cellular nuclei, especially by oxidation of alloxur bases which are
contained in nucleinic acid, the conclusion is obvious that the increase of uric
acid excretion in the course of leukemia may be referred to the destruction of
a relatively greater number of leukocytes than under normal conditions. How-
ever, the increased excretion of uric acid may also be an expression of in-
creased function, that is, of metabolism of the superfluous leukocytes, so that
an increase of uric acid excretion in the course of leukemia is by no means a
proof of great decomposition of leukocytes and their nuclei.
The excretion of urea usually does not differ from the normal; in two
cases of severe leukemic cachexia in my clinic Fleischer and Penzoldt noted
an increase of urea excretion, but this was in the late stages of leukemia, when,
as in carcinomatous cachexia, a marked decomposition of organic albumin
with increase-of the excretion of nitrogen occurs. Hematuria is also observed
in the course of leukemia. a, :
This symptom is connected with the general hemorrhagic diathesis of the
24
354 LEUKEMIA
leukemic, one of the most important symptoms of leukemia as regards diag-
nosis, and especially as regards prognosis. Hemorrhages may occur in the
urinary passages and in various parts of the body, i. e., in the respiratory pas-
sages, in the digestive tract, in the skin (purpura), in the subcutaneous con-
nective tissue (sometimes in the form of colossal hemorrhagic tumors), in the
muscles, in the internal parts of the ear, etc.; hemorrhages are also noted
in the central nervous system in the course of leukemia, and may give rise to
apoplectic attacks with paralysis, or they may result in sudden death; these
intercurrent hemorrhages are usually the cause of the fatal outcome of leu-
kemia, or, at least, they predispose to it. Multiple effusions of blood occa-
sionally occur in the peripheral nervous system, in the sheaths of the nerves
or in the nerves themselves, and these result in fatty degeneration of the nerves
and the muscles supplied by them. In some cases of leukemia the hemorrhagic
diathesis may so dominate the clinical picture that the cases appear to be
purpura hemorrhagica until the examination of the blood discloses the error.
[This is especially true of the cases of acute lymphatic leukemia.—Eb. |
The symptoms of leukemia—the increase in the number of leukocytes in
the blood as well as the enlargement of the spleen and lymph-glands—may for
a time ameliorate greatly in the course of intercurrent infectious diseases.
[Or even without any known cause. Some of these spontaneous remissions
happen to coincide with the inception of a special method of treatment and
lead to the reports of curative drugs, etc.
Of the remissions under X-ray treatment, mention will be made later.
—Eb. |
The classification generally in vogue until lately by which individual cases
of leukemia were grouped as “myelogenous” or as “lymphatic” leukemias,
according as the spleen or the lymph-glands were enlarged, can no longer be
maintained from a hematological standpoint, chiefly because of the impor-
tant researches of Neumann and Ehrlich. For some time we differentiated
not only between splenic and lymphatic leukemias, but also between cases of
the splenic-medullary variety, or those of the pure medullary form (“ myeloge-
nous leukemia”). But these designations for the individual varieties of leu-
kemia, based as they are on the changes prominent in the clinical picture in
organs more or less implicated in the formation of the blood, are not justified
either from a hematological or from a clinical standpoint. For, in both
forms, the lienal and the lymphatic, the bone-marrow is primarily implicated
in the changes of the hematopoietic process, and, on the other hand, the char-
acteristic blood picture, which in one case may show a marked preponderance
of lymphocytes, in another a great majority of leukocytes and their primary
stages, is usually not at all altered, whether the lymph-glands or the spleen
are enlarged or not. We therefore recur to my chosen differentiation of only
two varieties, according to the point of origin of the cell forms which are
markedly increased in the blood—lymphocyte lewkemia and leukocyte leu-
kemia. The differentio-diagnostic points of these two varieties of leukemia
are the following: 5
_1. Lympnocyte Levxemra. The blood picture is characterized by a con-
spicuous preponderance of large and small lymphocytes in comparison to the
SYMPTOMS AND BLOOD-CHANGES 355
leukocytes. Nucleated red blood cells and megaloblasts, although found in
the blood in lymphocyte leukemia, yet, compared with their usual abundance
in leukocyte leukemia, are by no means prominent.
According to the course of the affection, two varieties must be differen-
tiated, the acute and the chronic.
Acute lymphocyte leukemia (“acute lymphemia”), the recognition of
which we owe above all to Ebstein and A. Fraenkel, is characterized by its
rapid, often febrile, course, resembling a severe infectious disease. Besides the
usually insignificant enlargement of the spleen and lymph-glands, the other
clinical phenomena of leukemia are present, stomatitis, retinitis, ete. Most
prominent in the clinical picture is the hemorrhagic diathesis, so that the
affection has the appearance of purpura hemorrhagica and may be confounded
with this, all the more so as the hemorrhages occasionally occur before the
characteristic blood picture of acute lymphemia is formed. The blood picture
itself is highly characteristic: Preponderance of the lymphocytes, especially
of the large ones, very rarely of the smaller, with a vesicle-like, sometimes
deeply indented nucleus; erythroblasts are present although few in num-
ber; the polynuclear cells are not only relatively but also absolutely decreased.
The number of white blood cells compared to the red ones may be extraordi-
narily great (up to 1 to 1!). [In the majority of cases, however, it is not
excessive—much less than in myelogenous cases.—Ep.] The affection may
terminate fatally in a few days or a few weeks.
Chronic lymphocyte leukemia is differentiated from the above-described
form by its greatly protracted course: Gradual enlargement of the lymph-
glands, especially those of the neck, also enlargement of the spleen to a greater.
or less extent. In rare cases, even in a very chronic course (in one case
under my observation the affection lasted at least two years), only insignificant
enlargements of the glands appear. The lymphoid hyperplasia of the bone-
marrow is present here, as in the acute form. The hemorrhagic diathesis is
also quite marked in the chronic form of leukemia, and as consequences of
anemia there may be a great variety of symptoms, such as dilatation and
insufficiency of the heart, etc., which may threaten life. The blood picture
in the main resembles that of the acute form, i. e., mononuclear lymphocytes,
but usually the small forms are most prominent, whereas the other colorless
blood cells are almost absent. Large lymphocytes are also found in chronic
lymphocyte leukemia during the entire course of the affection, and in rare
cases, as in the acute form, they may even dominate the blood picture.
2. LeuKocyTs LEUKEMIA, by far the most frequent form of leukemia, may
be easily differentiated from both of the last-mentioned varieties of leukemia by
its entirely different blood picture. The increase of the white blood cells is
usually very marked; here, however, the polymorphonuclear leukocytes are
greatly increased in the microscopic picture: neutrophiles, and, above all,
eosinophilic polynuclear cells are, as Ehrlich has found, always absolutely in-
creased. There is invariably an absolute increase of the mast-cells which occa-
sionally are twice as numerous as the eosinophiles, and their determination is
of great importance in a diagnostic respect because a marked increase of the
mast-cells is only observed in leukemia. [The absence of mast-cells was espe-
356 LEUKEMIA
cially noted in 3 of my 41 cases—Ep.] The phenomenon, however, which
especially characterizes leukocyte leukemia, and shows its origin to be the
changes in the bone-marrow (“myelogenous leukemia”), is that, besides the
polynuclear cells, their ancestors, the mononuclear granular leukocytes, i. e.,
the neutrophilic and eosinophilic myelocytes, are always found in the blood
and occasionally are found in such great numbers (up to 100,000 per ¢.mm.)
as to simulate at first sight the blood picture of acute lymphemia with its
large mononuclear cells; some of the myelocytes show, as has already been
stated, coarse eosinophilic granules (eosinophilic myelocytes). The cells
which have been described, the polynuclear cells as well as the mononuclear,
are occasionally large, at other times remarkably small (“dwarf forms”).
Besides these immature leukocytes (the myelocytes), which normally are not
met with in the circulating blood, other immature forms of erythrocytes also
originating in the bone-marrow are found in the circulating blood stream of
patients with leukocyte leukemia, such as normoblasts and, more rarely,
megaloblasts in varying amounts, at times in great numbers.
The enlargement of the spleen in this variety is especially well marked,
the enlargement of the lymph-glands is sometimes quite prominent, at other
times less so. [See editorial note on page 351—Ep.] It is remarkable that
we rarely have an opportunity to observe the development of the tumors step
by step. Usually the physician sees the disease in its full intensity, so that
we must assume that leukocyte leukemia rapidly reaches the acme of its devel-
opment. Besides the splenic tumor and the enlargement of the glands, the
other clinical phenomena have already been fully described: The hemorrhagic
diathesis, the retinitis, the increase of uric acid in the urine, ete.
From an etiological standpoint there is little of value in the diagnosis of
leukemia. In some cases leukemia appears to follow infectious diseases (ma-
laria, diphtheria, the puerperium, influenza, etc.), or occurs in connection with
trauma, as concussions (perhaps especially of the bones). These “causes”
of leukemia, considered as direct agents producing the disease, are of very
questionable nature. This, therefore, justified the sensation which followed
the “discovery” of Léwit (who had already distinguished himself by his
studies regarding the leukemic process) that the disease was due to the pres-
ence of amcebe: in the blood and in the organs producing the blood cells. In
leukocyte leukemia Léwit found a form of ameba which he believed to increase
in the blood by sporulation (hemamceba leucemie magna); in lymphocyte
leukemia another form of parasite differing from the former by its active
motility (hemameeba leuc. parva vivax). Doubtless Léwit’s discovery, if con-
firmed, would be of the greatest value in the explanation of the nature of leu-
kemia; but, unfortunately, we cannot as yet reckon with this factor, as the
investigations are by no means concluded and have called forth many contra-
dictory opinions. [There are, I think, no contradictory opinions among those
who have studied Lowit’s preparations, and repeated his technic. Competent
observers are unanimous in believing that Léwit’s supposed. parasites were, in
fact, artefacts. No competent investigator has confirmed Léwit’s work.—Ep.]
In the author’s opinion, leukemia is due to a specific poison, which impairs
the process of blood formation, especially that of the white blood cells. In
SYMPTOMS AND BLOOD-CHANGES 307
his opinion, the important question, in all blood diseases, is this: What kind of
powson is tt which is affecting the process of blood formation in each individual
case? On this depend the changes manifest in the blood.
1. If the damage chiefly affects the red blood cells, simple “ anemia” re-
sults, in which the erythrocytes deviate more or less from the normal in their
number, shape, maturity and hemoglobin percentage, while the white corpus-
cles are affected only incidentally, and especially as to their number.
2. If the poison affects chiefly the process of generation of the white cor-
puscles, so that their number is increased and their morphotic relation is ,
pathologically altered, the blood disease presents itself in the form of a leu-
kemia.
3. If the damage affects all components of the blood equally, blood dis-
eases result that represent a complete upsetting of the process of blood forma-
tion with changes in the number and form of both the white and the red blood
cells—blood diseases usually described as transitional or mixed forms of per-
nicious anemia and leukemia. It is difficult to classify satisfactorily the
individual cases of this group as anemia or leukemia, if the usual terms,
anemia and leukemia, are used as mutually exclusive. I believe, therefore,
that it is advisable to give them a special name, for instance, “leukanemia ”
or something similar.*
In this form of blood disease, as already remarked, the production of red
and white blood-corpuscles is wholly upset, and accordingly, in the blood pic-
ture, decided changes appear in the leukocytes as well as in the erythrocytes,
such changes as we are accustomed to note, on the one hand in leukemia, and on
the other hand in pernicious anemia. Blood formation may cease entirely,
and this deficiency can no longer be compensated in any manner, so that the
organism soon succumbs to the pernicious blood disease. Clearly to illustrate
the affection which I designate as leukanemia I shall quote the complete history
of a case observed in my clinic:
A boy, K. L., aged ten, entered the hospital May 6th, and died May 9, 1900.
Patient is said to have been always weak, but never seriously ill, and attended
school regularly up to April 22d. Mild symptoms; twice vomiting occurred,
so that the patient was compelled to remain at home from April 22d to
April 29th. On April 29th he sang as a choir boy in church, and on May ist
again attended school, but on May 5th, on account of his pallor, which the
1In my opinion, it is well to carry out, in the main, this classification of blood
diseases, in spite of the fact that in typical leukemias not only normoblasts are found
but also now and then megaloblasts, and although, vice versa, apart from the alterations
in the differential count (the predominance of lymphocytes), a few myelocytes are
occasionally found in severe anemias. But these findings are of subordinate and second-
ary importance compared with the primary condition, according to which the disease,
in consonance with the fundamental principle of nosology “a potiori fiat denominatio,”
is to be spoken of in one case as leukemia, in another as anemia gravis, and by all
diagnosticians is thus commonly designated. A disease can only receive the name of
“leukanemia’”’ when both leukocytes and erythrocytes are uniformly and decidedly
damaged in their development, when the case can neither be put in the category of
leukemia nor in that of pernicious anemia, and when the division of blood diseases into
two groups is no longer possible.
358 LEUKEMIA
teacher noticed, he was sent home. From May 3d to May 6th he still took
his food with appetite; then, four days before his death, epistaxis occurred,
with yellow discoloration of the skin; pain in the nape of the neck and tooth-
ache appeared, as well as pain in the epigastrium. In the course of the day
severe apathy became more and more noticeable, increasing to complete loss
of consciousness, so that the patient was brought by his relatives to the Julius
Hospital.
Status presens: The appearance of the patient denoted serious illness;
skin and mucous membranes deathly pale; eyelids and hands markedly edema-
tous; the skin over the rest of the body slightly bloated, showing yellow
discoloration but not jaundice; conjunctive snow-white. Coma. No opis-
thotonus, no rigidity of the neck and no spasms. Pupils dilated, reacting
normally. Liver and spleen moderately enlarged and hard; sensitive to pres-
sure. The muscles of the calves of the legs not especially sensitive to pressure,
but the bones of the thigh as well as the sternum extraordinarily so. Lungs
normal. The cardiac dulness extended to the right sternal border; heart
sounds clear; gallop rhythm, undulation of the veins of the neck. Urine
contained traces of albumin; no albumoses, no casts. The ophthalmoscopic
examination showed feeble filling of the vessels, especially of the arteries,
which were mere threads—“ marantic thrombosis of the central artery with
numerous disseminated hemorrhages.” Temperature 102° F. to 104° F.
As the symptoms of extraordinary impoverishment of the blood were
present, besides a slight enlargement of the liver and spleen, the diagnosis
was set down as “severe anemia.” On account of the edema of the skin
and the presence of albumin in the urine, a nephritis was at first thought
to be the cause. This assumption, however, was dropped when it was found
that only traces of albumin, but neither blood cells nor epithelium, nor even
casts, were present. An acute infection seemed much more likely, and the
rapid course of the disease, the severe disturbance of the general condition,
the high fever, the enlargement of liver and spleen and the albuminuria were
in favor of this. Yet the clinical picture did not correspond to any of the
usual infectious diseases. It was obvious that only an exact examination
of the blood would clear away these diagnostic difficulties.
The blood count showed an excessive diminution in the number of eryth-
rocytes: 256,000 per cmm.! The blood-corpuscles varied in size (with some
megalocytes), and the triacid stain showed that some red corpuscles contained
nuclei: Normoblasts 76, megaloblasts 152, in aemm. The amount of hemo-
globin of the entire blood was not more than 10 per cent., the hemoglobin
contents of the individual blood-corpuscles (color-index) was therefore rela-
tively increased.
The absolute number of white blood cells was scarcely increased, 10,600,
though when compared with the total number of the erythrocytes it seemed
high, 1:24. The morphology of the leukocytes and the proportion of the
individual leukocyte varieties to each other deviated greatly from normal con-
ditions, so that the blood picture resembled that of leukemic blood. Besides
the usual neutrophilic, polynuclear leukocytes which were present in dimin-
ished amounts (4,680), many myelocytes were seen (1,380 neutrophiles and
SYMPTOMS AND BLOOD-CHANGES 359
76 eosinophiles) ; mast-cells were absent; however, there were large mono-
nuclear leukocytes (228) and remarkably numerous lymphocytes (4,260),
large and small—almost as many as polynuclear cells. Expressed in per-
centage the blood contained: Lymphocytes 40.2 per cent. (large 35.3 per cent.,
small 4.9 per cent.) ; polynuclears (neutrophilic leukocytes) 44.1 per cent.;
myelocytes 13.6 per cent. (neutrophiles 13 per cent., eosinophiles 0.6 per
cent.) ; large mononuclears 2.1 per cent.; and but very few mast-cells (only
one found in all the blood preparations examined).
The course of the affection during the four days in which the patient was
in the hospital was extraordinarily rapid. The temperature, which varied
between 102.2° and 104° F. from the first to the second day, dropped on the
third day to 100.4° F., falling upon the fourth day, when death occurred, to
91.1° F.; consciousness, which had been lost prior to his admission to the
hospital, returned on the second day, and continued until death. The energy
of the heart, however, weakened from hour to hour. The cardiac dulness,
which was normal at the onset, became more and more extended without
the appearance of murmurs. Weakness increased until death occurred on
May 9th.
The clinical diagnosis entered at the Pathological Institute was: “ Pro-
gressive pernicious anemia, enlargement of the liver and spleen, infectious
degenerative processes in the bone-marrow with disturbances in the formation
of red and white blood-corpuscles; dilatation of the heart, myocarditis (?).”
The main points in the autopsy report (v. Rindfleisch) may be mentioned
as follows: Excessive anemia of the entire body. The marrow of the femur
in its lower half everywhere red, that of the sternum reddish. Spleen some-
what enlarged, 13.5 cm. in length, 8 cm. in breadth, 34 cm. in thickness; upon
section lighter than normal, consistence somewhat soft; Malpighian bodies
enlarged, indistinct. Liver of firm consistence, gives a distinct amyloid reac-
tion, which, however, soon disappears when the organ is placed in water.
The heart is distinctly dilated, particularly in the right ventricle; the left ven-
tricle somewhat less so. The muscles of the heart are very anemic, parts
showing grayish discoloration and punctiform hemorrhages; fatty degenera-
tion of the muscular trabeculz in the left heart. No enlargement or change
in the lymph-glands. Kidneys pale, in part showing a dappled anemia;
capsule peels easily ; consistence somewhat firmer than normal.
The anatomical diagnosis (v. Rindfleisch) was as follows: Anemia maxima
corporis totius; Hyperemia ossium cum infiltratione cellulart partim leuko-
cytica partim erythrocytica. Lien hyperplasticus ex intumescentia leukocytica
corpusculorum Malpighii. Hepar modice auctum degeneratio hepatis amy-
loidea. Degeneratio cordis adiposa presertim ventricult sinistri, dilatatio
ventriculi sinistri. Myocarditis. C2dema pulmonis, atelectasis.
Microscopical examinations (v. Rindfleisch) showed: In the spleen areas
of softening, in the internal parts of which were abscess-like accumulations
of polynuclear cells but without pyogenic cocci; a softening of all the Mal-
pighian bodies with transformation of their lymphocytes into pus cells. Amy-
loid degeneration of the liver not affecting the interstitial tissue but merely
the liver cells proper, which alone gave the amyloid reaction. The blood-
360 LEUKEMIA
vessels as a whole were free from amyloid but contained numerous detached
large myelocytes besides red corpuscles. As a curious finding may be men-
tioned small foci of liquefaction about one-fourth the diameter of an acinus
filled exclusively with polynuclear leukocytes and liver cells in the process
of gradual dissolution, but containing no cocci. These foci were situated
sometimes near the edge of the acinus, sometimes near the center, and were
rarely confluent. No siderosis could be determined in several examinations.
The heart muscle showed fatty degeneration with fragmentation of the fatty
muscle fibers and hemorrhages the size of a millimeter. Kidneys principally
anemic. The bone-marrow contained chiefly large myelocytes with large nu-
clei, slightly or not at all granular. Normoblasts were found mostly around
the small hemorrhages; megaloblasts were more scanty.
Epicrisis.—The blood findings, in so far as they relate to the red blood-
corpuscles (250,000 erythrocytes, 76 normoblasts, 152 megaloblasts in a
e.mm.), would class this affection as pernicious anemia, and at that the usual
form—the metaplastic—with transition of the yellow bone-marrow into red,
with formation of profuse, nucleated red blood-corpuscles, and especially of
megaloblasts in the marrow, and their entrance into the circulating blood.
The erythrocytes were relatively rich in hemoglobin, corresponding to the
usual finding in pernicious anemia.
The condition of the white corpuscles in the case in question is more
important than that of the red. We note, point for point, that the findings
correspond to leukemic blood, yet there is no absolute increase worth men-
tioning in the white blood cells.
The great number of myelocytes in the blood (and also in the bone-
marrow) is primarily conspicuous; they form one-seventh of all the leuko-
cytes. According to our present knowledge of the genesis of the leukocytes,
myelocytes may be looked upon as the product of blood cell formation in the
bone-marrow, and as the prior stage of the polynuclear leukocytes of the blood.
It can hardly be disputed that in our case the transportation into the blood
of these immature leukocytes (the mononuclear neutrophilic and eosinophilic
myelocytes) represents a process in the blood analogous to the emigration
of the immature erythrocytes, the normoblasts and the megaloblasts. This
analogy is so natural that the question may well arise whether this condition
—emigration of immature leukocytes with the simultaneous emigration of the
immature erythrocytes from the bone-marrow into the blood—does not occur
frequently in pernicious anemia, and even whether it does not invariably
occur. T’o decide this question, only the latest investigations, based upon
methods of staining that are in use to-day, should be considered. From re-
searches which are in this respect decisive it is shown that the appearance
of myelocytes in the blood of patients suffering from pernicious anemia is not
usual; generally none or apparently but few (at the utmost up to 0.5 per
cent.) of these immature leukocytes are found. In our case, however, the
blood was rich in myelocytes—they represented one-seventh (!) of the white
blood cells and the one-hundred-and-eighty-fourth part of all the blood cells.
We must, therefore, assume in this rare case, that we were dealing with an
msufficiency in the function of the bone-marrow, affecting simultaneously the
SYMPTOMS AND BLOOD-CHANGES 361
formation of the red as well as of the white cells, so that the embryonic forms
of the red and white cells did not come to maturity. These cells, i. e., of the
(nucleated) normoblasts and megaloblasts as well as of the myelocytes, appear
to have emigrated into the blood before their transformation into normal,
finished blood cells could be completed.
Another striking feature of the case was that (besides the neutrophilic
or eosinophilic granular myelocytes) non-granular myelocytes and even, what
is more conspicuous, non-granular polynuclear cells could be demonstrated
with certainty in the circulating blood—a fact that may perhaps be explained
by supposing that in this rapid and abbreviated hematopoietic process not
even granulation could take place, much less complete maturity of the leuko-
cyte forms produced in the bone-marrow.
While the individual points in the blood picture of our case which have
been described up to this time can be brought into genetic connection only
with a severe damage in the function of the bone-marrow, this source of
disturbance of the blood formation is questionable because of the remarkable
relative increase of the lymphocytes in the blood (40 per cent. of lymphocytes
compared with 44 per cent. of polynuclears).
We might at first suppose the latter to be only an expression of the mark-
edly diminished production of the polynuclears in the bone-marrow, i.e., a
relative increase of the lymphocytes because the formation of polynuclears in
the bone-marrow is reduced, while that of the lymphocytes in the spleen and
lymph-glands continues unhindered—and this corresponds to the important
fact which Strauss determined—the relative increase of the lymphocytes in
pernicious anemia. The circumstance that 35 per cent. of large, and only
5 per cent. of small, forms were found in the blood is opposed to this view.
Therefore a disturbance in the formation of lymphocytes must in this case
be assumed. It has lately been regarded as certain that lymphocytes are nor-
mally produced not only in the spleen and in the lymph-glands but also in
the bone-marrow; hence it appears rational to hold the damaged function
of the bone-marrow responsible also for the disturbance in lymphocyte forma-
tion which, in our case, no doubt existed. But, in my opinion, this is im-
possible, since the lymphocytes in the bone-marrow, examined post mortem,
were very few, while, in contrast, the tissue fluid taken from the spleen one
hour after death contained profuse amounts of large and small lymph-cells.
It appears to me, therefore, that any other view than the following would be
forced, namely, that the increase of lymph-cells in the blood was due to a
greater formation of these cells in the spleen. This idea is the more plausible
since the lymph-glands in our case were everywhere absolutely unchanged.
The results of the analysis in this case may, therefore, be summarized
as follows: ; ;
A simple pernicious anemia was not present, in spite of the fact that the
blood showed the characteristic changes of pernicious anemia in the hemoglo-
bin-containing cells circulating in the blood, the erythrocytes. Against perni-
cious anemia was the enormous production of myelocytes and their transporta-
tion into the blood, the scanty presence of megaloblasts in the bone-marrow,
and the absence of siderosis of the liver. But the diagnosis of leukemia does
362 LEUKEMIA
not fit the facts any better; for, in this case, there was no absolute increase of
the white blood-corpuscles and no absolute increase of the eosinophile cells;
in fact, the number of them in this case was decidedly diminished (0.6 per
cent.) ; moreover, Charcot’s crystals were not present in the bone-marrow.
These facts scarcely coincide with the assumption of a leukemia which, in
this case, must certainly have originated in the bone-marrow (it must be
remembered that the myelocytes alone constitute one-seventh of all the leuko-
cytes).
e We may, therefore, say that in this case we were dealing with a severe,
perhaps infectious, disturbance of the process of formation of the blood cells
in the bone-marrow, and that this affected the red as well as the white blood-
corpuscles, with the result that both remained in an immature condition, the
white cells not even being perfectly granular, This reduction of the function
of the bone-marrow in a few days led to the complete cessation of blood for-
mation, and this to the destruction of the vitality of the organism. Besides
the cessation of the function of the bone-marrow, the function of the spleen
was severely damaged as regards the production of lymphocytes, which
were produced in a hurry and hence entered the blood chiefly as large
lymphocytes.
The essential feature of this case of lewkanemia is the fact that the devel-
opment of both red and white corpuscles was affected. In leukemia, on the
other hand, it must be supposed that the specific poison is concentrated essen-
tially upon the white corpuscles, sometimes the lymphocytes, sometimes the
leukocytes, according to the nature of the irritant. The process in leukemia
is probably as follows:
By the continuous, not transitory, action of the poison, a more rapid
production and washing out of white cells is brought about, and during this
process, not only mature forms but also immature elements, sometimes more,
sometimes less, pass into the blood—in the leukocytic leukemia the myelo-
cytes, in the lymphocytic leukemia large lymphoid cells (which may be re-
garded at least with probability as immature elements, normally not yet fit
to pass into the blood). The emigration of the complete polynuclear cells
(and partly perhaps of the myelocytes) may be easily explained as a conse-
quence of their ameboid contractility, whereas the enormous emigration of the
lymphocytes which in lymphocyte leukemia are incapable of ameboid move-
ment is apparently difficult to understand. However, I believe there is nothing
against the assumption that the lymphocytes, because of their production in
excessive numbers, may also enter the circulating blood in large numbers, as
they do under normal conditions, i.e., by “passive exudation,” owing to an
unusually strong lymph circulation, ete., provided the processes which nor-
mally cause the entrance of the lymphocytes are more active, which is true
to a varying extent in different cases.
This of itself leads us to discuss the question of the part in the leukemic
process which is taken by the various organs in which blood cell formation
normally takes place. It may to-day be regarded as certain that the bone-
marrow is particularly implicated in leukemia, not only in leukocyte leukemia
but also in lymphocyte leukemia.
SYMPTOMS AND BLOOD-CHANGES 363
We may assume that normally the majority of the lymphocytes are pro-
duced in the spleen and lymph-glands, and only a few in the bone-marrow.
As, however, hyperplasias of the spleen and lymph-glands occur without
lymphemia (“ pseudo-leukemia”), as well as with it (lymphocyte leukemia),
and since, moreover, there are cases of leukemia with lymphadenoid changes
of the bone-marrow but without enlargement of the spleen or lymph-glands,
we may conclude that the implication of the bone-marrow, i. e., the super-
vention of increased marrow activity in simple hyperplasia of the spleen and
lymph-glands, represents the most important element in the development of
leukemia (Neumann). However, in my opinion this does not explain why an
increase of the lymphocytes in the blood may not occur in hyperplasia of the
spleen and lymph-glands without an affection of the bone-marrow. As the
small lymphocytes which are formed in the lymph-glands under normal con-
ditions permanently enter the circulating blood, it is not apparent why, with.
an increased production in the lymph-glands and with a marked migration
into the blood, they should not appear there in greater numbers. On the
other hand why do we always have lymphemia when the bone-marrow is
implicated? The explanation that in hyperplasia of the tissue of the spleen
and lymph-glands their capsule also dilates, and therefore (in contrast with
the conditions in hyperplasia of the bone-marrow), no mechanical migration
of the lymph-cells into the blood occurs, is contradicted by the reflection that
if this were true every disturbance in the expansile power of the capsule
should result in a marked overflow of lymph-cells into the blood. In my
opinion, it is better for the present not to consider pseudo-leukemia at all
in connection with leukemia, and also not to look for the nature of leukemia
in the increase of the white blood cells alone.
We cannot, I believe, refrain from asking what becomes of the white
blood cells which are so enormously increased in the organism in leukemia.
That in health the leukocytes are partly excreted and partly destroyed in
the internal parts of the body is not to be doubted. If, with the enormous
increase of white cells in the blood of leukemics, the consumption does not
go hand in hand with the increased production, a surplus of white cells in
the blood must result. But there is no cogent proof as yet for the view that
there is any such increase in the consumption of leukocytes, which in this
instance would have to be enormous in order to keep pace with the increased
production.
My conception of the pathogenesis of leukemia is, therefore, the follow-
ing: The action of a specific agent causes a pathologucally great stimulus to
the growth of the hematopoietic tissues of the body, which especially affects
the production of white blood-corpuscles. As a result of this, a flooding
of the blood, at one time with lymphocytes, at another time with leukocytes,
with mature and immature forms of the same, occurs. This change in the
blood is continued, partly by the pathologic irritation of the blood-forming
organs, partly because the superfluous white blood cells are insufficiently used
up in the economy of the body.
364 LEUKEMIA
DIAGNOSIS
The diagnosis of leukemia is in the majority of cases not difficult ; indeed
it is very easy in well marked cases of the disease. We are always dealing
with leukemia when the proportion of white cells to red is 1 to 15 or less,
and the absolute count of leukocytes or lymphocytes (according to the case)
is 30 to 50 times greater than normal, and when, besides the relative and
absolute increase in the number of white cells, an immaturity of the cells
is strikingly manifest. One finds in the blood besides mature leukocytes and
lymphocytes many large mononuclear cells and abundant myelocytes, large
lymphocytes and also immature forms of erythrocytes, i.e., nucleated red
blood-corpuscles in large or small amounts, and in most striking profusion
in leukocytic leukemia. In leukocytic leukemia we are struck, moreover, by
the absolute increase of eosinophiles and mast-cells.
Having diagnosticated leukemia, we must now determine to which form
it belongs, whether to the lymphocytic or leukocytic type, which is not diffi-
cult if we remember the above mentioned points of distinction.
If the immature forms of blood-corpuscles are absent from the circulating
blood, and if a “ polymorphia ” of the white corpuscles is lacking, we are not
dealing with a case of leukemia, at least not of leukocytic leukemia, but with
a leukocytosis in which myelocytes are never found (except in the very rare,
isolated cases in which there is an excessively hasty production of blood cells).
[Myelocytes are not at all infrequently found in leukocytosis, i.e., in peri-
tonitis, in diphtheria, in pneumonia and in malignant diseases—Ep.] As
the blood pictures of leukocytosis and leukemia resemble each other in so far
as an increase in the number of leukocytes is concerned, we must now discuss
more thoroughly the manner in which leukocytosis originates, and the blood
picture of leukocytosis.
LEUKOCYTOSIS
In some physiological processes, viz., during digestion, pregnancy, after
bodily exercise, etc., we find, upon examination of the blood, an increase of
the white cells. [That there is no leukocytosis of digestion or of pregnancy
seems to me demonstrated by the more careful researches of recent years.
There is a midday leukocytosis in most persons and this may coincide with
the after-dinner period. But after breakfast and after supper there are no
changes to speak of.
The supposed leukocytosis of pregnancy is not observable, as a rule, until
a few days or hours before labor; sometimes not until labor has begun. After
parturition there is usually a well marked leukocytosis lasting several days.
—Ep.] In this “ physiological” leukocytosis the proportion of the various
forms of leukocytes to one another does not vary greatly from the normal,
whereas it is characteristic of pathological leukocytosis that, according to
the nature of the disease in the course of which a leukocytosis appears, marked
alterations are noted in the proportionate numbers of the various leukocyte
forms, According to whether the lymphocytes or the leukocytes are increased,
DIAGNOSIS 365
we speak of “lymphocytosis” or “leukocytosis” in a restricted sense, and
in this way, according to the prominence of one or the other leukocyte forms
in the blood picture, we may differentiate between a polynuclear neutrophilic,
and an eosinophilic, leukocytosis.
It has been declared at various times that the lymphocytes have no inde-
pendent, active motility; if, therefore, in the course of pathological condi-
tions a one-sided (symptomatic) increase of lymphocytes is noted in the
blood, we must consider that large numbers of them have reached the circu-
lating blood by reason of an increased cell production in the cytogenic tissue
of the lymph-glands (and of the bone-marrow to a much less extent) and
by a more active lymph circulation (“ passive leukocytosis,” Ehrlich). This
form of leukocytosis, “lymphocytosis,” is quite rare, occurring especially in
catarrhal affections of the stomach and intestines of nurslings, in pertussis,
in severe rickets, syphilis, etc., after injections of pilocarpin and tuberculin,
and after extirpation of the spleen.
More frequent is the second form of leukocytosis, polynuclear leukocytosis.
Various irritations (infectious agents, chemical poisons, etc.) cause these
leukocytes, which are always present in great amounts in the bone-marrow
[as well as in the capillaries of the liver and especially of the lungs.—Ep. ]
and which, on account of their ameboid movement, are always ready to pass
into the blood, to emigrate, and to enter the blood by “ chemotaxis ” (“ active ”
leukocytosis). As a rule, it is the neutrophilic polynuclear leukocytes which
circulate in the blood in large numbers in leukocytosis; i. e., almost all intozi-
cations and infections lead to this, the “usual” form of leukocytosis. Such
causes are: Poisoning by potassium chlorate, phenacetin, oil of turpentine,
albumoses, arseniuretted hydrogen, ete.; also cachectic conditions as a result
of malignant tumors, phthisis, severe blood loss; and, above all, the various
infectious diseases—pneumonia, sepsis, diphtheria, erysipelas, etc. On the
other hand, in certain pathological conditions we note a one-sided increase
of the eosinophilic cells (eosinophilic leukocytosis). This is the case in bron-
chial asthma, in various diseases of the skin, in malignant tumors, and espe-
cially also in helminthiasis (due to the presence of tenie, ascarides, ankylos-
toma, etc., in the intestine. [As well as in echinococcus disease, trichiniasis,
Bilharziosis, trypanosomiasis and practically all the diseases due to animal
parasites.—Ep. |
Leukemia represents a morbus sui generis, the nature of which, as we have
seen, depends upon a pathological blood formation, i.e., not only upon an
excessive increase of the white blood cells but also upon their qualitative
change (the passage of immature forms into the blood). In leukocytosis, on
the other hand, the condition is only a functional alteration of the blood-
forming organs, and in the majority of cases (leukocytosis in the restricted
sense) exclusively of the bone-marrow, which reacts to pathological irritation
by the formation and expulsion of large numbers of normal and mature
colorless blood-corpuscles. This explanation of leukocytosis, the strict con-
ception of which as an increased function of the bone-marrow was formulated
by Ehrlich, has lately been fully confirmed experimentally by Rubinstein
[and still more fully worked out by Longcope in his studies of the marrow
366 LEUKEMIA
in typhoid, pneumonia, and peritonitis—Ep.]. After the injection of an
agent causing leukocytosis, he followed step by step the changes in the bone-
marrow. As soon as the leukocytes appeared in the blood in large numbers,
the granular, mature elements in the bone-marrow almost wholly disappeared,
and, instead of these, in a few days, the immature forms, especially the
myelocytes, increased. The latter, therefore, covered the loss due to the
enormous emigration of the polynuclears into the blood as a result of the
leukocytosis. The spleen and the lymph-glands, however, in Rubinstein’s
experiments, took no part in making up the loss of white corpuscles in poly-
nuclear leukocytosis, but, according to our present opinion regarding the
separate development of leukocytes and lymphocytes, this is not to be won-
dered at.
From what has been stated, it is clear that the diagnosis of leukocytosis rests
primarily on the discovery of a disease which is recognized as usually giving
rise to leukocytosis. The diagnosis becomes more certain if the increase of the
white blood cells is a transitory one (i.e., disappearing with the cessation
of the underlying affection), and remains from the onset within moderate
limits. While in leukemia ratios of 1 white to 10 red corpuscles, and even
1 to 2, are quite usual, in leukocytosis there is a much slighter relative in-
crease of leukocytes, and only in exceptional cases, as in cachectic conditions
when there is a decided decrease of the erythrocytes simultaneously with
leukocytosis, does it happen that proportional figures of 1 to 20 are observed
for a long time. Under such conditions these cases may simulate leukemia,
but here the recognition of morphological alterations in the white. blood-
corpuscles leads to the correct diagnosis, because the excessive appearance
of myelocytes, eosinophiles, and mast-cells in the circulating blood (in short,
a markedly polymorphous condition of the blood elements which is quite
foreign to leukocytosis) directly favors the existence of leukemia. The diag-
nosis of the latter disease is also aided by the decided enlargement of the
spleen and lymph-glands, and the absolute and relative increase of uric acid
excretion in the urine, ete.
These last named factors especially must be taken into consideration when
we are dealing with a lymphocytosis, because here the most important point
of distinction between leukemia and (polynuclear) leukocytosis, the poly-
morphia of the blood cells, is of no avail. In practice, however, the diagnosis
of lymphocytosis is never doubtful, the difficulty in differentiating between a
lymphocytosis and a feebly developed lymphocytic leukemia being theoretic
rather than actual. [On the contrary, mistakes have actually occurred. See
Steven (Lancet, 1902, vol. xx) and Cabot (“Clinical Examination of the
Blood,” 5th edition, 1904, p. 194).—Ep.]. For, in the acute form of lympho-
cytic leukemia, the large lymphocytes almost always predominate, and this
alone is sufficient to prevent confusion. between lymphocytic leukemia and
lymphocytosis; even in chronic lymphocytic leukemia the large lymphocytes
are not entirely absent in the microscopical preparations, although, in the
great majority of cases, only small leukocytes are found.
Above all, the usually enormous increase of lymphocytes in lymphocytic
leukemia, the progressive, pernicious nature of the disease compared with the
TREATMENT 367
transitory, benign character of the increased number of lymphocytes in
lymphocytosis, determines the correct diagnosis. On the other hand, the
following symptoms point to leukocytosis: The absence of enlargement of
the spleen and of the lymph-glands which is almost always present in lympho-
cytic leukemia; and, secondly, the presence of a primary disease which would
lead to leukocytosis (gastro-enteritis infantum, etc.).
PROGNOSIS
The prognosis of leukemia may be briefly summed up: it is absolutely
unfavorable; death is the only outcome of the disease. This is true not only
of the acute form of leukemia in which death occurs usually in a few days
or weeks, but also of chronic leukemia, of leukocytic leukemia, as well as of
chronic lymphocytic leukemia. However, in both forms of chronic leukemia,
especially leukocytic leukemia, remissions may occur with considerable im-
provement of symptoms, and the disease may sometimes last for from one
to four years. But since we have learned positively to recognize leukemia
by new methods of blood examination, no actual cure has as yet been ob-
served. From this standpoint we must look with suspicion on “ recoveries ”
reported from time to time, and I do not hesitate to pronounce as doubtful
a case of cure which came under my observation twenty-five years ago, since
the diagnosis made at that time does not conform to the requirements of
to-day.
This gloomy view concerning the prognosis of leukemia is, however, based
on the present state of our experience, and it is to be hoped that when we obtain
more exact knowledge of the nature of the specific poison causing this disease,
our therapy will become more effectual, and the prospects of cure more
favorable.
TREATMENT
At the present time there is nothing that can be regarded as the fulfilment
of an indicatio morbi. All that has been thus far attempted in treatment
may be regarded merely as efforts to feel our way, and these have so far been
abandoned as soon as undertaken. A few drugs only have held their place
in the treatment of leukemia, and by most physicians, as well as by myself,
are employed faute de mieux, though it is true that the long duration of a
few cases treated in this manner, and the transitory but decided remissions
in the course of the disease may, at least in part, be referred to the action
of the remedy. —
Arsenic is the drug which most deserves our confidence. During its ad-
ministration, we see in some cases an improvement in the condition of the
blood (not only an increase in the number of red but also a decrease in
the number of the white corpuscles), an arrest of the splenic enlargement, and
the disappearance of the hemorrhagic diathesis.
The best way of administering arsenic 1s In the form of Fowler’s solution
with two parts of aqua cinnamomi:
368 LEUKEMIA
KR Solutio kalii arsenicosi...............eeeeeeee 10.0
Ag. CiNMAMOM] «0.6.20. eee eee eee eee eee eee 20.0
M., D., S.: Gtt. xv-xxx, three times daily.
We begin with 15 gtt. tid. (taken after meals), and increase gradually,
ie. after one week 20 gtt. t.id., after the second week 25 gtt. t.id., and after
the third week 30 gtt. t-i.d.; this dose we maintain for some time. I am not
enthusiastic regarding the subcutaneous use of arsenic. The injection of
arsenic into the circulating blood could only be desirable if the results obtained
by this method were incomparably more brilliant than after the administration
of arsenic by the mouth, and this is decidedly not the case.
Another remedy producing apparently favorable results is quinin. Its
action is asserted to be remarkable, especially if it be combined with arsenic
or iron. In this respect, the mineral waters containing arsenic and iron, as
Levico and Roncegno water, and the Levico water used in the form of baths,
deserve consideration.
In the majority of cases the erythrocytes decrease to one-half their number
or less with the increase of white corpuscles (at least in the latter course of both
leukocytic and lymphocytic leukemia), and here the administration of arsenic,
iron and quinin, whose favorable influence on the red corpuscles cannot be
denied, is warranted from a theoretical standpoint, as well as empirically.
Iodin preparations, formerly prescribed to some extent, have recently been
less used; no appreciable results of their use have been noticed. The same
is true of phosphorus in doses of 0.001 to 0.005, which has been praised, espe-
cially by English physicians.
Two therapeutical measures which were recently hailed with enthusiasm,
oxygen inhalations and organotherapy (preparations made from lymph-glands
and bone-marrow), have produced no striking results, although amelioration
and a slower progress of the disease have been supposed to follow their admin-
istration. In general, what has been said of the administration of arsenic,
iron, and quinin is true also of this method of treatment. We may use these
remedies, indeed, we must use them, but we can only hope for a partial suc-
cess; the disease up to this time has been invariably fatal, but, as a rule,
lasts a year or longer, and calls for a display of humanity on the part of the
physician which is not shown by quietly folding his hands and rejecting any
method of treatment which offers the patient the slightest hope of recovery or
even improvement.
Although I strongly recommend the trial of the above-mentioned thera-
peutic measures in the treatment of leukemia, just as strongly must I con-
demn local procedures. Not only does the lack of results militate against their
use, but we are thoroughly convinced that the nature of leukemia is not to
be found in the affection of the spleen or of any individual lymph-gland, nor
in any other organ accessible to local treatment. I believe that the time has
come to discontinue all efforts to cure the disease by injections of arsenic,
ergotin, etc., into the spleen, by faradization or galvanopuncture of the organ,
or even by extirpation of the glands, or by splenectomy which, without an
exception, has been rapidly followed by death.
TREATMENT 369
It is much more sensible to retard the increased albumin waste in the
organism by rational diet, or, in its later stages, to compensate it, at least
partially, by increased nutrition. A nourishing diet, rich in nitrogen, is
therefore to be advised because a well-nourished organism will always offer
more resistance to the disease than one debilitated by cachexia. To strengthen
the body, besides judicious diet, moderate systematic exercise in the open air
and the avoidance of too great physical exertion must be insisted upon.
Of course, the indicatio symptomatica may require different expedients.
Marked diarrhea must be combated by tannigen and opium, dyspeptic symp-
toms by regulation of the diet, lavage, etc., exhausting sweats by camphoric
acid and atropin, a marked hemorrhagic diathesis by ergotin or other prepara-
tions of ergot in large doses (ergotin 0.2, five times daily, secale 10.0 to 150,
to be used in two days), cardiac asthenia by camphor, etc. It is unnecessary
to enumerate these indications in greater detail, for the treatment of individ-
ual symptoms and complications is in accordance with the same rules as in
other diseases. Only I must caution against the too liberal use of drugs in
leukemia; we must not forget that we are dealing with the debilitated, the
desperately ill, in whom it might be dangerous to act according to the prin-
ciple “anceps remedium melius quam nullum.”
[The treatment of leukemia by X-rays certainly deserves mention. Since
Senn’s original observation in 1902, 30 or 40 cases have been published in this
country in which the disease has been treated by exposure of the spleen or
(in lymphatic cases) of the spleen and glands to the Roentgen rays,
Cases are treated daily, biweekly, or weekly according to the condition of
the skin and its ability to resist “burns.” In a few cases, the rays have been
made to fall upon the long bones.
In the majority of these cases improvement, sometimes remarkable and
(so far) lasting, has followed the treatment. A few cases have been altogether
unaffected, a number have relapsed after temporary improvement, and a small
number have been worse after the treatment. In acute febrile cases there has
been no success.
The rationale of the treatment is not at all clear, for the exposures have
usually been made over the spleen, and not over the marrow where the disease
is most active. We know from the researches of Warthin and others that
the X-rays have a specific leukocytolytic effect on the blood forming organs
of animals, and if the over-production of leukocytes were occurring in the
leukemic spleen instead of in the marrow the effect of the X-ray would be
comprehensible. At present it remains a mystery, but it is none the less
advisable that all subacute and chronic cases of either variety of leukemia
should be given X-ray treatment, which at present offers the best possibility
of retarding (or curing?) the disease—Eb. ]
20
PSEUDO-LEUKEMIA
(HODGKIN’S DISEASE AND BANTI’S DISEASE)
By H. SENATOR, Bertin
WE often meet with cases characterized by the following lesions: a more -
or less well-developed anemia, together with multiple lymph-gland enlarge-
ments, a very decided enlargement of the spleen, or both. This glandular and
splenic enlargement also occurs in leukemia, which, however, differs from
pseudo-leukemia in possessing a characteristic condition of the blood, particu-
larly a great increase of leukocytes, which is not present in pseudo-leukemia.
To this difference from leukemia, which these cases often resemble greatly,
Bonfils and Wilks in the year 1856 were the first to call attention, though
Virchow had described leukemia eleven years previously, in 1845.
Soon the publication of cases of this kind increased, and new names were
repeatedly invented for them. Bonfils designated his cases as “ cachexia with-
out leukemia”; Wilks called his “ anemia lymphatica,” and later “ Hodg-
kin’s disease,” since Hodgkin had described such cases explicitly, long before
the discovery of leukemia, that is, in the year 1832. The counterpart to
“anemia lymphatica” (in which enlargement of the lymph-glands is the only
lesion or is much more marked than that of the spleen) is the term “ anemia
splenica,” a condition in which the lesions are confined to the spleen. The
combination of both conditions has been called “ anemia lymphatico-lienalis.”
Still other names have been proposed which I do not intend to mention, since
they are based wholly on the anatomical condition without regard to the
clinical phenomena, and are not adapted to all the cases belonging in this
category. ‘They have all been superseded by the term introduced by J. Cohn-
heim in the year 1865, “ pseudo-leukemia,’ which, in spite of all objections,
has maintained its place until to-day and will probably maintain its vogue
for a long time.
It is true that “pseudo-leukemia” has become a collective name for a
number of different affections, but since these affections cannot always be
separated from one another, and since this name is short and conveniently
expresses what is common to them all (namely, that they resemble leukemia
but still are not leukemia, at least clinically), the name pseudo-leukemia will
be employed in this article.
The difficulties in the nomenclature of this disease are the same as, for
example, in “ileus.” Every physician knows that the clinical picture desig-
nated by this name is brought about by various anatomical changes of the
370
HODGKIN’S DISEASE 371
intestine. But as we are not always able to differentiate these changes we
cannot discard the name which describes the typical clinical picture.
This, of course, must not prevent us from investigating so far as is posst-
ble the anatomical conditions in each individual case of pseudo-leukemia, and
finding, if we can, the exact lesion present, particularly as support may be
gained in this way for prognosis and therapy. [The studies of Dorothy Reed,
confirmed by those of Longcope and of Simmons, have, I think, established
Hodgkin’s disease upon a definite histological basis, and differentiated it alike
from tuberculosis, from sarcoma, and from leukemic infiltrations. In view of
these findings, the diagnosis can and should be made by the excision of one (or
more if need be) of the superficial lymph-glands and examining it histo-
logically.— Ep. ]
The organs which are to be considered in pseudo-leukemia, the lymph-
glands and the spleen, are almost always simultaneously affected, although not
often to the same extent. In pseudo-leukemia we know but little regarding
the third organ which is important, or probably important, in blood forma-
tion, namely, the bone-marrow; it has sometimes been found hyperemic and
of the same consistence as in leukemia, but in regard to this further investiga-
tion is necessary.
In the majority of cases the enlargement of the lymph-glands is more con-
spicuous than that of the spleen. Hence some clinicians recognize as “ pseudo-
leukemia” only those multiple lymph-gland enlargements first described by
Hodgkin, and distinguish sharply the cases in which enlargement of the spleen
is more prominent, or is present alone. To me it appears that this limita-
tion of the conception “ pseudo-leukemia” is unwise, for an enlargement of
the lymph-glands alone or of the spleen alone rarely occurs. Even though
during life we find many cases with decided enlargement of the glands, and
no apparent enlargement of the spleen, still I believe that at the autopsy the
spleen is almost invariably found enlarged. On the other hand, in cases with
predominant enlargement of the spleen, some enlarged lymph-glands are almost
always found at the autopsy, if not the superficial ones then those of the abdo-
men or of the thoracic cavity. A sharp distinction therefore cannot be drawn
here, and there are many cases in which the spleen and lymph-glands are
equally—or, rather, proportionately enlarged.
If, however, we wish to lay special stress either upon lymph-gland enlarge-
ment or upon the spleen, in the former case we may use the terms “ pseudo-
leukemia lymphatica,” or true Hodgkin’s disease, in the latter case * pseudo-
leukemia lienalis” or “splenica”; finally the cases with equal implication of
the lymph-glands and of the spleen may be designated as “ pseudo-leukemia
lymphatico-lienalis”’ or “ spleno-lymphatica.”
We shall first describe the more common form, pseudo-leukemia lymphatica
or Hodgkin's disease.
¢
HODGKIN’S DISEASE
The most conspicuous and usually the first symptom is the enlargement of
a gland or of a few glands in the neck, oftenest at the angle of the jaw. This
enlargement occurs as a rule quite gradually, so that only in the course of
372 PSEUDO-LEUKEMIA
several weeks or even months does it become noticeable. By this time the
individual gland has attained the size of a cherry or a small walnut, or a
group of swollen glands has become conspicuous to sight and touch.
The swellings are painless. After a latent period of varying duration
they begin to increase following a definite course next to be described. First,
more glands are involved, usually those in the neighborhood of the one first
affected, i.e., those in the lower part of the neck or in the back of the neck,
later those in the axilla, at the elbow, in the inguinal region, occasionally those
in the popliteal space. Next comes an increase in the size of the individual
glands, which may become as large as a man’s fist or even larger. The glands
of the neck and axilla, which are those first affected, are always most advanced
in growth, while those of the inguinal region and of the thigh are less mark-
edly enlarged.
The enlarged glands can usually be felt and defined with ease; in other
cases they are more or less matted together; they are more frequently soft
than hard in consistence, and in many cases they may be readily’moved about.
As a rule the skin above the glands can easily be raised, but shows no other
change. The spleen, as has been said, in this form of pseudo-leukemia, Hodg-
kin’s disease, is almost always implicated, but to a much less degree than the
glands, so that its enlargement cannot always be determined with certainty
during the life of the patient.
Add to these facts the vista of a gradual increase in the glandular enlarge-
ment, while almost exactly in proportion to this the general condition of the
patient deteriorates so that he becomes anemic, loses his strength and emaciates,
and we are in possession of the most important features of the clinical picture.
But in these outlines the entire symptom-complex is by no means revealed.
Indeed it may be very complicated.
The symptoms are in part purely local consequences of the existence of
the tumors, and hence depend particularly upon the pressure which these
glands exert, or upon the metastases which they produce. But there are other
symptoms of a general nature, which result partly from the anemia and
cachexia, partly from the actual nature of the disease which is wholly unknown
to us.
Before recounting the symptoms I must add that, besides the glandular
enlargements which are externally visible and palpable, there is almost in-
variably an enlargement of the internal lymph-glands, those of the thoracic
and abdominal cavities. These internal glands are sometimes large, some-
times small and therefore not always clinically recognizable. Cases do occur
in which only the internal lymph-glands are enlarged, the external ones not
at all or to an exceedingly slight degree. I have myself seen a very remark-
able case of this type, to which I shall recur later. We must admit that such
cases are not likely to be diagnosticated clinically; the pathologist designates
them as multiple lymphomata or as lymphomatosis, the same title given by him
to the external enlargements which occur in Hodgkin’s disease.
It is these internal glandular enlargements which bring about the most
severe pressure phenomena, especially in the thorax where there is less room
for growth than in the abdominal cavity. Enlarged glands in the anterior
HODGKIN’S DISEASE 373
mediastinal space press particularly upon the innominate vein, and thus pro-
duce swelling of the veins of the neck and the wall of the chest with cyanosis
and edema of the face, to which may be added dropsical effusions into one or
both pleure. These phenomena, however, are not so frequent or so marked
as with other tumors and tumor-like formations in the thoracic cavity, for the
glandular swellings are usually softer and less resistant than other tumors. It
is true that harder forms occasionally occur depending upon histological vari-
ations the discussion of which will follow later on, and these hard tumors may
produce all the phenomena of pressure and stasis.
The development of dropsical effusions may be produced in three ways:
(1) by venous stasis; (2) by displacement of the lymphatic trunks, caus-
ing a hindrance to the absorp-
tion of tissue fluid; and (3)
by progressive anemia and ca-
chexva.
More common than stasis
phenomena are difficulties in
respiration. These are caused,
(1) by direct pressure which
the glandular swellings exert
upon the larynx, trachea or
bronchi; (2) by pressure upon
the vagus, or (very frequently)
upon the recurrent laryngeal
nerve; (3) by the decrease of
erythrocytes which are the neces-
sary oxygen carriers in the func-
tion of respiration. Difficulty
in deglutition as the result of
pressure upon the pharynx or
esophagus is rare.
Enlargements of the thoracic
lymph-glands also produce both
dropsical effusions into the
pleura, and true inflammations
of the plewra (unilateral or Pe ae
bilateral) , which cannot always Fig. 21.—Casr or Hopexin’s Dispase IN Dr. Sat-
be differentiated from dropsy, INGER’S WARD IN THE JEFFERSON MEDICAL
since there are fluids intermedi- Coutuece Hosrirau. Operated upon by Prof. W.
acer Soe W. Keen for the removal of large masses of lymph-
ate between dropsical effusions glands pressing upon the trachea, which produced
(transudates ) and inflamma- i eyaleavon mia Ee HORT
tory effusions (exudates).
“Another symptom which is probably to be referred to the local pressure
exerted by the glandular tumors is neuralgia. I have seen it most frequently
in the lower extremities, especially in the course of the sciatic nerve or the
crural nerve. In a case of this kind in which the patient was troubled with
painful contractions in the left ilio-psoas muscle, I could feel in the corre-
374 PSEUDO-LEUKEMIA
sponding abdominal region distinct glandular enlargements which probably
exerted pressure upon the muscle and the nerve which supplied it, and thus
caused the pains and contractions.
The urine shows nothing special; its composition is that which is usual in
anemia provided no complications are present. Occasionally, as in leukemia,
it is found conspicuously rich in alloxur bodies, particularly uric acid. These
bodies, together with the nucleo-histon which was once found in the urine in
pseudo-leukemia by A. Jolles, are explained by an increased destruction of
leukocytes.*
Finally, as a frequent but not invariable symptom, we must mention hem-
orrhages from various organs, particularly from the nose and in the skin in
the form of petechiw of varying size, rarely as larger effusions of blood. It
appears to me that the tendency to hemorrhage is particularly great in cases
with glandular enlargements in the internal parts of the body, in the thorax,
and, above all, in the abdominal cavity. The case previously referred to, in
which only these internal glands were enlarged (and very decidedly so), ran
its course with the clinical picture of Werlhof’s disease, 1. e., with hemorrhages
from the nose and mouth, hematemesis, and blood in the urine, but without
other noteworthy symptoms except slight fever. The autopsy showed hemor-
rhages in almost every organ, and numerous lymphomata in the thorax and
abdominal cavity of which we had no suspicion during the patient’s life.
Shall we look upon these glands as the cause of the hemorrhages? This
is hardly possible, for they are invariably absent in Werlhof’s disease, while,
on the other hand, glandular enlargement is often present without any tend-
ency to extensive hemorrhages. We can only say that glandular enlarge-
ments sometimes lead to a radical change in the blood in consequence of which
hemorrhages occur, and that these changes are particularly noted when the
lymph-glands of the internal parts of the body are diseased.
In this case, as I have said, only the internal lymph-glands were enlarged ;
in other cases the lymph-gland chains situated in the digestive canal, i.e., the
tonsils, the glands of the mucous membranes of the mouth and cheek, the
solitary and agminate glands of the intestine may be affected, with or without
involvement of the external lymph-glands. In consequence of these enlarge-
ments all sorts of otherwise inexplicable disturbances occur.
Fever does not belong to the typical picture of Hodgkin’s disease. Now
and then slight rises in temperature occur, particularly when fresh glandular
enlargements develop rapidly, but fever is not characteristic, and in some
cases may be entirely absent until the anemia becomes very grave, or until
near the end of life. This last type of fever corresponds to the febrile condi-
tions which are observed in other severe anemias. Of course there may be at
any period in the disease a pyrexia due to complications.
I am not unmindful of the fact that some isolated cases have been described
in which fever was-a most prominent symptom, but which, nevertheless, have
shown in the main the clinical course of Hodgkin’s disease. In these cases
1 From the communication of Jolles it could not be determined whether in his case
a lymphatic or a lienal pseudo-leukemia was present,
HODGKIN’S DISEASE 375
the fever is usually remittent or intermittent, with regular or irregular pauses
some of which last several days (recurring). Such cases have been described
by Pell, Ebstein and others as “chronic relapsing fever” or as “recurring
glandular fever.” “But in many, perhaps in the majority, of these cases, tuber-
cle bacilli and other changes indicating tuberculosis have been found in the
glands, and the question has therefore arisen and been discussed whether these
cases should be designated as “ pseudo-leukemia.”
DIAGNOSIS
This brings us to the difficult realm of diagnosis, difficult for the reason
mentioned at the beginning of the article, viz., because the conception of
“ pseudo-leukemia ” is not a sharply defined one, or, more accurately expressed,
because there is no unanimity as to which glandular enlargements are to be
considered as belonging to the disease. There is general agreement only on
one point, that all cases of secondary or symptomatic adenitis, i.e., all those
which appear in the course of other infections and are in causal relation with
them, are not to be designated as “ pseudo-leukemia,” but only those appearing
as primary, multiple, glandular enlargements which dominate the clinical
picture.
Such lymph-gland enlargements, however, are by no means always of one
type; indeed, from a pathological standpoint they vary greatly. I have already
mentioned that in the cases described as “chronic relapsing fever,’ or as
“recurring glandular fever,’ tuberculosis is often found in the enlarged
lymph-glands. But it is also true that in a large number of the cases described
as “ pseudo-leukemia ” and showing the typical clinical picture of that disease
without fever or with only an occasional rise in temperature, tuberculosis of
the glands has been found. In other cases anatomica! investigation has re-
vealed sarcomatous changes, and the disease for this reason has been desig-
nated lympho-sarcomatosis (Kundrat). Finally, in still other cases the
glandular swellings resembled leukemic lymphomata.
This latter form of multiple lymph-gland enlargement, and this alone,
Ehrlich and Pinkus desire to have designated as “ pseudo-leukemia.” They de-
fine the latter as a disease with lymphadenoid cell-accumulations which in every
respect resemble the lymphatic leukemic form, running its course with an in-
crease of the lymphocytes at the expense of the multinuclear leukocytes but
without any material increase in the total number of the leukocytes. Their pro-
portion to the erythrocytes is said not to exceed 1 to 200 or 1 to 100. In such
cases the lymphadenoid proliferations occur, not only in the lymph-glands, but
in the organs of the chest and abdominal cavity and in the skin, just as in lym-
phatic leukemia. Whether the bones are affected in pseudo-leukemia as in
leukemia is, as I have already remarked, still questionable.
This discovery represents (if true) an essential advance in the conception
of pseudo-leukemia, even although for the time it has no great practical impor-
tance, particularly for clinical diagnosis. For, in the first place, if the blood
condition required by Ehrlich and Pinkus is actually present, the differentia-
tion of pseudo-leukemia from leukemia may be difficult or even impossible.
376 PSEU DO-LEUKEMIA
The ratio of white cells to red cells which is set up as a limit (namely, 1 to
200 or 1 to 100) allows wide space for variations in individual opinions ;
indeed, such a ratio is often found in well-recognized cases of leukemia.
Further, it is not easy to determine during life that the glandular enlarge-
ment actually depends upon lymphadenoid proliferation. Even if an en-
larged gland is extirpated, and these proliferations are found in it, we cannot
conclude with certainty from this that in all the other enlarged glands the
same changes, and only these, are present, and that the condition is not due
in part to other processes, particularly tuberculosis, a combination which has
been actually observed (Askanazy, Fischer, Freudweiler and others). Fur-
ther, the blood conditions designated as characteristic by Ehrlich and Pinkus,
an increase of lymphocytes without much if any increase of the leukocytes is
not constant, a fact of which I have convinced myself in at least one case after
prolonged observation. The proportion of the mononuclear to the polynuclear
leukocytes varies, and for a time may be even normal. The increase in lympho-
cytes is not always present from the onset. Finally, I do not believe that we
can exclude the possibility of finding the blood-picture required by Ehrlich
and Pinkus, in connection with glandular enlargements which do not show
the pure leukemic character, i.e., with tuberculosis or sarcomatosis of the
glands, and especially with the complicated or mixed forms previously men-
tioned. [The Ehrlich-Pinkus formula certainly is not present in every case
of pseudo-leukemia—and is not at all uncommon in other diseases—e. g., in
debilitated and neurasthenic conditions, in variola, in some syphilitic cases,
and in some acute septic enlargements of the lymph-glands——Eb. ]
The greatest difficulty is always experienced in the differentiation of tuber-
culosis of the lymph-glands from true lymphomata, and it is rarely possible
(except when a gland has been extirpated and examined) to decide this ques-
tion with certainty. As points of support for a probable diagnosis the fol-
lowing may serve: Tuberculosis of the glands is rare in those beyond the
twenty-fifth year of hfe. The appearance of glandular enlargements without
any other symptoms in later life would therefore be evidence against the
tubercular nature of the affection. Pain and tenderness in the enlarged glands
is frequently observed in tuberculosis; it is rare or does not occur at all in
lymphomata. Tuberculosis of other organs is greatly in favor of the assump-
tion of a glandular tuberculosis, and also fever, which, as I have already said,
is certainly absent or appears very rarely in the non-tubercular form. Fn-
largement of the spleen, in the absence of fever, is against tuberculosis.
Finally, tubercular lymph-gland enlargements adherent to their surroundings
usually break down from caseation, and if they are superficially situated rup-
ture externally. In a case of this kind it is easy to make the diagnosis. But
caseation and abscess formation do not occur at the onset, but only, if at all,
after a lapse of time; hence until this happens this criterion for diagnosis is
not present. Apart from this there is a form of glandular tuberculosis which
leads to very slight caseation or none at all; I refer to the indurative form.
The nature of such cases is obviously difficult to determine. In short, the
differentiation of tubercular adenitis from lymphoma, or the so-called lymph
adenomata, is very frequently difficult or impossible during life.
HODGKIN’S DISEASE 377
The same is true of the third previously mentioned form of glandular
enlargement, lympho-sarcomatosis. According to Virchow, a hard and a soft
form of lympho-sarcoma have been differentiated, depending upon whether or
not the proliferation of the reticulum of the gland and of the connective tissue
predominates over the cell proliferation. The softer forms, however, show
gradual transition stages to the pure lymphomata or lymphadenomata, so that
even for the pathologist the decision between these varieties of tumors may
be very difficult. Hence, the harder composition of the lymphosarcomata, com-
pared to the lymphomata, has very little diagnostic importance, as the differ-
ence is not decisive. Somewhat more valuable in diagnosis is the fact that
lymphosarcoma has a greater tendency to invade the capsule of the gland
and the neighboring tissue, and to rupture through the skin, which never
occurs in pure lymphomata, but which does occur, as has just been stated,
in tubercular adenitis. The tendency to metastasis, which has been mentioned
as characteristic of lymphosarcoma, is of very slight value in diagnosis during
life, for three reasons: First, adenitis of other types readily causes metastases
in internal organs, either by way of the lymph stream or blood channel; sec-
ondly, metastases are frequently not recognizable by symptoms; and thirdly,
in the presence of certain symptoms it may be difficult, even impossible, to
decide whether these symptoms are due to actual metastatic tumors in an
organ or are only caused by the pressure and irritation which glandular tumors
in the cavities of the body exert upon a neighboring organ. Thus, for exam-
ple, symptoms which point to an affection of the respiratory apparatus, dysp-
nea, cough, etc., may be caused by metastases in the lungs or in the bronchi,
as well as by pressure of enlarged mediastinal glands.
To all this we must add that, even in quite unquestionable cases of lympho-
sarcoma, we find the blood-picture which Ehrlich and Pinkus have designated
as characteristic of pseudo-leukemia produced by multiple lymphomata.
It will, therefore, not be looked upon as an exaggeration when I say that
only in a small minority of cases is it possible to recognize with certainty the
anatomical nature of the glandular enlargements which are the foundation of
the clinical picture of pseudo-leukemia. [See note on page 371.—Ep.]
ETIOLOGY
As to etiology very little has been determined with certainty. The affec-
tion appears in childhood and in adolescence, somewhat more frequently in
the male than in the female sex. Occasionally several cases have been noted in
the same family, for instance, among brothers and sisters or in one of the
parents and a child, and this suggests a hereditary or family predisposition.
Not infrequently pseudo-leukemia occurs in connection with other dis-
eases as, for example, malaria, and often in my experience, after diseases which
are combined with an inflammatory irritation of the nasal cavities and of the
tracheo-bronchial mucous membrane, i.e., after inflammations of the throat.
measles, whooping-cough, influenza and the like. One might assume that
from the areas of mucous membrane just mentioned an irritation is exerted
upon the glands which causes enlargement, but then it remains unexplained
378 PSEUDO-LEUKEMIA
why these inflammatory affections which are so exceedingly common rarely
cause much glandular enlargement, and it is also inexplicable how the enlarge-
ment of the glands originally irritated can distribute itself to distant parts,
and, finally, to all or nearly all the glands of the body. The irritation theory
must be supplemented by assuming a special predisposition to disease of the
lymph-glands, and this view must serve to elucidate those cases in which no
causal factor that could produce irritation has preceded the glandular enlarge-
ment. More plausible is the view that a poison is at work in the blood, and
that the glandular lesions are only symptomatic. In the cases which appear
to develop spontaneously and without any evidence of such a poison, it is
probable that there has been noticed irritation from the tonsils, or from the
whole pharyngeal mucous membrane. Many years ago I pointed out the fact:
that the so-called “ vestibulum pharyngis” was a “vestibulum malorum,” an
ante-chamber by which innumerable pathogenic agents found their entrance
into the body. According to this hypothesis, in Hodgkin’s disease a damag-
ing agent finds its way from the pharynx through the lymph-glands into the
blood and thus causes enlargement, first in the glands of the neck, and later
in the others.
That in the later stages of the disease a deleterious agent must actually
be present in the blood, is proven by the almost invariable implication of the
spleen, which of late has very aptly been designated as a lymph-gland of the
blood.
COURSE, DURATION AND RESULT
I have very little to add to what has been said regarding the course, dura-
tion and outcome of Hodgkin’s disease. The disease runs its course with
paroxysms of varying duration; as a rule it lasts from one to five years, very
rarely longer. Two years is an average duration. The usual outcome of the
disease is death, which is the result either of the previously mentioned pres-
sure and stasis, or of an increase in the anemia, producing exhaustion which
is not infrequently intensified by copious hemorrhages. A termination in
recovery is exceedingly rare. Occasionally, prior to death, a transition into
true leukemia has been observed, with the addition, therefore, of characteristic
blood-changes to the glandular enlargements.
THERAPY
Treatment of the fully developed disease is not very effectual, as an actual
and permanent recovery can scarcely ever be brought about, but, at the most,
only a cessation in the glandular enlargement with more or less prolonged
improvement of the general condition. Whether early treatment accomplishes
more, 1. e., complete recovery, is questionable. Nevertheless, an effort should
be made to combat the glandular enlargement as early as possible.
For this purpose various remedies are at our disposal to which a certain
beneficial effect cannot be denied; besides extirpation of the gland.
Among the remedial agents, Billroth has advised arsenic which has proved
most efficacious. This is given either internally, or, more generally, in injec-
tions subcutaneously or in the parenchyma of the gland. For internal use
HODGKIN’S DISEASE 379
we give Fowler’s solution, one to five drops once or twice daily, best given
diluted with twice or three times this amount of ordinary or aromatic water.
T believe arsenious acid to be even more effective, either in the form of the
pilule asiaticee (Rj Acid. arsenicos. 0.06, piperis nigri pulv. 1.5, rad. liquir.
pulv. 3.0, mucilag. gummi arab. q. s. ad pil. lx) of which one pill is taken
once to three times daily To avoid irritating the stomach, these, like all
other arsenic preparations, are not to be given upon an empty stomach, but
only while eating or immediately after a meal. A very serviceable arsenic
preparation is sodium cacodylate, also known under the name of arsycodile,
which contains considerable arsenious acid (nearly two-thirds) and is well
borne. The dose for adults is 0.025 to 0.1, and this is gradually increased
in pills (sodium cacodylate 0.25 to 0.1, sacch. et gummi arab. q.s. ad pil. xx,
daily one to five pills) or for children in solution (1:15, according to age
three to ten drops). After prolonged use of this preparation, in some cases
a disagreeable garlicky odor of the breath appears and causes us to desist from
its use.
Arsenic acts more readily by subcutaneous or parenchymatous injections
(into the glandular substance) than by internal administration. Usually
Fowler’s solution is employed (beginning with 0.1 and cautiously increasing
even up to one gram) or the solution of sodium arsenite advised by v. Ziems-
sen, of which a somewhat larger dose is injected. But even here cacodylic
acid is to be preferred on account of its greater solubility and larger contents
of arsenic. A 10 per cent. solution of sodium cacodylate in sterilized water is
used for about a week (one-half of a Pravaz syringeful being injected) ; it is
then stopped for a few days, and then resumed, the same dose being injected,
until gradually, with pauses of a few days, the dose is increased to an entire
syringeful.
Recently a preparation containing a large quantity of arsenic atoryl (ani-
lidmetarsenite) has been advised by Walter Schild, and this seems to deserve
preference even above the cacodylate. Of a solution of two parts in ten of
water, two to ten divisions of the hypodermic syringe are injected and the
dose is gradually increased. The injections are almost painless, and are well
borne. In the only case of Hodgkin’s disease that I treated by this method
the result appeared to be satisfactory, but the duration of observation was too
brief to permit me to speak of a permanent success.
A good auxiliary remedy in every arsenic treatment is formed by the min-
eral waters containing arsenic and iron, those of Roncegno, Levico, Srebrenica
(Guber spring), and of Cudowa (Eugene spring), which, on account of the
arsenic they contain (and this is greatest in the Roncegno water and smallest
in the Cudowa water), must be administered with all the caution with which
we prescribe other arsenic preparations (therefore not upon an empty stom-
ach), in from one to five tablespoonfuls for adults and as many teaspoonfuls
for children; these waters are best administered in milk or Seltzer water.
Besides, preparations of iodin have been administered internally and used
as inunctions over the enlarged glands. They have, however, not proven par-
ticularly serviceable.
More effective are inunctions with potassium soap which, as is well known,
380 PSEUDO-LEUKEMIA
is frequently beneficial in scrofulous glandular tumors. Ordinary green
soap (sapo kalinus venalis) or the somewhat more agreeable fluid potassium
soap (sapo kalinus) may be employed; of the former, according to the size
and number of the enlarged glands, a piece the size of a cherry to that of a
walnut, of the latter a teaspoonful to a tablespoonful and more, may be daily
rubbed into the skin with a pellet of cotton until redness and burning are
produced, when the rubbing is stopped and is not resumed until these irrita-
tive symptoms have disappeared.
Since it is often impossible to determine the nature of the glandular swell-
ing, as I have previously stated, it is well to add to the soap substances which
have a more or less specific action in particular diseases, for example, iodo-
form in certain tuberculous processes (and also in many syphilitic ones).
The potassium in the soap loosens the epidermis and the cement edges in the
skin, and in this way the direct entrance of iodoform into the diseased tissue
is facilitated. An inunction of this kind that I have used in other affections
consists of: Iodoform 5.0, sapo kalinus and lanolin or unguentum adipis lane
or vaselin, 44 20.0.
Eaztirpation of the glands, in so far as they are susceptible to operative
interference, is unquestionably indicated in those cases in which a single gland
or the pressure of several glands in this area causes disturbance or becomes
dangerous. Opinions differ as to whether extirpation is advisable at an early
period when only one or a few glands are slightly affected, since the results of
such early excisions have varied. Some observers believe that extirpation of
the glands, performed once or several times, induces a slower course or a long
cessation of the disease, while others, on the contrary, have observed a more
rapid growth of the glands to follow. The explanation of this variation may
be that frequently, besides the external visible glands that may be reached,
others lie more deeply hidden, or cannot be reached by the knife of the sur-
geon, and the operative removal of the former, perhaps also of others which up
to that time had not been implicated in the morbid processes, causes irritation.
Early extirpation, therefore, can only be looked upon as an experiment
which may meet with success, and this is the more likely the earlier it is
attempted.
Besides this treatment which is especially directed to the glandular swell-
ing we must try by every means to reduce the anemia and improve the gen-
eral condition. Above all, the patients should have the advantage of the most
favorable hygienic conditions, nutritious food, fresh air either in the country
or other suitable climate, as well as such measures as are possible in the indi-
vidual circumstances for stimulating metabolism from the skin, such as fric-
tion, baths, ete.
All this may be most readily secured in properly chosen sanatoria. The
most popular among these, probably on account of their well-known effect
upon scrofulous glandular affections, are the sodium chlorid springs (particu-
larly the stronger salt springs), and especially the iodin- and bromin-containing
salt springs, such as those at Hall in U pper Austria, Krankenheil, Kénigs-
dorff-Jastrzemb, Kreuznach and others. These springs are used for bathing,
for poultices, and, with necessary caution, also for drinking.
BANTYS DISEASE 381
The most useful remedial measures for the latter purpose are tonics and
roborants, and chiefly the preparations of iron and quinin. Arsenic when
properly used has a tonic effect, and so improves the nutrition that if it is
administered internally other remedial agents may be dispensed with, or sim-
ply combined with arsenic. Lately a combination with ferrum cacodylicum
in doses of 0.25-0.38 gram daily has been advised according to the following
prescription: Ferr. cacodyl. 1.0, Aqu. cinnam. 25, of which 20 to 40 drops
are taken three times daily.
I need hardly say that in every dietetic and drug treatment attention to the
digestive organs is of great importance, and if these show any disturbance of
function, amelioration must here be first attempted.
It is also self-evident that febrile conditions or possible complications are
to be treated according to their special indications. [The X-ray treatment of
Hodgkin’s disease seems at this time to promise more than any other. The
number of cases is not large, but the results are often favorable. The technic
is very simple; the affected glands are exposed to the X-ray for as long a
period (every day or every second day) as the skin will stand without sustain-
ing any “blush.” Pressure symptoms due to substernal glands have thus been
very notably relieved.—ED. |
BANTI’S DISEASE
We turn now to the description of the second form of pseudo-leukemia,
the lienal or splenic variety, in which enlargement of the spleen is predomi-
nant or apparently occurs alone, i.e., without glandular enlargement. I say
apparently, for, according to my investigations, the lymph-glands are almost
always implicated. It is true that sometimes the enlargement affects only the
deeper ones, particularly those glands situated in the abdominal cavity, and
therefore recognizable only at autopsy. There are numerous cases, as I have
mentioned previously, in which the spleen and lymph-glands are attacked
simultaneously, and these cases are designated as pseudo-leukemia lymphatico-
lienalis, and constitute a transitional stage between the two other forms.
Aside from the glandular swelling and the course of the disease the elinical
picture in the lienal form scarcely differs from that of the lymphatic form
(Hodgkin’s disease), and the description may consequently be brief.
Besides the enlargement of the spleen, or even before this becomes notice-
able, the earliest symptom is anemia, and Gretsel (Griesinger) has therefore
designated the disease as “splenic anemia.” But this name is not distinctive
for, as later researches have shown, the blood finding does not, or at least not
always, correspond morphologically to that of simple anemia. On the con-
trary, manifold changes, particularly in regard to the number and proportional
relations of the leukocytes, are met with, but never such a decided increase as
in leukemia. At one time the blood may, in fact, resemble simple chronic
anemia, i.e., the number of erythrocytes may be more or less decidedly de-
creased, the hemoglobin to the same degree or even more decidedly diminished,
and the proportion of leukocytes to erythrocytes, although varying not mark-
edly, exceeds normal limits. [The very low color-index has been especially
382 PSEUDO-LEUKEMIA
emphasized by Osler.—Ep.] At other times, with. the same relation of the
erythrocytes and of the hemoglobin, leukopenia is present; that is, there is
a conspicuous diminution of the leukocytes below the lowest normal limits.
In still other cases there is a relative decrease in the polynuclear neutrophilic
leukocytes, which normally make up about three-quarters of the leukocytes.
Sometimes the cells designated as lymphocytes are predominant, i.e., a lym-
phocythemia is present. In conclusion, a blood change is found which in some
respects resembles pernicious anemia; namely, nucleated erythrocytes of nor-
mal or larger size (normoblasts and megaloblasts) are seen, and with this an
increase in the leukocytes, sometimes of the polynuclears, sometimes of the
lymphocytes.
This latter blood composition is observed pre-eminently in infancy, and
has been described by v. Jaksch as anemia infantum pseudoleukemica. This
is a pseudo-leukemia which has special characteristics in the infantile organ-
ism. Normally the infant’s leukocytes are more numerous than those of the
adult, and in the child the lymphocytes also are more profuse, and from the
hyperemic red marrow of the growing bones nucleated young erythrocytes
more readily enter the circulation. These nucleated erythrocytes, according
to our present views, are to be regarded as immature corpuscles.
Other blood lesions such as poikilocytosis, increase of the blood: plaques,
etc., are not characteristic.
We must not expect that the same blood condition will be present in every
case and at all times for, in the first place, these changes arise gradually in the
blood with an increase of the anemia, and probably also with the growth in the
spleen, corresponding to the growth in the glands, as in Hodgkin’s disease.
Thus, in this malady, as in the other form, periods of transitory improvement
in the condition occur and the blood composition improves. Further febrile
conditions may arise under the influence of which the number of leukocytes
may change; for example, a leukopenia may give place to a leukocytosis; or,
again, profuse hemorrhages in the disease may entirely alter the blood picture.
In the splenic form of pseudo-leukemia, certainly in adults, hemorrhages
are even more frequent than in the lymphatic form, especially hemorrhages
from the nose and from the gastro-intestinal canal; but there are also hemor-
rhages from the gums, from the skin, and from the vitreous body of the eye,
ete. [Osler has explained the gastric hemorrhages as due to the inability of
the stomach veins (anastomosing with those of the spleen through the vasa
brevia) to empty themselves on account of the cirrhotic process which forms
part of the changes in the spleen—Ep. ]
The urine is very similar to that of the lymphatic form.
The implication of the liver in splenic pseudo-leukemia is very interest-
ing. In the lymphatic form enlargement of the liver also occurs, due to the
previously mentioned metastatic lymphomata or lymphomatoid formations.
But these lymphomata are rarely of decided extent and rarely give rise to
marked disturbance. In the splenic form, however, the liver is very fre-
quently and conspicuously involved. Banti deserves credit for having first
called attention to the combination of pseudo-leukemic enlargement of the
spleen with cirrhosis of the liver, and for having remarked the causal connec-
BANTI’S DISEASE 383
tion between them; therefore quite properly this combination is designated
as Banti’s disease.
The chief symptom by which cirrhosis of the liver may be recognized is
ascites. Yet this may occur, as I have seen, in pseudo-leukemia in which the
lwer is not attacked, or to but an insignificant extent, so that besides cirrhosis
of the liver, to which Banti refers the ascites in all cases, other causes
may be operative. As such a cause I have mentioned displacement of the
lymph channels in the abdominal cavity by enlarged lymph-glands, which,
especially if combined with an anemic composition of the blood, and perhaps
with stasis due to the marked enlargement of the spleen, may give rise to
ascites. In some cases, disease of the portal vein may possibly be the cause.
[A calcified thrombus of the portal vein has been found by Warthin in two
cases of this disease (splenic anemia).—ED.]
Banti reports that in the disease named after him the intima of the portal
vein from the anastomosis of the splenic veins to the liver has been found
covered with coarse plaques similar to the sclerotic and atheromatous coats
of the aorta. He assumes that toxic substances from the originally diseased
spleen have reached the portal vein through the veins of the spleen, and later
reached the liver, thus causing the pathological changes. In two cases belong-
ing to this category upon which autopsies were held, and in which neither
ascites nor liver cirrhosis was present (which, therefore, did not strictly rep-
resent Banti’s disease), these changes were not found either in the portal vein
or in the splenic vein. They belong perhaps to a more advanced stage of the
disease.
But even if ascites is present the clinical picture deviates in many essential
points from ordinary hepatic cirrhosis, that form known as “ alcoholic liver.”
The enlargement of the spleen in pseudo-leukemia is much greater than in
the latter, and the skin does not show the grayish yellow discoloration which
is so usual in cirrhosis of the liver. On the contrary, it is pale, as in anemia,
provided unusual circumstances do not bring about a darker pigmentation.
For example, Osler has observed in some cases a melanotic discoloration due
to an old malaria. Furthermore, the urine is usually of a different compo-
sition, without bilirubin and urobilin, provided special complications, such as
decided stasis due to ascites and the like, are not present.
We must, however, agree with Banti that in the clinical condition named
after him the enlargement of the spleen is the primary affection and not the
result of enlargement of the liver. In the other cases of spleriic pseudo-leu-
kemia not associated with hepatic cirrhosis, it can no longer be doubted that
' the enlargement of the spleen is the primary affection to which the other
disturbances, particularly the anemia and the abnormal composition of the
blood, may be attributed.
The anatomical condition of the splenic tumor is usually reported as
dependent upon hyperplasia, but microscopic investigation shows variations
which depend upon the extent to which the pulp and the Malpighian bodies
as well as the trabecule are implicated in the hyperplasia. It appears, or so
I conclude from a case observed by me, that in early cases only the tissue of
the pulp is hyperplastic owing to a decided increase of the lymph-cells in the
384 PSEUDO-LEUKEMIA
reticulum. Afterward an enlargement of the Malpighian bodies with an in-
crease in their cells is observed, so that they stand out as grayish white nodules
of the size of a pea, having the characteristics of lymphomata. Finally, with
the lapse of time the connective tissue proliferates, the capsule of the spleen
becomes thickened, the spleen itself hardens and is permeated by more or less
. tense connective tissue strands by which the pulp is more and more obscured
or absorbed. The follicles become thickened and enlarged and gradually lose
their reticular structure and cellular stratification, being changed into tough
fibro-cellular nodules. At last the normal structure of the spleen disappears
to a greater or less degree, and only tough trabecular tissue remains.
In this process, the larger vessels, the arteries, and particularly the veins,
are often found thickened, sometimes also covered with chalk plates, such as
Banti observed in the trunk of the splenic vein in cases complicated with
hepatic cirrhosis.
The cause of the enlargement of the spleen, i.e., the actual cause of the
disease, is unknown. In the relation of the spleen to the blood, which, as I have
already stated, may be compared to that of the lymph-glands to individual
areas of tissue, it may certainly be considered that a deleterious element pres-
ent in the blood exerts an irritation upon the spleen. What the nature of
this irritation is we do not know. Specific bacteria or toxins, which nowadays
so readily come into consideration, have not been found. Much favors the
view that the damage originates in the gastro-intestinal canal, and thence
reaches the blood. The circumstance that digestive disturbances, especially
diarrhea, frequently precede enlargement of the spleen, and the fact that
swelling of the lymph-glands in the abdominal cavity is rarely absent, favor
this hypothesis.
From this point of view the assumption is certainly justified that the dis-
ease of the liver ts not necessarily caused by enlargement of the spleen, but that
it is the independent consequence of the same deleterious process. By this we
do not intend to deny that the abnormally constituted blood which circulates
from the spleen to the liver may cause pathological effects. It may be in con-
sequence of the simultaneous action of both poisons—that of the gastro-intes-
tinal canal and that of the spleen—that the hepatic cirrhosis sometimes devel-
ops very early, at other times hardly at all.
As a contribution to our knowledge of the etiology of pseudo-leukemia, it
must be stated that in a fair proportion of cases the malady develops in the
course of diseases in which enlargement of the spleen or a chronic splenic
tumor already exists, or in the course of which it appears, e.g., in malaria,
syphilis, particularly in that form which occurs in children, hereditary syph-
ilis, and in rickets. The characteristic symptoms of the latter diseases grad-
ually retrograde, while the splenic tumor persists or even increases; anemia
and cachexia become more prominent, and gradually the boundary line between
these maladies and pseudo-leukemia disappears, and it becomes impossible to
say where the one begins and the other ceases.
The character of the blood may in such instances decide the diagnosis,
particularly if the change described by Ehrlich and Pinkus is present—or,
at all events, a relative increase of the lymphocytes with a low count of leuko-
BANTI’S DISEASE 385
cytes such as would exclude leukemia. But I have already mentioned that
a hematological condition of this kind is not always present, even in cases that
are to be strictly considered pseudo-leukemia. In these, another state of the
blood combined with a characteristic enlargement of the spleen is of impor-
tance in the diagnosis, namely, a simple high-graded anemia, i. e., oligocythe-
mia and oligochromemia and this is especially so if leukopenia be also present.
The recognition of splenic enlargement in cases of this kind can hardly be
difficult, for the spleen early attains a size that is scarcely ever seen except in
leukemia. Its lower border may reach anteriorly to the true pelvis, to the
median line and even beyond. The surface is smooth, and upon pressure the
organ is but slightly or not at all painful.
In the differential diagnosis all other hypertrophies of the spleen must be
excluded, and this is usually not difficult, for acute enlargements do not come
into consideration. The chronic enlargements, including tuberculosis and
amyloid degeneration, which are somewhat rare, may be readily recognized,
provided the etiologic factors and the condition of the other organs are con-
sidered. [“ Idiopathic” splenic enlargement with anemia very slight or
absent and no other symptoms at all is at times difficult to separate from some
of the cases in this group.—Ep.] The diagnosis is made with less ease when
ascites is present, not because there is any difficulty in determining the enlarge-
ment of the spleen, but because the question then arises whether hepatic cir-
rhosis is also present, and whether this or the enlarged spleen is the primary
affection, i.e., whether Banti’s disease has or has not developed. Here again
an examination of the blood will aid in the decision provided the above-men-
tioned changes are present. The enlargement of the spleen in primary hepatic
cirrhosis is never so great as in Banti’s disease, and, according to my experi-
ence, the appearance of the skin and the condition of the urine in the latter
affection are not the same as in hepatic cirrhosis.
The course and termination, and therefore the prognosis of splenic pseudo-
leukemia, do not differ greatly in adults from the lymphatic variety. The
condition is different in children. Here not infrequently it is possible to bring
about a decided improvement in the anemia and in the general condition, and
even a diminution in the size of the spleen. I do not know whether or not this
retrogression may be complete, but in cases not too far advanced I believe it
possible. This difference in the nature of the disease in adults and in chil-
dren may depend upon the action of the blood-forming organs, particularly the
bone-marrow, which in children shows a more vigorous function. It is for
this reason that children react more readily to deleterious agencies, and for
this reason also an improvement is more easily brought about in children than
in adults.
In the treatment of this form of pseudo-leukemia the same factors must
guide us as are decisive in the other variety, only that here not the enlarge-
ment of the lymph-glands but that of the spleen is to be combated. Unfor-
tunately drugs have even less power to influence this process than in the former
instance. There are a certain number of so-called “splenic remedies,” but
they owe their reputation chiefly to their efficacy in malaria and in the en-
largement of the spleen dependent upon this disease. Quinin is to be men-
26
386 PSEUDO-LEUKEMIA
tioned first among these drugs, then piperin and eucalyptus. But, even in
cases in which malaria has preceded, they have no effect upon the remaining
splenic tumor; and, besides, these patients have already taken quinin, arsenic
or other remedies to a considerable extent. If not, arsenic in one of the forms
previously mentioned may be employed, at least internally, on account of its
stimulation to metabolism, and perhaps also because of its power in blood pro-
duction. Subcutaneously atoxyl, which has already been mentioned, is espe-
cially worthy of a trial. Parenchymatous injections of arsenic, of carbolic
acid, etc., have been resorted to, but as these are not absolutely harmless, and
are of questionable value, they are not advisable. Inunctions in the splenic
region are useless, nor have I seen any benefit from massage or electricity.
Somewhat more effective, it appears to me, is the application of cold to the
splenic area, particularly in the form of the cold douche, the jet douche after
Fleury, or the fan douche. These are best employed while the patient lies
upon the right side of the body in a warm bath, with the left side of the abdo-
men exposed.
The most certain means of overcoming the splenic tumor and (in so far as
this is considered to be actually the first of the main symptoms of the disease)
to bring about recovery, is splenectomy. But this is neither so easy nor so
harmless as the removal of the enlarged lymph-gland. Adhesions of the tumor
to surrounding organs and marked hemorrhage present great difficulties in
the operation, and endanger the life of the patient. Nevertheless lately,
owing to improvements in technic, extirpation of the spleen has been success-
fully accomplished in pseudo-leukemia, and in a number of cases has brought
about the disappearance of the anemia and of the cachexia; for what length of
time is another question. Of course success is to be expected only when the
disease has not existed for too long a time, and severe sequele, such as cirrho-
sis of the liver, multiple lymph-gland enlargement, etc., have not appeared.
If ascites is present the attempt may be made to prevent its recurrence,
and to bring about a decrease in the size of the spleen, producing a collateral
circulation with the venous system of the body, by attaching the omentum and
the spleen to the abdominal wall (after Talma or Schiassi).
Extirpation of the spleen in children is less likely to be considered, for
in them, as mentioned, the hygienic, dietetic and drug treatments are more
effectual. Iodin and iron have proven serviceable, as well as arsenic; baths
and a change of climate are to be recommended as in the lymphatic form.
The same treatment is of course to be employed in adults.
LITERATURE
Askanazy, Ziegler’s Beitr. zur path. Anatomie, Jena, 1888.
Bonfils, Société méd. d’observation, Paris, 1856.
G. Banti, “Lo Sperimentale,” 1894, 1895; Ziegler’s Beitr. zur allg. Path., etc., 1898,
Xxiv.
Clarke, Brit. Med. Journ., 1901, ii, p. 701.
J. Cohnheim, Virchow’s Arch., xxiii.
W. Ebstein, Berl. klin. Wochenschrijt, 1887.
LITERATURE 387
P. Ehrlich and F. Pinkus in Nothnagel’s Spec. Path., 1901, vii, i.
Fischer, Arch. f. klin. Chir., 1897, lv.
Freudweiler, Deutsches Archiv f. klin. Med., 1897, lxiv.
Gretsel, Berl. klin. Wochenschrijt, 1866, Nr. 20.
E. Grawitz, Klin. Pathologie des Blutes, Berlin, 1902, 2 Aufl., p. 351 ff.
R. v. Jaksch, Wiener klin. Wochenschr., 1889, Nr. 22, 23.
A. Jolles, Zeitschr. f. klin. Med., 1898, xxxiv.
Kundrat, Wiener klin. Wochenschr., 1893, Nr. 12, 13.
J. H. Musser, Transactions of the Association of Amer. Physicians, 1901.
Osler, Amer. Journ. of Med. Sc., 1900, January.
Pel, Berliner klin. Wochenschr., 1885, 1 und 1887, 35.
M. Reed, Johns Hopkins Hosp. Reports, x, 1902, Nos. 3-5.
W. Schild, Berliner klin. Wochenschr., 1902, Nr. 13.
H. Senator, Berliner klin. Wochenschr., 1901, Nr. 46.
Sternberg, Centralbl. f. d. Grenzgeb. Med. u. Chir., 1899, ii.
Wilks, Guy’s Hosp. Reports, 1856, ii.
Talma, Berliner klin. Wochenschr., 1898, Nr. 38.
B. Schiassi, “Un nuovo trattamento del Morbo del Banti,” Bologna, 1902.
THE HEMORRHAGIC DIATHESES
By M. LITTEN, Berun
THERE is a group of diseases in which the essential symptom is a tendency
to more or less extensive hemorrhage, which distributes itself over various
organs and thus becomes dangerous to life.
We designate this tendency to external and internal aes which
probably depend upon a change in the blood or in the blood-vessels, or in both,
as the hemorrhagic diathesis. The diseases which belong to this group, which
in some cases resemble one another so closely that it has sometimes been
thought possible to combine them as one disease, were formerly designated
“scurvy.” But to-day there is much diversity of opinion as to how far this
division is justified.
In accordance with the present state of our knowledge, the following
groups will be considered separately: 1. Scurvy; 2. Hemophilia; 3. Morbus
maculosus Werlhofii. But even with these subdivisions it must be empha-
sized that our knowledge does not often permit a sharp separation; the boun-
daries are partly artificial, being neither etiologically nor pathologico-anatom-
ically defined with accuracy.
SCURVY
By scurvy we understand a general disturbance of nutrition which rarely
occurs sporadically but usually epidemically, and almost always under the in-
fluence of unfavorable, unhygienic circumstances, particularly that of improper
food; it is usually of insidious onset and slow course, and may terminate either
in complete recovery or in death.
The disease is characterized by a severe general cachexia and by a series of
local disturbances chiefly due to a transitory hemorrhagic diathesis; this may
present symptoms that completely coincide with those of hemophilia, of pur-
pura hemorrhagica, or purpura rheumatica, but is sharply differentiated from
the first by the fact that the changes are hereditary in the former affection
and permanently present in the individual, while in the latter and in scurvy
we are always dealing with an acquired disease which is generally transitory,
and terminates in recovery or death, although frequently many relapses take
place.
HISTORY
The history of scurvy is exceedingly interesting and important, as it dem-
onstrates most forcibly the progress of hygiene and of scientific investigation.
388
SCURVY 389
When, after the discovery of America, shipping acquired new interest,
when voyages which formerly were limited to the coasts of countries were
extended over the open, wide sea, the brave seafaring men were confronted
with new and quite peculiar conditions of life. Cut off for many months
from land, exposed to the mercy of the winds and the waves, limited to the
narrow confines of their ship, where they huddled together in large numbers,
often exposed to great hardship, in the choice of food and drink they were
entirely restricted to that brought from thcir homes, and particularly to such
food as could be kept for a long time. Frequently they were compelled to
subsist on food more or less tainted. It is obvious that such conditions would
inevitably result in disease; and, great and brilliant as are the discoveries of
that time, the great and hideous figure of scurvy, the disease which developed
from these voyages of discovery, and which caused the failure of many expedi-
tions, cannot be forgotten.
In the year 1498, when Vasco de Gama undertook his celebrated voyage
around the Cape of Good Hope, the crew was attacked by scurvy, and of 160
persons he lost in a short time more than one-third. We know well the deci-
mating character of the disease which occurred in the expedition of Cartier
in 1535, and in those of v. Monts, Pontgrave and Poutrincourt to Canada
toward the end of the sixteenth century; in the French expedition of Dellon
to India; in the journey of the English fleet under Lord Anson around the
world (1740-1744), in which voyage the disease recurred repeatedly in various
latitudes, and 380 out of 500 men succumbed to the malady; in the North
Polar expedition of Ellis (1746-1747) in search of the northwest passage to
Hudson Bay; in the fleet of the English admiral, Gleary, who in 1780 re-
turned with 2,400 scurvy patients, and in other expeditions.
The reports of these expeditions are so definite that there can be no doubt
of the identity of the disease. We have less information regarding the occur-
rence of scurvy upon land, the first reliable report of which dated about a
hundred years later, at which time the name scurvy or “ scharbock” for the
first time appeared. Our knowledge of the occurrence of the disease in an-
tiquity is very limited, although it may be assumed that the peculiar condi-
tions which favored the appearance of the pest, as later investigation has
taught, must also have produced scurvy in earlier epochs.
The best historical accounts of scurvy we owe to August Hirsch, whose
description we have mainly followed.
He succeeded, however, in finding in old medical writings only one form
of the disease described which so far corresponds to the picture of scurvy
that their identity may be assumed; namely, in the Hippocratic collec-
tion, an affection described as eideos aiparirys. Although the disease des-
ignated as SwAqjves peyddae [Magni lienes] by Hippocrates, Areteus, Cel-
sus, Czlius, Aurelianus, Paulus Afgineta, Avicenna and others has been
by some authorities taken for scurvy, Hirsch demonstrates that this disease was
malaria. Pliny mentions two diseases, stomatokaké and skalotyrbé, the first
in particular running its course with an affection of the mouth resembling
scurvy. :
But it is quite as likely that this was “stomatite ulcéreuse,’
> an army dis-
390 THE HEMORRHAGIC DIATHESES
ease, as the herba Britannica was used for stomatokaké and skalotyrbé. Some
have considered oscedo (a disease mentioned by Marcellus) as probably scurvy,
although the nature of this affection is otherwise not known, and we do not
know what plant was meant by herba Britannica.
The occurrence of scurvy in the Middle Ages is quite certain. Several
descriptions exist of decimating diseases which followed the massing of great
armies, as during sieges, etc.
Thus, Jacques de Vitry reports the outbreak in 1218 and 1219, in the
Army of the Crusaders while besieging Damiette, of a disease in the course
of which the gums became gangrenous, the extremities painful, the tibia later
turned frightfully black, and the patients were unable to eat; thus the disease
ran its course, the patients suffering intense pain from which most of them
were only relieved by death. Joinville explicitly describes a similar disease
which appeared in the army of Louis IX while besieging Cairo in 1250. If
we can conclude from these descriptions that the disease was scurvy, we may
also assume that this disease had certainly occurred previously.
Cordus was the first to use the term “scharbock” for this malady. But
Hirsch believes it questionable whether he himself ever observed the disease.
On the other hand, quite accurate descriptions are given by Olaus, Magnus,
Echthius, Ronsseus, Wierus, Dodoneus, and Bruceus. Most of these ac-
counts refer to epidemics that occurred in northern countries bordering on
the sea, in North Germany, Scandinavia, and The Netherlands. From these
descriptions it also appears that the disease usually occurred under circum-
stances of great stress, such as famine, war, sieges or other unfavorable social
conditions. Descriptions of certain diseases as scurvy, to which their symp-
toms show only a partial similarity, are unreliable. This is the case with an
epidemic which is said to have occurred in the year 1486 in Saxony, Thuringia,
and some neighboring countries.
The earliest description of scurvy by Fabricius, rector of the princely
school of Meissen, is found at the beginning of the eighteenth century, but
Hirsch proves that the condition was ergotism, the nature of which was still
unknown to physicians of that time. Medical history of the seventeenth cen-
tury, and especially that of the eighteenth, inclines us to believe that during
this entire period Europe was afflicted with seurvy which was more prevalent
than any other disease. The fact that during so long a period of time a single
disease should have predominated to such a marked extent is at once sus-
picious, and close investigation has shown that the exact opposite was really
the case; that persons who had rarely seen scurvy declared almost everything
to be scurvy, and thus brought about tremendous confusion in medical sci-
ence. The cause of this must be ascribed to Eugalenus, whose book, “ De
morbo scorbuto liber,” which appeared in the year 1720, Hirsch declared to
be patchwork which could not be equalled in medical literature, either in the
ignorance of its author, or in the results which it nevertheless achieved, since
for more than a century it remained the canon regarding scurvy, and the best
physicians of the age were unable to free themselves from its influence. The
book made a great sensation, particularly the teaching that all children were
born with a predisposition to scurvy (Drawitz), and that the cause and root
SCURVY 391
of every disease could be recognized in scurvy (Bontekoe). Not even Boer-
haave was able to rise entirely superior to these views, but he was sufficiently
critical to state that the disease had, during his time, appeared much more
rarely in The Netherlands. Keen and earnest critics were not lacking who
not only were opposed to the scurvy delusion, but went to the other extreme,
and denied absolutely the existence of scurvy. Sydenham with others pro-
tested against this, and asserted the rare occurrence of scurvy, while Kramer
furnished an accurate description of cases actually observed by him in which
he also declared that the disease was least known by those who most frequently
described it. In the year 1752 Lind’s masterly treatise appeared, which up to
the present time remains one of the best descriptions of scurvy; in this he
compared the first accounts of the disease (which he characterized as chaos)
with the later views maintained regarding the affection, and anew so accurately
portrayed the clinical picture that it subsequently admitted of little change.
Notwithstanding Lind’s proof that scurvy was not an infrequent disease
in the previous century, the fact still remains that it occurred far more fre-
quently in the period in which Lind wrote than in our time. Hirsch has
zealously investigated these epidemics, and collected the records of all others
occurring on land, from 1556 to 1877, in so far as they have borne the test of
scientific criticism.
Although we must admit that this compilation is not a complete history of
outbreaks of scurvy, since not every pandemic, and not nearly all of those lim-
ited to a small area, or occurring in a single institution, have been described,
still it enables us to draw conclusions regarding the frequency of the disease,
its geographical distribution, and the probable causes of its development. In
all 143 epidemics are mentioned, of which two occurred in the sixteenth, four
in the seventeenth, thirty-three in the eighteenth, and one hundred and four
in the nineteenth century. These figures make it strikingly apparent that the
views of Eugalenus and his adherents were exaggerated.
Of the epidemics in the course of the previous century, that of Paris is
to be particularly mentioned ; it occurred in 1870-71 during the siege of the
city, and spread owing to the scarcity of food. Among the French troops
who, in 1871, were held as prisoners of war in Germany, an epidemic occurred
in Ingolstadt which, however, according to Déring, did not attain great dimen-
sions; among 10,000 prisoners only 159 were attacked. In the Milbank Peni-
tentiary in London scurvy prevailed in 1824 and 1840; also in the prison in
Prague in 1831,1836 and 1842; in the workhouse of Ludwigsburg in Wirttem-
berg in four successive years, from 1850 to 1853, and in the prison of the same
city, in 1857. The last epidemic in Germany worth mentioning occurred in
1875-76 in a penal institution in the city of Moringen; the last in France in
the spring of 1877 in the prison at Mazas. Epidemics occur more frequently
in Russia, even to-day, usually under the influence of extraordinary circum-
stances, suchas crop failure, famine, or other social evil.
The majority of the epidemics in Hirsch’s tabulations are found to have
occurred in Russia, and this country also furnishes interesting details regard-
ing the geographic distribution of the disease. Russia with 35 epidemics 1s
followed by Germany with 19 epidemics, France with 15, Sweden, Norway
392 THE HEMORRHAGIC DIATHESES
and Denmark with 14, and England with 11. The other European countries
present much smaller figures. Of foreign countries India heads the list with
14 epidemics, then follows North America with 17, and Algiers with 7. The
disease may even to-day be looked upon as endemic in Russia, and occasionally
it shows extraordinarily wide distribution, as is evident from the reports of
the Obuchow Hospital in St. Petersburg.
In the great epidemic of 1849 which distributed itself over a wide area of
the Russian Empire, Krebel reports that among 260,444 persons 60,958 died.
In Asiatic Russia also, especially along the coast of the Arctic Sea, in the
Siberian-Chinese boundary land, and upon the peninsula of Kamchatka, scurvy
is frequently seen to-day. In northwestern Europe scurvy never played a
prominent réle, and although, for example, a famine with scurvy appeared in
Iceland in the years 1836-37, the scurvy did not assume an endemic character.
The conditions are the same in other European countries; only now and then
localized epidemics are reported from prisons. Epidemics have prevailed ex-
tensively in Algiers without assuming a distinctly endemic character; scurvy
appeared among the French troops in Egypt in 1801; in Abyssinia the disease
has been observed almost exclusively in travellers, the natives being spared,
although they usually live under decidedly more unfavorable and insanitary
conditions than the strangers, and these conditions are powerful factors in the
distribution of the disease. On the other hand, in the Eastern Soudan and
in the entire rain zone of East Africa the disease is said to occur frequently
among natives as well as strangers. In South Africa, on the contrary, the
disease is reported to be quite unknown among the negroes.
In Asia, India in particular is subject to the disease; a great number of
epidemics there are reported; these occurred chiefly among the poorer popula-
tion, and were widespread. Upon the coast of Dschemenia (Arabia) the dis-
ease is endemic; in 1839 the English troops in Aden were attacked by it; in
China, especially in the northern provinces in which the population live in a
squalor elsewhere unequalled, epidemics are not rare; also among the poorer
population in Japan scurvy is quite frequent.
In Australia, in numerous expeditions to the interior which were under-
taken for purposes of discovery, the affection has been very serious, and lately
it has appeared endemically among the shepherds upon the wide grazing plains
of that country.
In the southern parts of America the disease appears to be unknown,
and in the north the natives show no susceptibility to the affection. The epi-
demics which have been reported occurred among United States troops who
were exposed to great privations at outlying stations, in lumber camps in the
interior of Canada, but particularly in California during the gold fever, among
adventurers who had collected from all parts of the earth and who lived under
circumstances of great privation. These reports now have renewed interest
because great numbers of people have rushed to the gold fields of Alaska,
where, after Greenland, scurvy is more prone to occur than in any country of
the Arctic regions, and where all the conditions are favorable for the outbreak
of an epidemic.
Among the members of the well-known Nansen expedition, from July,
SCURVY 393
1893, to August, 1896, which was one of the most important voyages of scien-
tific investigation of all times, not a single case of this disease occurred.
Later, when considering the prophylaxis, we shall refer to the important meas-
ures by which the celebrated leader prevented an outbreak of the disease
which might have brought the expedition to an end.
An important American investigation of scurvy in children, in the year
1898 (the American Pediatric Society’s Collective Investigation of Infantile
Scurvy in North America), has given the following results: Of 372 cases,
367 occurred in the white, 4 in the black race, and 1 in the Chinese; 51 per cent.
were males, 49 per cent. were females. The greatest number of cases occurred
between the seventh and fourteenth months. We shall refer to this again.
ETIOLOGY
In spite of many endeavors it has been impossible to discover a cause
which can be considered at all reliable; all search for the pathogenic agent
of the disease, though it is often assumed to be of miasmatic, or even of
infectious origin, has been without result.
The question of food remains the alpha and the omega in the etiology of
scurvy, as in so far as the food supply is influenced by the conditions of weather
and the seasons the latter will always have a more or less decisive influence in
the production of the disease.
It is generally assumed that improper nutrition in a certain direction is
pre-eminently responsible for the affection, particularly a deficiency of vege-
table acid potash in the daily food. It has repeatedly been noted that during
long sea voyages in which salted or pickled meat exclusively was consumed
scurvy appeared. As the ash of pickled meat contains much less potassium
than that of fresh meat, an attempt has been made to ascribe scurvy to the
deficient intake of potassium, but perhaps quite improperly so, for in prisons
where the diet consists almost exclusively of vegetables rich in potassium,
scurvy is not infrequently noted. On the other hand, it has been remarked
that many races in the far north are often compelled for months continuously
to live on pickled meat or salted fish without being attacked by scurvy.
Later investigations, in which an amelioration of the scorbutic affection
is said to have followed the addition of fat to the diet, appear to indicate
that scurvy is due rather to a diet limited in variety and deficient in fat than
to a lessened amount of potassium salts in the food.
' Besides this, a number of other causes are considered to be active: Gen-
eral deficiency in food, the close huddling of many persons in cramped, unclean
and wet dwellings, excessive corporeal labor and psychical depression, and,
above all, the ingestion of tainted food (ptomain poisoning).
In considering more minutely the factors which are mentioned, we must
first consider the view that scurvy is a miasmatic or infectious disease.
The first experimental investigations of this subject were made by Murri
in Bologna, who injected subcutaneously rabbits with blood taken from scurvy
patients. A rise in temperature and small petechie developed in the lobes
of the ears of these animals. Upon killing the animals hemorrhages were
394 THE HEMORRHAGIC DIATHESES
also found in the serous membranes and in the internal organs. Murri quite
properly avoids drawing conclusions regarding the transmissibility of the dis-
ease from these results. Analogous findings were obtained by Contt and
Mari in similar experiments. Further investigations resulted in the cultiva-
tion of the pathogenic agent of the disease from the blood of scurvy patients.
Wieruszskij obtained from scurvy blood in numerous cultures on various
media, partly negative results and partly well-known bacteria, so that he con-
cluded that scurvy could not be regarded as an infectious disease due to micro-
organisms which could be found in the blood. Babes conducted further ex-
periments. He started with the presumption that scurvy is an infectious
disease, and that the point of entrance for the pathogenic agent must be
sought for in the mucous membrane of the alveolar processes. He therefore
extirpated small portions of the gums of scurvy patients, and in the prepara-
tions, which had been hardened in alcohol he demonstrated a definite bacillus
with which he infected rabbits by intravenous injection. Hemorrhagic foci
occurred in various organs in which the bacillus was also found. Babes de-
scribes the bacillus as an elongated, bent organism, pointed at the ends, about
0.3 » wide and of about the same length, often forming waving threads twice
as long and of various lengths, somewhat thinner and decidedly longer than
the cholera bacillus. The youngest specimens are double structures, and show
the tendency to form metachromatic bodies which stain dark violet with
methylene-blue, and are thicker than the rods. The rods themselves stain
only weakly with rubin, and do not stain according to Gram. The bacilli
resemble the bacillus e described by Miller, and are probably always present
in the oral cavity. The investigations of Babes certainly require further
confirmation, for they are assuredly open to doubt. He himself admits that he
has not found the pathogenic agent of scurvy, but only speaks of a “ bacillus
that causes gingivitis and hemorrhages in scurvy.” The findings of Rosenell
and Borntrager are quite unreliable; the latter does not even consider the
cocci found by him as the pathogenic agent of sctirvy.
Jackson and Harley’ regard scurvy as a ptomain poisoning. To prove
this view experimentally they have attempted to produce scurvy in monkeys
by feeding them with tainted meat. Some of the animals had rice and maize
given to them with fresh meat; a second group was fed on the same food
except that the meat was tainted by prolonged standing; a third group ate
the same food as the second with the addition of fresh fruits. Prolonged
observation of the animals gave the following results: The first group of ani-
mals showed no characteristic symptoms except slow emaciation and diarrhea
which appeared after some time. The monkeys of the second group showed
decided diminution in strength, and in the majority of them there was a
muco-hemorrhagic diarrhea as well as, in some of them, spongy, bleeding, and
ulcerative gums. In two of these animals the blood examination revealed a
decided decrease of hemoglobin with a slight decrease in the number of erythro-
cytes and marked leukocytosis; a decrease of specific gravity dependent par-
ticularly upon a diminution of proteids; increase of fibrin and. of coagulabil-
1“ An Experimental Inquiry into Scurvy.” Lancet, April 28, 1900.
SCURVY 3905
ity; therefore, in the main, a picture which resembled the anemia of human
scurvy. The authors mentioned, therefore, believed themselves justified in de-
claring the disease of the monkeys to be scurvy, although the autopsies estab-
lished no proof. In the third group the addition of fresh fruits but slightly
influenced the disease of the animals. These investigations, although requir-
ing further demonstration, may be looked upon as proof that contaminated
meat has deleterious effects even in monkeys and as confirmation of the prac-
tical experience that only the intake of fresh meat can prevent the outbreak
of scurvy (compare prophylaxis). ,
These investigations in connection with recently expressed views as to the
importance of oral affections in the development of pernicious anemia (?) led”
Home * to assume that an affection of the gums is the origin of scurvy. He
believes that microérganisms still unknown (which may develop from tainted
food) infect the digestive tract, first producing a disease of the gums, and
then an anemia which leads to hemorrhages and ulceration. Outbreaks of
scurvy occurring under circumstances which preclude cleanliness of the oral
cavity are in conformity with this theory.
Turner,? according to the data gathered by him during the great scurvy
epidemic in the eastern provinces of Russia during the year 1899, believes
scurvy to be due to a specific pathogenic agent which is still unknown, and to
be an infectious disease which is transmissible by contagion. In this he rea-
sons only from a clinical standpoint, whereas bacteriologic investigations in
this epidemic have given no positive results. The foundations for his belief
that the disease results from infection and not from errors in diet are: 1. The
epidemic character of the disease; 2. Its appearance in definite localities while
neighboring districts or those with which there is but slight communication
remain free; 3. The frequency of the disease among the rich; 4. The com-
mon occurrence of the disease in persons who are in daily contact with the
patients. He relates his experience with these conditions in a collection of
villages in the Government of Kazan which are populated by various races
(Russians, Tartars, Tchuktchis), living isolated from each other. While the
Russian villages remained almost free from the disease, the villages in which
there was but little communication with other races showed many cases of the
affection, particularly among the rich Tartar population. But in this region,
a village in which very poor heathen Tchuktchis lived entirely isolated re-
mained uninfected. The fact that the Tartars and their relatives ate salted
meat almost exclusively and no vegetables is, in his opinion, not proof to the
contrary. He lays the greatest stress upon the cases in which the disease was
contracted through nursing; among eight nurses who were active there, four
were attacked, and even the author himself had a mild form of the disease.
The previously mentioned collective American Report shows that so-called
infantile scurvy must be regarded as the consequence of a chronic intoxica-
tion (chronic ptomain poisoning) produced by unsuitable food, for which
1“ The Etiology of Scurvy.” Lancet, August 4, 1890.
2“ Le Scorbut est-il une maladie infectieuse ou contagieuse?” Arch. génér. de Méd.,
Aofit, 1900,
396 THE HEMORRHAGIC DIATHESES
intestinal fermentative processes have prepared the way. In 167 of 372 chil-
dren in the first year of life, scurvy was preceded by another disease, usually
disturbance of the digestive organs. The nutrition prior to the appearance
of scurvy had consisted in 10 children of breast milk exclusively, in 4 of unster-
ilized, in 68 of sterilized, milk, and in the remainder of artificial foods.
We shall now consider what other factors may also be regarded as causes
of this disease.
It is certain that age and sex do not play a réle in scurvy, although it has
been erroneously maintained that in single epidemics particularly persons of
a definite age, or of one sex, have been attacked (for example, according to
Fauvel, in the Salpetriére in Paris in 1847 only old women had the disease).
Scurvy occurs more frequently in men than in women; the reason for this
is quite obvious, for it is men who are chiefly exposed to the causes of the
disease.
The same circumstances make it apparent why the disease usually appears
during middle life, but no age can be said to be exempt, as the disease has
been noted in the aged, occurring epidemically, and also in foundling asylums
which were improperly conducted. The so-called infantile scurvy occurs in
nurslings in the first year of life, particularly in the ninth and tenth months;
it has so far been impossible to determine that any particular variety of food
is the cause; breast-fed children are affected as well as those brought up on
sterilized cow’s milk or artificial foods. It has lately been maintained of
Barlow’s disease that milk which has been cooked too long, or that which has
been subjected to too high a temperature, may be the cause. Those who adhere
to this view may easily assign the same cause for infantile scurvy.
It has been shown in most scurvy epidemics that individual predisposition
plays a certain réle as well as the constitution of the patient. It is unques-
tionable that persons who have recently recovered from other diseases, or are
still suffering from them, are particularly liable to an attack of scurvy. As
predisposing diseases we may mention malaria, dysentery, enteric fever, tuber-
culosis, trauma as well as syphilis, especially after a very active mercurial
treatment (Krebel). It is needless to enumerate all of the predisposing dis-
eases, but I should like to point out that I have repeatedly observed isolated
cases of severe scurvy in immediate connection with influenza. Quite recently,
too, I treated three cases of the severest form of scurvy, two fatal cases in
female children of thirteen and fifteen years, in whom the disease was con-
nected with measles and tuberculosis, the third case in a diabetic aged sixty-
four. Moreover, I should like to emphasize that occasionally cases of scurvy
with very extensive cutaneous hemorrhages and intense oral implication occur
in absolutely healthy and well-nourished individuals, living under the most
favorable circumstances, in whom not one of the recognized causes can come
into question at all. Such obscure and entirely incomprehensible cases con-
vince us that up to the present time we have no absolute knowledge regarding
the cause of the disease ; they make it probable, however, that we should consider
the view, sometimes expressed and constantly rejected, that predisposition to
scurvy may be hereditary, even though to-day a discussion of this question
does not appear to be timely. The facts mentioned have nevertheless been
SCURVY 397
proven beyond doubt, and I could cite other typical and convincing cases
from my own experience.
That a particular climate cannot be considered etiologically is evident
from the geographical distribution of the disease. Great stress has been laid
upon the prevalence of damp, cold weather during the time of epidemics, yet
it appears from numerous communications that in winter and in summer, with
a moist as well as with a dry air, the disease has been widely distributed. The
conditions of the sotl have little absolute importance.
According to our present knowledge the disease appears to be induced by
unhygienic, above all by improper alimentary, conditions. The enumeration
of these ‘and the history of the disease show that by far the greatest number
of epidemics have occurred upon long sea voyages, in camps, in besieged for-
tresses, in barracks, in prisons, in almshouses, in foundling asylums, ete.
Under such circumstances a great number of injurious factors act conjointly,
and it is a question to which of these the greatest importance is to be attached.
Besides insufficient clothing, contaminated air as the result of over-crowding of
rooms, and other influences that take part in the etiology of the disease, there
is great unanimity among observers of all times and countries as to the decided
influence of faulty nutrition in the causation of scurvy. However, the views
diverge widely as to what errors in diet are most important. Scurvy has sel-
dom occurred after a famine, although very frequently after a failure of crops.
On the contrary, it has been attributed to the almost exclusive use of salt
meat; this was the prevailing opinion before modern methods of preserving
made it possible to supply better food to ships, and at a period when sea voyages
were much longer than at present, so that a crew for months at a time sub-
sisted exclusively on meat which had been salted. Many races in the far
north, however, year in and year out, live almost wholly upon salt meat and
fish, and in spite of this scurvy is almost unknown among them; numerous
observers, too, have reported epidemics in which there was absolutely no de-
ficiency of fresh meat. The lack of fresh water has also been mentioned, but
only in isolated cases (the report of Beckler of the expedition of Burke to the
interior of Australia in 1861).
The number of observations showing the importance of a deficiency of
fresh vegetables in the food is almost overwhelming. We regret we cannot
enter into the details of these, but refer the reader to Hirsch, who, in a “ short ”
compilation to which he devotes many pages, relates the full particulars.
We shall only briefly state that Bachstrom was the first to point out the
influence of a deficiency of fresh vegetables in the food. Lee tells us that
the severe epidemic in 1823 in the south of Russia began when great swarms
of grasshoppers devastated the fields. Almost all the reports of the epidemic
of scurvy during the siege of Paris in 1870-71 agree in stating that it devel-
oped only when the supply of fresh vegetables, especially of potatoes, was ex-
hausted, in spite of the unhygienic and evil social conditions previously ex-
istent.
Delpech cites the case of a wine merchant, aged forty-five, who was attacked
by scurvy although living in easy circumstances, in a sanitary, dry, and well-
heated house, and partaking plentifully of fresh meat, yet in his dietary no
398 THE HEMORRHAGIC DIATHESES
fresh vegetables were found. He recovered on eating vegetables and juicy
fruits. We can rarely prove the post hoc, propter hoc with such certainty as
here, where the eating of fresh vegetables, particularly those belonging to
definite categories, is the best preventive, and in an existing scurvy is the best
remedy.
The fact that certain vegetables, above all potatoes, have such a positive
action caused Garrod to note that potatoes in particular contain a great amount
of potassium carbonate. He then examined other foods to ascertain the
amount of potassium carbonate (potash) which they contained. According to
him they contain in one ounce (= about 30 grams) as follows:
Potatoes, large (cooked), (1 gr. = about 0.06 gram).........- 1.875 grains
Potatoes, small (raw)....cceceecere eee rece ee eeeeseneences 1.310 “
Lime juice ..... ce cece ccc eee ce erence eee ee eee e ence reeees .852 grain
Lemon juice... ...ccecec ccc e teen cece ence eee eeenenenencee 846
Oranges (UNTIPC).... cece eee cern erence eee t etree eee eneeeee 675
Mutton (cooked)......ceeec eect eee eee e ence eee teeneeeees 673
Beef (raw)... cecceec eee e cree eect eee eeeeeee creer ceeeees 599“
Meat, pickled (slightly salted)..........sseeeeeer errr eeeeee 872
PeaSisos ss cea sawisein steeds se age ee ttm aeny 06 MRT STTN OEE TE SE 529
Beef (salted)... ...ceccen cece e eee enc ceeeeee reer eeeeetetes 394“
(0) <0 00): .333
Wheat bread........ 2. cece cece eee e cece eeeeee genes 258
Cheese (Holland).........020ce eee e eee eee eee n ene teeeeene .230 0
Wheat flour (the best)....... 0... cece eee reece ec ee eee eee 1000“
OER, cesansctranareileccasin avec ontuevnaiaras aie gee REASON OOTE EDS 054“
FRAC Gis 2 ceehvsamatppwendacedanivie Sarva ovens * ESE POMS eae 010.
In consequence of these investigations Garrod supposes that a too slight
intake of acid vegetable potassium is the primal cause of scurvy, and cele-
brated authors, above all J. v. Liebig and Hirsch, coincide with him.
The part that the potato plays in regard to scurvy may be recognized from
the fact of the decrease of the disease with the increase of potato culture. How
much the cultivation of vegetables was neglected in former times is shown by
Hirsch’s statement that Katharine of Arragon, the wife of Henry VIII, in
order to obtain a salad, was obliged to send her gardener to The Netherlands
for the material.
But scurvy has not developed exclusively where there was a deficiency in
vegetables, and particularly those rich in potash. Hirsch relates a great
number of examples confirmatory of this. Indeed no one will now maintain
that other causes are no longer to be considered; on the contrary, the excep-
tions prove that a great predisposing importance may be attached to them.
We may perhaps suppose that in the above-mentioned exceptions sufficient
potassium was consumed in the food, but for some reason, perhaps as the
result of other deleterious causes, the organism was unable to assimilate it.
Bunge believes that a cause may be found in the immoderate and extensive
use of salted meat, for the reason that in pickling the meat the salts and also
the potassium are extracted from it.
A. E. Wright * had previously expressed the opinion that the disease de-
1“ On the Pathology and Therapeutics of Scurvy.” Lancet, August 25, 1900.
SCURVY 399
pends upon a kind of acid intoxication, owing to the fact that the diet which
experience shows is a cause of scurvy contains a great excess of mineral acids
in comparison with the bases. This agrees with the fact that antiscorbutic
remedies in general contain a superfluous amount of bases in comparison to
mineral acids. In conformity with this view the readily oxidizable salts con-
tained in organic acids would be particularly adapted to the prophylaxis and
therapy of the disease. Wright tested this in 7 cases of scurvy (for the most
part in soldiers during the siege of Ladysmith). He gave appropriate salts,
particularly sodium lactate (also acetates, carbonates and oxalates), and tested
simultaneously the alkalinity of the blood by a method which he proposed, now
known as the “hemoalkalimetric.” In all of these cases the alkalinity of the
blood was at the onset very low; and by this treatment an increase almost or
quite to the normal occurred remarkably soon in all (with the exception of a
fatal case) and at the same time a retardation of the other symptoms of the
disease. These results confirm the view that there is an acid intoxication in
scurvy.
However fascinating the potassium theory may be, it is by no means abso-
lutely proven, and it does not contradict the view that scurvy may, in spite of
this, be an infectious disease. Scurvy may perhaps be assumed to be an infec-
tious disease of a non-contagious nature produced by a microérganism which
finds in a body deficient in potassium a favorable culture medium for its
development.
PATHOLOGICAL ANATOMY
The cadavers are characterized usually by only a slight degree of post
mortem rigidity, and by the appearance of numerous livid areas. There is
also a tendency to rapid cadaverous alterations. The various cutaneous hem-
orrhages present during life remain distinctly visible after death. The lower
extremities are frequently edematous. Upon microscopic investigation of the
hemorrhagic areas we note that in the smaller (petechie) the point of exit
of the blood is usually the capillary network in the area surrounding the hair
follicle; the larger hemorrhages (suggillations and ecchymoses) originate
quite differently from superficial or deeper layers of the corium according to
their seat and their extent. The erythrocytes which have exuded show all
stages of decolorization and of decomposition. The surrounding tissue is per-
meated by hemoglobin of various colors.
As the cause of the hardenings and ecchymoses in the subcutaneous con-
nective tissue and in the muscles, various infiltrations of blood are found,
partly diffuse, in part sharply demarcated, and, according to the time of their
appearance, of different colors and consistence. In the old foci where the
tissues are not yet regenerated, instead of the fibrin coagula we find tough
cicatricial masses of connective tissue in the surroundings of which the mus-
cular tissue is partly rigid, partly atrophic, and the tendons either to a great
extent adherent to the muscles or so hardened that movement is impossible.
In this way ankylosis and deformities occur, such as club-foot, which will be
discussed later. In the cavity of the joints a serous or even hemorrhagic effu-
sion is occasionally found. The walls are frequently unchanged. If, how-
400 THE HEMORRHAGIC DIATHESES
ever, hemorrhages have occurred, more or less extensive ulcerations of the cap-
sule of the joint, hemorrhagic effusions between the bones and the cartilage,
and hemorrhagic softening of the epiphyses are noted. Corresponding to the
clinical symptoms, we find between the periosteum and bones effusions of blood
in different stages of coagulation or decomposition, ulceration of the periosteum,
wasting and even suppuration of the cartilage of the joint, and necrotic changes
in the bones. Sometimes the insertions of the muscles are loosened by these.
In the interior of the bone also, particularly in the spongiosa, hemorrhagic
effusions take place.
In the bone-marrow lymphoid transformation has not infrequently been
observed.
In infantile scurvy an epiphyseal separation is occasionally observed, and
in about 45 per cent. of the cases rickets also is present.
Very important changes occur in the digestive tract. The mucous mem-
brane of the mouth, except that of the gums, is but slightly altered; now and
then hemorrhagic areas and erosions are noted. The gums are invariably
swollen, moderately reddened, and completely permeated by red blood-corpus-
cles. In older cases there is a coarse thickening as the result of proliferation
of the connective tissue. Frequently the surface is ulcerated or necrotic.
Babes differentiates microscopically five layers in a sequence from without
inward which he describes as follows: 1. The upper-layer for the most part
is denuded of epithelium, moderately thick, pale, resembling a diphtheritic
membrane, and permeated with but few nuclear fragments and by various
bacteria, particularly streptococci; 2. A layer about 0.1 mm. in thickness,
without structure; upon staining with Léffler blue it is seen as a film of bent,
extraordinarily fine bacilli, often showing long wavy forms which may reach
the deeper tissues and the superficial layer in the form of sheaves or lines,
and in the latter form they permit the recognition of granular decomposition ;
3. Mononuclear and polynuclear round cells; 4. Mucous membrane tissue with
edematous swelling, and a granular exudate with numerous bacilli of the
variety described under 2. In the walls of the vessels and in their surround-
ings swollen spindle cells with reticulated protoplasm which may be well
stained by methylene-blue; 5. Markedly dilated larger vessels with large spindle
cells in their walls.
Upon the gastric and intestinal mucous membranes infiltrations of blood
are frequently found; also ulcerative losses of substance, besides necrotic and
diphtheritic changes. In those cases which run their course with bloody diar-
rhea, special pathological processes are found in the colon. The mucous mem-
brane is swollen, friable, and covered with a hemorrhagic mass which may be
bist peeled off. The tissue lying beneath is softened or completely decom-
posed.
Cases are also noted in which the follicles show pathological changes, and
in which the alterations have been limited to these. They are frequently ulcer-
ated, surrounded by dense hemorrhagic infiltration.
In the large glandular organs of the abdomen, the liver and the pancreas,
no special changes are found except hemorrhages and fatty degeneration. The
spleen is usually enlarged, soft, even fluctuating, and occasionally exhibits
SCURVY 401
infarcts over which the capsule of the spleen shows the remains of an inflam-
mation that has run its course (circumscribed perisplenitis). The kidneys
rarely reveal pathologic changes; only when much albumin has been excreted
in the urine a more or less advanced parenchymatous nephritis may be noted,
while milder grades of albuminuria leave no trace.
Amyloid degeneration of the kidneys I have never seen in scurvy, and this
as well as infarcts appears to occur very rarely. However, hemorrhages under
the capsule, and into the mucous membranes of the urinary passages, are not
rarely met with.
The pleure and the pericardium are very frequently covered with hemor-
rhages. The pleural cavities and the pericardium occasionally contain very
large amounts of a slightly hemorrhagic fluid or even pure blood. Fibrinous
deposits are not rare.
The heart muscle is pale, flaccid, often permeated by hemorrhages, occa-
sionally showing fatty degeneration. The valves are intact, provided an acute
endocarditis has not complicated the course of the disease; if so, the signs
of an acute endocarditis verrucosa or ulcerosa may be met with.
In the lungs there is usually hemorrhagic edema and hypostatic congestion
in the lower lobes posteriorly ; occasionally, as severe complications, croupous
pneumonia or hemorrhagic infarcts, but rarely gangrene. The mucous mem-
brane of the respiratory passages is often covered with petechie and with a
hemorrhagic mucus; there is edema of the larynx.
Besides fatty degeneration and occasionally hemorrhagic imbibition of the
heart muscle, the same changes are found in the muscles of the body, particu-
larly those of the back, thigh and arms.
SYMPTOMATOLOGY
The disease is characterized by two main groups of symptoms: 1. By an
intense swelling of the gums combined with loosening and hemorrhage, to
which are often added ulceration and decomposition with extreme fcetor ex
ore; 2. By numerous extravasations of blood under the skin, in the mucous
membranes, in the coats of the eye, in the muscles, into the cavities of the
body, into the joints, under the periosteum, etc. ; these give rise to further dis-
turbances which are to be looked upon partly as mechanical, as, for example,
the pressure of the intrapericardial effusion of blood upon the heart. In
severe cases a general cachexia of the most serious nature is added. This
cachexia is usually the first, and for a long time the only, symptom of the
disease, and as a rule appears gradually. At first the patients are languid and
show a loss of energy, without, at the onset, being unable to follow their usual
occupations; the lassitude, however, increases steadily, even slight exertion
becomes difficult, and gives rise to palpitation and dyspnea. To this is added
as a very important and almost constant symptom pain in the limbs, and partic-
ularly arthritic pains, which are of marked rheumatic character and may occur
in all the joints, but which, as a rule, are generally localized to the lower ex-
tremities, and are, therefore, not infrequently confounded with Schonlein’s
peliosis rheumatica. Increasing weakness and sensitiveness upon exertion, and
absolute loss of appetite are combined with a growing sensation of chilliness,
402 THE HEMORRHAGIC DIATHESES
as well as a great tendency to somnolence, the latter symptom, however, beir
by no means relieved by frequent slumber.
Corresponding to ‘the advancing symptoms of the disease, the extern:
signs of the affection become noticeable. The expression of the face denoti
suffering, the lines are flaccid, the freshness of the complexion gives way to
cyanotic pallor, the visible mucous membranes are of a livid color, the eye
are dull, sunken in the orbits and are surrounded by rings. The skin of tk
body loses luster and smoothness, it becomes dry and fissured, and occasional]
desquamates as in pityriasis of the aged. Upon the skin brownish spots a1
observed, similar to the. bronze discoloration in Addison’s disease. At th
onset fever is usually absent. With loss in strength advancing emaciatio
goes hand in hand. ‘To the same extent the pulse loses in tension and volum
and is slow, but becomes for the time full and frequent whenever the patien
makes a comparatively slight bodily exertion. The subjective sensation o
palpitation of the heart is combined with this, without, however, either i
rest or after movement, any conspicuous change being revealed by physice
examination of the heart. ;
The constitutional phenomena just mentioned, to a certain extent prc
dromes of the disease, may be entirely absent, and the patient be attacked sud
denly—without a prodromal stage—with the characteristic symptoms. Usu
ally, however, these symptoms precede by a considerable time, the perio
varying between several days, usually from eight to fourteen, and, in excep
tional cases, several weeks.
The most conspicuous site for the characteristic symptoms of scurvy is th
gums, and we must emphasize that only those areas of the gums are attacke
which correspond to points in the jaw in which the teeth are inserted; so that
for example, in children and in the aged, in those areas in which no teeth hav
appeared, or in those from which they have already fallen out, the gums shov
no lesion. Where, however, through carious processes the teeth have partiall:
decayed, or where, after disappearance of the crown the alveoli still posses
roots, the disease preferably localizes itself. The anterior gums usually, anc
especially at the onset of the disease, are decidedly implicated, but not the res
of the mucous membrane of the mouth. At first the free border of the gums
particularly the bit which projects in the intermediate space between two teeth
begins to swell, rising above its surroundings, at the same time assuming :
deep bluish-red color. This color is not only the expression of an edematou
hyperemia but usually of a hemorrhagic infiltration as well, whereby it differ
distinctly from other forms of stomatitis. :
The affection of the gums rapidly advances, the swollen areas are fre
quently extremely painful, and a very characteristic symptom appears; mod
erate pressure, a mere touch, causes profuse hemorrhage. The longer thi
duration of the disease, and the more severe its form, the more extensive thi
affection of the gums. At the same time, the swelling becomes greater anc
greater, so that frequently nothing of the teeth can be seen.
Simultaneously an intensely disagreeable odor of decomposition proceed
from the mouth, and in the later course of the disease becomes quite unbear
able. The inflammatory swelling increases still further, deposits of a dirty
SCURVY 403
grayish white color resembling those of diphtheria form, adhering closely
to the mucous membrane, and after their removal the mucous membrane suf-
fers a more or less decided loss in substance, and a bleeding, very painful sur-
face remains. Sometimes the mucous membrane even becomes gangrenous.
The surface is coated with a dirty, fetid deposit, the upper layers of which
slough off, and are expectorated with the saliva. If this state continue for
a long time the gums may become gangrenous and necrose, the alveoli may
be exposed to a great extent, and the teeth may become loose and fall out.
The unfortunate patient now suffers tortures, for these symptoms increase
in severity and usually many others go hand in hand, and particularly the
extremely severe cachexia. The latter is probably not a consequence of the
various severe local symptoms. On the contrary, it ushers in the affection,
forms a principal factor in all the phases of the disease, and is the primal
cause of the intensity of the individual symptoms.
In many patients, and according to the severity of the disease of the
gums, there is an increase in the secretion of saliva, probably due to reflex
causes, so that a hemorrhagic fetid fluid, in which infusoria and low fungi
may be recognized, streams almost continuously from the mouth.
If the affection terminate in recovery, complete restitution may occur,
and the teeth which were previously loose may again become firmly rooted.
More frequently a tough tissue resembling cicatrix forms and remains for life.
Mechanical effects produced by chewing and mechanical irritation have
been assumed to be the cause of the almost invariable inflammation of the gums
in scurvy; to these may be added the inherent tendency of the disease to
inflammation.
In children, besides the usual form of simple stomatitis, another variety
designated as aphthous stomatitis, an inflammatory affection of the mucous
membrane of the mouth, sometimes occurs, particularly during the period of
dentition, i.e., between the ninth month and the middle of the third year.
Henoch says regarding this: In some of the cases a disagreeable odor from the
mouth is added to the symptoms described, and minute investigation always
reveals a hyperemic gum which bleeds readily, which may even show a grayish
yellow detritus of friable character that may be readily loosened with a spat-
ula. This form of stomatitis, which is of a decidedly contagious nature,
usually runs a favorable course; more rare is another which is designated by
the name of ulcerative stomatitis. While the fibrinous plaques which are
invariably present in the latter affection are absent in the former, the impli-
cation of the gums requires the careful attention of the physician. These are
dark red or bluish red and swollen, they bleed readily and decompose from the
edge surrounding the tooth, gradually forming a grayish yellow paste; the
crown of the tooth is exposed, and finally becomes loosened. Upon pressure a
purulent fluid exudes from the space between the loosened gums and the teeth,
a fetid odor comes from the mouth, and the surrounding soft parts. The
cheeks and the submaxillary connective tissue frequently show edematous
swelling. Occasionally the process attacks the periosteum of the jaw, extend-
ing down into the alveolar processes, causing the teeth to fall out, and finally
gives rise to partial necrosis of the jaw.
404 THE HEMORRHAGIC DIATHESES
This description, after Henoch, corresponds to analogous processes in
scurvy with the exception of the necrosis of the jaw, and this probably occurs
very rarely in scurvy. Henoch, one of our greatest pediatric clinicians, in his
description of stomatitis fails to mention scurvy, and assigns no place to this
disease in his lectures upon diseases of children; I conclude from this fact
that he is of the opinion that the stomatitis of infancy has nothing in common
with scurvy and, moreover, that he has not observed scurvy in nurslings or in
the years of infancy.*
That there is, however, such a condition as infantile scurvy may be seen
from the American Collective Report, in which it is stated that among 372
cases which occurred during infancy, particularly during the period between
the seventh and fourteenth months, in only 16 cases were the gums unaffected ;
in the remaining 313 cases there is mention of either swelling and loosening
of the gums or of ulcerative processes in the gums. Certainly, Henoch’s cases
were not scurvy, for he reports in them no extravasations of blood into the
skin or the mucous membranes; neither can we doubt that cases of ulcerative
stomatitis which are not of a scorbutic nature may occur also in adults.
In view of the entirely different etiology of stomatitis and scurvy we must
clearly separate the oral affections of the two diseases, and we shall only refer
to scurvy if, besides the stomatitis, other symptoms, to be more minutely de-
scribed later, are also present. Among these are hemorrhages into the skin,
into the subcutaneous connective tissue, in the mucous and serous membranes,
into the joints, muscles, etc.
The hemorrhages into the skin usually occur in the form of petechiz which
vary greatly in size. They occur early and most profusely upon the lower leg,
particularly upon the extensor surfaces; the trunk and the other extrem-
ities are often affected later, the face invariably remaining entirely exempt.
If they appear in great numbers the impression is given that a paint brush
has been dipped in blood and spattered over these areas. Traumatic influ-
ences, a blow, pressure, especially such as is caused by the wearing of tight
clothing (garters, girdles, belts, etc.), not infrequently produce these hemor-
rhages and give to them a definite, under some circumstances a characteristic,
form and shape; for example, the form of streaks (vibices). Often an ex-
tremity is profusely covered with them, and, according to their age, they pre-
sent a dark red, brownish red, green or yellowish color, corresponding to the
well-known changes in color which extravasated blood or hemoglobin presents
when undergoing alteration. These hemorrhages have a special predilection
for the gluteal region, where they occasionally develop extensively.
The first effusions into the skin frequently form around a hair follicle, so
+In the latest edition of Henoch’s book, in the description of Barlow’s disease, there
is mention of a change in the gums, as follows: “To these symptoms almost invariably
is added a spongy swelling of the gums with fetor and tendency to hemorrhages as in
the case of scurvy, and this is most marked in the cases where teeth are already present.”
Then follows another statement of importance: “For the present we may only assume
that we are here dealing (in Barlow’s disease) with a form of the hemorrhagic diathesis
that has much in common with scurvy but does not appear to be identical with it.”
A special description of scurvy is, however, not found in his latest edition.
SCURVY 405
that apparently the capillary vessels of the latter may be looked upon as the
starting point of the hemorrhage. The effusions of blood appear as though
punctured by the little hairs in this area. The hair then becomes dry, fibril-
lates, and falls out. The region about the nails is also frequently the seat of
hemorrhages; when these suppurate, the process often extends to the bed of
the nail so that it leads to paronychia, that is, an onychia scorbutica, as the
result of which the nail dies. The ulcers upon other parts, particularly upon
the lower extremities and the buttocks, may be of extraordimary size. Some
are covered with dark, firm crusts, some have a dirty base which is covered
with decomposed purohemorrhagic shreds of tissue, or flat granulations may
be seen which bleed at the slightest touch. Usually the ulcers secrete continu-
ously a thin hemorrhagico-purulent, sometimes even ichorous, fluid which has
a most offensive odor. Unless cicatrization of the ulcers occurs previous to
general improvement (and this is rare) these frequently spread to the sur-
rounding tissues, or even invade them deeply, thus causing the erosion of
larger vessels and hemorrhages which may terminate fatally. But even with-
out this serious outcome these cutaneous ulcers are of bad prognosis, for their
profuse secretion greatly debilitates the organism.
The hemorrhages into the subcutaneous connective tissue and into the
muscles may be widely distributed, and attain the size of a plate or even be
larger. Sometimes they develop acutely, sometimes slowly; in the former
case they are usually accompanied by pain and an increase in temperature.
The skin above them, as a rule, can be but slightly moved or not at all, it
has a doughy sensation, is painful upon pressure and feels hot. In the case
of these subcutaneous hemorrhages the lower extremities are the chief seat,
as they are of petechiz, particularly the region of the tendo Achillis and the
popliteal space. At the onset there is noticed a soft swelling which later
becomes harder, and is finally as hard as wood. The margins of the tumor
are not always sharply defined. The skin above the swelling is not movable
and the swelling is often not sharply marked off from the surrounding tissues.
Over the swelling the skin shows decided redness and edema; it is shiny, hot
and painful. After a few days these symptoms ameliorate, and the redness
turns to a dull brown. Then absorption occurs, the skin desquamates, and
always retains a dark pigmentation. But the swelling may soften and even-
tually rupture, and a quantity of necrosed gangrenous tissue mixed with
blood sloughs away. The result is a deep ulcer. The course is, however, not
always so acute. The swelling and hardening may occur much more grad-
ually; pain and fever may be absent. Upon the skin there may appear the
signs of a more or less well-developed suggillation, according to whether
the process runs its course superficially or in the deeper tissue. As a matter
of course such foci decidedly limit the function of the muscles, whether they
are located in the muscles themselves or in the neighboring connective tissue.
When disease of the muscle is combined with disease of the connective tissue,
it is often impossible for the physician to make a differential diagnosis. In
the muscles quite isolated foci may be found which are characteristic in that
the integument over them scarcely shows change. These foci vary greatly in
the symptoms which they produce; some are circumscribed, some diffuse,
406 THE HEMORRHAGIC DIATHESES
some painful, some painless, some acute and accompanied by fever, some grad-
ual in onset and afebrile in course. ;
Hemorrhages from the mucous membranes are decidedly less frequent,
but they may cause death or hasten death by inanition. We must mention
hemorrhages from the nose, hematemesis, enterorrhagia, hematuria, metror-
rhagia and hemoptysis. For a long time, severe epistaxis has been greatly
dreaded; it is, however, not very frequent, but can rarely be stopped without
packing, and sometimes causes death. These hemorrhages rarely occur spon-
taneously, but are usually the result of slight injuries to the nasal mucous
membrane; they may follow strenuous blowing of the nose. The fact that an
external cause is usually required to produce the hemorrhages which are so
characteristic of scurvy, Immermann believes will explain the circumstance
that the gums are usually the seat of these symptoms. He is of the opinion
that the stomatitis marginalis of scurvy is also secondary, inasmuch as the
gums, considering the delicacy of their histologic structure, are so frequently
and decidedly exposed to mechanical, chemical and thermic irritations—par-
ticularly as the development of the affection of the gums is always appar-
ently associated with the presence of teeth in the jaw, and therefore with the
process of chewing. It may also be here emphasized that the gums are not
exclusively the seat of the disease, nor are they the first typical points, but
severe cases may run their course without an implication of the gums, and in
general the sequence of the individual symptoms and the number of the impli-
cated organs may be very variable.
Hemorrhage from the mucous membranes of the stomach and intestines is
decidedly more rare than from the mucous membrane of the nose, and is prone
to occur when the bowel is stimulated to decided peristalsis; as, for example,
after the administration of purgatives. Its development may, therefore, be
compared with epistaxis after violent blowing of the nose. In rare cases dys-
entery is simultaneously present. Hemoptysis occurs only occasionally owing
to a coexisting tuberculosis or a fibrinous pneumonia, the latter disease then
having its starting point in a hemorrhagic pulmonary infarct.
Besides these hemorrhages which appear upon the surface, or from organs
with an external outlet, others may occur in the internal cavities, or there
may be bleeding even into the organs themselves. These represent a severe
form of the disease; they cause extreme debility or may even be the immediate
cause of death. Among these we must mention first the pleural and peri-
cardial hemorrhages some of which may be looked upon as forms of non-
inflammatory hemothorax which occasionally leads to an inflammation of the
serosa, some as inflammatory hemorrhagic effusions which, by compression of
the lungs or paralysis of the heart, decidedly increase the danger to life.
That these effusions into the serous cavities (which may also occur in the
peritoneum) are susceptible of absorption is unquestionable.
Meningeal hemorrhages have also been observed, and may be diagnosticated
by pain, paresthesia, spasms, contractures, paralyses, and apoplectiform attacks.
In some cases death occurs with the symptoms of apoplexy, but actual cases
of true cerebral hemorrhage appear to be extraordinarily rare. More frequent
are scorbutic changes in the eye. Hemorrhages and inflammation of the con-
SCURVY 407
junctiva, hemorrhages into the anterior chamber of the eye, or choroiditis
hemorrhagica have been noted. The subconjunctival hemorrhages may cause
loosening of the conjunctiva, and to such an extent that the membrane swells
out under the eyelid, frequently covering the eye-ball to a great extent. Occa-
sionally iritis also occurs. All of these symptoms may improve or may lead
to corresponding permanent changes. In very severe cases, bilateral pan-
ophthalmitis usually occurs and leads to entire loss of sight. These cases
invariably terminate fatally. Seggel observed in a mild case hemorrhages into
the vascular wall of the retinal vessels, besides frequent repetitions of sub-
conjunctival hemorrhages, and a swelling due to hemorrhage into the pia
sheath of the optic nerve with a slight cloudiness of the papilla. Not infre-
quently in the course of the disease, as prodrome, or as+sequel, hemeralopia
or night-blindness is observed—a condition in which the sense of sight is more
or less lost during dusk and at night. Nothing is known of the causal rela-
tion of the underlying affection to these phenomena.
A particular and important group of symptoms is that affecting the tissues
constituting the joints, including the cartilage and the bone. Besides the
more or less widely distributed rheumatoid pains in the joints, painful swell-
ings of the latter, due to effusions, are observed. These latter may be purely ser-
ous, but more frequently consist of a sanguinolent fluid. Sometimes there is
also suppuration of the joint with subsequent erosion and deformity, and finally
true ankylosis. Inasmuch, however, as the affection usually terminates in re-
covery, these effusions are generally absorbed without ankylosis developing. In
the bones, particularly after mechanical injuries not necessarily at all severe,
hemorrhages occur, or inflammatory periosteal effusions between the periosteum
and the bone arise. Indurated and very painful swellings result, which, how-
ever, may slowly subside, or may lead to local necrosis and the formation of
sequestra. At the epiphyses the coverings of the cartilage become detached.
The long tubular bones of the lower extremities are chiefly attacked, next those
of the upper extremity, frequently also the ribs, in which case the process leads
to detachment from the sternum. The kind of aid given by scurvy to many
intercurrent affections may be suspected if we notice how in fresh cicatrices,
or in those previously formed, it produces a softening of the callus.
During the progress of the symptoms described the constitutional condi-
tion of the patient deteriorates. He becomes cachectic looking, the fat and
the musculature gradually disappear. Fever may be absent, in other cases
may be slight, without conforming to any definite type. Decided rises in
temperature are generally due to complications or to suppuration. Sometimes
swelling of the spleen is noted; this, however, can by no means be looked upon
as specific. The symptoms on the part of the heart correspond with those
of other anemic conditions—systolic murmurs and dilatation. Clinically the
most prominent symptoms are cardiac palpitation and dyspnea upon compara-
tively slight movement and exertion. The small, frequent, and slightly irreg-
ular pulse is notable. In the course of the disease endocarditis occasionally
occurs, but clinically, in the majority of the cases, can scarcely be recognized,
being anatomically characterized by a delicate circle of excrescences upon the
free border of the mitral valve or the aortic valve. Under some circumstances
408 THE HEMORRHAGIC DIATHESES
it runs its course with the symptoms of ulcerative endocarditis. It is to b
hoped that we may succeed in discovering in the endocardial deposits the
pathogenic agent of the disease, which so far has been unsuccessfully lookec
for in the blood. On the part of the digestive-tract we have occasional diar.
rhea which may be of a dysenteric character. Several times the combinatior
of scurvy with true dysentery has been observed. Kidney troubles are com.
paratively slight; occasionally transitory albuminuria is met with, without om
‘being able to conclude from this the presence of genuine nephritis, which is ¢
rare complication. Reports of marked hematuria are rare. The urine is fre.
quently of a dark color, which Kretschy ascribes to an increase of the normal
coloring material due to a greater destruction of red blood-corpuscles. In se.
vere cases the quantity of the urine, especially during the progress of the disease,
is greatly diminished; peptonuria occurs as well as albuminuria. According
to v. Jaksch the peptone does not originate in the blood itself, but from the
hemorrhages of the skin, of the subcutaneous cellular tissue, ete. To this he
ascribes the origin of the profuse urobilin.
Of course, special importance has been attached to the amount of potash
in the urine, but the reports regarding the quantity found are very contra-
dictory. Phosphoric acid is said to be increased; unquestionably the amount
of uric acid is great, especially at the height of the disease, but it rapidly
decreases with beginning convalescence.
In the blood, apart from Klebs’ questionable nomads, nothing character-
istic has been found. The findings correspond in the main with those of severe
anemia. The amount of hemoglobin is decreased, and in severe cases not only
the number of erythrocytes but also their hemoglobin contents; poikilocytes
and microcytes I myself have frequently found, some with basophilic granula-
tions. Particularly common is the form of achromic cell described by me
resembling a pessary. Penzoldt also reports the presence in the blood of
granular, and some markedly refractive, bodies which he looks upon as embry-
onic forms of red corpuscles. Macrocytes also are said to have been found
in large numbers. According to the reports of Laboulbéne the number of
leukocytes is increased ; this Iam unable to confirm from my own observations.
The reports are contradictory regarding the amount of iron in the blood.
According to Opitz and Schneider it is somewhat increased; according to
Duchek it is nearly normal, and according to Becquerel, Rodier and Chalvet
it is decidedly decreased. The latter has also determined a decrease in the
amount of potassium.
_ Asa result of our review of the great number of accounts of severe symptoms
in past epidemics we must emphasize our impression that, at least in Germany,
the severe forms of the disease are now only very rarely observed.
Frequently the symptoms are limited to great lassitude, pain in the joints
and limbs, extensive hemorrhages into the skin and elsewhere, and more or
less decided hemorrhagic inflammation of the gums. In these cases the entire
course 1s comparatively short.
Scurvy may terminate in death or in complete or partial recovery. Gen-
erally recovery is exceedingly slow, and weeks and months pass before the
different processes have run their course. The disease of the gums, if great
SCURVY 409
loss of substance has not occurred, steadily improves, the swelling disappears,
and restitutio ad integrum takes place. On the other hand, permanent changes
in the form of cicatricial retractions or hyperplastic thickening of the tissue
may remain, which, however, do not give rise to any difficulties. Of the
processes in the skin, the small hemorrhages improve most readily. They go
through all the changes that hemoglobin shows, and finally disappear. With
an improvement in the general condition, the cutaneous ulcers also pursue a
favorable course. Their surfaces become clean, and finally skin is formed
in which a dark pigmentation remains for a long time. The swelling in the
muscles and connective tissue also gradually recedes, although very slowly, so
that a callus is often evident long after complete recovery. Not rarely, too,
connective tissue proliferation occurs (as in the gums), the result of which is
permanent contraction or fixation of the muscles and joints, with, for example,
the formation of club-foot.
DIAGNOSIS
In view of the marked symptoms, the conspicuous epidemic character of the
disease, and the extraordinary circumstances under which it usually arises, the
diagnosis of scurvy can scarcely be difficult.
Difficulty arises only when we are dealing with sporadic cases, and even in
these a careful history of the previous conditions of the life and residence of the
patient will lead to a recognition of the affection. If we remember that the
greatest number of epidemics occur upon ships, in fortresses, among isolated
bodies of troops, or in penal and eleemosynary institutions, that quite definite
etiologic factors such as insanitary conditions of life, and, above all, improper
food have preceded the outbreak, no further proof is needed for us at once to
recognize the disease. The disease may break out in so many places that it is
only very rarely that symptoms are at all scanty in a given case; almost always
a number of the usual symptoms appear simultaneously. Serious diagnostic
difficulties will, therefore, only occur in isolated cases of unusually mild char-
acter. But these are just the ones which to-day present themselves for pro-
fessional treatment.
First among the external symptoms we have learned to recognize those
which almost always precede the local phenomena of the disease and increase
with its advance; i.e., the general cachexia. Next come the various effusions
- of blood into the skin, into the deeply lying connective tissue and the muscles,
the rheumatoid arthritic pains occasionally present, and, above all, the affec-
tion of the gums. The number of diseases which may be confounded with it
is very small. First, those diseases which form a common group with scurvy
(hemophilia and morbus maculosus Werlhofii). Neither is epidemic in any
sense; and as both are to be described later they need not now be considered.
I will state here, however, that, in spite of the external similarity of many
cardinal symptoms, the disease of the gums is the predominant feature in
scurvy, and is not present in either of the other diseases mentioned.
Cutaneous hemorrhages, especially petechiz and small ecchymoses, are met
with in a number of cachectic diseases. When associated with rheumatoid or
arthritic pains a confusion of scurvy with peliosis rheumatica may occur. If,
410 THE HEMORRHAGIC DIATHESES
in such cases, the diagnosis is difficult, it must be remembered that scorbutic
hemorrhages are generally of an inflammatory character, while in the other
diseases this is by no means the case. Finally, it must be borne in mind that
in scurvy we have excellent therapeutic measures under the action of which
the symptoms usually disappear rapidly, while in the majority of the other
diseases therapy is for the most part of no avail.
PROGNOSIS
While the prognosis during past historic epochs was usually very grave,
to-day, fortunately, it is very favorable, especially in cases other than the most
severe. Naturally, we must be cautious in prognosis, for even in mild and
moderately severe cases intercurrent affections may bring about death. The
earlier the therapy is begun the more favorable the ultimate result and the
shorter the course, although even under favorable circumstances it always
requires considerable time for the patient completely to regain his strength.
Complete recovery is, of course, only to be expected in those cases in which the
disease has shown itself to be mild; in other cases recovery is usually incom-
plete. Only in cases in which no loss of substance has occurred can a complete
restitutio ad integrum be expected.
In cases which terminate fatally, the patient usually suffers for a long
time, and passes through many complications before he finally succumbs to
general exhaustion. Yet many circumstances may lead to an early death.
Among these by far the commonest are hemorrhages of lethal extent. These
may be from the gums, from the nasal mucous membrane, from cutaneous
ulcers, eroded arteries, or from the digestive tract.
More frequently death results from complications, particularly dysentery
and croupous pneumonia, more rarely malignant endocarditis, the cause of
which is to be sought for in the entrance of infectious germs from the ulcers.
Quite often excessive effusions into the pleural cavity or into the pericardium
threaten life; sometimes extreme cardiac asthenia leads to a fatal result, and
if the patient makes an unusual exertion or rises suddenly, he collapses life-
less, as occasionally happens in children who have had an attack of diphtheria.
PROPHYLAXIS AND TREATMENT
Garrod’s teaching that a deficiency in acid vegetable potassium is the chief
cause of the disease indicates the direction in which a prophylaxis in scurvy
is to be attained. The theory of Garrod, although correct in its fundamental
principles, does not appear to be absolutely well-founded throughout, for cases
of scurvy develop where there is no deficiency of potassium in the food. In
the epidemic in Rastatt (1851-1852), for example, there was no deficiency in
fresh vegetables; nor in that of Ingolstadt where, in spite of good food, such
as meat and potatoes, an epidemic occurred among the prisoners of war. It
has therefore been assumed that it is not the deficient administration of potas-
sium, but the insufficient retention of potassium in the organism, which causes
the disease. Unquestionably, among other conditions, the increased consump-
tion of potassium in the body plays an important réle. If the theory of Bunge
SCURVY 411
is correct, the excessive ingestion of table salt produces an increased excretion
of potassium. Thus the fact can easily be accounted for that the continued
use of salted meat frequently causes scurvy, although this is denied by many.
In consonance with opinions generally held, plentiful amounts of acid
vegetable potassium should be administered to the organism in the form of
fresh green vegetables such as new potatoes, spoonwort (scurvy grass), cabbage,
spinach, water cress, radishes, sorrel, sauerkraut, carrots, turnips, onions, arti-
chokes, asparagus and lettuce, also juicy fruits, oranges, milk, fresh meat, meat
extract, meat juice, particularly puro (from the laboratory of Scholl in
Munich), meat juice, essence of beef, and good potted meats. In view of the
comparatively low price of vegetables, the daily diet may be well supplied with
acid vegetable potassium even in the feeding of prisoners for whom but a
small allowance is made. Lately the diet in prisons has been decidedly im-
proved by the addition of fish.
It is more difficult to prevent scurvy at sea. In long sea voyages the supply
of fresh vegetables is soon exhausted, and a portion is likely to spoil. But
canned vegetables may readily take their place without decidedly increasing
the cost, owing to the abundance of good material upon the market. Upon
long trips a substitute for fresh meat is furnished by meat extract.
On many ships in order to furnish the requirement of acid vegetable potas-
sium, lemon juice is regularly given to the crew. In the English marine it is
obligatory that the crew shall receive a corresponding amount of lime juice
in a mixture of ten parts of lime juice to one part of spirits. The best method
is to carry the fresh fruit upon the trip, and prepare lemonade from it. Arti-
ficial lemon juice is sometimes adulterated, and decomposes very readily.
Nordenskjéld advises preserved mulberries for expeditions, as these are said to
have a particularly favorable action. Neale believes fresh meat (with the
blood) to be the most efficient antiscorbutic. When this is not at hand, green
or canned vegetables and lemon juice must be used. Potatoes and milk are
also advised, as well as cider and Moselle wine.
Great stress is also laid upon drinking-water and, if necessary, this must be
obtained from salt water by distillation. Nansen advises that in Polar regions
the ice which projects above the surface be melted for drinking, since these
parts have been exposed during the summer to the rays of the sun, and have
to a great extent lost their salt. He believes it unnecessary to distil this
water for drinking in order to escape the danger of scurvy, and considers the
belief erroneous that a small amount of salt is harmful. Good beer (pine
beer) is useful for the prevention of scurvy, and the present status of brewing
makes it possible to take large amounts of inexpensive beer upon long sea
voyages.
Pickled meat, as universal experience has shown, has a deleterious effect,
and for this reason its use is to be limited as much as possible.
In regard to epidemics at sea, the conditions of seafaring in modern times
have changed; steamers have greatly shortened the voyages, and provisions are
earried in smaller quantity than formerly. These causes, and also the excel-
lent naval regulations in which England has shown itself superior to all sea-
faring nations, have made the disease so rare in the English Navy that in
412 THE HEMORRHAGIC DIATHESES
the years from 1856 to 1861 only 1.05 per thousand of marines were attacke
by the disease. In the Austrian Marine the number of affections from 1863 t
1870 = 1 per cent., but in 1871 and 1872 it declined to 0.34 per cent. Ih
the German Marine during the period from April, 1875, to March, 1880, onl
16 cases of scurvy and 76 cases of scorbutic gum affection occurred, thes
groups collectively giving a proportion of 0.475 per cent. ;
The occurrence of scurvy upon ships depends neither upon sailing in north
ern nor in southern latitudes, in this nor in that season, but particularly upoi
the supply of provisions in proportion to the length of the voyage. Thi:
readily explains why conditions are more unfavorable upon sailing ships thai
upon steamers. In the former only the most careful ship hygiene can preven
an outbreak of the disease, and upon such ships general hygienic conditions ar
still unsatisfactory.
Besides proper kinds and sufficiency of food, general hygiene is most impor.
tant in prophylaxis, particularly perfect cleanliness of body as well as of hab.
itation, avoidance of excesses, protection against cold, etc. Isolation of the
patients when possible, and the greatest attention to cleanliness on contact witl
them, form the best means for limiting the spread of the disease, that is, foi
arresting it. Too much stress cannot be laid upon exercise in the open air, by
which the psychical condition of the patients is improved. Where a change
of residence is possible we should always take advantage of it.
I should like to mention a few points of importance from the interesting
book of Nansen, “ Farthest North,” which reports one of the greatest sea
voyages of all times, in which during three years no case of scurvy occurred,
In regard to provisions he holds the view that in prolonged Arctic expeditions
meat and fish that have been preserved by salting, smoking or incomplete
drying are to be regarded as objectionable, and are to be rejected. The lead-
ing thought in provisioning must be to preserve the food either by careful and
complete drying, or by sterilization. “ What I wished to attain was to have
not only a nourishing and wholesome stock of provisions, but to see to it that
there was as much variety as possible. We took fish of all sorts in hermetically
closed tins, dried fish and preserved fish, potatoes, dried as well as in tins,
all sorts of dried and preserved vegetables, cooked and dried fruit, preserves
and marmalade in large amounts, sweetened and unsweetened condensed milk,
preserved butter, dried soups of various kinds, etc., even bread, dried vegetables,
ete., in zinc cases. As drink we used at breakfast and in the evening choco-
late, coffee and tea, occasionally milk. For supper at first beer, later lemon
juice with sugar or syrup. Aside from beer and some malt extract the expedi-
tion had no alcoholic drinks. Occasionally a grog was made from mulberries
or other fruit syrup with the addition of some spirits.” Meat and fish were
carried in a desiccated condition, free from fat, cartilage, etc., and mixed with
kidney fat, also Vaage’s fish flour; flour (previously stewed), so that it could
be eaten without further preparation; dried cooked potatoes, pea soup, choco-
late, bread (carefully dried, hard, wheat bread) and aleuronat bread (wheat
flour with 30 per cent. of aleuronat) and butter.
It may be interesting to quote the menu of the 25th of December, 1893:
1. Oxtail soup, 2. Fish-pudding, with potatoes and melted butter, 3. Reindeer
HEMOPHILIA 413
roast with peas, French beans, potatoes and preserved cranberries, 4. Mulber-
ries with cream, 5. Cake with marchpane.
The general treatment of scurvy is entirely analogous with the prophylactic
diet. Warm baths often have a favorable action.
Special treatment: In the drug treatment of scurvy, cochlearie has long
been prominent. A formula greatly employed is:
Bi Herb. cochl. rec. conc... 2... eee eee ees 50.0
Sem. sinap. cont..... 2... cc cece cece teen eee ee ee eas 12.5
Vani; fall, albass gail eas bad WEY ee eas o eee nae 300.0
Macera per biduum, colat. adde spir. eth. chlor...... 6.0
M., D., 8.: Half a wine-glassful three times daily.
There are further employed: Astringents, such as tonica amara, and aro-
matics, such as tannic acid, quinin, cascarilla, myrrh, ratanhia, calamus, and
gentian.
The employment of beer yeast, pure or with the addition of water and
sugar, 44 200 to 300 grams, daily, is very popular.
Disease of the gums is best prevented by the early removal of all carious
teeth and deposits of tartar; later this is not so feasible, and the affection of
the gums must then be treated locally with astringent solutions. Tincture
of myrrh, potassium chlorate and potassium permanganate in weakened solu-
tion are especially employed.
In scorbutic cutaneous ulcers, poultices containing potassium permanganate
in solutions of 1 to 300 and bandages are serviceable.
Hemorrhages are treated by styptics and tampons, as well as by ergot.
Surgical interference may be very dangerous; even simple bandages that cause
pressure may bring about deep tissue hemorrhages and deep ulcerations.
In case of constipation all purgatives which have a decided action are to be
avoided unless absolutely necessary. The bowels must be opened by the cau-
tious administration of enemata, or by the employment of the mildest laxatives,
such as tamarinds, for by the too active stimulation of peristalsis fatal intes-
tinal hemorrhages may be produced. In the treatment of such bleeding little
or nothing is gained with styptics such as ergot and sesquichlorid of iron; ice
externally or internally serves the purpose best.
HEMOPHILIA (BLEEDER’S DISEASE)
By the term hemophilia we mean a peculiar hereditary anomaly of con-
stitution, characterized on the one hand by traumatic hemorrhages of extraordi-
nary stubbornness, and on the other hand by a conspicuous tendency to spon-
taneous and repeatedly recurring hemorrhages, for which, up to the present
time, no plausible anatomical substratum has been determined. Combined
with this is a marked predisposition to “rheumatic ” affections which is mani-
fested by painful arthritic swellings. In the recognition of the disease, the
congenital and hereditary factors must be considered as well as the habitual
tendency to bleeding, and in the present conception of the disease these two
peculiarities dominate the clinical picture. They form a basis, too, for the dif-
414 THE HEMORRHAGIC DIATHESES
ferentiation of hemophilia from related clinical pictures which are included ix
the conception of the hemorrhagic diathesis, i.e., from scurvy and morbu
maculosus Werlhofii. The former differs from hemophilia decidedly by thi
fact that it is rarely sporadic, but usually endemic or epidemic. Still mon
characteristic, however, is its dependence upon external conditions; it is th
expression of severe disturbance of nutrition produced by obscure diseases 01
by long-continued insufficient and improper nourishment. Morbus maculosus
Werlhofii differs from hemophilia particularly in that it unquestionably belong:
to the acquired diseases, in which the factor of heredity plays no part. This
affection is never congenital as is the case with hemophilia, and this differential
peculiarity also applies to scurvy. Unlike the scurvy patient, the bleeder is fre-
quently well nourished and strong, and except for his tendency to spontaneous
hemorrhages he might almost be considered healthy.
In comparing hemophilia with related diseases in the group of the hemor-
thagic diatheses, one peculiarity of hemophilia stands out prominently. In
contrast with what is found in the diseases previously named, it is not a
pathologic process but a permanent condition which manifests itself sometimes
after recognizable causes (traumatic hemorrhages), at other times following
unknown ones (spontaneous hemorrhages). or this reason hemophilia has
been designated as a “ vitium prime formationis.”
Hemophilia is probably in all cases a congenital, and also a hereditary con-
dition. The intensely hereditary character of this pathologic condition has
been from the earliest times a source of great interest. Grandidier calls it
“the most hereditary of all hereditary diseases.” Only very exceptionally is
a single case of hemophilia observed in a family. The most striking point is
the frequency of the cases in one and the same family. From a study of the
total number of known hemophilia cases and their distribution in individual
families, it may be noted that in every family of bleeders there are at least
three bleeders. Sometimes the transmission is immediate from the parents
to the child. Much more frequently, however, the transmission of the disease
follows a peculiar law of heredity, peculiar because it reveals a remarkable
sex difference in the frequency with which hemophilia is acquired and trans-
mitted. Females show a greater tendency to transmit the disease; while,
in contrast to this, in the male sex a predisposition to acquire the disease is
prominent. The latter predisposition is evident from the fact that the major-
ity of bleeders are of the male sex. The tendency of the female to transmit
hemophilia is characterized by another peculiarity. A woman from a bleeder
family may transmit hemophilia to her offspring without herself being hemo-
philic, the disease skipping a generation. This order of transmission is indeed
the rule. Formerly, when fewer reports of cases were at hand, it was believed
that only males were affected by the disease, females being exempt, and that
it was women exclusively who transmitted the disease. On this assumption
first the laity and subsequently also scientists designated the women in families
of bleeders as “conductors.” Close investigation and increasing experience
have, however, taught us that females also may be attacked by hemophilia,
although far less frequently than males. For every thirteen males there is
one female bleeder. The view that women exclusively transmit the disease
HEMOPHILIA 415
can no longer be strictly maintained on account of many exceptions to this
tule. Grandidier has described the predisposition, transmissibility, and the
hereditary sequence in hemophilia in the following paragraphs:
UL Men from families of bleeders who are bleeders themselves, whose
wwes are not descended from bleeder families, by no means always beget
hemophilic children; on the contrary, in these cases the children are frequently
healthy with no tendency to the disease. Vice versa, however, it appears that
hemophilia quite invariably appears among the children of women who are
bleeders.
2. Men descended from bleeder families without being bleeders themselves,
and whose wives are from normal families, rarely beget hemophilic children;
on the other hand, women belonging to bleeder families who are not themselves
bleeders, give birth almost invariably to children who suffer conspicuously from
hemophilia.
On account of the gravity of hemophilia, its continuity in families, and
the fatal outcome which is usually due to severe hemorrhage, also because of
popular interest and the mysterious character of the affection, it is natural
that records regarding bleeder families extend far back into the past.
Grandidier, in his well-known monograph, cites 200 bleeder families with
609 male and 48 female bleeders (13 to 1). In the bleeder family de-
scribed by Stahel there were 24 males, all bleeders, in four generations. Al-
though females are much more rarely attacked by the disease than males, yet
transmission most certainly occurs through the female members of the family.
In Bollinger’s collection of cases it appears to be the rule, as in color-blindness
(Daltonism), that the sons of women whose fathers were bleeders are most
liable to hemophilia.
Otto and Nasse have published reports regarding the first recorded bleeder
families. Among those that have become especially well known are the fam-
ilies at Tenna in Graubiindten, the American family, Appleton-Browe, and the
Mampel family at Kirchheim near Heidelberg, whose genealogical tree was
first described by Chelius in the year 1827, then by Mutzenbecher in 1841,
and lately by Lossen (Fig. 22). This ancestral tree shows that the tendency
to bleed is transmitted exclusively through the female members of the family
who themselves without exception remained unaffected, a peculiarity which
we shall later discuss in another affection, hereditary Daltonism. Vice versa,
from marriages between male bleeders and female non-bleeders healthy chil-
dren are born.
Worthy of note also is the proportion between boys and girls in the vari-
ous generations: In the first generation from the common ancestors, there
are four boys and two girls; three of these boys (or 75 per cent.) are bleeders,
but none of the girls. In the second generation there are 14 boys and 9 girls;
of the former 13 (or 93 per cent.) are bleeders, of the latter, none. Finally,
in the third generation, among at least 50 children, there is only one bleeder,
a male who was the offspring of a non-bleeder mother belonging to the same
ascending line. There is, therefore, a conspicuous diminution of the disease
in the third generation, and this is probably due to intermarriage with healthy
families.
416 THE HEMORRHAGIC DIATHESES
Another tree of a well-marked bleeder family was described by M. Fischer
in 1889 in his dissertation on this disease. This family, comprising more
than four generations, lived in a village in Wiirttemberg, and though otherwise
not of distinction was characterized by a few remarkable facts. Thus the
apparent male ancestor who was a bleeder (he married twice, one wife evi-
dently not being hemophilic, there being bleeders among the children of both
marriages) himself directly transmitted the predisposition, whereas this is
ordinarily the case only with the female members of the family. Further-
more, among the female “ conductors,’ there were two who were themselves
bleeders, which is contrary to the rule. On the whole, among 114 members of
the family there were 17 bleeders, 13 males and 4 females, the implication of
the female sex being excessively high. The length of life of these bleeders
was from nine months up to sixty-two years. In most members of the fam-
ily, especially among the bleeders, there was another pathologic predisposition,
namely, to rheumatic affections, headache, congestions, and affections of the
teeth.
Only continuous and prolonged study of the genealogical history of a
bleeder family will reveal whether the disease is likely to assert itself for a
longer time, or whether the tendency is so diminished in the mothers of the
third generation that it will no longer betray itself.
i 2
ee eg
i +
LO Le) EL COE Le) udodwod
Fie. 22.—GenratocicaL TREE oF THE BLEEDER Famiuy Mampen. (After Lossen.)
Bleeders are shaded.
GUIDE TO FIGURES 22, 23, 24, AND 25.
female descendants
well
O
i a a
©
+
female | bleeder
Daltonist
male “ J hemeralops
died from hemorrhage
HEMOPHILIA 417
The fact that hemophilia may be directly transmitted also by the male
descendants forms an exception to the rule that women, even healthy women,
transmit the disease, that is, act as conductors. In a family in Bremen the
affection was transmitted by the father to the male members through three
generations, Also in the bleeder family from Wald in the Canton Zurich
such a tendency is noted, while on the other hand, the transmission from the
healthy mother occurs in the sons. In this case, in the first generation that
showed bleeders, among 16 persons there were 7 bleeders. In the following
generation, among 28 members there were 16 bleeders. In the third genera-
tion, there was a noteworthy decrease in that this showed only 1 bleeder and
Fic. 23.—GENEALOGICAL TREE OF A BLEEDER Famrity. (After H. Gocht.)
Bleeders are shaded.
12 non-bleeders. That from a hemophilic mother bleeders as well a3 non-
bleeders may be born is demonstrated by the following ancestral tree which is
taken from a communication of H. Gocht (Arch. f. klin. Chir., Bd. 59)
(Fig. 23).
The disease proved itself most stubborn in a family in the little village
of Tenna in Graubiindten, consisting of about 170 persons, whose family tree
was first described by Grandidier and Vieli, and then carefully revised by
Hosli who eliminated many incorrect statements of the first communication.
Here the hereditary transmission could be followed through six or seven gen-
erations. However, bleeders twice married into the family, which may explain
the long persistence of the pathologic predisposition. Several times the dis-
ease skipped two generations in this family, then reappeared in the third. In
the direct descendancy still longer pauses occurred; but probably only the
severest cases have been recorded. ;
The disturbances to which we may ascribe hemophilia may be designated
as “ parablastic,’ if we with His ascribe the development of the connective
tissue and of the blood and lymph apparatus to the parablasts in opposition
to the archiblasts, this latter designation being reserved for the epithelial
tissues that compose the ectoderm and the entoderm.
Although the development of the parablasts may still be questionable,
28
418 THE HEMORRHAGIC DIATHESES
and it may not be as yet quite certain, as His assumes, that this is an exch
sively maternal formation, still pathology furnishes a number of remarkab
facts emphasized by Klebs, which assign to the connective tissue germ (“ par:
“plasts”) a definite position in the structure and economy of the body. Asi
the controversy in regard to the origin of the parablasts and their compariso
with the archiblastic tissue, no matter how it may be decided, His has prove
the entrance of the parablastic endothelia into the cavities of the heart an
the vessels (a view which has been given new support by Kélliker and by (
Hertwig) and this indicates a great advance in pathology. If this speci:
position of the parablasts is recognized, quite new view-points are presente
for the production of pathologic predispositions during fetal development, {
which Klebs particularly refers. For it may be proven that in a varyin
development of the connective tissue extraordinarily important congenital an
pathological processes are combined, and that these are processes in which tl
transmission of both sexes plays throughout a very different réle, the femal
element representing the carrier of the disturbance, without in all cases pai
ticipating in the disturbance itself, while the male element is the passive par
We might be inclined from this general fact to ascribe to the parablasts ¢
least a predominant feminine nature, as might easily be possible if they actuall
arose from leukocytes that had wandered in. As this, however, has not ye
been proven we must content ourselves with looking upon the parablast as
structure upon which the male pronucleus (sperm cell) in the main has
slight influence, much less than the female pronucleus.
We incline to this view for the reason that individual parts, particularly th
bony tissue, by reproducing paternal forms from the parablastic tissues, as i
very frequently seen, may be recognized as under the influence of the mal
pronucleus. Nevertheless, we may assume that in certain cases this influenc
is much less operative in females than in males, and thus the non-appearanc
of the disease in the female members of a hereditarily affected family may fin
an explanation.
The same peculiarity of the transmission of properties through the mothe
who herself may show no traces of them, is observed (as may be mentioned her
in passing) also in other disturbances which cannot be traced exclusively t
the parablasts, such as hereditary Daltonism. In this, as in bleeder families
the law of transmission to the male descendants is seen, as was mentioned b:
Ribot and Darwin. Horner reports two very conclusive ancestral trees, th
correctness of which is due to his personal knowledge of the members of th
family. The ancestral tree is here given for comparison (Fig. 24).
This affection occurs exclusively in the male descendants, and is trans
mitted by the female who remains free. The single exception of a transmis
sion from father to son, which occurred in the fifth generation, is only a
apparent one, for the mother belonged to a collateral line affected with th
same defect. It is noteworthy that from this marriage a great number 0
grandchildren who were color-blind were begotten, the mothers of all, corre
sponding to the law, remaining unaffected, although in this case the hereditar,
transmission appears to have attained an unusual development.
The same law of heredity as in hemophilia and in color-blindness is als
HEMOPHILIA 419
operative in another remarkable affection—night-blindness (hemeralopia).
Although this disease, strictly considered, is not within the realm of our
theme, nevertheless it is so interesting that this slight digression is permis-
sible. Our knowledge regarding the etiology of night-blindness, in so far as
heredity is concerned, is limited to the following points: First, that hemeral-
opia, if it is hereditary, attacks more men than women, and that the disease
is frequently met with when the parents are blood relatives; further, that the
disease has been observed in several children of the same family, and has been
followed through several generations, from four to six. In literature we find
that where the disease has appeared in successive generations partly sons and
partly daughters were attacked (Sédan, Recueil d’ophthalm., 1885: Two fam-
Fic, 24.—GrnraLocicaAL TREE oF A Faminy suowine Dauronism. (After Horner.)
Daltonists are shaded.
ilies: in the first there are only 12 members, 5 females and 7 males, that
were affected, and in the second family, of 9 that were affected, 5 females
and 4 males. Savenzy (Irish Hospital Gazette, 1872) reports a family of 5
brothers and 5 sisters, of whom 2 brothers and 3 sisters had night-blindness) ;
or the disease may attack only the sons in a generation, and in such cases we
occasionally find the type of heredity which is characteristic of hemophilia and
of Daltonism.
We owe to E. Ammann, eye specialist in Winterthur, the knowledge of the
fact that night-blindness is transmitted according to the same laws as hemo-
philia and Daltonism. Ammann reports the family tree of a hemeralopic fam-
ily from which the law of heredity may be determined with absolute certainty
(Fig. 25). At the same time the observation that night-blindness and myopia
are often combined receives an important confirmation from the fact that
he determined the constant occurrence of both these affections in this family.
It was demonstrated that in the latter family only the hemeralopes were
nearsighted (Ammann found nine dioptrics), while the members who were
LT Ld OOOO
Fig. 25.—GENEALOGICAL TREE oF A Hemeratopic Famizy. (After E, Ammann.)
Hemeralops are shaded.
HEMOPHILIA 421
not attacked by night-blindness showed almost normal refraction. If we con-
sider the genealogy of this family, which is shown under Fig. 25, it is noted
first that the ancestor of the family, Andreas St., born in 1750, was healthy.
Whether he was the son, or his wife the daughter or sister, of a person who
had night-blindness, cannot now be ascertained. His three sons were all
night-blind, but did not marry. His daughter, Mrs. Lehmann-Steiner, unfor-
tunately became the ancestress for the further transmission of the disease.
She transmitted the affection to her two sons; of her two daughters, one
(Mrs. Vogel-Lehmann) transmitted the disease to two of her four sons.
Therefore, not all of the sons are night-blind, as in the second and third gen-
erations, but only one-half of them; of the four married daughters only two
- became conductors for the following generation, and of these two only one
transmitted the disease to her two sons, while the other (Mrs. Frey) had three
sons of whom one only showed the disease. The four daughters of Mrs. Frey
have very large families, but the sixth generation of this line remains com-
pletely exempt from the disease.
Therefore a decided diminution of the disease is here apparent, as had been
previously observed by Cunier in the year 1838. The condition is different in
the families where the disease is transmitted from the male side, i. e., from the
affected father through the daughter to the grandchild: Walter Reifer, the
grandchild of Adolf Vogel, is a descendant of the sixth member, and inherits
the disease to so high a degree that he can scarcely go about alone at night.
In the fifth generation also there is a grandchild affected by night-blindness,
in whose line the affection perhaps may be propagated; therefore the disease
may not rapidly die out in this family, but it is certainly on the decline. It
would be interesting to know the further fate of the family; whether a mem-
ber of the family with night-blindness in a manifest or latent form may, for
some unknown reason, become the progenitor of a race that will show a decided
tendency, or whether the disease will gradually disappear. The question also
interests us whether the affection may arise spontaneously without any hered-
itary predisposition, and may then be only accidentally transmitted in this or
that way, or whether such sporadic cases as are actually observed depend
upon a poorly maintained family tradition, or upon insufficient observation
of the individual members of the family. To decide this, further accurate
professional observations will be necessary.
The hereditary form of hemophilia is unquestionably and by far the most
frequent, but a so-called congenital form of the disease also appears to exist.
We understand by this that from the marriage of healthy persons originating
from healthy families children are born who are bleeders, and from these latter
the disease may be further transmitted. :
The importance of marriage between blood relations in favoring the devel-
opment of hemophilia has been emphasized, as well of psychical influences
(such as fright, anger) during pregnancy. Up to this time there is no sci-
entifically founded theory in support of these views.
Spontaneously, and without heredity, the disease certainly occurs only in
a very small number of cases, and in these the twenty-second year of life is
looked upon as the absolute limit of time up to which persons previously
422 THE HEMORRHAGIC DIATHESES
healthy may develop symptoms of hemophilia. These conditions, which in
themselves cannot be accounted for, are increased in importance by the fact
that spontaneous cases of “ hemophilia ” which develop in later life occur only
as quite localized hemorrhages limited to an individual organ.
Regarding the geographic distribution of the disease it appears that Ger-
many furnishes the main contingent of cases; yet other countries are not
entirely exempt from the disease. The following table, compiled by Gran-
didier, gives the following figures:
Bleeder ndivi 4
CounTRIES. Families. iesdone Males naman
Gein ccc kos biaeaawasaiaes naan onenaees 93 258 236 22
Hi eA 0. 224 aro easercs d ornva simceneieraonice aoe aes largy nian 46 141 134 7
TER ILC Oi adc sccvirre ave csatin the gestern op a aye rales 20 80 15 5
North, Ameritaysiocas ocas gneemravese da te eeoes 15 61 60 1
R888. oa anes 3 eaeateed ¢ vicemes Boas eee 7 11 7 4
Switzer lands... siesvoun casas widcnstes ooce e's de ecsisunione 5 48 48 na
Sweden-Norway......... cc cece eee eee ee eee 3 9 6 3
FAG TG ares cexerc evs ate elind sodi a aucrnaeateltn aviv ba van ataistiooses 2 9 vi 2
Bel BAW ascace vac paresieyy Satureairoe 1 4 4 ci
Denmark.... 1 3 2 1
East India... 1 6 5 1
MOLE sivpccuaance torn aneeeknvara cas Genunions 194 630 584 46
=92.6% =7.44
The actual causes of hemophilia are entirely unknown to us; everywhere
we meet with hypotheses. If the disease, as is assumed, be a parablastic
disturbance this may take place in the course of fetal development in two
ways; either in a greater or less development of the connective tissue germ
or because individual portions of this structure suffer particularly. Of special
importance is the fact that it is the maternal element which transmits the
disease without being itself necessarily involved, this property being an inherent
function of the maternal body, and much more marked in the feminine
descent than in the masculine. This faculty can exist only in the parablastic
tissue, and especially in the vascular system which arises from it. Conse-
quently it is very likely that the parablast, of all the tissues of the organism,
is most influenced by the mother, being less subject to paternal impressions
than any of the other constituents.
There are two factors which stand out prominently in the investigation of
the causes of the disease: the structure of the vascular system and the com-
position of the blood itself. As hemophilia is not to be considered a temporary
but a permanent pathologic condition which is congenital and hereditary, we
are compelled to assume a disturbance in “the first formation,” which affects
a portion of the connective tissue germ. Nevertheless, hypotheses of this
nature are not at present capable of verification by scientific investigation;
therefore, in regard to the actual condition, we have been compelled to rely
upon the scant anatomical findings which have now and then been reported,
but which, considered collectively, have not solved the puzzling nature of the
disease in question,
HEMOPHILIA 423
The abnormal composition of the vascular system is said to consist in the
greater tendency of the vascular walls to rupture, and this has been thought
to be due to a peculiar thinness and narrowness of the arteries, as well as to
their very superficial situation. Even were this condition more common than
is actually the case, these vascular alterations would not sufficiently explain
the spontaneous hemorrhages, for we find similar changes in the narrowed
aorta of chlorosis but no hemorrhages. In discussing the pathological anatomy
we shall revert to this; at present it need only he stated that some investigators
such as Hooper, Liston, Fischer and others found the walls of the arteries
in hemophilia very thin and showing fatty degeneration. Virchow laid
special stress upon the fact that in a bleeder, aged twenty-four, the aorta was
not only very thin and elastic but also very narrow, almost of infantile dimen-
sions, while the capillary vessels showed no change. Elastic arteries which
are too narrow propel the blood into the capillaries with too great force, and
this circumstance favors the hemorrhagic diathesis, or at least the continuance
of the bleeding. This narrowing of the arteries cannot be ascribed to any
special disease of the walls of the vessel, but to a disturbance of development,
analogous to the condition in chlorosis; this is consistent with another special
characteristic of hemophilia, namely, the marked hereditary tendency of the
affection. Whether the fatty degeneration of the intima, which has been found
in some cases but by no means in all, is not rather the result of the post-
hemorrhagic anemia than the cause of hemophilia is also questionable. At
the autopsy of some cases of hemophilia, hypertrophy of the left ventricle
with extreme thinness of the right has been found, and this circumstance has
been suggested as an explanation of the hemorrhages. If the blood be pro-
pelled with great force through the narrow, thin-walled arteries, the increased
pressure of the hypertrophied left ventricle may cause a rupture. Apart from
the comparative rarity of hypertrophy of the left ventricle, it must be remem-
bered that a great number of the hemorrhages are of a diapedetic nature, and
cannot be referred to rupture of the vessels alone; besides, we note the same
symptom-complex in congenital narrowing of the aorta without the sequence
of extensive hemorrhages such as frequently recur in hemophilia!
The fallacy of these mechanical explanations became more evident as opin-
ions multiplied that an insufficient coagulability of the blood was the cause.
The latter conclusion concerning the blood was the result of experience that
in hemophilia all hemorrhages, even with the most insignificant beginning,
are difficult to control. The blood does coagulate, however, as may be seen
from the surface of wounds; spontaneously it forms coagulated masses from
beneath which new quantities of blood exude, and these also soon coagulate,
and thus enlarge the blood clot. Gradually the oozing of blood ceases, and
the hemorrhage is arrested. Sometimes, however, in more severe hemorrhages,
there is complete cessation of the production of the fibrin ferment, the blood
gradually loses its power of coagulation, the hemorrhages progressively drain
the tissues, and death results from excessive loss of blood. Any form of
hemorrhage may be fatal, but this is most frequent in epistaxis; next, after
extraction of teeth; and, occasionally, in intestinal hemorrhages, etc.
Microscopic and chemical examination of the blood has shown normal
424 THE HEMORRHAGIC DIATHESES
conditions in by far the great majority of cases, so that the expectation of
finding there the actual cause of the disease has not been realized. Neither
is it possible to determine any deviation from the normal in the amount of
salts in the blood, in the quantity of fibrin producers, in the corpuscular
constituents of the same, in the numerical relation of the blood-corpuscles to
one another, or in the amount of hemoglobin. The anticipation of finding
the amount of fibrin decreased is also unconfirmed; Heyland found 5 to 1,000,
Gavoy-Ritter 2.6 to 1,000, and Otte 4.3 to 1,000. In the numerous contro-
versies regarding hemophilia the coagulability of the blood continues to be
the main and interesting question, and has played a great réle. While some
authors, such as Grandidier, Lossen and others, found diminished coagulabil-
ity of the blood, according to other authors this occurs only in the later stages
after severe hemorrhages (Hoffmann, “Text-Book of Constitutional Dis-
eases”). Grawitz does not consider these findings contradictory, for, under
ordinary circumstances, after prolonged hemorrhage, an increase of coagula-
bility occurs, and the blood which exudes last in hemorrhage frequently coagu-
lates immediately. Therefore, the slowing of coagulation in the later stages
proves conclusively the diminution in the power of coagulation.
These theories of the coagulation of the blood have been recently confirmed
by Alex. Schmidt, and applied by him to explain the conditions existing in
hemophilia. According to his observations, the blood of a patient coagulated
four and a half minutes after exuding, and in consideration of the amount
of blood previously lost he pronounces the time preceding coagulation as an
abnormally long one. In his patient the action of a “zymoplastic substance,”
produced by him, was first tested for its power in increasing coagulation; it
was placed in a test-tube with the blood of a hemophilic, and coagulation
occurred after ten seconds, whereas previously the time was four and a half
minutes. Locally applied to bleeding gums, as soon as contraction of the
vessels and a momentary cessation of bleeding had been brought about by an
injection of cocain, the “ zymo-plasma” also proved an excellent styptic, and
therefore holds out the possibility of a substance which may be used to
increase coagulation. *
The deterioration of the blood in functionating erythrocytes, as an ex-
planation of the hemorrhages, which Cohnheim assumed, is absolutely un-
proven; I have repeatedly taken specimens of the blood of hemophilics which
had been stained according to various methods, and have shown them to
blood experts who could detect nothing abnormal in them. Blood counts have
repeatedly shown normal conditions, as well in regard to the erythrocytes as
to the leukocytes. The blood-plaques are said to be increased in amount.
My own experience of hemophilia, which in all amounts to four cases, has
been gained by the same methods of blood investigation which we employ
in all other blood diseases. In two cases in which there was no marked anemia,
no definite changes were found. In both of the other cases, in which repeated
hemorrhages caused severe anemia, the patients being respectively eight and
sixteen years of age, I found the same changes as in cases of anemia after
acute and profuse losses of blood; namely, conspicuously pale color of the
erythrocytes, absence of well-developed rouleaux formation, decrease of hemo-
HEMOPHILIA 425
globin (30 to 35 per cent., according to Sahli), macrocytes, poikilocytes,
microcytes, increase of blood-plaques; no leukocytosis. These conditions im-
proved under suitable treatment (good nutrition, fresh air, processes for
hardening the body, avoidance of everything detrimental to health). I should
like to mention here that frequent inhalations of oxygen did not show the
slightest influence upon the general condition or upon the composition of
the blood.
G. Cohen reports a very remarkable blood finding in a bleeder (Zeitschr.
f. klin. Med., Festschrift, 1890): The blood was almost colorless, did not
coagulate upon beating, and upon standing left only isolated, friable, white
coagula of fibrin of the size of a bean; microscopically the well-known poly-
morphia of the red blood cells was found, such as occurs in anemic conditions,
but no rouleaux formation.
Various theories have been proposed in literature as to the origin of hemo-
phiha. Among the best known that of Immermann is the most important
and most widely circulated. It depends upon certain views of Virchow to
which we have already in part referred, but to which we must now recur.
Immermann expounds this theory in the following way:
Hemophilia is a form of the hemorrhagic diathesis which is chiefly charac-
terized by a hereditary predisposition? and a habitual manifestation; the
hemorrhages which are readily produced, frequent, severe, stubborn, and dan-
gerous, are chiefly caused by a hereditary and habitual disproportion between
the blood volume and the capacity of the vascular apparatus, which results in
an unusual increase of secondary pressure in the latter. Functional erethism
of the heart and unusual development of its muscles may in some cases of the
affection be responsible for the production of hemorrhages, as well as for its
abnormal clinical course, and for the tendency to fluxion in the affected indi-
vidual; possibly other neurotic influences may occasionally arise to increase
periodically the continuously fluxionary diathesis.
Oertel expresses himself likewise regarding the nature of hemophilia. He
is of the opinion that hemophilia is to be regarded as a hydremic plethora of
high degree. Following the same train of thought as Immermann and Oertel,
G. Cohen (Zeitschrift f. klin. Med., Festschrift, 1890) has founded a general
treatment of hemophilia, the main object of which is to combat the hydremic
plethora by an energetic cataphoresis and diuresis. The decided improvement
which Cohen brought about—this refers only to a single case—furnishes some
evidence of the correctness of this theory.
Cohen’s patient was the ninth of eleven children and was born in 1852;
at the time she came under treatment she was thirty-eight years old. Her
father suffered repeatedly from severe epistaxis ; twice tampons had to be used.
A grandchild of her sister suffered from morbus maculosus with effusion of
blood into the joints and renal hemorrhages and died of this disease when
twenty years of age. There is no other history of hemophilia in the family,
except a severe hemorrhage after extraction of a tooth in an older sister of
the patient. This patient was a delicate chlorotic girl, with scant menstrua-
+ Differently expressed: “The heredity of certain pathological properties.”
426 THE HEMORRHAGIC DIATHESES
tion and without tendency to hemorrhages. A far more decided hereditary
taint was noted in the nervous system; the father was a person easily upset
by the slightest psychical irritation, e.g., if he were going upon a journey,
vomiting and marked agoraphobia would occur. He died of heart disease.
One sister of the father suffered from hysterical spasms, and another was
very “nervous.” Among the children, one daughter cannot walk upon the
street without an attendant, and the patient in question suffers from cardiac
palpitation and an ill-defined feeling of fear unless accompanied by her
brothers and sisters. In this patient’s twelfth year the first marked hemor-
rhage occurred after the extraction of a tooth; a few months later menstru-
ation began, at first quite regular and not especially profuse. A year later,
after exertion in walking, upon the fourth day of the period, the first prolonged
metrorrhagia occurred, with syncope, palpitation of the heart, nervous attacks
of fear and excitement; the menses now became irregular, very profuse and
prolonged. During her attendance at school attacks of epistaxis were first
noted, and these were repeatedly followed by spasms. In the year 1869 the
patient was bedridden almost the entire summer, using iron waters, whey and
baths. She was in bed most of the time in 1870 on account of frequent
epistaxis and severe uterine hemorrhages; for the first time marked edema
of the feet was present. Toward the end of the year epistaxis was again
severe. In 1872 there were frequent attacks of epistaxis, but injections of
ergotin checked the hemorrhages for from six to eight weeks. In the next
year, after a trifling wound of the finger, hemorrhages occurred, lasting for
several weeks. Uterine bleeding was almost continuous. Ergotin was of no
avail. In 1874 hemorrhage occurred after the extraction of a molar. Two
years later, following a very severe attack of dysentery with hematemesis and
enterorrhagia such a severe epistaxis occurred that it was necessary to keep
a tampon continuously in the nose. Later, bleeding from the nose lasted
several hours. Galvanization of the sympathetic, combined with ergotin treat-
ment, temporarily improved the general condition. In the year 1881, for the
first time, large purpuric spots with decided, painful swelling appeared upon
the left upper arm. Menstruation lasted uninterruptedly from November of
the same year until February, 1882. Vaginal tampons were continuously
necessary. In March, 1882, for the first time, and then very frequently, there
was hemorrhage from the uninjured tip of the finger. During January of
the next year several intact fingers and the nose bled daily. Subcutaneous
hemorrhages followed, the blood in large areas of the right thigh and of the
left upper arm finding its way through the skin. In 1884 there was profuse
diarrhea, with frequent vomiting accompanied by massive hemorrhages, and
prolonged elevation of temperature which lasted for months. The urine be-
came exceedingly scant, one-eighth to a quarter of a liter in twenty-four hours;
it was pale, free from albumin, of very low specific gravity (1.002 to 1.005.
The average loss of blood in twenty-four hours amounted to one pound (358
grams). Galvanic baths decreased the number of hemorrhages. Improvement
was brought about exclusively by treatment based upon the decreased amount
of urine and an energetic diaphoresis was persistently carried out for over three
years; injections of pilocarpin which for a time were substituted by packs
HEMOPHILIA 427
lasting for hours, by effusions of folia jaborandi, flor. tilie, and the admin-
istration of large doses of digitalis. The patient was cured at the age of
thirty-eight after suffering from the disease for twenty-five years,
In the study of the etiology of hemophilia, those who adhere to the Im-
mermann-Oertel theory doubt much the prominent réle which the hereditary
narrowing of the aortic system is said to play. This hereditary anomaly also
produces chlorosis, a disease which, in spite of the similarity of individual ana-
tomical relations, has nothing in common with the manifestations of hemo-
philia. It may possibly be opposed to this that a second injurious factor, an
abnormal composition of the blood, is added to the smallness and narrowness
of the vascular system, and from this combination hemophilia arises, or, more
correctly, some of the symptoms of the affection. In opposition to this is the
fact that the examinations of the blood in hemophilia up. to the present time
have shown nothing constant nor positive; only in quite isolated instances
have microcytosis, macrocytosis, poikilocytosis, and absence of rouleaux for-
mation been observed. Similar deficiency of hemoglobin in the erythrocytes
and in the total blood has been repeatedly noted in anemic individuals after
successive hemorrhages (especially of a traumatic or neoplastic nature) with-
out the tendency to an acquired hemorrhagic diathesis, so that a characteristic
or pathognomonic significance cannot be ascribed to it. All hypotheses which
attribute hemophilia to an abnormal composition of the blood are lacking in
the proofs upon which a scientific proposition should be based.
That hemophilia is a neuropathic diathesis is v. Recklinghausen’s hypothe-
sis (Handbuch der Allg. Pathol. des Kreislaufes und der Ernihrung). In
the next article, when describing morbus maculosus, we shall refer more
minutely to the spontaneous hemorrhages due to the vasomotors, and shall
here only mention that this author ascribes to these hemorrhages (in support
of his theory) the prominent nervous symptoms which occur in certain cases
of hemophilia and occasionally in entire families of bleeders. But the ques-
tion arises whether in a general disease such as hemophilia the spontaneous
and unexpected manifestations which occur may not naturally keep the patient
in a constant state of tension and expectancy, and thus implicate the nervous
system, and whether or not the nervous disturbances are of a secondary
nature.
Finally, we must mention another view, already referred to in scurvy, that
hemophilia is a toric infectious disease. This is the opinion of W. Koch of
Dorpat, but it has received but slight attention in scientific circles. Koch,
in his book “ Bleeder’s Disease and Its Varieties,” analyzes the evidence on
which is based the conception of hemophilia as an independent affection. He
criticises adversely the reports of the disease which have been obtained up
to the present time. He points out how faulty these are, and their many
contradictions. The conclusion which he reaches is, approximately, that hemo-
philia is not an independent disease, but that it is an infectious disease and
identical with scurvy. “TI believe,” says Koch, “ that the blood of hemophilics
exudes through the walls of the vessels, which give no evidence of anatomical
change, because specific toxins are mixed with the blood; I therefore believe
hemophilia to be an infectious disease, and, on account of the coincident symp-
428 THE HEMORRHAGIC DIATHESES
tomatology and pathological anatomy, I believe it to be the same infectiou
disease as scurvy. In order to prove its parasitic nature, I must first refe
to the supposedly congenital form of hemophilia, to that form in which th
symptoms are present from the time of birth, and which can only be ascribe
to transmission from hemophilic parents. This hereditary condition can neve
be explained by the theory of a pes varus congenitus or a meningocele con
genita, i.e., by a vitium prime formationis in which definite observable ana
tomical changes (no matter how complicated in origin these may appear t
the eye of the observer) result in disturbances of function. For nearly
century such anatomical conditions have been sought for in hemophilia, anc
in spite of improved methods of investigation, only vascular anomalies ca:
now be found, a lesion the unimportance of which admits of no dispute, par
ticularly as in only a few cases has it*been found. In opposition te thi
theory, I believe congenital hemophilia to be quite similar to congenital syph
ilis, and from the standpoint of infection I note the association of hemophili
with wounds and ulcerative processes such as humid, benign, tuberculous am
syphilitic skin eruptions, glandular tuberculosis, discharges from the ear, sup
puration of the navel, etc.
“‘ Some hemophiliacs have a marked and abnormal desire to eat sand, earth
chalk, peat, acid and pungent vegetables. Some have febrile attacks; som
perish with surprising rapidity after only slight hemorrhage or other localiza
tion; almost all have an enlarged spleen. I lay great stress upon these facts
as well as on one which, so far as I know, has not yet been mentioned, mucl
less discussed, namely, the connection between hemophilia and infection. Fur
ther we must consider the presumption that, in those hemophilic familie
who made no change of residence for generations, particularly if the hemor
rhages occurred only in later life, the process may often be referred to influ
ences of the ground instead of to heredity.”
Koch’s theory of hemophilia as a toxic infectious disease, both as a whol
and in its premises, is so purely visionary that it scarcely appears worth dis
cussion. The association of heinophilia with glandular tuberculosis, tubercula
and syphilitic cutaneous ulcers, discharge from the ear, febrile states and th
other pathologic conditions which he mentions is so extremely rare as to b
scarcely noted at all by other authors. The same is true of the splenic tumor
which Koch says hemophiliacs almost invariably show, and upon which h
especially bases his theory of the infectious nature of the disease. Othe
symptoms which he emphasizes are not due to hemophilia, but to the anemi:
produced by the hemorrhages, as is the case with neuropathic symptoms
Above all, his theory of an infectious etiology is untenable inasmuch as th
presence of pathogenic agents has never been proven; all investigations as t:
this point have been negative. Still more unwarranted does it appear to m
to ascribe the pathologic processes of hemophilia to telluric influences instea:
of to heredity.
Fully as I agree with Koch that the origin of hemophilia cannot be looke
for in purely anatomical causes—that is to say, be dependent upon them—
cannot concur in his assumption of a toxic infection. Even if this coul
explain the nature of the congenital form of hemophilia, it can never expla
HEMOPHILIA 429
the mystery of the transmission of the disease in a hemophilic family, why the
mother herself should remain unaffected while she transmits the disease, why
the male members of the family only are attacked, why men from bleeder
families do not beget hemophilic children, whether they themselves are bleeders
or not, etc. Moreover, congenital hemophilia is much rarer than that form
in which children in the second year or adolescents manifest the signs of the
disease! Are the pathogenic agents latent in such cases? And what causes
them to assert their virulence ?
In rare cases mothers with relapsing fever have given birth to children
with relapsing fever! This is probably analogous to the “toxic infection ”
which Koch assumes as the cause of congenital hemophilia.
In the last few years, Kolb, Babes, Gartner, Tizzoni and Giovannini have
demonstrated bacteria in patients suffering from purpura hemorrhagica as
well as in hemophilia of the newborn; these bacilli were apparently also
pathogenic in animals, and upon inoculation produced a disease characterized
by hemorrhages. These maladies are probably analogous to the hemorrhages
often seen in other infections, and we may assume these hemorrhages to be due
partly to local changes in the vessels caused by collections of bacteria, and
partly to the toxic effect of bacterial products. These may, therefore, to some
extent be classed with toxic hemorrhages, but have not the slightest element
in common with human hemophilia,
That with the hemophilic predisposition severe or even uncontrollable
hemorrhages follow trifling occasional causes such as never produce hemorrhage
in the healthy is a generally well-known fact, and this has led to a differentia-
tion between spontaneous and traumatic hemorrhage. But obviously in this
division the conception of “trauma” must be very elastic. The hemophilic
tendency to hemorrhage shows itself during the period of physiologic develop-
ment, particularly in the two periods of dentition, at puberty, and at the
climacterium. Even in tying and severing the umbilical cord we sometimes
produce severe, even fatal hemorrhage, and we recognize by this and other
signs the hemophilic predisposition of the newborn.
Severe hemorrhages from the gums are prone to occur in the first period
of dentition, and we are forced to look upon the cutting of the teeth as trauma.
Quite slight corporeal punishment may produce cutaneous hemorrhages and
infiltrations of blood out of all proportion to the nature and extent of the
injury. Blowing the nose may cause uncontrollable epistaxis; profuse con-
junctival hemorrhages may be produced by touching the eye. Purgatives may
result in severe intestinal hemorrhages. At the menstrual period and in
normal labor extraordinarily severe hemorrhages have been observed.
Especially frequent are effusions of blood into the joints.
From the observations of surgeons it is evident that the first hemorrhages
into the joints, as well as also the great majority of the later ones, are caused
by external conditions. This explains why children are not attacked by hemor-
rhages into the joints before they learn to walk; the “trauma” 1s absent.
But when they first begin to walk, when the joints are utilized and the entire
muscular system comes into action, trauma after trauma occurs, and arthritic
hemorrhages are apt to appear. We quite often observe severe hemorrhages
430 THE HEMORRHAGIC DIATHESES
into the joints which occur while the patients are in bed, and when we are
unable to detect the slightest external cause. In such instances we are almost
always dealing with joints which have repeatedly been the seat of effusions
of blood.
Most bleeders perish in infancy, a large proportion before the eleventh
year. Rarely do they reach old age, seventy and above. The hemophilic
predisposition diminishes with advancing years. ;
If we study the reports up to the present time, we are convinced that the
true causes of hemophilia are absolutely unknown. Even of the two etiologic
factors most frequently and invariably mentioned—an abnormal composition
of the vascular walls (which is said to consist in great fragility) and the
insufficient power of coagulability of the blood, to which I shall again refer—
we do not possess a single positive proof which will bear criticism.
Heredity assumes such importance in the etiology of this disease that it
is well to point out that a highly nervous temperament on the part of the
ancestors has often been noted. Of course, the reports of the patients and
their relatives must be accepted and utilized with extreme caution; yet a num-
ber of well-authenticated cases are on record which certainly prove the neuro-
pathic predisposition of the ancestors of bleeders.
PATHOLOGICAL ANATOMY
The anatomical examinations in fatal cases of hemophilia have, up to the
present time, shown nothing that is characteristic or invariable; in particular,
very little has been revealed to explain the tendency to spontaneous hemor-
thages, except in the case of the joints. Here, by the tireless researches of
surgeons, we are permitted a deeper insight into the mechanism of arthritic
hemorrhages.
The number of autopsies by experts on the cadavers of bleeders is very
small ; consequently the number of anatomico-pathological findings is also very
scant. In general the following is reported: The cadaver is conspicuously
anemic; the skin is waxy pale. In cases in which death has occurred from
hemorrhage after trauma, petechie, ecchymoses, suffusions of blood and signs
of injury are found upon the skin itself with comparative frequency. The in-
ternal organs throughout are extremely anemic. The small amount of blood
flowing from severed vessels is decidedly watery. Of the abdominal organs,
in which there are often signs of preceding hemorrhages, the spleen is par-
ticularly interesting; W. Koch maintained—as we have seen—that it is in-
variably enlarged; it has occasionally been found enlarged, but is usually
normal. This enlargement of the spleen in hemophilia has sometimes been
deemed especially important, particularly as proving the infectious nature
of the disease; but the knowledge that this finding is inconstant has led to
the rejection of the theory.
The blood-vessels of the skin which are superficially situated have been
often described, the arteries as well as the veins. The muscle of the heart
frequently, but by no means invariably, shows fatty degeneration. Its size
has in some cases been found normal; in other cases it is hypoplastic, and in
still others hypertrophic, especially as regards the left ventricle. In a number
HEMOPHILIA 431
of instances the large arteries and their first branches show an unusually
narrow lumen. In the examination of the structure of the larger and smaller
arteries, the extremely thin, sometimes actually transparent condition of the
intima is often conspicuous. Partial fatty degeneration is not rarely observed.
Virchow called attention to the smallness of the heart in hemophilia, to
the narrowness and thinness of the walls of the vessels, which is similar to that
in chlorosis. On account of the rarity of autopsy reports in this disease, it is
highly interesting to refer. to this finding in a case observed by Virchow, upon
which he held an autopsy, and which he has detailed (Deutsche Klinik, 1859,
and Canstatt’s Jahresb., 1859). “The blood, as in other cases of hemophilia,
was not deficient in fibrin; it formed a decided buffy coat. The arteries and
veins showed no large ruptures—in fact, no conspicuous changes; the hemor-
thages, therefore, must have been from the capillaries. The veins were very
wide, the arteries very elastic and narrow. The capillaries and nerves showed
no decided alterations. In the central part of the vascular apparatus an
abnormality was found which was certainly congenital; the thymus gland was
still very large, the heart pale and small, the aorta narrow, its walls thin and
very elastic, with wavy rises due to slight sclerosis and fatty degeneration of
the intima, particularly in the descending thoracic aorta. This entire finding
closely resembled chlorotic conditions to which I (Virchow) have previously
called attention. The development of the heart from the aorta is much re-
tarded in chlorotics; enlargement of the heart is late and occurs only occa-
sionally. Hemorrhages are very frequent and severe in chlorotics, and these
ean probably be traced to the arterial changes which have been observed; at
all events the round ulcers of the stomach which occur chiefly in chlorotics
certainly bear a relation to individual arteries. There is much in favor of the
congenital, or at least very early, development of the predisposition to chloro-
sis; and this may be positively maintained in the case of hemophilia. The
blood collected from this case rapidly decomposed, depositing xanthoglobulin
crystals as well as triple phosphates and leucin. This case teaches us that in
hemophilia it is not an unusual fluidity, a dissolution of the blood, which
produces the tendency to hemorrhage, because blood rich in fibrin, just as in
scurvy, may be found in the hemorrhagic diathesis. Nowhere was tendency
to rupture of the blood-vessels noted. Therefore the question arises whether,
in this case, as in chlorosis, the narrowness and extreme elasticity of the
vessels (arteries) so increase the blood-pressure in the capillaries that a pre-
disposition to rupture and consequent hemorrhage is produced. In this case
the cause of the hemorrhagic diathesis was to be sought in a deficiency of the
vascular formation, and it is certainly noteworthy that the thymus gland had
persisted for so long a time.”
Virchow, therefore, considered retardation of vascular development to be
an especial pathologico-anatomical sign in hemophilia. He observes, how-
ever, that exactly the same conditions as were noted by him in hemophilia
oceur also in chlorosis. The question why retardation in vascular develop-
ment causes two such entirely different diseases as chlorosis and hemophilia
has not yet been answered. If we are inclined to be critical, we may assume
from this condition of affairs that retardation of vascular formation cannot
432 THE HEMORRHAGIC DIATHESES
be the determining cause of hemophilia. Nevertheless, the descriptions of
Virchow are highly important, as they form the basis of the Immermann-
Oertel theory of hemophilia.
But the positive findings mentioned above which have been observed in a
number of autopsies in cases of hemophilia are opposed—tfew as they are—by
a much greater number in which, after minute investigation, experienced
pathologists were unable to determine anything noteworthy.
More widely known are the changes in the bleeder’s joint, a knowledge
of which we owe to the valuable work of surgeons. In the first stage of the
arthritic disease, we find the symptoms of a simple effusion of blood. The
joint cavity is filled with fluid blood and dark coagula of fibrin. The latter
are partly free, partly adherent to the walls, and by proliferation of the cell-
layers of the synovial membranes they are made integral parts of the wall of
the joint. The capsule is thickened, shows bloody infiltration, and is discol-
ored. Moreover, fibrin deposits are found upon the capsule and upon the
surface of the cartilage, causing the formation of brownish pigmented villi
and cartilage proliferations. If the effusion of blood is not absorbed the joint
swelling remains, and inflammation is produced which pathologically resembles
the condition Konig has designated as hydrops tuberculosus fibrinosus. The
contents of the joint are either serous or hemorrhagico-serous, and of a light
brownish color. The perisynovial connective tissue is sclerotically thickened.
The synovial intima shows swelling and reddish-brown or brownish discolora-
tion, and a great number of synovial villi of a brownish tint. The blood
coagulum in some cases attains the thickness of a finger. The cartilage has
lost its white color and its luster, and appears of a brownish hue. Coagulated
masses of blood are found in layers which show organization and connective
tissue change. The cartilage is partly softened by the disappearance of its
upper layer. Continuous small and large depressions, sharp-edged and map-
like, invade deeply the surface of the bone surrounding the cartilage. The
surface of the cartilage is uneven on account of an irregular disappearance of
substance. Following this second inflammatory stage, a third occurs in which
regenerative changes play the principal réle. By adhesion of the joint sur-
faces, and by processes of shrivelling in the soft parts and capsules, stiffness
of the joints supervenes. The joint cavity becomes denuded, the joint ends
deformed; subluxation takes place; contracture and ankylosis may occur.
Examination with the Réntgen rays has, according to Gocht (Arch. f. kl.
Chir., 1899), given constant and important findings: It is at once evident that
the lower end of the femur upon the affected side is very much smaller than
that of the opposite side. The bones upon the diseased side are atrophic and
decidedly too permeable, as may be noted in the lighter color of the Réntgen
picture—the epiphysial lines upon the femur and the tibia lack the normal
rounded curves, and are irregular, often serrated, with a double contour.
While upon the normal side a broad, open space marks the presence of normal
cartilage, and the osseous ends of the femur and the tibia present their well-
retained smooth surfaces, the conditions upon the diseased side are quite
different. A decreased joint space is found, owing to destruction of the
cartilage. The ends of the bones appear completely changed. The arthritic
HEMOPHILIA 433
portion of the femur is serrated and irregular, the cavity normally existing
between the two condyles has been obliterated; the same is also true of the
intercondylar eminences of the tibia which are irregular and broadened. Still
more advanced lesions are seen in older patients; the space in the joint car-
tilage disappears entirely, the tibia seems dislocated toward the femur out-
wardly. Occasionally adhesions may be noted between the femur and the
tibia. The condition of the capsule cannot be accurately determined on
account of the effused blood.
The microscopic investigations of the vascular changes in hemophilia, made
by Buhl and Birch-Hirschfeld, deserve attention.
The former found in a preacher, aged seventy-four, suffering from chronic
dermatoses and presenting hemophilic symptoms, an immoderate growth of
the capillary vessel loops with a great increase and subsequent transformation
of their nuclei. Buhl himself does not believe this anomaly to be peculiar to
hemophilia. Birch-Hirschfeld examined the heart and the large vessels, a
portion of the spleen, the kidney and the skin of a child, aged one year, who
had succumbed to congenital hemophilia, and remarks concerning these organs:
“Tn the heart and in the vessels connected with it I discovered no changes.
It may be stated that the vessels of the heart, considering the age of the child,
were quite of normal size. In the heart muscle there were but slight indica-
tions of fatty degeneration. The valves, as well as the intima of the larger
vessels, were delicate and normal in structure; the same was also true of the
muscularis and media of the arteries. In the kidneys the cortical canals were
swollen and there was slight granular cloudiness of the epithelium. There
was nothing noteworthy in the spleen except moderate hyperplasia of the
stroma of the pulp. But I must mention—with reserve—a finding which I
noted in the capillaries and the transitional vessels of other organs, particu-
larly of the liver and kidneys. In some areas the endothelia were obviously
enlarged, their nuclei swollen; here and there were granular deposits in the
protoplasm. In some rather poor preparations which were stained with silver,
the epithelial arrangement appeared to me irregular, disarranged, with occa-
sional wide spaces between the endothelia. I do not lay special stress upon
this condition. In delicate changes of this kind it is not always possible to
determine how much is artifact, and it must not be forgotten that such changes
are, perhaps, not rare in the last stages of other chronic cases.” Kidd de-
scribed in the finer vessels of the subcutaneous connective tissue and of the
muscles an increase of the endothelia with dropsical swelling of the muscularis
and proliferation of their nuclei—changes which Legg in another case was
unable to recognize. I should like to mention the simultaneous occurrence
of hemophilia with multiple sarcomata.
Obviously pathological anatomy affords no clue for the comprehension of
the clinical picture. The belief that blood formation is periodically increased,
which is mentioned by some authors, has but little to support it, and the same
is true of the hypothesis that the overfilling of the narrow, perhaps friable,
vascular system of hemophiliacs by a hypertrophied heart through which newly
formed blood is occasionally forced in large amounts leads to a rupture of the
markedly distended capillaries.
29
434 THE HEMORRHAGIC DIATHESES
SYMPTOMATOLOGY AND COURSE
The phenomena of the disease are quite often revealed purely by accident ;
the patients are attacked either spontaneously, or, in consequence of very slight
injuries, by profuse hemorrhages or such as are very difficult to control.
Among such cases I wish to mention the hemorrhages which occasionally
follow ritual circumcision, and sometimes cause the surgeon great difficulty,
as well as those which occur after perforating the lobe of the ear for earrings,
and, finally, the muscular hemorrhages which occur in older children of a
hemophilic predisposition, when they are chastised by the teacher in school;
these, under some circumstances, bring the guiltless teacher into court.
The disease shows various grades of development, and by no means the
same intensity of symptoms in all cases. The history of families of bleeders
has shown that in individual members all types of the disease, from the
mildest rudimentary forms up to the severest ones, may be found. The milder
forms are characterized by an evident tendency to hemorrhages, but the bleed-
ing never assumes such proportions as directly to threaten life.
In nearly three-fourths of the cases the first hemorrhage occurs before the
end of the second year, and the latest period for its occurrence is the twenty-
second year of life; only in quite isolated cases has the first hemorrhage
happened at a later age. A great tendency to hemorrhage is noted in bleeders
at about the period of physiological development. Most hemophiliacs die in
the first year; a large proportion before the end of the tenth year. Only very
rarely is old age reached—seventy years and beyond. Experience teaches that
with increasing years the hemophilic predisposition declines, until finally it
disappears entirely.
As has been stated, the physician or the family often becomes aware of the
hemophilic tendency of an individual quite accidentally, by the difficulty of
controlling a hemorrhage, which returns again and again. This is especially
apt to be the case if the patient is not a member of a bleeder family, and has
not older relatives, particularly brothers, in whom severe hemorrhages some-
times occur as the result of quite trivial injuries while at play. In other
cases, surgeons while performing operations make the unpleasant discovery
that the hemorrhage from an operative wound does not cease, and that they
are dealing with a bleeder. The hemorrhagic or hemophilic predisposition of
the newborn is earliest recognized if hemorrhages appear after severing the
umbilical cord; these occasionally are uncontrollable, and result in the death
of the child. However, we can by no means refer all hemorrhages from the
cord of the newborn to a hemophilic predisposition of the child. It has been
proven that umbilical hemorrhages in the newborn may also be due to the
influence of bacterial blood infection. The next event which may lead to the
discovery of the disease is ritual circumcision, which, as is well known, is
performed upon the eighth day after birth. On the other hand, vaccination,
according to usual experience, is relatively harmless. The disease may, how-
ever, not show an early spontaneous development but may be latent, and only
appear after an exciting cause and upon occasion. The most common time
for this is the period of first dentition, and thus we frequently note decided
HEMOPHILIA 435
signs of the disease in the form of severe hemorrhages from the gums. Some-
times in girls, although quite rarely, there may be no evidence of the disease
throughout infancy and childhood, the first symptoms appearing at the time
of puberty and recurring at each menstrual period, the menses being unusually
profuse and persisting for a long time. Even after an easy and uncomplicated
labor occasionally severe, even fatal, hemorrhages occur, so that: Kehrer has
Ree the interruption of pregnancy in hemophilic women by artificial
abor.
The most obvious and important sign in the clinical picture of hemophilia
is the appearance of well marked hemorrhages either without an assignable
cause or as the result of very slight external injuries. In about 50 per cent.
of the cases the mucous membrane of the nose is the seat. of the hemorrhages ;
next follow bleeding from the gums and intestinal hemorrhages (each about
12 per cent.), then pulmonary, gastric and renal hemorrhages (each about 6
per cent.). Most frequent are the hemorrhages from the skin and mucous
membrane, next from the joints, to which I shall later refer explicitly, and
finally, metrorrhagia. Apart from arthritic hemorrhages, hemorrhages from
the serous membranes without assignable cause are quite rare. On the other
hand, hemorrhage from the conjunctiva is occasionally noted, apparently
occurs without cause, and may sometimes be so severe as to result fatally.
This was seen in the case of two brothers, both bleeders, who were quite
young. Occasionally the hemorrhages are so profuse that death takes place
in a few hours. It is often astonishing to observe what enormous amounts
of blood hemophiliacs may lose, and how rapidly they recover from this. In
Cohen’s case the patient lost a pound of blood (3858 grams) per hour, and in
another case of hemophilia, within eleven days twenty-four pounds of blood
were lost. Occasionally syncope, the result of cerebral anemia whereby blood-
pressure falls to a minimum, causes a cessation of hemorrhage. With an
increase of the blood-pressure, hemorrhage begins anew. The disproportion-
ately rapid regeneration of the blood must be referred to the previously men-
tioned increase of the hematopoietic function of the bone-marrow in hemo-
philia (Fischer) which, however, is of a somewhat hypothetical nature.
It is customary in hemophilic bleeding to differentiate between spontaneous
and traumatic hemorrhages. All hemorrhages are designated as spontane-
ous for which no plausible reason can be assigned. But it must also be
considered, in the study of the hemorrhagic diathesis, that there are condi-
tions in which the organism of the hemophiliac reacts by hemorrhages to
very slight influences—influences of such an insignificant character that the
person who suffers a lesion scarcely notes it at all or but very slightly. With-
out doubt some of the hemorrhages which in this diathesis have been looked
upon as spontaneous are in reality traumatic. We differentiate in these
hemorrhages (spontaneous as well as traumatic) two forms: The superficial
and the interstitial.
Spontaneous hemorrhages are occasionally preceded by prodromes such as
cardiac palpitation, congestion of the head, vertigo, tinnitus aurium, anxiety,
nausea and even vomiting. Prior to very severe hemorrhages, decided red-
ness of the face is often noted; in the visible arteries rapid and strong pul-
436 THE HEMORRHAGIC DIATHESES
sations may be seen. The general condition, also, is decidedly influenced; the
patient becomes restless; he is filled with fears or there is lassitude. For
a long time the fleeting character of these hemorrhages has been noted. After
the hemorrhage has ceased, the affected persons usually feel relieved and easy
in mind. In other cases these premonitory phenomena are entirely absent.
The hemorrhages may come on without any noteworthy prodromes. Super-
ficial spontaneous hemorrhages occur most frequently from the mucous mem-
branes; first from the most exposed, as those of the nose, then the mucous
membrane of the mouth. Spontaneous hemorrhages may also occur from the
mucous membrane of the urinary organs and from the female.sexual organs,
also from the lungs, the stomach and the intestines. The hemorrhages from
the skin are most likely to occur in cicatrices, or from cuts or ulcers, and the
hemorrhage then takes place during a period in which the rupture of con-
tinuity is beginning to heal. Spontaneous mucous membrane hemorrhages
are occasionally combined with those of the surface of the skin. In subeu-
taneous effusions of blood which embrace a wide area occasionally suppuration
is noted, leading to gangrene of the skin and external perforation, after which
a slough consisting of brownish and gangrenous shreds is discharged. The
blood in the subcutaneous hematomata remains fluid for a long time similar
to the condition in arthritic hemorrhages, and the careless opening of such
foci may lead to uncontrollable and fatal hemorrhages; the latter may even
occur when these hematomata rupture spontaneously.
Interstitial spontaneous hemorrhages occur most frequently in the scalp
and in the face, next in the scrotum, more rarely in the extremities, and least
frequently upon the trunk. Often the tips of the fingers are implicated, and
the blood may exude or spurt from them as from a sponge dipped in blood.
Although these hemorrhages appear spontaneously, i.¢., without visible ex-
ternal cause, it may be regarded as certain that they, as well as the “ trau-
matic” ones now to be described, are due to very slight, scarcely determinable,
mechanical insults. Intraparenchymatous hemorrhages of internal organs,
perhaps with the exception of the kidneys, very rarely occur in areas which
are protected from external influence, a circumstance which, according to
Striimpell, forms an essential difference between hemophilia and the acquired
hemorrhagic diathesis.
Superficial traumatic hemorrhages may take place in any superficially lying
part of the body, in all areas of the skin, and upon the superficially situated
mucous membranes, as well as upon those mucous membranes whose secretions
are discharged per vias naturales. To these must be added the serous mem-
branes of the thoracic and abdominal cavities. Hemorrhages from the surface
and from the mucous membranes which are susceptible to ordinary inspection
may be produced by a laceration, a puncture, a bite or other wound, also by
a blow, a fall, and by surgical operations. It is to be remarked in this
connection that accidental ruptures of continuity, particularly those of an
irregular form, cause hemorrhage in hemophiliacs much more readily than
those produced by design, as in surgical operations. Cutaneous areas with
ulcerating processes and cicatrices are loci minoris resistentia. Of the various
regions of the body, the head is the one in which the hemorrhage of hemo-
HEMOPHILIA 437
philiacs assumes an exceptionally severe character. Probably the most copi-
ous hemorrhages occur after the extraction of teeth. In one case reported,
the rupture of the hymen was followed by lethal hemorrhage. It is a peculiar
fact that small wounds in hemophiliacs bleed in proportion much more pro-
fusely than larger wounds. Fordyce controlled a hemorrhage by enlarging
the wound with a knife. This method appears to be the best in the case
of lacerated wounds which bleed profusely. Traumatic surface hemorrhages
usually occur from only one isolated point. The blood exudes from the wound
as from a sponge saturated with blood; nowhere can a spurting artery be
found.
Interstitial hemorrhages after trauma occur particularly in the skin and
the subcutaneous connective tissue. They follow the slightest external causes.
A push, a blow in sport, or prolonged pressure as in sitting or lying, may
produce interstitial hemorrhages. Blood tumors are formed (hematomata).
Those areas on the surface of the body are most liable to interstitial hemor-
thages, which, from the habit of life, are most exposed to pressure, the but-
tocks and the upper posterior parts of the leg, as well as the back.
Diffuse hematomata are found especially in the soft parts of the arms and
thighs, as well as occasionally in the sheath of the psoas muscle. They occa-
sionally resemble an abscess, with tense, glistening, hyperemic skin, and are
very painful. The subcutaneous effusions of blood may extend over a wide
area; upon suppuration, gangrene of the skin and external rupture have been
observed as in spontaneous hemorrhages ; a chocolate-colored mass intermingled
with gangrenous shreds is then discharged.
The other most important symptom of the disease is the great difficulty
with which the hemorrhage is controlled. This forms the chief danger of
the malady, and is the reason why bleeders very rarely attain old age. The
open, hemophilic bleeding reveals perfectly the characteristics of parenchyma-
tous hemorrhage. From the entire surface which has been exposed by the
traumatic rupture of continuity, the blood oozes continuously for many hours.
Even by the most careful observation it is impossible to find a spurting
vessel.
How long the hemorrhage may continue in the individual case cannot be
foretold. It is quite uncertain, but the excessive loss of blood in itself acts
favorably in controlling the hemorrhage. The bleeding hemophiliac is at-
tacked by syncope; shortly afterward the hemorrhage ceases. Frequently,
however, it lasts for so long a time as to bring about a fatal issue. During the
hemorrhage, frequently there is at first increased cardiac activity; later, in
consequence of increasing anemia the pulse becomes small, sometimes imper-
ceptible, the patient is pale and feeble; in very severe cases there are delusions,
convulsions and delirium.
The exuding blood at first appears normal; if, however, the hemorrhage
is long continued, it constantly becomes lighter and of a watery, serous char-
acter, owing to the increasing anemia. Chemical and microscopical investi-
gations of the blood have not given noteworthy results. There is no evidence
to support Immermann’s theory that the hemorrhages are due to a plethora.
The interstitial hemorrhages under the surface of the skin form blood-
438 THE HEMORRHAGIC DIATHESES
tumors (hematomata), which, in accordance with the transformation of the
hemoglobin, may show the well known changes of color observed in all depos-
its of blood. Now and then a hematoma of this kind suppurates and ruptures.
Such hemorrhages damage the nutrition and constitution of the patient all
the more as they lead to certain complications which will be more minutely
described later. Moreover, the knowledge that he is affected with such a
disease as hemophilia severely disturbs the psychical condition and the nervous
system of the patient.
Among the characteristic complications of hemophilia the tendency to
“rheumatic” muscular and arthritic disease occupies the most important
place, partly for the reason that we recognize in this a close analogy to the
hemorrhagic diathesis in general. The arthropathies which may appear in
any of the joints are the most familiar complications of this affection ; first,
on account of their frequency, and secondly, because their recognition, partly
by means of the Réntgen rays, and partly by local surgical treatment which
frequently permits direct inspection of the open joints, has led to more accu-
rate knowledge of them. They occur spontaneously as well as in consequence
of trauma which may be extremely slight, for they occur even in bedridden
patients who can scarcely move. Frequently they are of undoubted “ rheu-
matic” nature, for the tendency of hemophiliacs to be affected by “ rheumatic
irritation” is very great. The peculiar relation which exists between the
hemorrhagic diathesis and diseases of the joints will be more closely consid-
ered in the next chapter. In hemophilie arthropathies the knee- and elbow-
joints are particularly often implicated. The disease begins with pain and
swelling which may lead to stiffness and a position of flexion, as in subacute
arthritic inflammation, or with a tumor albus. The diagnosis is not always
easy, and sometimes can be made only by noting the other hemophilic phenom-
ena which have preceded the joint disease. The latter occurs most frequently
in isolated attacks which may be recognized by the pain and swelling of
certain joints as well as by fever, exactly as in the case of polyarthritis
rheumatica. The course of the disease is naturally a very chronic one.
In the majority of cases it is young males who are affected by hemophilic
arthritis.
F; Konig divides the arthritic affection of bleeders into three stages: First,
the stage of initial hemorrhage, the hemarthros of bleeders. With proper care
the hemarthros may heal and the disease may terminate in this stage. If this
is not the case the blood acts as an irritant, more blood is added, and a peculiar
form of inflammation develops (second stage) which shows itself as a pan-
arthritis, and which in the pathology as well as in its clinical symptoms shows
great similarity to tuberculosis of the joints. This stage is to be designated
as the inflammatory, the hemophilic tumor albus. The third stage is the
retrogressive, the stage which leads to permanent deformity of the joints, the
contracted bleeder joint with dissolution of the joint cavity, adhesions, and
displacements of the arthritic surfaces, and finally ankylosis and deformity
of the joint ends.
K6nig’s division appears to have found general acceptance among surgeons.
The first stage is not to be viewed as though we were dealing with but a single
HEMOPHILIA 439
hemorrhage. On the contrary, the most characteristic feature of this stage is
the fact that one or more effusions of blood are promptly absorbed without
any external derangement or even diminution of function remaining which
can be recognized by disturbance or change in the joints. Gocht, in Hoffa’s
Clinic, observed in different hemophilic youths quite a number of more or less
severe arthritic hemorrhages, either without a determinable trauma or as its
direct consequence. The knee-joint, which he mentions as the one most fre-
quently affected, at times appeared to be enormously thickened by a large
effusion which occurred very suddenly, sometimes in from five to ten minutes.
The joint was sometimes in slight flexion, at other times also in extension;
sometimes there was pain, at other times none. Sometimes the joint was fixed
and immovable, again the function was not at all disturbed. A patient in
Hoffa’s Clinic had more than 45 severe hemorrhages in the right knee-joint
without suffering the slightest inconvenience in the use and function of the
joint. The left knee-joint which was contracted had sustained about 40 hemor-
thages; the first 39 gave rise to no injury; only the last effusion of blood
led to permanent contracture. If the effusion is not absorbed, the swelling
in the joint remains and is not amenable to treatment, as, for instance, was
the case in this last mentioned knee-joint which led to contraction. Pains
appear, and the function is much interfered with. According to Kénig we
are then dealing with that peculiar form of inflammation (second stage)
which, as well in its pathology as in the clinical symptoms, closely resembles
tuberculosis of the joint, and which was called by this author hydrops tuber-
culosus fibrinosus. The picture of the latter disease is simulated even to the
most minute detail. In such cases the contents of the joint are hemorrhagico-
serous or serous with a brownish color. The synovial intima shows swelling
and brownish discoloration, and a large number of fluctuating, brownish,
discolored, synovial villi. The coagula of blood in some areas may attain
enormous thickness. The cartilage loses its white color and its luster, and
shows a brownish discoloration; it is partially softened because its upper
layer has been lost. It also shows defects and unevenness in its surface on
account of an irregular loss of substance. The investigation of such joints
with the Rontgen rays has been described by Gocht as follows: We recognize
that the lower end of the femur upon the deformed side, in contrast to the
other side, is decidedly smaller. The difference amounts to more than 1 cm.
The bones upon the diseased side are atrophic and too permeable to the
Réntgen rays, as may be recognized from the lighter color in the skiagram.
The epiphysial lines upon the femur and tibia do not show the normal rounded
edge, but they are irregular, serrated, with double contours. Upon the epiph-
ysis of the femur anomalous indentations are shown. While upon the normal
side an open space denotes the presence of normal cartilage, and the osseous
ends of the femur and tibia present their normal forms, the conditions upon
the diseased side are quite different: Corresponding to the loss of cartilage,
a decidedly decreased joint space is found. The ends of the bones appear
completely changed; the end of the femur is serrated and irregular ; the
indentation normally between the condyles is lost, and the intercondylar emi-
nence of the tibia is irregular and extended. The recent losses in structure
440 THE HEMORRHAGIC DIATHESES
and the recent deposits fit each other. The capsular shadows upon the inner
side of the contracted knee-joint are darker than upon the normal side.
In the case of an older boy, in whom remarkable changes had taken place,
the cartilage space in the joint had disappeared entirely, the tibia was markedly
dislocated outwardly. Between the bones adhesions could be seen, The rela-
tions of the capsule could not be judged from the picture, for at the time the
plate was made an enormous effusion of blood had occurred in the joint,
which was revealed in the picture as an oviform shadow the size of a hand.
In the diagnosis of bleeder affections of the joint, in accordance with
Konig’s views, Gocht differentiates three groups as follows:
1. Individuals who are well-known bleeders,
2. Those who have not been known to be bleeders, but who present charac-
teristic symptoms of hemophilia besides the arthritic affection,
3. Those in whom neither the history nor any prominent symptom indi-
cates the general affection.
If there is no history of hemophilia, such as preceding severe hemorrhages,
the very rapid development of an effusion into the joints without noteworthy
trauma and an accurate examination may lead to the proper diagnosis. The
pains are often out of all proportion to the severity of the case, and the
function of the implicated joint may be scarcely impaired. This is especially
the case if the patient is seen in the first stage of the disease. If, on the
other hand, a joint is found in the stage of inflammation, the diagnosis be-
comes more difficult, as the clinical picture of the bleeder joint is identical
with that of hydrops fibrinosus tuberculosus. The difficulty lies in the fact
that the investigator rarely considers the possibility that he is dealing with
the diseased joint of a bleeder. For, if hemophilia is considered at all, an
error in diagnosis is virtually excluded. The following phenomena point to
a hemophilic joint: subacute hemorrhages and scleroses about the joints;
freshly developed effusions into the joints, or hemorrhages under the skin
into the muscles, etc. ; last, and above all, the signs of previous disease in other
joints. Kénig also declares that in hemophilia the patients are generally
youthful males with a conspicuous pallor of the face. This latter symptom
Gocht quite properly denies, for, in the first place, bleeders may show a
healthy color of the face, and, on the other hand, patients with tumor albus
are for the most part extremely pale, though of course abscess and formation
of fistula, which are common with tumor albus, are exceedingly rare in
hemophiliacs. In doubtful cases one or more injections of tuberculin may
be used for diagnostic purposes.
From what has been said, it is evident that the recognition of a bleeder’s
joint may sometimes be very easy, at other times difficult but still possible,
occasionally impossible.
Gocht agrees with Linser that those bleeders who do not suffer from disease
of the joints are exceptions. Almost invariably the arthritic affection is
localized in one knee-joint. This may be due to the fact that the knee-joint
1s most exposed to injury on account of the great extent of its surface and its
exposed position. The first hemorrhages, as well as the great majority of the
later ones, are due to external causes. That children are not attacked by
HEMOPHILIA 441
hemorrhages of the joints prior to learning to walk is explained by the absence
of trauma. If, however, during the period in which they learn to walk, the
joints are brought into use as well as the muscles, the time for hemorrhage
of the joint has come, for the physiologic function of the joint is to be looked
upon as a series of traumatic influences! Quite often surgeons note the
appearance of arthritic hemorrhages of the most severe type even though the
patient remains in bed, and is apparently not exposed to the slightest external
injury. In such instances the joints affected are those that have been repeat-
edly the seat of effusions of blood. Probably because of the hyperplasia of
the synovial villi, in consequence of changes in the surface of the cartilage,
and on account of the great predisposition to hemorrhages, any slight motion
may cause a laceration of such synovial villi, and so give rise to severe
hemorrhages.
The question whether the predisposition to arthritic hemorrhages decreases
with time must generally be answered in the affirmative. For, as we have
already pointed out, according to the general views of hemophilia, the tendency
to bleed declines in later life, and disappears entirely in the aged. We must
likewise assume that a predisposition to arthritic hemorrhages gradually de-
creases, especially since the children become less active as they grow up and
greater care is taken to prevent injuries. Another point which Gocht also
considers in his observations is, whether the joints finally, in consequence of
pathologico-anatomical changes, lose their tendency to hemorrhage. If a joint
enters the third stage, the retrogressive, if destruction of the joint cavity has
developed, if the former hyperplastic villi have contracted, or if adhesions
in the connective tissue of a cartilaginous or osseous character have occurred,
hemorrhages will be much rarer, in the first place, for anatomical reasons,
and, secondly, because irritation due to motion is no longer present.
Still another factor must be considered—the variation in the individual
predisposition. If, as we have seen, one hemophilic patient is capable of with-
standing more than 45 severe arthritic hemorrhages without apparently suffer-
ing in function, while another readily develops a panarthritis, it follows that
the power to absorb the effusion of blood in the joints also varies greatly in
different patients. The question of the coagulability of the blood in the hemo-
philiac, which is still open and undecided, need not enter into this discussion.
According to Gayet and Th. Hirsch, the clinical phenomena of the arthritic
affections of the hemophiliac resemble especially an acute or subacute arthri-
tis (on account of pain and swelling, fever, stiffness, and the flexed position).
On the side of pathogenesis, these authors believe that, besides hemorrhagic
processes, we cannot deny a rheumatic influence in the joint affections.
Of other complications, the neuropathic predisposition is to be mentioned,
which in some patients, chiefly women, presents itself in manifold ways.
Here the hereditary neuropathic predisposition is especially prominent. Neu-
ralgia is a relatively frequent occurrence in bleeders, and occasionally neuritis
has also been noticed. In some cases a long-continued fever without local
changes has been observed. Finally, I must mention the appearance of cir-
cumseribed, hard, painful infiltrations into the skin and the subcutaneous
connective tissue, above which the skin remains unchanged in color; later
442 THE HEMORRHAGIC DIATHESES
these may undergo the characteristic changes which occur in the extravasa-
tions, or they may disappear without these changes.
LOCAL HEMORRHAGES UPON A HEMOPHILIC BASIS
In the last decade a number of cases have been published in which the
common characteristic was a more or less profuse hemorrhage from a kidney,
the absolute integrity of the organ being determined either by clinical observa-
tion or by operation. In these important cases the question arises: What
factor is the cause of the hemorrhage? Although Lauenstein published his
fundamental case in the year 1887, and a large number of similar observations
followed (those of Sabatier, Schede, Anderson and Leguen in the years 1889
and 1890), only Senator’s article (“ Regarding Renal Hemophilia,” 1891) can
be accorded scientific, authoritative importance. JI shall therefore give a
synopsis of the case:
A girl, aged nineteen, in the year 1887, noted blood in the urine immedi-
ately after menstruation. The examination of the voided hemorrhagic urine
at that time showed a large amount of hemoglobin although no red_blood-
corpuscles. After the lapse of two years, during which time decided debility
and periodic cough gave rise to the suspicion of tuberculosis, the hemorrhage
recurred ; this time it was more profuse, and lasted with slight intervals more
than six months. The analysis of the urine showed actual hematuria; the
blood discharged through the kidneys differed but very little from pure un-
mixed blood. Toward the end of February, 1890, Senator determined the
following: Patient is well formed, very pale, no trace of emaciation. The
internal organs present nothing abnormal; lungs and kidneys apparently
healthy. Urination painless, perhaps somewhat more frequent than normal,
but without tenesmus. The urinary sediment consists exclusively of erythro-
cytes; crystals, pus and other pathologic constituents are absent. No fever.
The examination carried out under an anesthetic shows no changes, neither
in the kidney nor in the bladder nor in the sexual organs, but it was demon-
strated by means of the cystoscope that the blood flowed from the right ureter.
After the usual causes of hemorrhage, such as stone, tumor and tuberculosis,
had been excluded, Senator made a diagnosis of hemophilia which was con-
firmed by the history. It was ascertained that the patient was a member of
a family in which hemorrhages occurred frequently. Four sisters, and a
brother aged seventeen, showed great tendency to epistaxis; the father, who
at the time was quite healthy, as a child had been frequently attacked by
nose bleed and hemoptysis without showing any pulmonary lesions. Eleven
brothers and sisters of the father suffer or have suffered from epistaxis; an
uncle of the patient, who for a long time suffered from epistaxis, in his
twentieth year had an attack lasting twenty-four hours, after which purpura
appeared over the entire body and hematemesis occurred; the disease ended
fatally after fourteen days. A second uncle is the father of two children
who have inherited epistaxis from him. The mother of the father, up to
the time of her death, menstruated profusely. Unquestionably, therefore, the
patient was a member of a bleeder family. Although no symptoms of hemo-
HEMOPHILIA 443
philia had previously appeared, Senator believes, in the absence of other
causes, that he may assume a hematuria of hemophilic origin. The continued
hemorrhage resulted in a severe anemia which resisted all internal remedies,
and for this reason nephrectomy was proposed and performed. The organ
was laid bare and removed, although apparently unchanged. The further
course of the disease was very favorable. Upon the second day after the
operation the blood disappeared from the urine and never recurred. Four
weeks later the patient left the hospital entirely well. The examination of
the extirpated kidney showed small inflammatory foci and extravasations;
otherwise the organ was absolutely normal.
I shall add to this two other analogous cases observed in v. Leyden’s clinic
and described by G. Klemperer:
1. A man, aged thirty-five, admitted to the clinic on the 15th of April,
1893. The father of the patient died of enteric fever, the mother is living
and since earliest childhood has suffered from frequent subcutaneous hemor-
rhages and marked bleeding even after insignificant injuries. A brother died
of hemorrhage during an amputation. Another brother of the patient is also
predisposed to hemorrhages. The patient himself, immediately after birth,
had a severe hemorrhage from the umbilical cord. In childhood hemorrhages
frequently occurred from the nose and other parts of the body after insignifi-
cant trauma. From his third year, he suffered from swelling of the joints
of the upper and lower extremities. As a rule these swellings occurred sud-
denly without cause, usually early in the morning; they were extremely pain-
ful, but often disappeared on the same evening; complete motility of the limbs,
however, did not return until some months after the attack. At fifteen the
patient had a fracture of the thigh and severe subcutaneous hemorrhages de-
layed normal recovery. His first attack of hematuria occurred at sixteen,
accompanied by dull pain in the right renal region, which soon became colic-
like; this was followed by nausea and vomiting. The urine was of a bloody
red or black color. This condition lasted for several months, the hemorrhages
recurring at intervals of from six months to two years. One attack of hema-
turia lasted thirteen weeks. The patient did not seek professional aid, as
he believed himself to be a bleeder, and looked upon the hematuria as a symp-
tom of the general affection. During the attacks he remained quiet, and
relieved the pain by large doses of morphin which had first been used at the
time of the enlargement of the joints. The patient came to the clinic princi-
pally for the treatment of his morphinism. He is pale, nervous; the internal
organs are normal. Upon the fourth day after admission a renal hemorrhage
occurred which lasted for two weeks. The urine contained pure blood. The
patient was discharged cured upon the 15th of May, 1893. Toward the end
of his stay in the hospital two hemorrhages into the wrist-joints occurred.
Subsequently this happened quite frequently. Up to March, 1896, the hema-
turia had not recurred.
2. The other case was that of an official aged twenty-six years, the history
showing but slight hereditary predisposition. The patient himself was a
bleeder. From the age of sixteen, almost every year attacks of hematuria
occurred, which occasionally were repeated several times in the year, and lasted
444. THE HEMORRHAGIC DIATHESES
for hours or weeks. With these the patient had insignificant pain in the
right renal region. He consulted a physician only when a hemorrhage lasted
longer than eight days. Upon the 2d of November, 1895, pain occurred in
the right renal region, and upon the 9th of November he voided bloody urine.
Examination showed nothing abnormal; no pathologic constituents except
blood were found in the urine. In spite of numerous remedies the hemorrhage
continued, and the anemia constantly became more marked. Upon the 28th
of December all drugs were stopped, and hydrotherapy was begun. The
patient had a bath each day lasting ten minutes, followed by affusions to the
renal region. The bath was begun at a temperature of 95° F., the water being
gradually cooled to 75.2° F. The affusions were at a temperature of 82.4° F.
to 60.8° F. Gradually the hemorrhages became slighter, and the urine finally
cleared. Upon the 15th of January the patient left the clinic cured.
A fourth case is published by 8. Grosglik: “ Ueber Blutungen aus anatom-
isch unveranderten Nieren” (Sammlung klin. Vortrdge, Nr. 203). An army
officer, aged thirty-six, of a bleeder family on both paternal and maternal sides.
The patient was of healthy appearance, but suffered frequently from marked
epistaxis and hemorrhage from the rectum. In September and December,
1896, he had severe hematuria for which clinically no cause could be assigned.
As the patient’s history was unknown at that time, the diagnosis wavered be-
tween a beginning tumor and tuberculosis of the kidney. After an observa-
tion of six months, as no further point of support could be determined for
either diagnosis, and after the patient had related his family history, Gros-
glik made the diagnosis: “Idiopathic renal hematuria upon a hemophilic
basis.”
In other cases of “ néphralgie hématurique ” in which the hematuria could
not be assigned to a hereditary hemophilic constitution, it has been assumed
that the cases were due to vasomotor or traumatic renal hemorrhage (i.e.,
due to corporeal over-exertion). Accordingly, varieties of hemophile vaso-
motor and traumatic renal hemorrhage might be described in which the possi-
bility of other causes for hemorrhages than an anatomical substratum could
not be excluded.
In regard to the diagnosis, if there is no enlargement of the kidney, and
if the composition of the urine and the accompanying symptoms do not favor
an organic affection, the following facts are of importance: The proof of a
hereditary hemophilic predisposition, a preceding exertion, or disturbances of
the nervous system (hysteria, neurasthenia, etc.) by which the vasomotor
center for the kidney might be implicated. If the history reveals anything
positive, the diagnosis of essential hematuria becomes likely. It only becomes
certain, however, when, after prolonged observation, no distinct signs of ana-
tomical change have appeared. :
The treatment of hemophilie renal hemorrhage, according to Grosglik,
should be expectant. If the course of the affection is severe internal remedies
are powerless, and if the hemorrhage threatens to prove fatal the bleeding
kidney must be removed as soon as possible. In so-called vasomotor renal:
hemorrhages the diagnosis should be immediately confirmed by surgical inter-
ference, which should not only embrace the exposure and palpation of the
HEMOPHILIA 445
organ but also an incision into the kidney, and a minute investigation of
the parenchyma. If the incised kidney is found to be anatomically unchanged,
it should be closed by suture and replaced. If this procedure affords no relief,
a secondary nephrectomy is to be performed. Primary extirpation is not
warranted in these cases.
How little data the exploration of an incised kidney in vivo may furnish,
Zondek recently demonstrated in a discussion before the Society of Internal
Medicine, when he arrived at the following conclusions:
1. Even in a kidney laid open by operation the presence of a small stone
cannot be excluded with certainty.
2. Even when surgical exploration of the organ gives a negative result,
inflammatory changes of the renal tissue may be due to a stone in a con-
cealed calyx.
3. Complete proof of the diagnosis of angio-neurotic hemorrhage from the
kidney necessitates the most careful investigation of the entire kidney after
it has been removed from the body, and also of the ureter down to its point
of entrance into the bladder.
Harris (Philadelphia Medical Journal, March 19, 1898) published two
cases of “essential” renal hematuria. In one of the patients the kidney was
exposed. In both cases the hemorrhage ceased.
Harris has collected 16 similar cases from literature. The majority of the
patients were cured by simple nephrotomy. He comes to the following con-
clusions: 1. Renal hemorrhages occur in which none of the usual causes, acute
nephritis, tuberculosis, sepsis, neopiasms, malaria, etc., are present. 2. The
pathological changes arising in the kidney are unknown to us. 3. These hema-
turias are not controlled by ordinary styptics. 4. If tonics, cold baths, etc.,
are without effect, nephrotomy must be performed. 5. Primary nephrectomy
is in no wise indicated.
J. Israel writes on the curative influence of renal incision in cases of uni-
lateral colic and unilateral renal hemorrhages in the obscure pathologic condi-
tion which up to the present has been called néphralgie, néphralgie hématurique,
renal hematuria without known lesions, essential or angio-neurotic renal hemor-
thage, all of which, according to his investigations, most frequently depend upon
chronic inflammatory changes of the kidney. Up to the year 1898 he had oper-
ated upon 14 cases of this kind. Five kidneys were examined microscopically,
and four of these showed different forms of nephritis. In eight of the remain-
ing nine patients, microscopic investigation of the kidneys showed organic
changes. Of the fourteen cases treated by nephrotomy three died, of whom
two had severe bilateral nephritis; six were completely and permanently cured ;
three after apparent recovery suffered from mild relapses of varying duration ;
in two patients the operation was designated as useless.
Israel has summed up the important knowledge obtained from these obser-
vations in the following: 1. There are cases of unilateral nephritis. 2. There
are cases of renal colic due to nephritis which may completely simulate colic
from calculi. 3. There are cases of bilateral nephritis which produce only
unilateral colic. 4. There are cases of severe nephritis with absence of albu-
min in the urine and absence of casts. 5. The urine may be free from albumin
,
°
446 THE HEMORRHAGIC DIATHESES
in spite of a profusion of hyaline, granular and epithelial casts. 6. There
are cases of nephritis with paroxysmal, profuse hemorrhages. 7%. Nephritic
hemorrhages may occur and run their course with or without colic; the hemor-
rhage is not the cause of the colic. -Both phenomena are the results of renal
congestion. 8. A great number of pathologic conditions designated up to
now as néphralgie hématurique are to be referred to nephritic processes. 9.
Incision into the kidney in many cases influences the nephritic process and
its symptoms favorably.—In a lecture, “ Hemorrhage from a Normal or Appar-
ently Normal Kidney,” Naunyn in the main agrees with Israel that interstitial
nephritis is the most frequent cause of this form of renal hemorrhage.
Pousson in two cases of apparently spontaneous renal hematuria extirpated
the affected kidney. The microscopic examination of the congested kidney
revealed inflammatory foci in the renal cortex without other abnormalities.
Poirier and Picqué advise in such cases only the operation of nephrotomy, as
frequently the other kidney also presents signs of chronic nephritis. In con-
trast to this Regnier believes that in such cases we are invariably dealing with
a beginning renal tuberculosis (?); he therefore strongly advises early
nephrectomy.
Hofbauer (Mitth. a. d. Grenzgeb. d. Med. u. Chir., 1899, V, 3) describes
a case of essential unilateral hematuria in a girl aged thirteen: It was espe-
cially difficult to determine in this case the etiology of the hematuria which
had persisted for two years. It had appeared without an assignable cause, and,
in spite of this great duration, had. produced no sequele with the exception of
anemia and its consequences. The examination of the urine revealed no
pathological constituents except an admixture of blood. Upon cystoscopy the
urinary bladder was found normal; the blood was seen to exude from the left
ureter while from the right ureter clear urine was being excreted. No signs
upon palpation. An exact clinical diagnosis was not made. On account of
marked loss of blood there was an exploratory incision only; this did not fur-
nish the hoped-for, absolute certainty. On exposure, the kidney was found to
be normal in size, and palpation revealed no pathologic changes.
When, to facilitate more exact inspection, the kidney was drawn forward,
a laceration of one of the larger vessels made extirpation necessary. The
hemorrhage ceased. Recovery followed. Macroscopically, the kidney, the
renal pelvis, and the ureter were perfectly normal. Microscopical investiga-
tion of the extirpated organ revealed a chronic glomerular nephritis. In this
case the diuresis following the nephrectomy was very interesting. The amount
of urine a few days after the operation not only equalled the former amount
but decidedly exceeded it. .
In 1891 Senator, in his case of renal hemophilia (Berliner klin. Woch-
enschr., 1891, Nr. 1), tested the activity of the remaining left kidney. For
this purpose he examined the urine daily for four weeks from the second day
after nephrectomy, in regard to amount, specific gravity, and its contents of
1T should like to remark in this connection that upon the occasion of the Tenth
Congress of Internal Medicine in 1891, when I demonstrated the centrifuge in Wiesbaden
for the first time, I called attention to the fact that “casts occur quite frequently in
urine free from albumin, and can scarcely be looked upon as pathological.”
HEMOPHILIA 447
nitrogen. The reaction was always acid. With the exception of the first
day upon which the urine still contained some blood, and upon the succeeding
day when a small amount of albumin was present, abnormal constituents were
never noted. The examination for nitrogen was conducted according to the
well-known process of Kjeldahl, and several times urea was estimated accord-
ing to Pfitiger’s modification of Liebig’s method. It was shown from the
table, published in Senator’s report of his case, that immediately after the
operation the remaining left kidney performed all the work of both kidneys,
perhaps at first functionating even a little more, for a daily excretion of
nitrogen of over 16 grams (such as was seen in this case) is the normal for
an adult person with a plentiful supply of food, and for a young girl in such
a condition (lessened amount of food after the operation) is a decided and
abnormal increase.
Floderus in Lennander’s Clinic observed a case of renal hematuria with
macroscopically unchanged kidneys. He examined microscopically the kid-
ney extirpated by Lennander, and demonstrated a disseminated sclerotic
glomerulitis with advancing sclerosis in the adjacent connective tissue, also
fatty degeneration and atrophy of the epithelium. In consequence of this
finding Floderus studied minutely the previously published cases of so-called
essential renal hemorrhage. He divides these cases into the five following
groups:
1. Renal hemorrhage in hemophilia.
2. Renal hemorrhage due to vasomotor disturbance.
3. Hematuria from mechanical causes.
4. Hemorrhage from kidneys which are the seat of nephritic processes.
5. Imperfectly described cases of essential renal hemorrhage.
After these literary deductions Floderus enters upon a discussion of most
of the cases published, minute reports of which are entirely lacking. For
this reason the last group must include the majority of the cases assigned to
the four other groups. His criticism of the cases described in literature per-
mits the assumption that in scarcely a single instance was the bleeding kidney
shown to be intact histologically.
In a woman aged forty-five, who for two years and six months suffered
from a left-sided renal hematuria, de Keersmaecker performed nephrectomy.
The kidney revealed interstitial and parenchymatous inflammatory nephritis
(with hemorrhage).
Rovsing has written a long article regarding unilateral hematuria of ques-
tionable origin and its treatment by nephrectomy.
Before making the diagnosis, “hemorrhage from normal kidneys” we
must determine by all methods at our command: 1. That the hemorrhage
actually originates from the kidney; 2. That all pathologico-anatomical
changes which may be assumed to be the cause of renal hemorrhage are abso-
lutely excluded. The cases published may be divided into two groups: 1.
The cases treated exclusively by medication; 2. The cases in which the kidney
was directly palpated by operation, was incised, or was removed. Only the
last-named cases, of which Rovsing collected reports of 13, are of particular
importance. In all of these observations the authors unanimously state that
A448 THE HEMORRHAGIC DIATHESES
they were unable to find any material or assignable cause for the hemorrhage;
while, from the circumstance that the hemorrhage ceased after operative in-
terference, whether by a simple exploration, a nephrotomy or a nephrectomy,
proof was given that the hemorrhage actually arose from the kidney in ques-
tion. For the explanation of the hemorrhage, therefore, the assumption of a
“1ocal hemophilia ” or an “ angioneurosis” is in these cases held sufficient.
If, however, the published clinical histories are critically examined, we
arrive at the conclusion that, as a matter of fact, in by far the majority of
cases, pathological conditions of the kidney or of the pelvis of the kidney
might have been determined which would explain the hemorrhage. Finally,
in the cases in which the kidney has been found apparently normal, the pos-
sibility was not considered that the starting point of the hemorrhage was not
in the kidney substance at all, but in the pelvis of the kidney, or in the ureter.
Rovsing communicates four personal observations, in three of which patho-
logical changes were observed, and comes to the following conclusions: 1.
Many of the published cases of hemorrhage of nervous origin do not stand
the test of critical analysis, as in some of them pathological conditions were
actually present which very readily explain the hemorrhage, while in other
cases the investigation was not thorough enough to exclude other affections,
not only those of the kidney but also those of the bladder, as cystoscopy was
not performed to determine the origin of the hemorrhage from only one ureter.
2. There is no doubt that in a number of cases of hematuria from normal
kidneys, dislocation of the kidney with torsion of the pedicle or kinking of the
ureter plays an important réle. 3. The first case mentioned by Rovsing dem-
vnstrates the fact, unknown till then, that lacing and the pressure of a corset
may directly cause very marked disease of the kidney. 4. After a careful
sifting of the cases a few still remain in which decided hemorrhage, which
was proved to originate from one ureter, disappeared permanently, although
the exploratory incision of the kidney in question showed no demonstrable
pathologic changes. 5. Such cases are so rare that they may be considered
purely as exceptions, and since serious disease can never be excluded clinically
as a cause for obscure cases of hematuria, in all doubtful cases an exploratory
lumbar incision should be made, especially since, according to experience, this
may have a curative effect upon the hematuria.
In the first session of the Fourth French Congress for Urology (October,
1899) a symposium upon “ essential hematuria” took place. Malherbe and
Legueu maintained that, besides hemorrhages occurring in tuberculosis, car-
cinoma, and lithiasis, a so-called essential hematuria had also been described
which is apparently independent of disease of the urinary organs. In an
accurate analysis of the cases published up to that time, particularly those cases
which had been pathologico-anatomically investigated, pathological changes
were almost invariably noted even though often slight, for example, calcareous
incrustation of a pyramid, or slight tuberculous disease. The most frequent
cause of so-called “essential hematuria” is evidently chronic nephritis. The
quite insignificant sclerosis of the renal parenchyma, as, for instance, after
contusion of the kidney, in floating kidney, and in pregnancy, may remain uni-
lateral, and not necessarily give rise to further symptoms of Bright’s disease.
4
HEMOPHILIA 449
The assumption of a “ hemophilic ” and an “ angio-neurotic ” hematuria is not
justifiable. “On peut dire, quw’il n’y a pas d’hématurie essentielle: toutes les
hématuries sont symptomatiques et relévent d’une cause générale (toxique ou
infectieuse) ou d’une affection rénale.”
Tédenat also questions the occurrence of true essential hematuria. His
own experience relates to four cases of which two were very probably con-
nected with nephrolithiasis; nephrotomy produced a cure. In another case
the hemorrhage ceased after the removal of a small hydatid cyst of the kidney.
In the fourth case the cause of the hematuria was a carcinoma of the colon
compressing the ureter, after the removal of which the hemorrhages perma-
nently ceased.
Pousson also denies the existence of essential hematuria; he calls atten-
tion particularly to the hemorrhages which result from the retention of urine,
in consequence of floating kidneys, or from other causes. For instance, he
observed an apparent renal hematuria in a patient in whom there was at the
left renal opening of the ureter a mucous membrane valve which caused, from
time to time, a more or less complete retention of urine. After division of
the valve and fixation of the kidney the hemorrhages ceased. In another case
a stone embedded in the mouth of the ureter produced the hemorrhage.
In this connection Albarran remarks that the cases of so-called essential
hematuria may be divided as follows: 1. Hematuria in floating kidney; 2. In
hydronephrosis; 3. Hematuria in early stages of chronic nephritis. Seven-
teen cases of this latter form are already mentioned in literature. He adds
another case occurring in a patient aged fifty-three. The hemorrhage ceased
after nephrotomy. The diagnosis of diffuse parenchymatous and interstitial
nephritis was confirmed by the microscopical examination of an excised por-
tion of the kidney. Boursier emphasizes that so-called essential hematuria
may for a long time be the only symptom of a nephrolithiasis. In the urate
and oxalate diathesis severe hematuria is also observed without any stone
being present; it may be that the small crystals produce an irritation of the
renal parenchyma and so eventually lead to periodic hematuria.
Hamonic calls attention to hematuria as a premonitory symptom of cer-
tain renal affections (parenchymatous nephritis, nephrolithiasis, tuberculosis,
carcinoma).
Galland-Gleize also confirms this fact. He communicates reports of four
cases in which for a year and a half to seven years hemorrhage had preceded
the disease later determined (kidney-bladder stone, tumor of the bladder).
Loumeau agrees with those who do not believe in essential hematuria ex-
cept when the microscopic investigation demonstrates that the “renal epi-
thelium” is normal. But we should require even more than this; not only
the integrity of the epithelium but also that of the entire parenchyma should
be determined after a portion of the kidney has been excised and examined.
This will be still insufficient for an anatomical diagnosis, as the pathologic °
process is not always uniformly distributed over the entire organ. But, apart
from the actual, diffuse disease of the kidney, this objection is much more vahd
for those diseases of the renal tissue which arise from a focus, such as a stone,
ete. Here the investigation of one, or even of several, portions of the kidney
30
450 THE HEMORRHAGIC DIATHESES
might show perfectly normal conditions, while in the immediate vicinity of the
excised portion changes might have taken place which gave rise to the hemor-
thage!
Pantaat has described a typical case of so-called essential hematuria in
floating kidney. Here the hemorrhages were connected with severe attacks of
renal colic, and were permanently relieved by nephropexy.
In opposition to many other authors, Castan believes in an actual essen-
tial hematuria, as a proof of which he mentions the following typical case:
A woman, during the menopause, and for a period of several months, had
very profuse hematuria without the slightest symptom of nephritis being evi-
dent. Complete and permanent cure was effected by means of baths, massage,
etc. In Castan’s opinion, a disturbance of menstruation may cause the reten-
tion in the body of certain toxins which, without causing demonstrable disease
of the renal parenchyma, may give rise to hematuria. To this category the
hematuria of the pregnant also belongs: “ La femme est en état de toxhémie
permanente.”
Guyon declares that among the causes of severe threatening renal hemor-
thages congestive conditions occupy the front rank. The kidneys, however,
macroscopically and microscopically, may present no changes to explain the
congestion. He admits, of course, that renal hemorrhages may be due to
inflammation, neoplasms, stone, ete. Guyon mentions cases of profuse con-
gestive renal hemorrhages in which neither at the operation nor at the autopsy
could pathological changes be detected in the kidney. Especially noteworthy
are three observations in which, during pregnancy and lactation, severe conges-
tive conditions led to profuse renal hemorrhages.
Briefly, the cases are as follows:
1. A woman, aged thirty-five, previously healthy, in the eighth month of
pregnancy voided for fourteen days urine of a coffee-brown color. In the
eighth month of her third pregnancy hematuria recurred and lasted for three
weeks. During this pregnancy there were no signs of nephritis. Three
months after this last labor, sudden, severe, continuous hematuria appeared,
and debilitated the patient greatly. There was a discharge of coagula, with
severe pain in the right renal region. Up to this time the patient had been
nursing her child. Upon advice she ceased nursing the child, and the hemor-
rhages immediately stopped. Right kidney somewhat enlarged; irregular
shape. Diagnosis: Neoplasm of the right kidney. Upon lumbar incision and
section, kidney found to be perfectly normal. Suture; recovery. Hemor-
rhage has not recurred.
2. Hematuria in the course of the fourth and fifth pregnancies ; otherwise
perfectly normal conditions.
_ 3. Severe hematuria at the end of pregnancy; sudden stoppage after ter-
mination of labor.
_ The same author mentions two other cases of hematuria during preg-
nancy. A total of twelve cases of this kind is found in literature. Guyon
does not believe that these pregnancy hematurias are to be looked upon as true
essential hematurias. Besides mechanical causes, inflammatory changes which
lead to congestion evidently play a great réle.
HEMOPHILIA 451
Desnos has seen in a large number of gouty patients hematuria which
either preceded or followed the attacks of gout. This gouty hematuria was
either accompanied by renal colic or ran its course without pain; the condi-
tion may be brought about by “ congestion,” but may find its explanation fre-
quently in the influence of stone.
On account of limitation of space, it is impossible for me to discuss more
minutely the literature of the last few years, and I shall refer only to the
very comprehensive discussion in the Berlin Society of Internal Medicine in
January, 1902, of the excellent article of Professor Senator, “Renal Colic,
Renal Hemorrhage and Nephritis,” which gives succinctly the views regard-
ing these questions of such prominent authors as Senator, James Israel, G.
Klemperer, and L. Casper. Any one desiring to learn the present status of
this question will find in this source material upon which to form his opinion,
although it is impossible at this time to state a definite conclusion. The sub-
ject is still open to discussion, and the combined labors of the surgeon and
the internal clinician will be required to clear it from all doubt.
I must emphasize a fact which is frequently observed, that in hemophilia,
hemorrhages from other parts of the body cease when hematuria occurs.
Senator was the first to throw light on this dark subject, and it is cer-
tainly owing to his labors that some renal hemorrhages have been recognized
as of hemophilic origin. Although some have doubted whether, in his case,
the condition was actually renal hemophilia or, on the contrary, hemorrhage
due to another and, at that time, unrecognizable cause, there is much in favor
of his view that cases of hereditary renal hemophilia have lately been observed
(Attlee and Guthrie, St. Bartholomew Hospital Journal, December, 1901, and
The Lancet, May 3, 1902, xviii; compare also Senator, “ Renal Diseases,” 2d
edition, p. 515, additions). No matter how we view this condition it is greatly
to Senator’s credit, and will remain so, to have been the first to recognize the
just importance of, and to throw the proper scientific light upon, the under-
lying cause!
Hematuria must not be looked upon as the only local hemorrhage in hemo-
philia.° Under similar circumstances pulmonary and gastric hemorrhages are
occasionally noted in bleeders, at the age of puberty or even later, who have
until then been free from hemorrhage, and for these there is not the slightest
anatomical basis. Cases of hematuria have awakened interest especially by
their being unilateral, and also because it has been possible by operative pro-
cedures to make an exact and certain diagnosis during life, which is impossi-
ble in the case of other organs, particularly of the stomach and lungs. In the
future the diagnosis of essential hematuria will necessitate much greater
exactness.
PROGNOSIS
The prognosis of hemophilia is unfavorable: 60 per cent. of bleeders suc-
cumb before the eighth year of life and only 11 per cent. reach the twenty-
second year. After puberty the chances are somewhat better; but, even in
later life, a slight injury may terminate fatally. In a family in Finland in
five generations from a‘stock not previously hemophilic fourteen male descend-
452 THE HEMORRHAGIC DIATHESES
ants succumbed directly to hemorrhage. The first symptoms of the disease
were noted after the children had reached the age of six months.
TREATMENT
General prophylaxis. On account of the hereditary nature of the disease,
and in view of the fact that the affection is mainly transmitted by the female,
it is obvious that the proper restriction of marriage would lessen hemophilia.
From considerations of this kind laws have been framed in accordance with
which the question of marriage in bleeder families should be considered. The
fundamental rules, based upon Grandidier’s rich experiences in this respect,
are as follows:
1. All females, members of bleeder families, whether they themselves are
bleeders or not, are to be advised not to marry.
2. All male members who themselves are not bleeders may unquestionably
be permitted to marry.
A male bleeder is only to be dissuaded from marrying if it can be proven
that in his family hemophilic males have reared hemophilic children, although
the males in question married healthy women from healthy families.
A factor which is said to favor hemophilia is the intermarriage of rela-
tives. Whether this is justifiable or not is difficult to determine. So far as
we have positive knowledge, the conditions are the same as in the intermarriage
of relatives generally. There can be no doubt that professional prohibition
of marriage has very little effect. The desire of a hemophilic family to see
a daughter married may be much stronger than the fear that from the marriage
bleeders may be born.
Of paramount importance in combating hemophilia is individual prophy-
laxis. This is to begin as soon as the child is born, and during the years of
infancy it must be very strict in accordance with the experience that at this
age the hemorrhages of hemophiliacs are especially prone to be exceedingly
serious. In nurslings in whom there is a suspicion of hemophilia, all attempts
to remove slight congenital defects are absolutely prohibited. To this cate-
gory belong the operations for hare-lip, malformation of the palate, severing
the frenum of the tongue, the operation for syndactylism, the removal of nevi,
ete. Ritual circumcision of the children of Jewish and Mohammedan families
is to be strictly prohibited. In girls the usual piercing of the lobe of the ear
for earrings must be omitted. Experience shows that vaccination of hemo-
philiacs does not give rise to threatening hemorrhage; it may therefore be
practised in infants (and also re-vaccination) without danger. Great atten-
tion must be paid to the teeth in the children of bleeder families. The peri-
odical observation of the teeth by a thorough and experienced dentist, and
the careful treatment of even the slightest affections of the teeth are necessary
in order to preserve them. In view of the extreme danger of surgical operations
upon the oral cavity, particularly extraction of the teeth, care must be exercised
to prevent such operations in so far as possible in children of bleeder families.
The application of leeches, blisters, wet-cups, in children as well as in adult
bleeders, is to be avoided. When the children begin to go about by them-
HEMOPHILIA 453
selves, their play with other children is to be watched. The nurse must be
instructed to see that the children do not injure themselves; their toys are
to be so chosen that injury to the skin may be avoided. Hemophilic children
must not be chastised. As soon as the children are intelligent enough, they
and their playmates are to be instructed that injuries by falling or blows,
a prick with a needle or pen, should be avoided. If the children are sent to
school the parents should inform the teacher that the pupil is a member of a
bleeder family. It is advisable that the physician instruct the teacher, in
so far as may be necessary for the welfare of the child while in school, as to
the symptoms of hemophilia. The teacher will then understand how to con-
duct himself toward a hemophilic pupil, and what instructions he should give
the other pupils as to their behavior to the bleeder. Hemophilic children
should not take part in gymnastic exercises; they should never be subjected
to corporeal punishment.
In the choice of an occupation the bleeders are limited at once by the cir-
cumstance that in comparison with others they are weak. They must, there-
fore, choose occupations in which great bodily strength is unnecessary. Those
without means should be advised to become clerks or designers. Among the
lighter trades they should not be taught those trades in which slight injuries
are apt to occur, such as watch-making, engraving, paper-hanging, and that
of goldsmith and barber. Bleeders whose circumstances permit may with
advantage pursue the learned occupations. Such students should not take part
in games, nor should they be accepted in the army.
General Treatment. Hemophiliacs should be placed on a special diet, and
fluids which slightly stimulate the vascular system (alcohol, tea and coffee)
are to be avoided. The use of milk, lemonade, orangeade, etc., is to be ad-
vised. Solid food is to be of the bland kind; spiced foods should be prohibited.
Vegetables (particularly fresh vegetables, fruit, salads) are beneficial. The
general nutrition is to be stimulated by baths, cold ablutions, occasionally sea
baths, and by residence in the country.
Special Treatment. Attempts have been made to control the disease by
the administration of drugs. In a case reported by Wickham Legg, the use
of iron chlorid is said to have brought about improvement, but in a case of
my own this was ineffectual. The following drugs have also been tested:
Mineral acids, sugar, lead acetate, magnesium sulphate and sodium sulphate.
Of the mineral acids, chiefly upon Werlhof’s advice, sulphuric acid in the
form of the elixir acidi Halleri has been employed. The freshly expressed
juice of lemons has been warmly advised. From this the deeply-rooted, popu-
lar belief in the lemon treatment, and, in milder cases, the orange treatment,
has developed, in which in a gradually increasing number, from one to ten
lemons daily, that is, their juice, are consumed. This “treatment” is con-
tinued for from six to eight weeks. But its benefits are as slight as from the
long-continued use of Haller’s acid.
The salines are perhaps of use in the sense that they relieve the congestive
conditions which play a réle in hemophilia. General strengthening and tonic
remedies have frequently been resorted to during the periods free from hem-
orrhage; and during this time, and also when any signs portend an approach-
454 THE HEMORRHAGIC DIATHESES
ing hemorrhage, ergot, lead acetate, hydrastis canadensis, as well as opium
and silver nitrate, have been employed to combat the hemorrhagic diathesis.
Upon the whole little is to be expected from the drug treatment of hemo-
hilia!
Regarding the treatment of special hemorrhages in the hemophiliae, at-
tempts must first be made to control the hemorrhage by mechanical means.
The member is to be elevated. Occasionally this alone is sufficient. Secondly,
the employment of local styptics comes into question, iron chlorid and gelatin;
under some circumstances the cautery may also be employed. Sometimes we
succeed with tampons; sometimes by the application of a rubber bandage to
the bleeding member and by compression of the nearest large artery. ‘Some-
times the tying of a large vessel becomes necessary. Hémard, to control the
hemorrhage after extraction of a tooth, tied the common carotid artery.
D. McKenzie (British Medical Journal, April 27, 1901) reports the occur-
rence in a hemophiliac of an apparently uncontrollable epistaxis which yielded
at once to a tampon of cotton soaked in suprarenal extract.
R. Heymann (Mtinchener med. Wochenschr., 1899) reports the case of a
bleeder aged twenty-eight, who, after removal of the tonsil, suffered from severe
hemorrhage which could not be controlled. Heymann injected under the skin
of the thorax 180 ¢.c. of a 2.5 per cent. neutralized and sterilized solution of
gelatin in a physiologic salt solution warmed to 40° C. After fifteen minutes
the hemorrhage ceased, and did not recur for thirty hours. The injection was
twice repeated, and the hemorrhages invariably became slighter. Heymann
concludes from this that an increasing coagulability of the blood was pro-
duced.
Nichols (Medical News, 1898) reports the history of a hemophiliac, twenty-
four years old, who, while intoxicated, fell upon broken glass and received
extensive incised wounds. For seven days the hemorrhage could only be par-
tially controlled, and the patient showed symptoms of a dangerous anemia;
Nichols then poured the contents of a culture tube filled with 10 per cent.
gelatin into the wound. The hemorrhage permanently ceased.
My own numerous experiments with gelatin for the purpose of controlling
severe hemorrhages and in the treatment of aneurism lead me to doubt the
correctness of these observations, although I do not wish to discountenance the
occasional use of gelatin for styptic purposes. But, in doubtful cases, we must
not expect great results from its employment.
Adrenalin locally has of late been successfully used in controlling bleed-
ing, and is worthy of trial in hemophilia under similar circumstances.
Of internal remedies ergot and its derivatives have been used. Their
effect, however, in the fully developed disease is very questionable.
During pregnancy in hemophilie women hemorrhages indicate artificial
abortion or early induced labor (Kehrer). Broock (Transactions of the Chi-
rurgical Society of London, 1900, page 103) reports the case of a woman,
a member of a bleeder family, who had borne two children with well-marked
symptoms of hemophilia, and, as she had suffered greatly from hemorrhage
in each labor, he endeavored to prevent it in the third. He instituted a treat-
ment which had for its purpose, on the one hand, a general strengthening of
HEMOPHILIA 455
the entire system (change of air in combination with the administration of
iron, quinin and arsenic) and, on the other hand, the increase of the coagula-
bility of the blood (calcium chlorid). The course of the labor was in exact
accordance with his expectations. The loss of blood was very slight, the child
showed no signs of hemophilia, and was stronger than the children previously
borne.
The treatment of the hemophitlic joints is especially important. F. Kénig
advises the following method: A fresh hemarthros, above all in a bleeder, is
to be so treated that the patient cannot use the affected joint; moderate com-
pression decidedly promotes absorption. The question whether any operative
treatment of the diseased joint is permissible Kénig answers affirmatively, in
so far as puncture of the joint is concerned. Kénig has performed puncture
in the knee-joint three times, twice with carbolic acid washing. The opera-
tion was always harmless, one patient was much improved, and the other
patient was cured; but Konig advises that this be the limit of operative pro-
cedure. Of three patients into whose joints he opened, by mistake, supposing
the condition to be tuberculosis, two bled to death, and one after many hem-
orrhages recovered, but had a stiff joint remaining. According to Guyot, the
treatment of the hemophilic arthropathies in the acute stage must be entirely
expectant; later, however, puncture of the joint and incision, with removal
of coagula, is said to facilitate recovery, after which recurrences of the bleed-
ing are less to be feared.
The latest reports regarding the therapy of bleeder’s joints are from Hoffa’s
Clinic, and in the article by Gocht, previously referred to, great importance
is attached to the prophylaxis of hemophilia. Improvement of the general
condition by good food, residence in pure air, and hardening of the body, as
well as the avoidance of all injuries which may give rise to hemorrhages, are
the most important measures. Boys must be trained to this from the onset,
and as early as possible they must be taught to avoid running, jumping, and
other active children’s games. If it is known that the child is a bleeder before
it learns to walk, the greatest care must be exercised. The joint hemorrhages
which follow the most insignificant, scarcely avoidable, injuries are numerous
enough, aside from the greater injuries which may bring about hemorrhage,
and must be carefully guarded against.
The first lesion to be described in Gocht’s article is a fresh effusion of
blood into the knee-joint. In marked cases enormous swelling arises. The
joint is so tense and so filled with fluid that the resistance of the capsule of
~ the joint checks a further exudation of blood. The symptoms are the same
as after severe contusions of the joint, except that in many cases from the onset
the function is scarcely disturbed. Sometimes the knee assumes the medium-
flexure position, at other times not so, or only for a few hours until the cap-
sule has accommodated itself to the exudation. The treatment varies. Where
there is decided pain, absolute rest, moist compresses, ice, or compression
with bandages may be beneficial; in other cases the patients are kept per-
fectly quiet or are permitted to walk about carefully. Gocht determined from
his experience in the Clinic that generally a moderate use of the joint in walk-
ing has no injurious effect upon the absorption of the effusion in the joint.
456 THE HEMORRHAGIC DIATHESES
The same period of time, about two to four weeks, is required for the disap-
pearance of the effusion, whether there is absolute rest or use of the joint.
A few days after the development of the effusion massage is to be cautiously
begun, not upon the joint itself, but in parts centrally situated from the joint.
This causes no pain to the patient, and by action upon the peripheral joint,
absorption is stimulated. At the same time this treatment prevents the mus-
cular atrophy, particularly of the extensor muscles, which so readily appears
in all diseases of the joints.
In the majority of cases these measures will suffice to bring about absorp-
tion of the effusion of blood, especially if the hemorrhages have not as yet
been frequent. The older the effusions and the more frequently the joint has
been attacked, the less rapidly does absorption of the hemorrhage take place.
Nevertheless, here also the treatment must be expectant, and usually recovery
will ensue.
If a joint has entered into the stage in which it resembles hydrops fibrinosus
tuberculosus, where inflammatory phenomena dominate the clinical picture,
orthopedic treatment becomes necessary. In opposition to Konig, Gocht main-
tains that only when the patient suffers great pain, and provided the physician
is absolutely certain in the diagnosis, should puncture be performed. As ex-
perience has taught that absorption, even although slowly, nevertheless almost
invariably occurs, removal of the blood need not be resorted to except for im-
perative reasons. Here, on the contrary, orthopedic treatment should be em-
ployed. Besides the measures which have already been mentioned, such as a
position of rest, compression, and (particularly for the beginning contracture)
extension, plaster of Paris is to be employed, and, above all, portable apparatus
so as not to keep the patient too long in bed. A brisement forcé, in fact all
force employed for extension of a contracture in a bleeder, is entirely contra-
indicated. Rail-brace apparatus, well manufactured and accurately fitted to
the extremity, is of even greater use in the third stage of the disease in which
permanent deformity of the joints has sometimes occurred. The many ex-
treme and violent stretchings of the capsule, and the inflammatory processes
following these, cause an increasing damage (i.e., flaccidity) of the capsule
of the ligamentous apparatus. Just as in tuberculosis, not only flexion but
subluxation and abduction of the tibia posteriorly and outwardly gradually
occur.
Changes in the ends of the bones are added to those of the capsule of the
joint, so that we have a mixed form of destruction and distention-luxation.
The processes of contractures which occur in the capsule, ligaments, muscles,
fascia, and skin increase the contracture and form a decided hindrance to cor-
rection. As to the different methods of extension, surgical monographs must
be consulted. Here it will only be stated that the patients in Hoffa’s Clinic,
during the entire time of extension, are out of bed and move about. When the
leg is completely extended, the apparatus is worn, according to the severity
of the case, for three months to six months and even longer to prevent relapses.
The employment of the rail-brace apparatus, according to the published
reports, has given excellent results, so that this method of treatment can be
warmly recommended.
MORBUS MACULOSUS WERLHOFII 457
MORBUS MACULOSUS WERLHOFII (PURPURA)
(PURPURA SIMPLEX, HEMORRHAGICA, RHEUMATICA SEU PELIOSIS
RHEUMATICA SCHOENLEINITI)
DEFINITION
PurRPuRA, on account of its obvious manifestations, has been known to
physicians for a very long time. Superficial hemorrhages arising from every
possible cause have hitherto been grouped together. Hence affectiors in which,
according to the present state of our knowledge, the purpura forms only an
auxiliary or symptomatic phenomenon (for example, diseases with jaundice and
hemorrhages) have been regarded as independent diseases. From the mass of
diseases in which purpura occurs upon the external skin, Werlhof, in the year
1775, isolated a distinct clinical picture which he designated purpura hemor-
rhagica, and which was subsequently named after him.
Later, other divisions were made in the group of hemorrhagic diseases.
Purpura simplex was isolated as an independent affection, and a variety called
purpura urticans was also described.
Finally, upon the authority of Schénlein, the term peliosis rheumatica
came into use. - It must be admitted that such a division was justified at that
period; it was necessary at a time when the conception of disease entities rested
chiefly on a subtle differentiation of clinical symptoms. From this point of
view great importance was attached to a single symptom, as is shown by the
fact that the term “ peliosis rheumatica” rests solely on the observation that,
in some cases of purpura, an affection of the joints is occasionally noted. The
fact was lost sight of that the latter often occurred in combination with all
hemorrhagic diseases, not only in those whose clinical pictures belong strictly
to purpura, but also in the course of scurvy and hemophilia. Of course the
old divisions of the different forms of purpura are no longer justified. As
a matter of fact, in the last twenty-five years a change in the conception of pur-
pura has taken place, and there is now a tendency to regard all purpuric dis-
eases as related, and the individual forms, previously supposed to he inde-
pendent, are regarded from a common standpoint. Upon the basis of my
own experience, which extends over many years and includes exceedingly
numerous observations, I believe strictly and absolutely that the individual
purpuric diseases are not essentially different, but are due to the same cause,
and only vary in degree; that is, the “varieties” depend upon the intensity
of the affection.
Occasionally these differences ‘are clinically presented in such a manner
that the inexperienced believes he has before him entirely different clinical pic-
tures that have nothing in common with one another. This is a difficult field
for polemics, and convincing arguments are useless if another is fully con-
vinced to the contrary. The only method leading to conviction is minutely,
carefully, and without prejudice to weigh all the facts bearing upon the ques-
tion. It will then become manifest that all these variations of the disease form
indefinable transitional stages which merge into each other, and only by
great circumspection can differentiations be made. The standard of identity
458 THE HEMORRHAGIC DIATHESES
accepted by me has been exceeded by other authors (e. g., Schwimmer and
Scheby-Buch) who are not satisfied with the inclusion of the various forms of
purpura, but desire also to include scurvy in this clinical group; other authors
even add hemophilia.
Apart from the facts demonstrated by bacteriology, which it is hoped will
be more certainly confirmed in the near future, purpura is an affection due
to the action of unknown deleterious agents, occurring sporadically and show-
ing a transitory tendency to different varieties of hemorrhage. In contrast
to hemophilia there is no congenital or hereditary factor, and, unlike scurvy,
there is no tendency to epidemiologic and endemiologie distribution, and the
hemorrhages are not associated with severe constitutional manifestations,
Scurvy is distinguished by the fact that it not only occurs sporadically but also
epidemically or endemically. More characteristic, however, is its dependence
upon external conditions; it is almost invariably the expression of severe
nutritive disturbance produced by obscure diseases or by the long continuance
of insufficient or improper food.
Morbus maculosus Werlhofii differs essentially from hemophilia in the
fact that it unquestionably belongs to the acquired diseases, in which the
factor of heredity is never operative. It has no congenital characteristics,
such as are so peculiar to hemophilia.
This is also a distinguishing factor between scurvy and hemophilia. Un-
like the scorbutic patient, the bleeder is frequently well nourished and strong.
Except in his tendency to spontaneous hemorrhage he may be looked upon as
quite normal. In the comparison of hemophilia with related diseases in the
group of the hemorrhagic diatheses, one peculiarity of hemophilia is particu-
larly prominent; it is not a pathologic process, but a permanent condition
which manifests itself sometimes in consequence of known, at other times of
unknown, causes.
In accordance with these views, we shall consider the purpuric affections
together, but we shall not forget the older clinical divisions; we shall bear in
mind that between the individual forms of the disease transitional stages
occur, and that the barriers between them are artificial.
The conception of purpura as a particular chapter of special pathology pre-
supposes the exclusion of all the affections which are combined with hemor-
thages of the skin, which hemorrhages, however, prove nothing essential or
definite, but are only a single symptom in the entire picture. Among such
affections are: Hemorrhagic variola, typhoid, acute atrophy of the liver, phos-
phorus poisoning, sepsis, ulcerative endocarditis, pernicious anemia, leukemia,
yellow fever, icterus gravis, snake-bite poisoning, etc.
Purpura should be differentiated only when the hemorrhages exist alone
or dominate the entire clinical picture. Of course, in investigating the disease,
a sequel, such as the resulting anemia, is of minor importance.
ETIOLOGY
In most cases it is impossible to determine any immediate cause for the
disease ; the affection appears in typical cases spontaneously. Cases of this
kind have led to the belief that scurvy, which may arise under similar condi-
MORBUS MACULOSUS WERLHOFII 459
tions, is identical with purpura, so that the latter has been designated as the
milder and more acute form of scurvy. This view, as we have shown, is
incorrect, even though there is occasionally a mild affection of the gums in
Werlhof’s disease. Often the symptoms of purpura hemorrhagica appear dur-
ing convalescence from severe infectious diseases, particularly after enteric
fever and malaria.
In rachitic children, as well as during pregnancy and in labor, the affection
has-also been noted. Isolated reports have been given of toxic forms of pur-
pura. The affection has also been observed after the inhalation of poisonous
gases.
In the ecchymoses which are distributed so numerously over the entire
body it is often possible to demonstrate, in the substance which occludes the
capillary vessel, the cause of the entire affection. In the multiple capillary
hemorrhages of septic affections, which show to the naked eye white centers
in the midst of the effused blood, occlusion of the capillaries and capillary
veins with emboli of micrococci may frequently be determined. So in hemor-
rhagic smallpox bacteria are found in the hemorrhagic and purulent foci
of the external skin and in the internal organs, the spleen, kidneys and lungs.
In the retinal hemorrhages of metastatic ophthalmia, I was also able to find
masses of bacteria in the occluded vessel, centrally or removed from the foci,
whereas in other cases which were evidently of septic nature, this proof could
not be demonstrated. This attempt to find thrombi in the vessels has failed
entirely in many cases of hemorrhagic exanthems. In many other diseases
and intoxications the most important clinical symptoms of which consist of
hemorrhagic conditions (cholera, plague, yellow fever, anthrax, poisoning from
snake-bite, petechial typhus, etc.) occlusion of the capillaries in the sur-
roundings or in the center of the ecchymoses have not been manifest, and we
have been forced to the conclusion that zymotic substances, ferment bodies,
ptomains or toxins produce the hemorrhagic diathesis.
How this occurs, whether they alter the blood directly and thus cause occlu-
sion of the capillaries, or whether they affect the walls of the vessels in their
structure, or in their functions as muscular and nervous apparatus, we do not
know.
Whether in morbus maculosus, that is, purpura hemorrhagica, microérgan-
isms or their toxins circulate in the blood, exerting a deleterious effect upon
it or upon the membranes of the vessel, and lead to the multiple ecchymoses
which are typical of this disease, has not been ascertained with certainty,
although such a view is likely. The facts at hand are not generally accepted.
Few authors have found well-characterized microdrganisms as the cause
of purpura. Ajello, who in a case of purpura demonstrated methemoglobin in
the spectrum of the blood, assumes that purpura hemorrhagica may arise by
autointoxication from the intestinal tract as the result of absorbed products
of proteid decomposition ; Schwab also believes an action of toxins to be the
cause of this disease. In other forms of purpura which arise in connection
with infectious diseases, the blood has been examined for bacteria, only in
part with a positive result. Earlier authors, such as Batemann and Grisolle,
have looked upon certain forms of purpura as infectious and contagious ; and,
460 THE HEMORRHAGIC DIATHESES
in a number of cases of purpura, as is evident from later investigations, the
proof of bacillary disease has been shown. Bazcilli were found by Klebs, Ceci,
Reher, Demme, Vessalle, Gendre, Ginnard, Simon-Legrain, Jones, Tizzoni,
Giovannini, Kolb-Petrone, Babes and Letzerich; Hanot and Luzet, Widal and
Thérése found streptococci; Lebreton and I each found staphylococci in one
case; negative findings on the other hand have been mentioned by Marfan,
Legendre, Demys and others.
The opinion, especially maintained by Petrone, that purpura hemorrhagica
in an infectious disease, Letzerich believes he has proven to be correct by bac-
teriologic investigation. In the case of a woman, aged twenty-five, who suf-
fered from a prolonged attack of this disease, who was, however, cured, he
found, in 1884, small, glistening, round granules in the blood. By culture
these proved to be the spores of a bacillus which he described and depicted
minutely as bacillus purpure. With several generations of this culture a large
number of rabbits were infected by injection into the abdominal cavity, and
always with a positive result; the animals showed a short time afterward,
especially in the ears, circumscribed dilatation of the capillaries with succeed-
ing hemorrhage, injection of the gums, etc.; if the animals were killed, sim-
ilar hemorrhages and vascular dilatations were found in various portions of
the body. The microscopic investigation showed in the blood-vessels in many
areas the previously described bacilli, that is, their spores. These were found
most constantly, and were most numerous in the enlarged liver.
Letzerich in this connection points to the frequent enlargement of the
liver in the human affection. This is not to be construed as a frequent occur-
rence, however; in the organs of the experimental animals he found very
marked accumulations of erythrocytes, and stasis in the capillaries due to this.
Further, in the areas of the dichotomous branching of the smallest vessels hya-
line plugs developed by the action of the chemical poison produced by the
bacteria upon the albumin of the blood. To these vascular plugs he refers
on the one hand the hemorrhages into the organs, and on the other hand the
decided circulatory disturbance. The bacillus enters the human body, prob-
ably through the mucous membrane of the oral and pharyngeal cavities.
Letzerich believes these investigations demonstrate with certainty that pur-
pura hemorrhagica is a chronic infectious disease, and points to its analogy
with syphilis and malaria. It is noteworthy that three years after these pri-
mary researches, and, as he states, in consequence of them, Letzerich himself
was attacked by a very prolonged purpura, running its course with marked
enlargement of the liver, and from his blood the previously described bacillus
was cultivated.
The bacillus described by Letzerich has some similarity to the bacillus
anthracis, particularly in regard to the conditions of its growth. In Koch’s
stab cultures both formed more or less irregular colonies (flocculi), the middle
point consisting of net-like threads which, toward the border, ran off in sheath-
like bundles. They differ decidedly, however, by their size and the form of
the spores. Although in both bacilli a segmentation of the apparent threads
occurs in various lengths, those of purpura are much smaller in their length
and breadth, Added to this the spores of Letzerich’s bacillus, in comparison
MORBUS MACULOSUS WERLHOFII 461
with the large oval structures of the bacillus anthracis, are very small and
perfectly round. The bacillus purpure liquefies gelatin with great difficulty—
scarcely at all—and only at high temperatures (25° to 30° C.) in the surround-
ing of the flocculi (colonies).
In the petechie of man and of the experimental animals a sheath-like
arrangement of the bacilli, sometimes with segmentation, is noted in foci;
these frequently are found equidistant from each other, not lying closely
together, and are spores beginning to develop.
The surface of the stab in Koch’s nutritive gelatin shows flat crescentic
grooves which are only recognizable upon close observation.
The chemical differences must also be mentioned. The bacillus purpure
does not form so toxic a substance (toxin) as the bacillus anthracis, but only
a feebly acting ptomain corresponding with the slight evening rises in tem-
perature that now and then occur. Pure purpura differs in this respect from
the acute forms of purpura (petechiz) usually observed in the course of the
infectious diseases, as these owe their origin to other microdrganisms.
Even with cultures of the third relapse, Letzerich produced purpura in
rabbits. In sections, through small petechie in the transverse section of the
capillary net, and also where dichotomous branches pass into the lumen of the
same, dense proliferations of purpura bacilli were readily recognized by sim-
ple methylene-violet staining.
The bacillus purpure is not found in all the forms of its development in
all of the petechie. Toward the end of the disease, or during the relapse,
only clumps of free spores and individual bacilli are observed. Examination
of numerous petechie is then necessary to find the cycle of development of the
microorganism as described. In the relapses of the disease, particularly, we
frequently note emboli of spores which, upon superficial observation, may be
looked wpon as micrococci emboli, but, upon closer study, merely from the cir-
cumstance that they are embedded in gelatinous plugs, their development from
threads and rods can be determined.
Lockwood also believes purpura to be of an infectious nature, and the
bacillus described by Letzerich to be the carrier of the infection and pathogenic
agent. According to this author, the very acute development and the course,
which is similar to that of an infectious disease, favor the view of an infec-
tious development, and he quoted 17 cases from literature. Of these 13 died
in from forty-seven hours to twenty-one days. He is also inclined to look
upon purpura simplex and purpura rheumatica as due to the same infection,
but showing a different intensity. Cases of purpura which ran a fatal course
in seven hours have never to my knowledge been published by others, and
under no circumstances can these be included among the cases of pure pur-
pura; the most severe case of fulminant purpura that I ever saw (to be detailed
later) terminated fatally in two days.
H. Neumann cites cases of hemorrhagic diathesis of the newborn. In the
first case, besides the staphylococcus pyogenes aureus as in former cases, the
bacillus pyocyaneus @ was found. He does not admit a direct relation of. the
latter to the hemorrhagic diathesis, but attributed the diathesis to syphilis
which was present.
462 THE HEMORRHAGIC DIATHESES
In another case (with melena) the bacillus lactis aérogenes was found,
but to this he ascribes no pathologic importance.
Lebreton describes in a young girl a case of fatal purpura which developed
very acutely after great fright. Large confluent ecchymoses appeared, from
the blood of which, upon culture, the staphylococcus albus and the staphylo-
coccus aureus were obtained in mixture. The disease was therefore looked
upon as infectious purpura. ,
Wikner also found the staphylococcus pyogenes albus in a case of morbus
maculosus Werlhofii.
In a number of cases of purpura IJ have examined small areas of the skin
covered with petechie# which were excised during life, and I have never been
able to determine the presence of microbes.
Later investigations and reports of this malady are not at hand; in the
last four volumes of the Virchow-Hirsch Year-Books, I have not observed a
single report of purpura in man. In this article publications up to the year
1898 have been referred to.
We now come to another series of reports which had their origin partly in
anatomical studies of the vessels in the course of the hemorrhage, and partly
in certain experiments.
Silbermann, who conducted one series of experiments, started from the
well-known researches of Armin Koehler, who, in his work at Dorpat upon
thrombosis and its relations to the fibrin ferment, mentions a series of experi-
ments in dogs, in which, by infusion of blood very rich in ferment, a disease
resembling Henoch’s purpura (see below) was produced, inasmuch as, in a
short time after the transfusion, multiple capillary eechymoses were noted in
the subcutaneous cellular tissue, and hematemesis, hemorrhagic diarrhea, and
intestinal colic occurred. The fulminant, and almost invariably fatal, course of
the pathologic process produced by Koehler, on account of the great amount of
ferment contained in the injected blood, caused Silbermann to choose a method
in which the animals either did not die or did not succumb so rapidly, and in
which the purpuric spots appeared more numerously and were distributed over
the entire skin. He tried this plan: The dogs, prior to the ferment intoxica-
tion, received small doses of pyrogallic acid (0.05 per kilograrn of weight of
the dog), by which only a moderate stasis in the veins and capillaries occurred.
This property of pyrogallic acid in small amounts depends upon a very
slight damage to the blood, a slight “shadow formation” and fragmentation
of the erythrocytes, by reason of which the circulatory disturbance occurs.
In a number of dogs, after stasis of the veins and capillaries of the entire
circulation had been produced by suitable doses of pyrogallic acid, Koehler’s
experiments were repeated, with the expectation that the cutaneous capillaries,
which, like all other capillaries of the body, were under high pressure with
decided strain on their walls, would become more permeable by the ferment.
blood. As a result of these experiments it was shown that in the animals thus
prepared—by injections of ferment blood—thromboses and hyaline vascular
changes could be invariably produced in the internal organs, less constantly:
in the skin. The consequences of these vascular changes were multiple hemor-:
thages into the internal organs and partially also into the skin. :
MORBUS MACULOSUS WERLHOFII 463
Since a rupture of the vessels could not be found microscopically (the
proof of this can only be certainly demonstrated with great difficulty) these
hemorrhages were assumed by Silbermann to be due to diapedesis, and this to
distention of the vessel walls. The vascular changes as well as the extravasa-
tions are themselves consequences, not causes, of the circulatory disturbance,
for alteration of the vessel wall never occurs alone but is always observed in
combination with thrombosis, while the opposite is very often the case. The
frequent closure of the capillary area by thrombosis may be explained by the
lessened rapidity of circulation therein, a factor which greatly favors the
occurrence of coagulation. The stasis which occurs in mild cases, and is fol-
lowed by thrombosis in the more severe ones, damages the vascular wall, how-
ever, so that it makes it permeable to the passage of blood. Indeed this stasis
may give rise to fatty degeneration and even necrosis of the vascular cells.
Since “purpura” with swelling of the joints, hematemesis, hemorrhagic
diarrhea and intestinal colic had been experimentally produced in animals by
means of a dyscrasic blood the question arose whether human purpura—no
matter in what form—might also be explained as a primary disease of the
blood. Silbermann believes that this question must be answered in the affirma-
tive, for the reason that, apart from certain important blood findings, the,
essential connection of the pathologic phenomena can only be uniformly ex-
plained upon the basis of a primary disease of the blood.
The hemorrhages into the skin and into the gastro-intestinal tract, the
hemorrhagic vomiting, the colic, and the swelling of the joints, which occur
in severe cases of purpura, Silbermann explains as due to a primary blood
alteration which leads to a slowing of circulation, stasis and formation of
thrombi. Upon the basis of these circulatory disturbances congestive hemor-
thages occur, and also hemorrhages which follow as the result of the occlusion
of vessels, and give rise to necrosis of the tissues. These stases and thrombi
damage not only the gastro-intestinal canal, but also the tissue of the liver,
the kidneys and the myocardium, and may cause fatty degeneration of the
cells and necrobiosis. All of these processes were observed lately by Tizzoni
and Giovannini in the organs of a girl succumbing to severe purpura. There
was occlusion of the vessels which had produced hemorrhage and necrosis of
tissue, and also caused the vascular changes previously observed in man and
animal attacked by purpura. Silbermann regards it as certain that this de-
generation of the walls of the vessels is secondary, because, in his experiments,
all stages of the obliteration of vessels have been followed, and the hyaline
deposits have been shown to be results of this obliteration.
In literature similar views in regard to the nature of purpura are constantly
met with. Thus Green, du Castel, Dusch, Mackenzie, Krauss and others
believe that there are alterations of the blood in certain forms of purpura.
Leloir, who has also observed stasis in the vessels, differentiates a purpura
“nar modification des vaisseaux” and a purpura “ par modification du sang.”
Riehl and v. Kogerer, on the other hand, believe the alteration in the vessels
to be the primary condition ; the change in the blood, i. e., the thromboses, the
secondary. The latter says, in his article regarding the development of cuta-
néous hemorrhages: “On the whole there can be no doubt that the thrombi
464 THE HEMORRHAGIC DIATHESES
which have been found are the direct cause of the hemorrhage. The thrombi
themselves are due to the combined action of local and general causes; hence
vascular changes, as is evident from the constancy of the finding, play the
main role even if they do not form a conditio sine qua non.” The view of v.
Kogerer that the thrombi are due to general and local causes is also the opin-
ion of Silbermann who, however, looks upon the alteration of the blood as the
general cause, and the pathologic change in the blood current of the capil-
laries (due to ferment blood) as the local cause. On account of these con-
stant anatomic findings v. Kogerer calls purpura a primary disease of the
vessels, while Silbermann believes these changes to be secondary. Other ob-
servers, for example, Leloir, have not noted the constant occurrence of dis-
ease of the vessels. He believes the occlusion of the vessels to be embolic,
while v. Kogerer and Silbermann declare this to be thrombotic.
v. Kogerer defines the result of his investigations in purpura in the follow-
ing scheme:
(a) Vascular disease,
(b) Thromboses,
(c) Extravasations of blood,
(d) Pigmentation.
While Silbermann comes to the following conclusions:
(a) Thromboses,
(6) Vascular disease,
(c) Extravasations of blood,
(d) Pigmentation.
As will be noted these authors agree that the disease of the vessels is the
underlying cause of the hemorrhages, but Silbermann looks upon stasis and
thrombus-formation (in the small veins and capillaries) as the primary condi-
tion which leads to disease of the vessels; while v. Kogerer believes thrombus-
formation to arise as the result of the disease of the vessels. The latter con-
dition in either case causes hemorrhage.
v. Kogerer examined 13 cases which ran their course with cutaneous hemor-
rhages; in these he excised particles of the skin, and studied microscopically
the changes in the different layers of the cutis and subcutaneous cellular tissue.
The diseases represented were scurvy, morbus maculosus, tuberculosis pul-
monum, carcinoma ventriculi, marasmus senilis, peliosis rheumatica, sepsis,
vitium cordis, ete. In all cases in which careful search was made thrombi
were found. These were mostly situated in the small venous trunks, but were
also found in the small arteries. Besides this many minute arteries and
capillaries were filled with fibrin coagula and blood-corpuscles, and it was
impossible in some cases to decide whether the condition was one of actual
thrombosis or only a vessel surcharged with blood (!). The thromboses were
occasionally numerous, at other times more scant, and frequently repeated
search was necessary to find them. In some cases the degeneration of the vas-
cular wall was conspicuous.
Riehl, even prior to vy. Kogerer, invariably found changes in the blood-.
MORBUS MACULOSUS WERLHOFII 465
vessels of the cutis and of the subcutancous connective tissue in scurvy, morbus
maculosus, and purpura rheumatica, as well as in the purpura of cachectic
individuals.
In cases of scurvy and morbus maculosus, diffuse endarteritis and thick-
ening of all the coats of the vessels, hyaline degeneration, and partial fatty
degeneration of the same, narrowing of the lumen and proliferation of the
endothelium, could (he said) be invariably demonstrated. Besides, it was
found that in some areas the connective tissue surrounding the vessels and the
fatty tissue showed decided round-cell infiltration.
In the hemorrhagic areas fresh and more or less altered extravasations
of blood were observed, i.e., coarsely granular or flaky blood pigment, em-
bedded between the bundles of connective tissue and in the cell infiltrations.
On the other hand, Riehl could never detect pigmented leukocytes, as in the
case of Addison’s disease, etc. In both processes the cross-striated muscles
which were examined showed fatty degeneration.
In purpura rheumatica and purpura cachecticorum as well as in a case
of hemorrhage into the skin occurring after sepsis, similar changes could be
determined, but the vascular alterations and infiltrations of the perivascular
connective tissue were less marked. In all instances the reticular stratum of
the cutis showed the greatest implication of the large arteries; next to these
the vessels of the adipose tissue, and least marked the vascular layers of the
subpapillary tissues.
In all cases examined by v. Kogerer the vascular changes which have been
described could be demonstrated, and he therefore concludes their certain
connection with the hemorrhages. He assumes further that the hemorrhage
results per rhexin. But in order that the pathologically changed layers of
the vessels shall rupture during life, other local conditions, he believes, must
be simultaneously active. These, in his opinion, consist in thromboses of the
smallest arteries, and he refers to the hemorrhages in the centers of which,
in septic endocarditis and similar processes, emboli of micrococci are found
(Weigert, Litten and others).
Besides the early investigations of Hayem and Stroganow, which have been
referred to, the more recent ones of Leloir and Riehl must be mentioned.
They confirm the finding of vascular changes in the reticular stratum of the
cutis and in other areas of the body, the changes consisting of thickening,
hyaline degeneration, fatty degeneration of the endothelium, and formation
of thrombi. v. Recklinghausen also finds these causes of hemorrhage; I shall
quote two of his remarks relating to this condition (Handbook of General
Pathology of the Circulation and of Nutrition) : “ As regards many cases of
multiple capillary hemorrhage, formerly included in the category of the hem-
orrhagic diathesis or of blood dissolution, etc., we are able to-day to prove
that they occur mechanically, by occlusion of the smallest vessels with indif-
ferent material, or with one of specially septic constitution,” and further:
“ Occasionally, as the result of obstruction of a vein, capillary hemorrhages
also appear in the area of stasis; this is, however, quite rare, and we may
therefore conclude that here complications, for example, senile vascular
changes, are operative.”
31
466 THE HEMORRHAGIC DIATHESES
Despite the report that by anatomical investigations vascular changes have
been found in the ecchymoses of neighboring capillaries as well as in the
smallest arterial and venous vessels, in my opinion no clinician will admit
these to be a constant etiologic factor in purpura. In order to reject absolutely
the theory that the described vascular changes are the cause of such processes,
one must have witnessed how the normal skin of the entire body may be
covered by hemorrhages in the course of a few hours, so that the entire surface
appears spotted like the skin of a tiger or a leopard. I refer here to the
illustration I gave in Nothnagel’s “ Special Pathology and Therapy,” Part ITI,
vol. viii. Such a possibility must be constantly borne in mind. We shall
discard absolutely the assumption of a vascular disease distributed over the
entire cutaneous surface, if we consider the appearance and disappearance of
the affection in the briefest time, the recurrence and repeated recurrence after
varying intervals, and the final complete recovery from the disease. That the
vessels in the hyperemic areas present the phenomenon of stasis is self-evident;
the exit of blood per diapedesin is itself the final and most extreme phenomenon
and expression of each extensive stasis. But a purpura hemorrhagica widely
distributed over the entire body, appearing acutely, and sometimes involving
the mucous membranes and the serous membranes, can never be due to a
hyaline vascular degeneration. How could this arise so suddenly and disappear
so rapidly? I admit the vascular degeneration as a cause in certain cases
running a severe and fatal course, particularly the forms which run a chronic
course, in which the cutaneous hemorrhages represent one of the secondary
symptoms of the disease, as, for instance, in senile marasmus, peliosis cachec-
ticorum or in pulmonary tuberculosis. But the mild cases (ordinary purpura)
which run a more or less rapid course, repeatedly appearing and disappearing
again, certainly do not depend upon stasis and hyaline vascular degeneration
but on internal causes entirely unknown to us at the present time.
The many microscopic investigations which I have made in cutaneous
hemorrhages in all forms of the hemorrhagic diathesis, and particularly my
numerous investigations of the blood-vessels of the eye (the optic nerve, the
choroid and the retina) in pernicious anemia, leukemia, scurvy, diabetes and
sepsis, I must admit have given results which are by no means satisfactory.
In many hemorrhages of the retina in these diseases, in spite of the most
minute and careful examination of numerous sections so thin that they per-
mitted the use of an immersion lens, I have not succeeded in detecting vascu-
lar changes in -the arterioles or capillaries supplying them. The conducting
vessel was quite intact, and each blood-corpuscle contained in it, as well as
the nuclei of the walls, and the patent lumen, could be distinctly recognized
almost up to the bleeding point, where frequently a dichotomous division
occurred. The two branches given off could be seen for a short distance and
were quite intact until they disappeared in the hemorrhage. The eye of the
investigator, no matter how practised, is unable to see in the midst of the hem-
orrhage which completely covers the arteriole or capillary what has become
of the vessel, and especially whether the hemorrhage has occurred per diape-
desin or per rhexin. Hence I must absolutely reject this theory, and can only
compliment those observers who were able to demonstrate a vascular change
MORBUS MACULOSUS WERLHOFII 467
in “every” case. At this point, I wish to refer to my later investigations
of the vascular changes in the retinitis of Bright’s disease, which are soon
to be published.
The conditions are not very dissimilar in hemorrhage, occurring as the
result of general septic disease, although they really do not belong to the same
category. There is no doubt that in cases of sepsis and malignant endocarditis,
in the midst of cutaneous hemorrhages, occasionally a white center is seen
which is analogous to the same processes in the retina. Although I have
sometimes succeeded in recognizing these white centers as small infarcted
blood-vessels filled with micrococci, this finding is not constant, and cannot
be proved to be a process which occurs during life; under no circumstances
can conclusions be drawn from this to explain the multiple cutaneous hemor-
thages in the various forms of purpura.
How far an infection may be assumed to cause the disease in these latter
cases must remain an open question until it is proven whether, and to what
extent, the bacillus purpure or some other pathogenic microbe is a constant
finding in the blood of patients suffering from morbus maculosus. If later
investigations should substantiate this, the view would also be permissible
that the toxins or ptomains circulating in the blood lead to an extensive stasis
formation in the capillaries and small veins, or that they directly alter the
blood, thus causing occlusion of the capillaries, or, finally, that they affect
the vascular walls in their structure or in the functions of their muscular
and nervous apparatus so that, for example, a stasis as the result of paralytic
dilatation of the smallest vessels might take place.
That the severest cases of this disease, designated as purpura fulminans,
terminating fatally in the briefest time, are of an infectious character, and are
probably due to the entrance of pathogenic microdrganisms which have a very
deleterious effect, I believe to be true beyond doubt, although, unfortunately,
this has not as yet been proven.
As a rule the disease is not frequent; females, according to reports, appear
to be somewhat more predisposed than males. An age limit does not exist,
but at middle life attacks appear to be most numerous. The aged and nurs-
lings are very rarely affected. Nevertheless, the report that prior to the fifth
year of life scarcely any cases occur is incorrect. I have certainly seen quite
a number of cases which occurred between infancy and the fifth or sixth year.
These cases were either pure “ purpura simplex ” or “ purpura hemorrhagica,”
or such forms as are complicated with disease of the joints (peliosis rheu-
matica), or, lastly, forms in which not only cutaneous hemorrhage but intes-
tinal symptoms, particularly vomiting, intestinal colic, and watery or hemor-
rhagic diarrhea, are prominent. In quite a large number of cases which
occurred in rachitic children in the second, third and fourth years of life
the only symptom was attacks of cutaneous hemorrhage, and after repeated
relapses these children made a complete recovery. Here also the female sex
was in the majority. ;
Immediate causes can be determined only in the rarest cases. The disease
seems to appear “spontaneously and primarily,” and either to exhaust itself
468 THE HEMORRHAGIC DIATHESES
in one attack or to extend through several relapses. In isolated cases the
duration of the attack may be‘many months or even years.
Chilling or wetting of the body, damp dwellings and insufficient food are
cited as causes, but without sufficient reason. Since unfavorable circumstances
of life and unhygienic surroundings reduce the bodily resistance and increase
the predisposition to all diseases, this is naturally the case also in the homor-
thagic diathesis. We see poorly nourished individuals with poor constitutions
forming by far the great contingent of sufferers from this disease, but we also
find the disease in millionaires who live in luxurious palaces, and who can
command all the advantages of life and the best of care.
The affection always occurs sporadically and as an isolated disease, never,
as in the case of scurvy with which it is often confused, showing an endemic
or epidemic distribution.
In isolated cases intoxication with marsh gas has been reported, but prob-
ably this is erroneous. On the other hand, it appears to be absolutely proven
that in convalescents from enteric fever and malaria, or after these diseases
have run a prolonged course, purpura sometimes follows. I have also observed
purpura as a sequel of scarlatina and measles, as well as in the late course
of diabetes mellitus and in pulmonary phthisis. Bright’s disease also belongs
to those affections in the course of which cutaneous hemorrhages occasionally
occur. Evidently the conditions are here somewhat more complicated. I
should like to refer to Mathieu’s view that the purpura which is seen quite
frequently in Bright’s disease is of vital importance, and develops under the
same conditions as uremia. We must recognize the absolute untenability of
this assumption. Purpura arises in all forms of nephritis, but especially in
interstitial nephritis; during the course of the latter it often recurs (a few
spots or a great many), and again disappears without being of decisive
importance in prognosis.
I shall revert later to the views of Bamberger, a very careful observer, but
here I may mention my own opinion based upon numerous observations. Pur-
pura and renal affections appear to me to bear double and varying relation-
ship. The evidence of this is the fact that after long continued, frequently
relapsing purpura, we often observe albuminuria (usually not exceeding 0.1
per cent.) with or without a very scant number of casts. After a shorter
or longer duration these signs gradually disappear without developing into
chronic nephritis. In a second group of cases the relation is unquestionably
the opposite, inasmuch as with a contracted kidney, repeated attacks of sim-
ple or hemorrhagic purpura occur. But in such cases the prognosis does not
assume a more serious character.
Dohrn once observed a child born of a woman suffering from purpura, the
child also being attacked by the disease. If this was not really a case of
hemorrhagic diathesis as a result of septic infection, the conclusion is justified
that the vascular system (blood and vessels) of mother and child suffered from
the same deleterious influences.
In conclusion, we must mention that in individual cases as an immediate
consequence of severe nervous shock, pain, fright and fear, severe cases of
purpura arise. In this connection I shall mention the case of Lebreton, who
MORBUS MACULOSUS WERLHOFII 469
saw purpura in a young girl after great fright, appearing very acutely and
rapidly running a fatal course. Upon the skin, large, confluent hemorrhagic
spots were found.
Bobrizki saw in a girl aged twelve, as the result of severe nervous shock
(an attempted rape), an immediate attack of morbus maculosus. The same
observer noted a second case in a boy aged ten, who, in consequence of a
fire, was severely frightened and was immediately attacked by the same disease.
Bobrizki is of the opinion that the irritation of the nervous centers produced
by fright caused a paralysis of the vasomotor nerves which permitted the
extravasation of blood per diapedesin.
GENERAL CLINICAL PICTURE
By purpura we understand an affection which appears spontaneously, its
chief characteristic consisting in transitory hemorrhages of the external skin,
the serous and mucous membranes, as well as hemorrhage into the parenchyma
of the internal organs.
Under purpura we include only such hemorrhages as denote the character
of the disease and stamp it as an independent affection, while the purely
symptomatic extravasations of blood which occasionally occur in the course
of cachectic or febrile affections (as, for example, in the course of sepsis or
acute articular rheumatism) are to be left entirely out of consideration. The
first form of the disease, in which bleeding occurs exclusively in the skin, is
designated “ purpura simplex.” When bleeding occurs not only in the skin
but in the mucous membranes, the serous membranes, and the internal (paren-
chymatous) organs it is designated purpura hemorrhagica. Finally, when the
hemorrhages run their course with pain and swelling in the joints, the disease
is called peliosis or purpura rheumatica. This terminology might be extended
much further. According to the etiology or clinical symptoms, we might speak
of peliosis or purpura gonorrhoica or of a purpura abdominalis or dyspeptica
(see below). But, as has already been stated, all these apparently different
forms depend upon a general cause, the so-called hemorrhagic diathesis, which
is probably due to a microparasitic pathogenic agent (up to the present time
entirely unknown) and which finds expression in forms that are only clinically
different and merge into each other in many ways. Altogether they form
one and the same essential hemorrhagic disease of varying grade and varying
intensity. But it must be always remembered that, besides the hemorrhagic
symptoms, no other primary affection is present in the clinical picture. Pur-
pura simplex is to be looked upon as the mildest form of the disease; we can,
however, never premise with certainty whether it will remain mild during the
entire course of the disease, or will change gradually into severe purpura hem-
orrhagica, or whether disease of the joints or other complications may even-
tually appear. For this reason we cannot look upon the various forms of the
hemorrhagic diathesis (mentioned by various authors) as distinct. They are
all aspects of one disease, produced in each individual case by separate condi-
tions. This disease we call morbus maculosus.
In describing briefly the history and development of this disease, we need
only follow a case step by step to demonstrate the difficulties which arise in
470 THE HEMORRHAGIC DIATHESES
an attempt to classify these hemorrhagic diseases in accordance with the usual
reports and designations.
For example, we will take a case of purpura with joint affection and intes-
tinal hemorrhage. Purpura with joint affection, provided it is not also com-
plicated by intestinal hemorrhage, would ordinarily be designated as peliosis
rheumatica. As most authors mention neither internal hemorrhage in pelio-
sis rheumatica nor joint affections in purpura hemorrhagica, embarrassment
would surely ensue as to the category in which to place the case if the teachings
of these authors were followed. But it is absolutely certain that such a case
should be included in the great group of the hemorrhagic diatheses.
According to the classic descriptions of the clinicians of the middle of the
previous century, it was generally accepted that purpura simplex, purpura
hemorrhagica, and peliosis rheumatica were to be viewed as entirely different
diseases, that in peliosis rheumatica no internal hemorrhages occurred, and
further, that in the different forms of purpura no joint affection was observed.
I need only mention here the revered names of Rayer, Willan, Wunderlich,
Schonlein, Hebra and Cannstatt. The last, in complete unanimity with
Wunderlich and Hebra, teaches that in purpura hemorrhagica, in contrast to
peliosis rheumatica, no joint affection occurs, and, moreover, that the absence
of joint affection is an important diagnostic point in the differentiation
between purpura and scurvy.
A differential sign between purpura simplex and purpura hemorrhagica,
according to the previously named authors, is the presence of large ecchymoses
upon the external skin and the occurrence of bleeding from the mucous mem-
brane and in the internal organs in the latter affection.
Accurate observation of typical cases among a great number of patients
has shown the unreliability of all of these views, and has demonstrated espe-
cially that the points in the history of the individual case regarding the form,
extent and seat of the hemorrhages, as well as in regard to the implication
of the joints, hitherto held to be diagnostic, can no longer be so regarded.
As we shall have to consider more minutely these important questions which
dominate the situation, I will only, at this point, demonstrate by some typical
examples to what confusion it would lead if, upon the basis of such purely
external symptoms and signs, the cases of hemorrhagic diathesis were to be
classified. I shall now show that other complications may occur in hemor-
rhagic diseases by which the external picture of the affection may be appar-
ently changed, while its essential nature remains the same.
I shall first mention two cases that came under my own observation: In
the first there were recurring paroxysms of petechie, large ecchymoses and
suggillations (particularly in the extremities) with painful arthritic swellings,
which passed rapidly away; besides these, there were severe gastric disturb-
ances with bilious vomiting, attacks of colic and recurrent hemorrhagic diar-
thea. The gums were swollen and bled readily, the teeth were loosened.
With what were we dealing? Without practical experience, it would be
very difficult to recognize the condition among the earlier classifications, and
we should lose our way in the devious paths of complicated and apparently
non-related symptom-complexes, Purpura, acute rheumatic fever, scurvy,
MORBUS MACULOSUS WERLHOFII 471
peliosis, dysentery, all these would be considered, and formerly would unques-
tionably have been diagnosticated.
Yet we know now, from careful investigations, that all of these symptoms,
apparently so different, may run side by side within the conception of a
severe purpura.
Which qualifying adjective we attach to the purpura in this case—“ rheu-
matica,” “intestinalis,” ‘“ hemorrhagica,” or perhaps, on account of the im-
plication of the gums, “scorbutica”—is quite immaterial; now one, now
another symptom-group may assume greater prominence among the phenom-
ena. As we shall see, however, all of the symptoms which have been men-
tioned may, and occasionally do, appear in purpura.
The second case also is a characteristic example of the diagnostic difficulties
which may arise under some circumstances. Besides the extensive cutaneous
hemorrhages which were of paramount interest, there were repeated multiple
and painful joint swellings, appearing and disappearing suddenly, and re-
lapses which almost always occurred if the patient attempted to leave the
bed. Symptoms on the part of the digestive apparatus, colic, bilious and
hemorrhagic vomiting, and hemorrhagic diarrhea were also present. There
can be no doubt that the case was one of so-called purpura rheumatica.
Cases with extensive cutaneous hemorrhages and multiple arthritic affec-
tions are often described in literature as “ anomalous” articular rheumatism.
Occasionally these are combined with inflammation of the serous membranes,
particularly with pericardial exudates presumably of a hemorrhagic nature.
A conspicuous feature of these cases is that the joint affection runs a more
rapid and more favorable course than it ordinarily does in pure acute articular
theumatism. As similar cases originated during the period when the favor-
able action of salicylic acid and its salts upon diseased joints was unknown,
it must be suspected that the authors in question failed to recognize the much
more rapid and more favorable course of the arthritic affections in purpura.
This should have attracted their attention to the fact that they were not
dealing with genuine articular rheumatism “with an atypical course,” but
with a complication of purpura.
Another complication of purpura which met with tardy recognition ex-
hibits phenomena on the part of the stomach and intestines, such as intense
colicky attacks with vomiting and hemorrhagic diarrhea.
The simplest and mildest forms of purpura are those in which isolated
hemorrhagic spots frequently appear in the form of minute petechie upon
the surface of the skin and are the only clinical symptom. These sometimes
occur very suddenly without being preceded by prodromes. More often this
eruption is accompanied by gastric disturbance, loss of appetite, epigastric
pressure, lassitude, vomiting and slight fever. The affection sometimes lasts
but a few hours, sometimes for a few days, and, exceptionally, from one to
two weeks, The cutaneous hemorrhages usually present themselves in the
form of numerous small and large dusky red or bluish red circular spots;
they appear particularly upon the lower legs and feet, often also upon the
abdomen and the arms, and frequently exhaust themselves in a single crop.
In fresh cases, they do not disappear upon pressure with the finger, and they
472 THE HEMORRHAGIC DIATHESES
-differ from flea-bites by the absence of the circumscribed circular areola,
which is only seen in acute cases and soon disappears. The face almost always
remains entirely exempt. Upon the extremities the extensor areas are invari-
ably more markedly implicated than the flexor areas. In form and size these
cutaneous hemorrhages usually resemble petechiz, i. e., they are of the circum-
ference of the head of a pin. Occasionally isolated, more extensive hemor-
rhages are observed, which are scarcely larger than a pea. In a short time the
hemorrhages change their color, and undergo the well-known alterations in
color of extravasated hemoglobin, or may cease quite suddenly, without leaving
any pigmentation. After a few days at the longest, during which time relapses
frequently occur, they become pale and disappear, and the disease may be
looked upon as having run its course. The patients, who are sometimes a
little anemic, convalesce and the disease terminates in complete restoration to
health; or one or several relapses of the same mild nature may occur. Never-
theless, after the process has run its course upon the skin, it is well to make
regular and careful examinations of the urine for albumin.
The disease designated as purpura hemorrhagica represents a severe and
tenacious type in which, besides cutaneous hemorrhages, bleeding also occurs
into the mucous membranes. This variety may also develop without pro-
‘dromes, and run an afebrile course. It differs from the previously described
form, above all, by the fact that the hemorrhages are more profuse and more
extensive, so that the body looks as if it had been sprinkled with blood. Be-
sides punctiform hemorrhages, extensive suggillations occur which sometimes
reach as deep as the cutis, forming hard infiltrations. Sometimes large con-
fluent blood spots, sometimes streaks and globular or concentric figures, or
confluent masses of irregular arrangement, are noted. Thus large areas, or
the greater part of the entire cutaneous surface, may be implicated so that
only small patches of skin between the hemorrhagic spots remain entirely
free. The deeply situated strie-like hemorrhages, over which the skin shows
all the colors of the rainbow, are very characteristic. These are frequently
found in the popliteal space, also upon the upper arm and thighs, occasionally
upon the buttocks, and give the impression, by their yellowish green or bluish
red color, that they were produced by a blow, a fall, or a contusion.
Similar discolored cutaneous areas are found in scurvy due to deeply-seated
extravasations which have undergone the same changes in color that extrava-
sated hemoglobin shows. These extravasations may be deeply situated in the
muscles and cause decided hematomata.
Fever may be entirely absent; if evening rises in temperature occur they
are usually slight, the temperature rarely exceeding 101.3° F.; more fre-
quently, however, this form runs its course without fever. Occasionally, but
by no means always, hemorrhages take place in the mucous membranes. The
earliest are in the nasal mucous membrane, and may produce more or less
severe epistaxis.
This is followed by hemorrhages of the mucous membranes of the lips,
cheeks, palate, and gums, without, however, as in the case of scurvy, giving
rise to loosening of the teeth or to ulcerative processes in the gums; yet occa-
sionally there is a loosening or swelling of the gums and also even hemorrhage.
MORBUS MACULOSUS WERLHOFII 473
Severe gastric conditions, or decided pain and swelling of the jomts are more
rarely noted, at most in 40 per cent. of the cases. But the process may last
a long time (six to fifteen months) owing to repeated relapses, and may cause
great debility. Severe grades of anemia combined with palpitation, vertigo
and syncope are not infrequently observed in such cases.
The debility is markedly increased when the disease runs its course with
fever and albuminuria. It is to be mentioned that in bed-ridden patients re-
lapses take place as soon as the patients attempt to leave the bed; it is at this
time also that joint affections are apt to appear or recur. The severe cases of
purpura hemorrhagica with gastric symptoms will be considered later on.
Purpura urticans has been described by authors as a special variety in
which, besides cutaneous hemorrhage, there is an urticarial eruption of the
external skin, the individual wheals of which appear to be hemorrhagic.
Occasionally these urticarial eruptions occur simultaneously with petechiw, in
other cases the two conditions alternate.
Strictly we should use the term “purpura urticans” to designate only
such cases of urticaria as leave behind them true petechise or purpuric areas.
I have observed such cases in which each time, after the patient had left his
bed, new patches of urticaria alternating with purpura appeared, and in which
the urticarial eruption invariably left purpuric areas behind. Such cases last
for many weeks, or even for months. Gastric symptoms are often present in
purpura urticans, as in true urticaria.
The forms of purpura which I have described thus far (including the
milder forms of the so-called erythema nodosum—boil-like, deep infiltrations
with hemorrhages) usually appear without conspicuous prodromata, and with-
out other local disturbances. In contrast with these forms of “ pure” purpura
are others in which, a few days prior to the appearance of the hemorrhagic
phenomena, mild prodromes of an indefinite nature, lassitude, headache, an-
orexia, may be observed. Finally a drawing sensation in the limbs and pain
in the joints may usher in the malady; then moderate fever, lasting several
days, with pain in the joints, particularly of the lower extremity, appear and
last until the outbreak of the true purpuric affection. Thus we reach the
form which has been designated peliosis or purpura rheumatica. It is to
Schénlein’s credit that he first recognized the unquestionable and intimate
relation existing between the hemorrhagic diathesis and certain arthritic affec-
tions; but he did not discern that this connection is a very general one. On
the contrary, he declared it to be only a limited one, and thus he failed to
apprehend the true nature of the hemorrhagic diathesis, the proper under-
standing of which was delayed for a long time.
The designation peliosis ( meAtwous ) is first found in the works of
Hippocrates and signifies “blood under the skin.” As is well known, Schén-
lein appropriated this term as a designation for the clinical picture, and added
to it the epithet “ rheumatica.” ; ;
According to Schénlein’s well known lectures, which were published by
“some of his pupils,” the following are the main symptoms of peliosis rheu-
matica: “The areas never coalesce. The patients have either formerly suf-
fered from rheumatism, or then exhibit rheumatic phenomena, mild periodic
474 THE HEMORRHAGIC DIATHESES
‘pains in the joints (in the ankles, in the knees, or in the joints of the hand
and shoulder). These joints are edematous and painful to the touch. The
spots characteristic of the disease appear in the majority of cases first upon
the extremities, particularly upon the lower, and then only up to the knees.
The hemorrhagic areas are of the size of a lentil or a millet-seed, light red,
not raised above the skin, and gradually turn a dirty brown and desquamate.
(The latter symptom in my experience is most often absent!) The eruption
occurs in crops during a period lasting often for weeks. Any change of
temperature, no matter how slight, may cause a new eruption. The affection
is mostly accompanied by fever, which is of the remittent type.
“ The disease has been confounded with morbus maculosus Werlhofii. The
absence of the so-called purpuric phenomena in the mouth which shows no
changes, the absence of free hemorrhages, the absence of nervous phenomena,
the character of the exanthem (never reaching the size typical of Werlhof’s
disease, never becoming confluent, and being a light red), the affection of the
joints which is lacking in maculosus, the great debility and loss of strength,
confirm the diagnosis.
“The clinical picture is seen in individuals with a delicate, vulnerable skin,
who have either previously suffered from rheumatism or in whom, as the
result of chilling, symptoms of peliosis simultaneously with those of rheuma-
tism appear.” So much for Schoénlein’s view.
Notwithstanding the great master’s beautiful and exact portrayal of the
clinical picture which has been named after him, it is evident that his experi-
ence in purpuric diseases was not extensive. We find in this description all
the errors which have so long dominated this department of clinical medicine;
they, have been propagated in the text-books for three decades, and have
retarded the recognition of the true nature of this group of diseases.
Particularly fallacious is the idea that the situation and the size, as well’
as the configuration of the hemorrhages, are characteristic of this or that
form, as well as the isolation or the confluence of the purpuric spots. It is
equally unimportant whether the hemorrhages occur only upon the external
skin or also upon the mucous membranes, But the erroneous interpretation
of the presence or absence of arthritic affections in the hemorrhagic diathesis
had more influence than any other factor in preventing a true understanding
of the nature of the malady. The recognition of the fact that in every form of
the hemorrhagic diathesis the joints may be implicated did not come till much
later. The correction of this error may properly be looked upon as the most
important advance in the knowledge of the hemorrhagic diseases.
Literature furnishes but a single autopsy report of the disease described
under the misleading term peliosis rheumatica. This case is from Traube’s
Clinic, and is reported by Leuthold. It deserves special consideration, because
Traube was for a long time Schonlein’s clinical assistant, and knew exactly
what Schénlein meant by the designation “ peliosis rheumatica.” The case is
briefly as follows: A carpenter, aged thirty-nine, after prolonged lifting in the
Clinic, developed slight pain in the joints. There was edema of the feet, and
upon the dorsum of both several small dark red areas about the size of a
pin’s head appeared; these areas did not rise above the level of the skin nor
MORBUS MACULOSUS WERLHOFII 475
disappear upon pressure with the finger. At the malleoli (which, like all the
joints of the feet, were particularly tender to the touch) there were areas of
the same kind but of larger circumference. The temperature rose. A few
days later there was distinct swelling in the right knee-joint; in the following
night there were tearing pains in the joint and a further eruption of petechia,
which was most profuse upon the forearm and lower extremity, occurred in
groups or isolated in parts of the body excepting the thorax and the face.
Besides this, marked edema of the hands and erythema of the finger-joints
developed ; in the same region after the appearance of petechie in the following
night with swelling of the left knee-joint, large extravasations of blood oc-
curred, raising the skin in the form of tense vesicles.
While some of the petechize became pale and disappeared, new crops of
hemorrhagic patches appeared simultaneously with an improvement in the
arthritic swelling. The fever during this time was partly of the continued
and partly of the intermittent type. Albuminuria was present. Among the
autopsy findings I shall only mention those of the diseased joints: In the right
knee-joint, which was somewhat distended, much colorless, viscid, ropy fluid;
the synovial membrane very pale, only in isolated areas in the upper part here
and there brownish points. The fatty areas show decided injection. The
semilunar cartilage is transparent, somewhat yellowish upon the border. In
the left knee-joint also much clear fluid and around the patella fenestration,
transudation and vascular injection; under the tendon of the extensor of the
knee, brownish extravasations, partly fresh, partly fading.
“The pathologico-anatomical findings in this obscure process which Schén-
lein has described as peliosis rheumatica, differ in no respect from the changes
shown at autopsy in the joints in acute rheumatism.” Near this the impor-
tant note is» found: “Not markedly different from the findings in gonor-
rheal rheumatism.”
A patient in the course of gonorrhea was attacked by ileotyphus, which
caused death at the beginning of the eighth day. In the autopsy report the
following is noted: “The right knee is perhaps somewhat wider than the left
externally ; otherwise very little that is abnormal. Internally there was a very
marked, fine, dark-red injection of the ligamenta cruciata, as well as of the
entire capsule of the joint, besides a gelatinous edema of the same, most
developed around the patella. The cartilage of the joint and the semilunar
cartilage present nothing abnormal. The fluid in the joint is scant, some-
what more viscid and darker than normal. In their sequele also, genuine
rheumatism and gonorrheal rheumatism appear to have a certain similarity,
as may be noted from the observation of an endocarditis, which occurred in
connection with the rheumatism of a long-existing gonorrhea, and, therefore,
must be looked upon as dependent upon it.”
Thus far the facts! Whether or not we recognize the existence of a clin-
ical picture such as Schénlein described and designated as peliosis rheumatica
must be left to the individual judgment. Probably all will agree on one
point, viz.: that if we adopt the name introduced by Schénlein we must under-
stand by it what he understood. Nevertheless we frequently find the name
used without any clinical picture in the remotest degree resembling the condi-
476 THE HEMORRHAGIC DIATHESES
tion described by Schénlein. JI shall mention here only the well-known cases
of Bamberger,’ the description of which the author introduces with the words:
“The so-called peliosis rheumatica in the lower extremities often occurs in
Bright’s disease. I find five cases of this kind among my observations. Usu-
ally the purpuric areas remain unchanged for many months. What connec-
tion exists here, if we do not use general expressions, is not at present clear.
In two instances an autopsy was held: I shall briefly describe the cases:
“4. A man aged thirty-nine, always well, admitted to the hospital on ac-
count of pain and hemorrhagic areas upon the lower extremities. After some
days edema; great amount of albumin. Pleurisy. Death. At the autopsy
hemorrhages were found in the skin, upon the mucous membrane of the stom-
ach, and in the kidneys.
“2. A woman aged thirty-six. Besides the usual symptoms of Bright’s dis-
ease, there was stenosis of the mitral valve, also engorgement of the liver.
Purpuric areas upon the lower extremity had existed over a year. Death due
to apoplexy. Autopsy. Fresh hemorrhagic focus in the brain; stenosis of
the mitral valve; wedge-shaped infarct in the spleen; pneumonia and chronic
nephritis.”
These cases do not in the least resemble the clinical picture of Schénlein;
in each case he was dealing with a chronic nephritis with purpura the result
of cachexia and the hemorrhagic diathesis due to this (peliosis cachecticorum).
Bamberger here uses the designation “ peliosis” as synonymous with “ pur-
pura,” and has no reason to speak of a rheumatic form as he in no way indi-
cates any disease of the joints. If one searches for the etiologic relationship
of the symptoms, one must surely find it in the loss of albumin which caused
the cachexia, and in the hemorrhagic diathesis dependent upon this.
I have seen great numbers of cases with hemorrhages such as Bamberger
described, in chronic nephritis as well as also in old valvular lesions of the
heart, and have only here described these in order to show that the clinical
picture presented by prominent clinicians a comparatively short time after
Schénlein’s teaching was so obscured that nothing was left of it but a pecul-
iar type of cutaneous hemorrhage. That this has been generally looked upon
as the main symptom of the affection is shown by an examination of the
literature. Here we are forcibly impressed with the fact that, step by step,
from the great group of purpura varieties which ran their course with arthritic
symptoms, one particular form was arbitrarily separated and presented as an
independent disease. As the number of cases accumulated it became clearer
that arthritic affections may occur, and do occur in every variety of hemor-
rhagic disease. Soon, without an exception, all those cases were described as
peliosis rheumatica in which the two symptoms were found. If the cases hap-
pened to differ very widely from Schénlein’s description they were explained as
a form of peliosis with “an atypical course.” Thus it came to pass that nei-
ther a definite form of hemorrhage nor any special type of joint affection was
considered typical of the clinical picture in question. and on the other hand no
importance was attached to etiology.
1 Wiirzburger med. Zeitschr., Bd. i, 1860.
MORBUS MACULOSUS WERLHOFII 477
In consequence of these slovenly methods of classification cases of ulcera-
tive endocarditis with purulent arthritis and multiple cutaneous and internal
hemorrhages finally came to be designated as peliosis rheumatica, and hemor-
thage in the latter disease was assumed to be embolic. But if we leave out
of consideration altogether the results of these blunders, we find in literature
an increasing number of cases described as peliosis rheumatica which have
nothing in common with the original Schénlein clinical picture except the
combination of hemorrhages and joint affection. Attention to a particular
type of hemorrhage soon ceased, and instead of the isolated, non-confluent,
lentil-sized petechiz upon the lower extremities, described by Schénlein, we
find writers including in their descriptions every form of cutaneous hemor-
thage, of mucous membrane hemorrhage, and of hemorrhage into internal
organs. If we attempt to bring order out of the chaos of pathologic entities
and clinical pictures described in literature under the name of peliosis rheu-
matica we find simple purpura, purpura hemorrhagica and purpura urticans,
morbus maculosus Werlhofii, scurvy, true peliosis rheumatica and, finally,
erythema nodosum.
Occasionally we find each of these maladies, running their course with
cutaneous hemorrhage, complicated with joint affections, as will be later ex-
plained in detail. Hence the decision as to the nature and character of the
disease should not depend upon the seat, nor the size, nor the form and conflu-
ence of the hemorrhages, nor upon the implication of the mucous membranes,
the serous membranes or the internal organs, nor even upon the sequence of
the individual symptoms, but wholly upon the etiology. This, however, in the
group of diseases above mentioned, must be looked for in those changes in the
blood which we have designated by the term hemorrhagic diathesis. Patients
suffering from this disease have a pale, delicate skin which upon the slightest
cause shows a tendency to hemorrhage; they also present the well-known symp-
toms of chlorosis and anemia. It is probably due to this vulnerability of the
skin, which is also unusually sensitive to changes in temperature, that such
‘individuals are more readily attacked by rheumatoid affections than others.
It seems arbitrary to isolate from this great complex of cases which have a
common cause, a single group particularly characterized by the behavior and
localization of the petechie, and to assign a particular name to it. In any
large batch of clinical material many cases will be met with which correspond
minutely to the description of Schénlein, with the sole difference that the
form of the hemorrhages varies, or that they have their seat in the mucous
membranes. How can the latter be reasonably described as peliosis rheu-
matica, and the former not? I have a large number of clinical histories which
I have been for a long time collecting because I was interested in the ques-
tion of the relation between the hemorrhagic diseases and affection of the
joints. I shall refer later to the conclusions based on these, and at this point
shall only state that I concur in the opinion at which Scheby-Buch arrived
after careful study: “The history of peliosis rheumatica is of itself sufficient
to show the untenability of the view that it is an independent disease, even if
we did not have other weighty reasons for the same conclusion.” .
No one would think of designating scurvy combined with arthritic affec-
478 THE HEMORRHAGIC DIATHESES
tion as peliosis rheumatica, yet carefully studied cases of purpura hemor-
thagica with joint affection have been described by some writers as peliosis
rheumatica, and by others as acute articular rheumatism with hemorrhages.
French and English authors were among the first to describe all such cases of
extensive hemorrhagic diathesis with articular affection as “acute articular
rheumatism with atypical course,” and thus to a certain extent constructed a
new clinical picture. This example shows what the results might be if, with-
out the protective guidance of etiology, and solely on the basis of obvious
symptoms, one should attempt to classify these cases! With a sharply defined
clinical picture such as scurvy usually presents, only an unusually slovenly
habit of mind could make it possible to mistake the relation of the symptoms.
But the case is quite different when we attempt to deal with the group of cases
last indicated. Some authors describe them as purpura or peliosis rheumatica,
according to whether the cutaneous phenomena or the joint affections are
more prominent; others call them rheumarthritis, without realizing that the
clinical picture does not correspond to Schonlein’s conception, and that in
acute articular rheumatism cutaneous hemorrhages do not occur except in the
presence of certain severe complications !
One who has seen much of acute articular rheumatism knows that it has
in uncomplicated cases no association with cutaneous hemorrhages, and will
not confound this disease with any other. Of great importance is the tend-
ency of rheumatism to produce secondary inflammations of the serous mem-
branes and of the endocardium, which is absent or extremely rare in the pure
form of peliosis and in the hemorrhagic diathesis. Further, the absence in
all forms of purpura of the very severe and exhausting sweats of acute rheu-
matism, as well as the absence of severe joint phenomena, is important. Cuta-
neous or internal hemorrhages (particularly of the retina) occurring in acute
rheumatism depend upon a complicating acute endocarditis, as I have explic-
itly pointed out in my monograph upon septic diseases.t Such cases are also
to be clearly differentiated from those in which, with a simultaneous septic
or so-called ulcerative endocarditis, purulent joint metastases with numerous
petechiz distributed over the entire skin and retinal hemorrhages appear.
The cardinal difference between these groups is that, in the former, acute artic-
ular rheumatism introduces the scene and represents the original disease, while
in the latter a wound affection (for example, diphtheria of the placental area,
etc.) or internal suppuration (such as thrombophlebitis suppurativa of the
pelvic veins due to abortion, or of the spermatic veins in the course of gonor-
thea) is the cause. In the last-named group of cases the joint affections are
invariably secondary. Many examples of both varieties of cases have been
given in my article upon septic disease. (See p. 380 et seq., and p. 588.)
; Having now proven, as I believe, that there is no justification for Schén-
lein’s clinical picture of peliosis rheumatica, and that the condition was a joint
affection combined with a hemorrhagic diathesis, I must mention that there
are cases which run a course exactly as described by Schénlein, except that
they are due to another cause, namely, gonorrhea. I have used the designa-
1 Zeitschr. f. klin. Med., Bd. ii, 1881.
MORBUS MACULOSUS WERLHOFII 479
tion “ peliosis gonorrhoica ” in my article upon this subject,? because I wished
to point out to the profession the external connection, and also that there
might be no misunderstanding of what I mean by the expression, but I shall
not consider further the form of joint affection with cutaneous hemorrhage
which arises in connection with gonorrhea.
In the main, Schonlein’s description is applicable to the milder forms of
rheumatic purpura. Some further explanation will be given in the descrip-
tion of the so-called Henoch’s purpura. With the appearance of purpura the
arthritic pains generally cease. Not infrequently the purpuric spots are asso-
ciated with urticarial eruptions and edema of the dorsum of the feet and
ankles, as well as with erythema multiforme exsudativum. The disease may
run its course in a few weeks. Frequently, however, relapses occur with re-
newed arthritic pain and fresh eruptions of purpura, and the disease some-
times lasts for months, even from eighteen months to two years and longer.
Fever may be present or completely absent.
The more intense the affection of the joint the higher the evening rise
of temperature. In very severe cases, in which the clinical picture may re-
semble acute articular rheumatism, we find prolonged febrile rises of a remit-
tent character. The affection differs from true typical articular rheumatism,
above all, by the absence of profuse sweats and of a tendency to endocardial
complications, to which the hemorrhages occasionally seen in true rheumatism
are to be referred. Nevertheless in rare and severe cases of rheumatic pur-
pura, the appearance of the diseased joints may very closely resemble that in
true acute articular rheumatism, even to such an extent that a differentiation
is impossible. In a case from Traube’s Clinic reported by Leuthold, which
ran a fatal course, the condition of the joint differed nowise from the changes
which are observed at the autopsy in acute rheumatism (see above). How-
ever, no report of purpura rheumatica is known to me in which a purulent
effusion was met with in the joint cavities. If the disease is very much pro-
longed, anemic symptoms become noticeable as in acute rheumatism, among
others anemic cardiac murmurs. Only rarely is enlargement of the spleen
observed.
Hemorrhages into the mucous membranes are not absent; thus Kaposi
found in one case hematuria, in another case, which terminated lethally, ecchy-
mosis with subsequent gangrene of the mucous membrane of the palate, while
Duhring described a bloody discharge from the genitalia. These cases resem-
bled the form, now to be delineated: Henoch’s “ purpura abdominalis.”
Henoch first noted in the year 1868 as a complication of purpura the fact
that the eruption of purpura and the arthritic phenomena may be accompanied
by a number of abdominal symptoms: Vomiting, hemorrhagic diarrhea and
colic. Henoch represented as characteristic the appearance of these symptoms
in paroxysms with an interval usually lasting several weeks, and occasionally
even as long as a year. In the earlier literature upon purpura, with the excep-
tion of a case by Wittan, there is no definite report of the occurrence of this dis-
ease in combination with joint troubles and severe abdominal symptoms. We
1 Dermatologische Zeitschrift, xxx.
480 THE HEMORRHAGIC DIATHESES
therefore regard this not as a special form of purpura but as a special mani-
festation of the same transitory hemorrhagic diatheses which in all cases have
one and the same pathogenetic cause.
According to v. Dusch and Hoche the affection occurs especially in youth.
In earliest childhood, from the first to the third year, and in advanced age,
beyond the forty-sixth year of life, no case is known; after the third year
the number of cases gradually increases to its maximum between the ninth
and twelfth years. The frequency then remains about the same up to the
twenty-fourth year. Beyond this age the affection again becomes quite rare.
Males are more frequently attacked than females; of forty patients whose
sex is mentioned 33 were males and 7 females. These reports regarding age
and sex differ decidedly from those of other authors. Regarding sex, I have
noted a decided preponderance of the affection in males.
As predisposing causes, besides recovery from a previous acute rheumatic
attack, unfavorable hygienic conditions, damp dwellings and insufficient nutri-
tion are sometimes noted, but among the cases there are also patients who have
not been subjected to these influences. It is necessary to emphasize this, as
purpura is still occasionally spoken of as a disease of the proletariat, and as
the expression of a certain general cachexia.
With more or less disturbance in general health of varying duration, accom-
panied by headache, lassitude, anorexia, etc., rheumatoid pains appear which
are drawing or tearing in character, not strictly localized, but in various parts
of the body, having their seat particularly in the lower extremity and in the
back. At times there is a transitory edematous swelling in the affected regions.
Some of the patients now take to bed, others continue to follow their ordi-
nary pursuits. Soon, however, severe pains occur in one or more joints, usu-
ally without any perceptible external change in the affected area; in other
cases one or more joints begin to swell, the skin reddens, becomes hot, and
in the surrounding areas edematous infiltrations appear, quite as in acute
articular rheumatism. In this stage sometimes mild fever is noted; tempera-
tures reaching 101.3° F. are rare, as are high temperatures in the later course
of the disease.
As a rule, the pains and immobility of the joints cause the patient to send
for a physician, and frequently he is the first to note the purpuric areas, which
are at the onset isolated, arising without any subjective symptoms. Usually
the eruption causes itching only when it begins with urticaria. Generally
a period of several days intervenes between the occurrence of the joint pains
and the appearance of the first eruption of purpura.
The purpura itself, in the beginning usually bright red and consisting of
small, irregular and isolated spots, or groups formed of these, gradually
coalesces into larger, irregular areas, which in the course of a few days show
a change in color and become bluish or yellow or dark brown.
From the lower leg (where they frequently but by no means always appear
first) they distribute themselves gradually by continuity, or in jumps to the
upper thigh, buttocks and gluteal regions. New eruptions appear upon both
arms, or upon the trunk, so that sometimes the entire body, particularly the
region of the larger joints, appears covered with purpuric spots.
MORBUS MACULOSUS WERLHOFII 481
While the pupura itself causes the patient great anxiety but does not actu-
ally give rise to suffering, other symptoms soon become prominent and are
much more troublesome, e. g., disturbances on the part of the intestinal tract
which are characteristic in that they generally resist all treatment. Patients
complain of severe colic-like pains in the abdomen, particularly in the umbil-
ical region, which are frequently so severe as to bend the patient’s body, and
evoke loud cries. The abdomen is also retracted and sensitive to pressure;
the bowels at the beginning of the attack are constipated. These difficulties
are increased by a stubborn vomiting, which at first contains the food last in-
troduced, then consists of yellowish green bilious masses frequently admixed
with blood. The pulse becomes small and rapid; the facial expression shows
anxiety; the entire condition is a pitiable one.
The constipation which is present at the onset soon gives way to a more
or less profuse discharge of thin yellowish feces often admixed with blood,
the occurrence of which sometimes coincides with the cessation of the pain.
The colic and the vomiting occasionally last for days; the patient eats little
or nothing. Now and then under the influence of severe retching, epistaxis
occurs. Gradually all of the phenomena ameliorate, the vomiting ceasing
first, then the abdominal pains, while the thin fecal discharges continue to
be voided from time to time until the period of apparent convalescence.
The pains in the joints have in the meantime ceased, and the purpura has
faded. In case none of the complications which are to be described have
appeared, the patient, aside from a certain exhaustion, is comparatively well
and believes that convalescence has begun. Occasionally no other attack
occurs, and convalescence proceeds uninterruptedly; in the majority of cases,
however, the symptoms are repeated, wholly or in part, after a period which
may vary from one day to several weeks, until finally recovery ensues. In
relatively rare cases death takes place.
But a schematic course such as described is not the rule; in children the
typical clinical picture is most often seen. The frequent deviations and
manifold peculiarities observed in the course of most adult cases can best be
explained by a description of the individual symptoms.
These will be minutely discussed under the special symptomatology, so that
at this place only a few concluding remarks will be made concerning this form
of purpura.
Among the peculiarities, a group of cases must be mentioned (rare and
in part insufficiently described) in which the arthritic affection is entirely
absent, and, besides the purpura, only marked intestinal disturbances exist.
The duration of Henoch’s purpura varies within wide limits; numerous cases
have been recorded lasting from seven days up to nine months; as an average
duration, six to twelve weeks may be mentioned.
The prognosis in children in the main is good—among nineteen cases there
was but one fatal case, and this was in consequence of acute nephritis. In
adults it is less favorable. In twenty-two cases recorded, five were fatal.
A definite opinion cannot be given on account of the paucity of records.
We now reach a special manifestation of the disease, which was also de-
scribed by Henoch in 1887 under the name of purpura fulminans. I described
82
482 THE HEMORRHAGIC DIATHESES
an analogous clinical picture nine years previously, in the year 1878, and also
described it and pictured it accurately in 1881, without, however, giving the
condition this very descriptive name. In all of these cases there is an ex-
tensive cutaneous hemorrhage which rapidly leads to death, of which Henoch
himself has seen three cases, while a fourth was described in 1886 by Charron
in Brussels.
All these cases have in common the feature that hemorrhages upon the
mucous membranes are wholly absent, but with great rapidity, extensive
ecchymoses appear which, in a few hours, change the entire skin of the ex-
tremities to blue and dark red, and represent a dense bloody infiltration of the
cutis. The formation of hemorrhagico-serous vesicles upon the skin occurred
in two cases, but gangrene has never been noted and no fetid odor has been
observed. The course is exceedingly rapid; within twenty-four hours after
the formation of the first purpura death occurred; the longest duration was
four days. No complication was present, and, with the exception of general
anemia, the autopsy showed an entirely negative condition; there was no sign
whatever of embolic or thrombotic processes. One of Henoch’s cases devel-
oped two days after the crisis in pneumonia, another one and a half weeks
after a very mild scarlatina. In both of the other cases, as well as in mine,
there was absolutely no known etiology. Two analogous cases have been
since published by Strém and Arctander. The first of these followed scarla-
tina; there is no autopsy report. According to Hervé three similar cases
were previously reported (1888) by Guelliot.
Before describing my own case, I shall briefly mention one of Henoch’s:
A boy, aged five; crisis in pneumonia upon the 22d of November. Since then
complete euphoria. During the night of the 24th, sudden pains in the left
leg; toward morning purpuric areas upon the chest and thighs, an hour later
upon the arms and lower legs. At eleven o’clock in the morning the entire
posterior and lateral area of the left thigh was of a bluish black color; toward
evening also the left calf and the right knee. Temperature 101.8° F. In no
organ could anything abnormal be detected. During the night of the 24th
the entire right leg with the exception of the foot became bluish black. Great
apathy and weakness; urine normal. At two o’clock in the morning death
in collapse. Autopsy absolutely negative.
My own case occurred in a man, aged twenty-eight, a tinsmith, who upon
the 23d of March, 1878, was admitted to Frerichs’ Clinic in a comatose con-
dition, and died upon March 25th. No history could be obtained from the
patient nor from the relatives. Only this much was certain, that he was well
and able to work two days previously. The disease began upon the morning
of the 21st. At that time the patient is said to have had a severe chill which
forced him to go to bed. A physician who was called the next morning noted
high fever and ordered his removal to the Charité. The diagnosis of typhus
fever was made.
March 23d, nine o’clock. Patient, a very muscular man, is comatose, con-
stantly mumbling, beating the air with tremulous hands, and continually throw-
ing himself about in bed. The face appears congested, markedly cyanotic,
and icy cold. The middle of the upper lip shows a protrusion resembling a
MORBUS MACULOSUS WERLHOFII 483
proboscis. This prominence is due to a deep hemorrhagic suffusion of the
mucous membrane beginning at the border of the lip, almost 2 ¢.c. in breadth,
and reaching posteriorly almost to the gums. The mucous membrane in
this area appears eroded and covered with thick crusts, upon the removal
of which the base of a superficial ulcer of bad color is seen. The mucous
membrane around the border of the ulcer is in the form of rolled-up
shreds. The gums are bluish red, swollen, in part hemorrhagically infiltrated.
The lips are covered with sordes, and from between them a blood-stained
mucus exudes. Under the conjunctive of both eyes there are circular flat-
tened hemorrhages. The skin is smooth and dry. The color is chiefly
yellowish, but is modified by a great number of pale to dark violet,
irregularly shaped hemorrhages, which appear partly as small spots and
partly as flat extravasations. In some areas these flakes disappear on pres-
sure; at most points, however, they persist. Aside from these spots the
skin, on account of stasis and uneven filling of the vessels, assumes a mar-
bled appearance.
Upon the lower extremities quite large suffusions are found which attain
an area of several square inches, and also hemorrhages which almost give the
impression of being of traumatic origin. Upon the external surface of the
thigh they are quite symmetric; there is also a certain symmetry upon the
back. In the joints of the feet, and upon the dorsum of each foot, there are
extensive suffusions, reddish blue in color, almost the size of a silver dollar.
Upon the right lower leg, and upon the dorsum of the left foot there are also
large suffusions besides ulcers covered with crusts. The sensorium shows
coma; there is no reaction upon deep pricks with a pin. The apex of the
heart cannot be felt; cardiac dulness is not increased; heart sounds clear.
Lungs normal. Spleen moderately enlarged, reaching 3 cm. beyond the ante-
rior axillary line. In the eye-ground the arteries and veins are dilated, the
papillary limits obliterated. No retinal hemorrhages. Temperature reaches
106.9° F.
Evening, eight o’clock. Patient is comatose with closed eyes, moaning, and
assumes the dorsal decubitus. Respiration increased (32 per minute) and
stertorous. Patient very restless. The muscles markedly contracted. There
is anesthesia of both cornea.
Half-past eleven at night. Complete unconsciousness. Marked prostra-
tion. The face is covered with sweat and feels cool, whereas elsewhere the
skin is dry and burning hot. Temperature 107.6° F. Upon the left thigh,
situated externally, a single bluish red suggillation the size of two hands, which
has resulted from the confluence of a number of smaller foci. When I saw the
patient three hours earlier, about eight o’clock, the individual points of the
eruption were still separated by large intervening areas of healthy skin. Since
eight o’clock, several fresh, bright red hemorrhages have appeared, among
them one the size of a silver dollar. Respiration greatly increased, loud,
snoring in character; the pulse very small and soft, 120 per minute. Paresis
upon the right side affecting the face and extremities. Ptosis of the right
eyelid. In the eye-ground nothing abnormal. Sedes inscie. Urine acid,
contains much albumin and numerous broad casts.
484 THE HEMORRHAGIC DIATHESES -
March 24th, nine o’clock in the morning. But little change in the clin-
ical picture. Complete insensibility. Temperature 106.9° F. Upon the skin
many new hemorrhages have appeared. To retain the picture of the skin, I
asked the artist, E. Eyrich, to paint a water-color of the case. He began upon
the morning of the 24th at a time in which the hemorrhages were so close
together that the individual flakes upon the arms, which he had already indi-
cated in contour, assumed an entirely different size and configuration from
those I had previously seen. While he was working on his picture the indi-
vidual flakes coalesced and enlarged. As this condition appeared extremely
strange to Mr. Eyrich, he sent for me in order that I might note the coales-
cence and enlargement of the individual areas. What, however, lent a pecul-
iar character to these hemorrhages was the circumstance that the larger ones
were grouped in concentric circles, and that each of these circles showed an
entirely different color tint. This peculiar arrangement was caused by the
striking rapidity with which the individual areas developed and enlarged. The
older center appeared much darker than the fresher peripheral hemorrhage;
I myself observed this change in different areas. Thus, areas developed in
concentric arrangement which consisted of three to four rings of different col-
ors. The development of these hemorrhages occurred with such enormous
rapidity that the change in color from the brightest red to the darkest brown-
ish red could be noted in the course of a few hours.
Evening, eight o’clock. Patient in collapse. The investigation of the eye-
grounds shows in the right a small centrally situated retinal hemorrhage, and
in the left two more.
12.30 a.m. Death. The temperature taken post mortem showed a rise
to 108.8° F.
The result of the autopsy was very unsatisfactory. The changes worthy of
mention were the following:
Cloudy swelling of the liver, spleen and kidneys. White striae of the
medullary substance of the kidneys. Very slight deposits of the finest ex-
crescences upon the free border of the mitral leaflet. Multiple hemorrhages
in all serous membranes.
The microscopic investigation of the skin gave an entirely negative result;
there were neither vascular emboli nor microérganisms inside the vessels.
Enormous masses of streptococci were found in the glomeruli and in the inter-
tubular capillaries of the kidneys as well as in the deposits upon the mitral.
valve.
That the diagnosis in such a case is not a very simple one, and that
great diagnostic errors are liable to occur, is taught by a case of hemor-
rhagic variola in which the clinical symptoms closely resembled those of
the case just described, and only late in the course of the disease several dis-
tinct umbilicated pustules appeared which in a brief time broke down, sa
ugly ulcers.
The diagnosis of hemorrhagic smallpoz, if the latter runs its course wathgut
pustule formation, and appears during a period in which other cases of small-
pox have not occurred, may give rise to great difficulties on account of the sim-.
ilarity to the clinical picture of purpura fulminans. In the course of severe
MORBUS MACULOSUS WERLHOFII 485
septic diseases, and in acute leukemia also, extensive cutaneous hemorrhages
occur.
To the forms of the hemorrhagic diathesis which have been described we
must add still another disease which lately has become quite prominent, and
which by some authors is looked upon as infantile scurvy. Yet it differs
from the latter affection in many important peculiarities. The disease was
described in 1857 by Mller in Konigsberg as “ acute rachitis” and was par-
ticularly studied by Barlow in 1883, since which time it has been called by his
name. In the last few years this affection has been repeatedly the subject of
close investigation, and particularly on account of the increasing frequency of
the disease among the children of families of the better class, has become
important. It occurs exclusively in children between the middle of the first
year and the third year of life. The onset is often, but not always, acute.
After a few days of general ill health, occasionally following an attack of diar-
rhea, sensitiveness and difficulty of movement in one or both lower extremities
appear, with sensitiveness to touch. The children are usually found with
their limbs extended or retracted upon the abdomen, immovable in bed. Either
active or passive motion is painful. Very soon a spindle-shaped, sensitive,
smooth, white tumor of elastic consistency is noted in the course of the diaph-
ysis of one or both thighs, rarely of the lower leg or of the upper extremities.
Occasionally crepitation is noted in the epiphysial border, which is due to a
loosening of the latter.
This deeply situated subperiosteal or subperichondrial tumor in the tract
of the long tubular bones is the pathognomonic, peculiar sign of this disease,
compared with which the rachitic or scorbutic symptoms are entirely secondary.
Neither clinically, by puncture or incision, nor after death, has pus ever been
found under the periosteum of the diseased bones, but invariably pure blood,
and there is no case on record in which it has ever been observed that the cap-
sule of the joint, in spite of its close proximity, was implicated in the process.
To these previously mentioned symptoms frequently, but by no means
always, the symptoms of the hemorrhagic diathesis, of scurvy and of rickets,
are added. ‘To the latter has been attributed the great tendency to sweating,
particularly of the occiput, as well as the swelling of the epiphyses. Scurvy
is thought to explain the loosening and spongy swelling of the gums with
fetor, and the tendency to hemorrhage, especially in the cases where teeth
are already present. Fever and gastric symptoms are frequent. Occa-
sionally purpura, hemorrhages into the mucous membranes, and albuminuria
occur; Henoch mentions hemorrhages under the periosteum of the frontal
bone, into the eyelids, and into the retrobulbar tissue with exophthalmos.
The appearance of the children is anemic, but very rarely, either by hemor-
rhage or other complications, does death occur.
Regarding the etiology of this important and interesting disease, it has
been maintained more and more lately that improper nourishment is respon-
sible. While by some authors the too great uniformity of the nutrition has
been looked upon as the cause, others emphasize the absence of fresh food. In
the exhaustive American collective investigation (Boston Med. and Surg. Jour-
nal, 1898), and in a great number of individual observations, it has been
486 THE HEMORRHAGIC DIATHESES
shown that Pasteurized and sterilized milk if used exclusively may cause Bar-
low’s disease, and that sterilization in the Soxhlet apparatus is sufficient to
produce it. Lately it has been assumed that the duration of the heating proc-
ess of the milk is the most important factor, but Heubner believes that heating
from ten to fifteen minutes is not productive of harm.
H. Neumann * states in regard to this matter: “ From my own experience
of the conditions in Berlin for the last five years, the following may be main-
tained: In nutrition with artificial milk preparations Barlow’s disease occurs
very rarely, either from the fact that the prolonged use of these foods has
become rarer, or that more care is taken in sterilization. In the year 1899 I
saw but one case which was due to Gartner’s ‘ fat-milk.’ Considering the
mode of preparation of this food only the sterilization, not the chemical treat-
ment, could play a réle; in my case the milk was sent for weeks in the sum-
mer to the seashore, and for this purpose was previously heated to a very high
degree. In another case, in the year 1899, cow’s milk prepared in a labora-
tory was powerfully heated—up to the point of browning. Up to the year
1900, I had seen four children who were taken ill in spite of the fact that the
thoroughly reliable raw milk was in two cases heated only for fifteen minutes,
and in two cases for only ten minutes in the Soxhlet sterilizer. In two of
these cases infant food was added to the milk, but I do not desire to attach
any importance to this. I should like to mention here, however, that in two .
of these cases intestinal catarrh preceded the disease; in the third case dys-
pepsia was present which may have hastened the appearance of Barlow’s dis-
ease. On the other hand a case occurred in the entirely normal child of a
colleague, and in this case the preparation of the milk must be held entirely
responsible for the disease (fifteen minutes in the Soxhlet apparatus). Since
the year 1901 Barlow’s disease, at least according to my experience (which is
also confirmed by Heubner) has increased in frequency in Berlin, and this
makes it possible minutely to investigate a very remarkable fact: For the
fourteen children that I had an opportunity of seeing in this time the Soxhlet
apparatus was always used, and in seven cases the milk was sterilized for ten
minutes, in two cases for fifteen minutes, and in five it was boiled for a longer
period than this. In spite of the fact that among our well-to-do classes
infant’s milk may be obtained from a number of reliable dairies, the milk
for the fourteen children treated by me was all obtained from the same dairy,
and from a dairy which since that time has employed its entire product in a
laboratory for heating, from which no exact records can be obtained. While,
according to my experience, the mere boiling of this milk does no harm, the
combination of sterilization according to Soxhlet with previous Pasteurization
may produce Barlow’s disease.
“ Besides the cases cited above, I later saw seven others, the infants being
from six to ten months of age when they came under treatment. Six of these
patients had been fed from birth on B’s milk; it was boiled for ten or fifteen
minutes in the Soxhlet apparatus, or ten to twenty minutes in Hartmann’s
milk boiler; in one child only did the disease develop while ‘exclusively nour-
1“ Verh, des Vereines fiir innere Medicin in Berlin,” 1908,
MORBUS MACULOSUS WERLHOFII 487
ished by condensed Swiss milk; but with the use of B’s milk it developed to a
great extent. Therefore, to summarize, Neumann has observed in the last
eighteen months twenty-one cases of Barlow’s disease, of which twenty may
be referred to the use of the same milk. If these cases were left out of con-
sideration Barlow’s disease would be as rare as formerly. Therefore, its in-
creased incidence may be referred to a purely accidental and perfectly recog-
nizable cause.”
PATHOLOGICAL ANATOMY
Cases of simple purpura which terminate fatally are rare. If death occurs,
this is either the result of profound anemia after profuse hemorrhage or in
consequence of complications or sequels. For this reason autopsy findings are
very scanty. The cadavers are extremely pallid, also somewhat bloated, and
usually covered with hemorrhagic blotches, which have taken on the livid post
mortem discoloration of altered hemoglobin. The muscles and fatty tissue are
in most of the cases unchanged; only in very protracted cases is the latter
decreased. According to the intensity of the disease we find more or less
extensive hemorrhages upon the mucous and serous membranes, and under cer-
tain circumstances these cover large areas. Occasionally these hemorrhages
are distributed to an astonishing degree upon the mucous membrane of the
bronchi, of the digestive canal, in the renal pelvis, ureter, bladder, etc. At
times the mucous membrane, if we strip off the inspissated blood crusts, may
show superficial erosions. Freshly effused blood is also occasionally found
in the mucous membranes of the bronchi with bloody mucus. This is also
noted in the renal pelvis and in the intestinal canal. In the cavities of the
serous membranes, in the pericardium, in the pleura, and in the peritoneum,
as well as in the cavities of the joints, besides small ecchymoses, we occasionally
find larger effusions of a purely hemorrhagic character, so that we are deal-
ing with hemopericardium, hemothorax, hemarthrosis, ete. We also find par-
enchymatous hemorrhages, particularly in the liver and kidneys; in isolated
cases the adrenals have been found containing bloody infarcts. In the mu-
seum collection at my hospital I have two such hemorrhagic adrenal infarcts,
each about the size of a medium-large apple. The spleen in a certain number
of cases, but by no means invariably, has been found enlarged; in isolated
instances it contains the same wedge-shaped hemorrhagic infarcts. In the
protracted cases running a febrile course there is cloudy swelling of the large
parenchymatous glands besides swelling of Peyer’s patches and of the mesen-
teric glands. The same is observed in the bone-marrow, upon the endocardium,
the vascular intima and the neurilemma. The bone-marrow has been found
traversed by profuse and small hemorrhages. Pigment infiltration, due to
the decomposition of extravasated blood,. has also been observed in different
organs, particularly in the lymph-glands. The pigment appears in flaky
masses and consists entirely of hydrated oxid of iron.
Nothing is known of other constant changes; minute reports are lacking
in regard to the condition of the membranes of the joints and cavities, particu-
larly in those cases in which during life rheumatic pains were present. The
knee- and foot-joints are the ones which are chiefly attacked with arthritic
488 THE HEMORRHAGIC DIATHESES
symptoms in purpura; for the present we must content ourselves with this
fact, and await further knowledge and results from the autopsy findings of
the milder forms of the hemorrhagic diseases. In a case of peliosis rheumatica
from Traube’s Clinic, upon which an autopsy was held, the findings in the
joints did not differ from those of acute articular rheumatism and gonorrheal
rheumatism (see above). The autopsy report is as follows: The right knee
appears somewhat thicker than the left. In the external parts there is little
that is abnormal; but in the interior of the joint is a very marked, fine, dark
red injection of the ligamenta cruciata, as well as of the entire capsule of the
joint, besides a gelatinous swelling of the same, especially marked about the
patella. The cartilage of the joints and the semilunar cartilage show no
abnormality. The fluid of the joint is scant, somewhat viscid, and darker than
normal.
In the main no constant changes have been found, not even such as might
be referred to anemia. The valvular apparatus of the heart is invariably
intact; in one case of fulminant purpura described by me there was a slight
deposit of fine warty excrescences upon the free border of the mitral leaflet,
as occurs so frequently in any disease running an acute course. But even these
have in other cases been entirely absent.
I shall revert later to the changes in the blood, that is, in its composi-
tion; here I will only briefly mention that some authors have found the coagu-
lability of the blood to be diminished, a finding which still requires con-
firmation.
The spleen and lymph-glands show no constant alterations, but the former
organ has repeatedly been found enlarged, and pappy softening of the pulp
has been noted (Billroth). It remains a question whether this is not due to
post mortem change.
The kidneys occasionally reveal a condition of hemorrhagic inflammation.
In cases of chronic albuminuria I several times observed isolated small-celled
foci of infiltration in the cortex. In other cases in which albuminuria had
existed for many months these were absent.
Hemorrhages upon the retina, as well as upon the cornea, have been deter-
mined during life and confirmed post mortem. Upon microscopic investiga-
tion of the eyes in question I found the vessels intact in both membranes of
the eye, which is by no means the case in analogous hemorrhages in the eyes
of patients with renal disease. More frequently meningeal and cerebral hem-
orrhages have been found at the autopsy, but these have been looked upon as
the cause of the epileptiform attacks and paralyses which had occurred dur-
ing life.
The changes in the vessels in the course and in the vicinity of ecchymoses
have been described explicitly in the etiology, and the investigations of
v. Kogerer, Richl and Leloir have been mentioned. Hayem states that throm-
boses have formed in the finer arteries by the agglutination of leukocytes.
Other authors found amyloid degeneration of the capillaries in the vicinity
of the petechie (?). Stroganow, whose investigations I have already re-
ferred to, discovered in the aorta, in the vena cava, and in the veins of the
liver infiltrations of the intima with red blood-corpuscles which from the
MORBUS MACULOSUS WERLHOFII 489
lumen of the vessels appeared to have directly penetrated the intima per dia-
pedesin. But this latter observation explained the nature of the disease and
the occurrence of the hemorrhages as little as any of the previously mentioned
researches.
Among the complicating processes which occasionally result in death I
shall enumerate the following: Large effusions into the pleura and abdomen,
pulmonary infarcts, purulent peritonitis, croupous-diphtheritic processes of
the small intestine, pneumonia, necrosis of the intestine, perforative perito-
nitis, gangrene of the large intestine with swelling of the mesenteric glands,
ecchymoses and ulcers of the descending colon.
Regarding the bacteriologic findings, besides those described in the etiol-
ogy, I should like to discuss here some further points. Tizzoni and Giovannini
isolated from a case of purpura hemorrhagica in which secondary impetigo
contagiosa developed, and upon which autopsy was held, a bacillus, the bacillus
hemorrhagicus velenosus. In the pustules of impetigo surrounded by the
purpuric areas of the skin this bacillus was found with the staphylococcus
pyogenes aureus; it was also found in the liver and in the venous blood, but
not in the spleen nor in the kidneys. The staphylococcus was present in the
pure hemorrhagic foci of the skin, as well as in the kidneys. The bacillus
hemorrhagicus velenosus is immotile, 0.2—-0.4 » broad, 0.7-1.3 » long; it stains
well with anilin colors, but not according to Gram. Spore formation was not
observed; but there was a certain resistance to drying. The colonies showed
irregular contours which resembled coiled locks of hair, and did not become
fluid. In a stab culture they showed granular growth, and upon agar a
growth similar to that upon gelatin. In older cultures a pungent odor is
noticeable. Upon potato only a superficial growth of an indistinct nature
with a dark yellowish discoloration at the point of inoculation is observed.
Upon culture in bouillon moderate turbidity appears, later becoming mucoid.
The bacillus is pathogenic in rabbits, dogs, and guinea-pigs, but not in pigeons
and mice. The bacilli increase only locally with formation of edema. They,
however, give rise to fever, hemorrhagic nephritis, vomiting, hemorrhagic
diarrhea, cutaneous hemorrhages. Upon autopsy of the infected animals
there are found incoagulability of the blood, coagulation necrosis of the liver
and renal epithelium, with a normal condition of the spleen. Cultures steril-
ized at 70° C. produce albuminuria. Repeated injections of such cultures
confer immunity to subsequent infection.
Kolb,? of the Imperial Bureau of Health, investigated bacteriologically
five cases of true idiopathic purpura: Among these were three cases of pur-
pura fulminans which terminated fatally after a brief course; the other two
cases recovered. Microscopic investigation, cultures and inoculation of the
blood taken from the living patient into mice, guinea-pigs, rabbits and pigeons,
gave no results. Positive results were, however, obtained by the bacteriologic
investigation of the cadavers. There were examined: (a) Blood from the
heart and from the portal vein; (b) some areas of the skin containing char-
acteristic purpura; (c) particles of hemorrhagic portions from the lung; (d)
1 Arbeiten aus dem kuiserlichen Gesundheitsamte, Bd. vii, 1891.
\
490 THE HEMORRHAGIC DIATHESES
the liver, spleen and kidneys; (¢) hemorrhagic portions of the intestine; (f)
lymph-glands from the thoracic and abdominal cavities.
In the sections from the large hardened glands of the abdomen, as well as
in the hemorrhagic cutaneous areas, there was found, after staining with
methylene-blue and after the Gram-Weigert process, a moderately large
bacillus averaging from 1-2 in length and 0.8» in breadth with rounded
ends. The bacilli were especially profuse in the spleen, some in the small
blood- and lymph-vessels forming larger clumps, some also in the interstitial
tissue, though here not so numerous as in the vessels, but found lying sepa-
rated from one another; now and then longer threads were found due to a
juxtaposition of the individual bacilli end to end. For the most part two rods
were found placed together lengthwise (diplobacilli). In the kidneys the bacilli
were mostly met with in the glomeruli, but were here not so numerous as in
the spleen. It was also possible to find the bacillus in sections from the liver,
and in sections of cutaneous hemorrhagic areas in which, even in the lowest
cellular layer of the corium, scattered bacilli were found. Particularly in-
structive pictures were furnished by sections of hemorrhagic glands. In fresh
sections from organs the same variety of bacteria was demonstrated. The
bacillus hemorrhagicus Kolb flourishes upon gelatin. The matured colonies
are circular in form, with many constrictions and serrations; in the interior
fine furrows are seen, and toward the border a more granular appearance
becomes prominent. In stab culture after a few days colonies are found
partly isolated, partly coalescent, with superficial flat, hyaline extensions
along their serrated borders. Upon inoculation a thin leaf-like distribution
of a whitish blue color and of porcelain-like transparency with indentations
and serrated borders is observed along the entire course. Kolb’s bacillus grows
upon agar, as in the gelatin stab culture, and somewhat more slowly upon blood
serum. Upon potato a white, moist, glistening streak is noted along the
course of inoculation. In bouillon cultures a feebly alkaline medium is the
best. Even on the first day the solution shows a general cloudy turbidity. As
the growth advances the bacteria sink to the bottom. In pure culture the
bacillus appears as a short, oval, somewhat plump rod with rounded ends;
usually two are found together. Its length amounts to 0.8-1.5 u. The appar-
ent threads which are frequently observed may attain in pure culture a length
of 30. The bacillus has no motility, and is a facultative aérobe.
Kolb’s bacillus is pathogenic in mice, and rabbits and pigeons are suscep-
tible; on the other hand, guinea-pigs very rarely or never succumb to the
infection. In susceptible animals the clinical picture corresponds to human
purpura hemorrhagica. In rabbits the characteristic purpuric spots may be
produced with cultures free from bacteria and mice may be killed in this way.
SPECIAL SYMPTOMATOLOGY
The most characteristic and prominent symptom of the disease, forming
its distinguishing feature, and attracting most attention, is the purpura which
develops upon an entirely normal skin without producing any inflammatory
disturbance. As the areas of the skin upon which the hemorrhages appear
are up to the moment of their development entirely intact, we may assert with
MORBUS MACULOSUS WERLHOFII 491
great probability that these hemorrhages have their origin chiefly in internal
causes, and are the expression of the so-called hemorrhagic diathesis. Al-
though the intensity and extent of the hemorrhagic efflorescence is no exact
indication of the severity of the disease, observation nevertheless proves that
the small, isolated, and rapidly disappearing petechiz represent the milder
type, while the more distributed and very diffuse suggillations, with a pro-
tracted course and a tendency to repeated relapses, indicate a more severe
form of the disease. At the same time, all the transitional stages from the
mildest to the severest of cutaneous affections may occur, and cause the body
to appear as if spattered with a large brush dipped in blood. There may be
extravasations of the size of a plate, which occasionally leave but few large
areas unaffected, and are of a violet to a dark red color. Deep-seated flat
hematomata may also arise and extend into the muscles, and over these the
skin presents the well-known changes of extravasated hemoglobin, showing all
the colors of the rainbow. Finally, streaks and strie-like “ vibices” appear,
particularly in the flexure of the knees, which resemble analogous conditions
in scurvy, and which go through all the changes in tint and shade from dark
blue to greenish yellow.
We have still to consider the relation of the hemorrhagic efflorescences to the
complications, particularly to the arthritic affections and to the gastric phe-
nomena.
The appearance of the purpuric areas in the complicated cases differs in no
respect from ordinary purpura. Occasionally the eruption begins with the
appearance of typical urticaria with vesicles, which gradually become filled
with a hemorrhagic fluid, and soon dry in the way so well known in urticaria;
the pustules then collapse and disappear without leaving residua. In other
cases the urticarial vesicle leaves behind it a hemorrhagic area. Occasionally
in the same individual alternating attacks of urticaria and purpura are noted.
It has often been remarked that patients who suffer from conditions of this
kind have previously suffered from urticaria. Sometimes the development of
petechiz is preceded by the formation of diffuse erythema, in the course of
which occasional miliarial vesicles appear.
The changes which hemoglobin undergoes in the hemorrhagic eruptions
of the skin correspond as a rule to the well-known processes. Occasionally,
however, we see very extensive suggillations of enormous size and of very
different ages; in such cases extraordinarily striking pictures are noted which
confuse the inexperienced, particularly so if recent hemorrhages are super-
added to old ones, which represent all the color modifications and all the tints
of altered blood. After absorption pigment is noted with the naked eye only
in those cases in which huge extravasations of blood have occurred. Even
this, however, disappears after some time, so that with the lapse of weeks or
months nothing remains to indicate the process which has taken place. The
conditions are different in the microscopic investigation; the pigment depos-
ited and accumulated in the rete Malpighii remains there for a long time,
so that after some months—after the disease has run its course—we are still
able to recognize in this area that the skin was once the seat of a decided effu-
sion of blood.
492 . THE HEMORRHAGIC DIATHESES
Besides small hemorrhages, not infrequently other forms of deeply situated
hemorrhages take place in the subcutaneous tissues; indurated, reddish or
bluish, scarcely movable suggillations and infiltrations appear between the
periosteum and the external skin (for example, upon the tibia and the vault
of the skull), also in areas in which no bones lie just beneath the so-called
erythema nodosum. These larger and smaller infiltrations, over which the
skin shows a bluish discoloration and is but slightly movable, are found par-
ticularly in areas upon which external pressure has been exerted for some
time. These are found occasionally in the course of purpura with and with-
out arthritic affection, but they do not make the slightest impression upon the
course of the disease.
Regarding the seat of the petechia, the lower leg is most frequently
attacked ; next, the abdomen, the back and the upper extremities; most rarely,
the face and the mucous membrane of the mouth.
I must not omit to mention that in undoubted simple purpura the gums
are sometimes very decidedly affected, while, as is well known, cases of scurvy
occur without disease of the gums. But we should judge very superficially if
we drew from this the conclusion that the latter is a mild form of scurvy, or
the former a severe purpura. In this connection I will refer to the descrip-
tion of scurvy (see page 402), and will here simply state the fact that in
the course of purpura disease of the gums occasionally occurs, and may lead
to severe changes therein with fetor but without the sponginess and ulceration
and destruction of the gums or the loosening of the teeth which is so common
in the case of scurvy.
The number of successive hemorrhagic eruptions on the skin varies within
wide limits from one to twenty attacks; on an average, four attacks have been
mentioned.
The relation between the time of the appearance of cutaneous hemorrhages
to the other symptoms is a very changeable one; usually, it is true, the former
is the earlier symptom. But in children, according to the descriptions of
v. Dusch, this rule does not hold and very frequently attacks of severe intes-
tinal phenomena without the simultaneous appearance of purpura are ob-
served, or vice versa. An inflammatory effusion is present in one or more
joints which, on account of its long existence, may remain until several crops
of purpura have appeared and disappeared. An effusion of this type in one
or another joint is somewhat more rare in children than in adults, in whom it
appears in about 50 per cent. of the cases; edema in the surroundings of the
affected joint is met with particularly in adults.
The effusion is rarely very marked, never becomes purulent, and leaves no
disturbances of motion behind. The visible swellings are preceded in almost
all cases by arthritic pains or by sensitiveness upon pressure and movement.
The joints of the lower extremities are most often attacked, after this the
joints of the hands. The differential diagnosis between purpura rheumatica
and purpura gonorrhoica may be very difficult under some circumstances, espe-
cially if the patient denies a preceding gonorrhea, The prognosis of the former
is usually favorable. Peliosis rheumatica differs from acute articular rheu-
matism in its entire clinical picture, in the course of its fever, particularly in
MORBUS MACULOSUS WERLHOFII 493
the absence of a tendency to profuse sweats and endocardial or pericardial
implication, and, finally, by the fact that -very frequently the joint phe-
nomena are quite transitory and appear much milder than in the other affec-
tion, although this cannot be designated as a constant, invariable rule.
The relation of the arthritic affection to the hemorrhagic disease appears,
apart from the arthritic hemorrhages, to be by no means clear. It becomes
somewhat less obscure if we consider that in the hemorrhagic diathesis the
serous membranes are especially liable to attack and we know from the analogy
of other arthritic affections that the serous membranes bear a certain relation
to the joints, so that both are often attacked at once.
It is hard to decide whether the implication of the joints of the knee and
of the foot, so frequently observed, can be explained by the suggestion that
the general predisposition to purpura would naturally fall heaviest on those
joints whose function it is to carry the weight of the body, and which for
this reason are particularly exposed. Of course this explanation should be
similarly operative in other multiple joint affections.
I suppose that the sum of our positive knowledge is this: There is an ana-
tomic relationship between the joint cavities with the serous membranes; hem-
orrhages into these occur under the influence of the hemorrhagic diathesis. Yet,
as regards the arthritic affections in purpura hemorrhagica and in morbus
maculosus Werlhofii, it appears to me by no means so firmly established as in
the analogous joint disease in scurvy and hemophilia that these are invariably
and absolutely hemorrhagic. The clinical symptoms, results of occasional
joint-puncture and the autopsy findings in the Traube-Leuthold case (already
mentioned three times) are all opposed to this.
Of the intestinal symptoms in severe and complicated forms of the disease
painful colics are the most characteristic. These resemble the form seen in
chronic lead-poisoning. The seat of pain is referred to the region of the navel,
from which it radiates to various places. Although at the autopsy hemorrhagic
infiltrations of the intestine with ulcer formation in various areas have
repeatedly been found, v. Dusch advises caution in the interpretation of
reports from the patient: “ Bloody vomiting occurred,” or, “'Tarry hemor-
thagic discharges occurred.” He is of the opinion that such reports prove
nothing, and especially not that the seat of hemorrhage is actually within the
intestinal canal. It must be remembered that in small children, in sleep,
and in comatose patients who maintain the dorsal decubitus considerable
quantities of blood may flow unnoticed from the nose into the stomach and
be discharged by rectum. I cannot suppress the opinion that this explanation
seems very forced and artificial, and I do not doubt that in the cases of severe
colic actual enterorrhagia often occurs, a view which is more firmly founded
upon the fact that the colics decrease decidedly in severity after profuse hem-
orrhage from the intestine.
Albuminuria is by no means a rare complication in the course of the vari-
ous forms of the hemorrhagic diathesis, for the most part without an inflam-
matory condition of the kidneys. In some cases I have seen the excretion of:
albumin in every attack, and occasionally it extends into the intervals. In
other cases the excretion of albumin lasts for ten months and longer, but
494 THE HEMORRHAGIC PIATHESES
finally disappears spontaneously without any medication. In other (but
much rarer) cases of morbus maculosus Werlhofii, contracted kidney develops,
becomes chronic and gradually leads to death. According to my observations
of many cases, even after a simple albuminuria (i. e., without casts and leuko-
cytes) has existed for many months, the hope of recovery must not be given up,
for this condition may disappear as suddenly as it arose.
In regard to the changes in the eye, retinal hemorrhages have occasionally
been observed; they sometimes show white centers. Hemorrhages have also
been noted in the choroid and in the sclera. The flow of tears may also show a
reddish discoloration. Nettleship saw bilateral neuritis after purpura.
We have no definite knowledge of the causes of febrile phenomena which
either precede the cutaneous hemorrhages or occur in the course of the same,
and which also are not rarely absent. A more exact insight into these condi-
tions can only be obtained when the etiology of the disease has been estab-
lished. One fact which I have demonstrated repeatedly appears worthy of
mention: even high temperatures may not be influenced in the slightest degree
by extremely profuse hemorrhages from internal organs (kidney, lungs, in-
testines).
In a case of intermittent fever with temperatures up to 102.2° F. which
Kaltenbach observed for a long time, defervescence occurred by lysis. The
case was not a typical one. Sudden appearance of high temperature is always
suspicious, and points to the existence of some complication.
Hemorrhages from internal organs are, in the main, rare; apart from the
likewise quite rare epistaxis, renal hemorrhages occasionally occur as the ex-
pression of a recent hemorrhagic nephritis; very scanty hemorrhagic casts
with normal and abnormal red blood-corpuscles in the urine determine the
diagnosis. The amount of albumin in such cases is always very great. Be-
sides the hemorrhagic form of nephritis, we may also see during the course of,
and in immediate connection with, the disease, a nephritis without hemor-
rhagic constituents. This form very frequently gets well; in rare cases, how-
ever, it may lead to edema and uremia.
Pulmonary hemorrhages rarely occur in persons with previously healthy
lungs. If it is certain that hemorrhagic sputum is present, the first assump-
tion should be that the blood may come from the bronchi. Among other hem-
orrhages which are, however, most uncommon, I must mention meningeal and
cerebral hemorrhages.
Regarding the condition of the spleen but very little can be said; it is cer-
tain that in some cases distinct enlargement has been determined and the
organ has been felt below the ribs as a more or less soft tumor. In the great
majority of cases, however, this enlargement is absent during the entire course
of the disease, even in the severest type. of hemorrhagic purpura running a
fulminant course.
The composition of the blood in cases of pure hemorrhagic purpura is men-
tioned by some authors as having shown a slight decrease of the red and an
Increase of the white blood-corpuscles.
Ajello found the red decreased to 2,500,000 to 3,000,000, while the specific
gravity of the blood was 1.043, The erythrocytes are said to undergo an
MORBUS MACULOSUS WERLHOFII 495
especially rapid regeneration and show no morphologic changes, except that
Spietschka found after protracted hemorrhages nucleated red-blood cells with
polychromatophilic protoplasm. In two cases of hemorrhagic purpura he
made frequent blood-examinations, counting the blood-corpuscles, estimating
the hemoglobin, and staining permanent preparations with gentian violet and
aurantia. In one case the number of blood-corpuscles in the hemoglobin re-
mained constant; in another only showed transitory variations. In both cases
after each severe hemorrhage a conspicuously large number of erythrocytes
showed distinct nuclear staining. Spietschka looks upon these nucleated
blood-corpuscles as juvenile forms, and regards their appearance as a sign of
a markedly increased regeneration of the blood.
In a child which died of anemia following purpura hemorrhagica, Billings
found in the blood only 500,000 to 700,000 red, 4,000 white corpuscles, and
1” per cent. of hemoglobin; 75 to 80 per cent. of the leukocytes showed no
mononuclear forms; no poikilocytosis, no nucleated reds. The blood findings,
in the absence of signs of blood regeneration, resembled those of pernicious
anemia.
According to my own numerous investigations, the hemoglobin is fre-
quently greatly decreased; more so than would correspond with the diminu-
tion in the absolute number of the red blood-corpuscles.
Silbermann found in a case of Henoch’s purpura most of the red blood-
corpuscles normal, a few containing but little hemoglobin, others entirely with-
out color (“shadow-corpuscles”’). The leukocytes were numerous and rap-
idly deliquesced ; the blood-plaques were markedly increased. To determine
any functional damage in the morphologically intact red blood-corpuscles, their
properties were tested according to the method of Maragliano: 1. After en-
closure in paraffin; 2. After heating; 3. After compression; 4. After mixture
with 0.6 per cent. salt solution. The result of this investigation was the follow-
ing: In the fresh blood examined under paraffin, he found normal erythrocytes
with few exceptions, and very numerous leukocytes. Two hours later, in the
same preparation, numerous “shadow-corpuscles” were seen, many feebly
stained red blood-discs, and a few microcytes; the majority of the white blood-
corpuscles were destroyed. In their place there was found a granular, grayish
white heap. Five hours after the enclosure of the blood in paraffin but few
blood-corpuscles were to be seen, the majority of them being completely de-
stroyed. In the fresh, undiluted blood the red dises were destroyed by slight
pressure exerted upon the cover-glass with a needle; the same occurred upon
heating of the blood at 30° C. In 0.6 per cent. NaCl solution a great number
of the red discs lost color at once; the white blood-corpuscles were very soon
destroyed, and formed glassy clumps. In sharp contrast with the results just
described are the blood-findings during the days of the disease when the patient
was still quite well. In this blood neither shadows nor numerous leukocytes
are to be seen, nor even greatly increased blood-plaques ; under the influences
previously mentioned the erythrocytes show a normal resistance, i.e., they
neither lose color very rapidly, nor are many of them destroyed. ;
For many years I have examined minutely the blood of patients attacked
by various forms of purpura, and have found by no means uniform results.
496 THE HEMORRHAGIC DIATHESES
In many cases very few deviations from the normal were recognized, in many
others the signs of anemia were distinctly observed. Anemia-is the sum and
substance of the blood changes in this affection, if such changes exist at all.
Microcytosis, poikilocytosis, numerous pessary forms, a relative and absolute
decrease of hemoglobin, blood-plaques increased, occasionally very much so,
and profuse cylinder-formation in the blood, such are the important changes
which I have observed. An increase of leukocytes, a slight destruction of the
same, and the appearance of isolated, nucleated red blood-corpuscles are occa-
sionally but by no means constantly seen. Moreover, the number of leukocytes
is subject to extraordinarily rapid change. The many “ pessary forms” of
red cells which are quite frequently found, in fresh preparations as well as in
smears stained with eosin, are only a sign of the scant hemoglobin contents
of the erythrocytes, and it is, therefore, not remarkable that in spite of a nor-
mal number of red cells the hemoglobin may be decidedly diminished. In the
investigation of the fresh blood of patients who suffered from purpura, upon
a warm slide (heated to 30° C.), no change in the corpuscles, either in the red
or in the white, was perceptible; they resembled perfectly the blood-corpuscles
of healthy persons or were, for example, like those in malaria patients whose
blood I had used for comparison.
TREATMENT
Prophylaxis.—On account of the spontaneous and unexpected appearance
of purpura there can be no question of prophylaxis. The frequency of re-
lapses should be a warning to those who have recovered once or repeatedly
from the disease, to protect themselves for a long time against deleterious
external influences, particularly chilling the body. Change of climate has
proven very beneficial.
General Treatment.—The patient must remain in bed for a long time, even
if no fever is present. The more rigidly this rule is adhered to, the more
certainly will relapses be prevented. He is to move about just as little as
possible. The more experience I have with cases of this kind, the more thor-
oughly I am convinced of the great value of rest in bed. The absolute neces-
sity of this must be impressed upon the patient, so that, from conviction and
not merely to please his physician, he will submit and adhere to this very
tiresome régime. Every arrangement must be made for the patient’s comfort
during this prolonged rest in bed; he should be taken down into the garden,
or upon a shady veranda, balcony, or the like. Further, the nurses must see
that no part of the patient’s body is subjected to external pressure, and that
he does not bruise or injure himself. With this end in view his bed must be
very carefully prepared. Above all, folds in the bed sheets must be prevented.
The covering is to be light, the sick room to be kept cool. Psychical excite-
ment and mental exhaustion are to be strictly avoided under all circumstances.
The nutrition must be bland. All foods are to be given cool. Strong
coffee, tea, and alcohol are prohibited ; only with symptoms of collapse may
the latter he made use of. Of foods, milk is most important, perhaps mixed
with somatose. Lemonade or orangeade may be used as a drink.
MORBUS MACULOSUS WERLHOFII 497
It is important that attention be paid to the fecal discharges on account of
possible hemorrhages and intestinal parasites (or their ova). In case of con-
stipation no salines should be used, but only mild vegetable laxatives, such as
castor oil, tamarinds, rhubarb, cascara sagrada and others; enemata ‘and irri-
gations of water may also be utilized. Laxatives should be changed frequently
so that the intestine may not become accustomed to a certain remedy.
Special Treatment.—Upon the authority of Werlhof, sulphuric acid is
given, even to-day, in the form of Haller’s acid elixir, which Werlhof praised
as a specific. He also advised in purpura decoctum cortex chine (8-10: 200,
a tablespoonful every two hours). The administration of ergot, of lead ace-
tate, turpentine, and liquor ferri sesquichlorati has been based upon the
pathology of the disease. In very stubborn, frequently relapsing cases, I
have seen good results from arsenic in the form of Fowler’s solution, espe-
cially in combination with carbonated or warm baths rich in salt. I can
highly recommend this treatment, particularly in the cases in which all other
methods have been without result.
Henoch has used ergot in the following manner:
Ag Ae e a epcaa ee, Gees eae a 150
M., D., S.: For children a teaspoonful, for adults a tablespoonful, every
three hours.
I cannot so strongly recommend this. Liquor ferri sesquichlorati may be
given in gruel, from one to five drops three times daily.
The following medication is also advised, although I have never seen any
results from it: Twenty to thirty drops of the fluid extract of hydrastis cana-
densis every two to three hours.
In peliosis rheumatica the employment of sodium salicylates, aspirin and
antipyrin is worthy of trial.
In epistaxis, dorsal decubitus with the head low, cold to the nape of the
neck, and liquor ferri sesquichlorati are indicated. The insufflation of cold
water, to which a few drops of the previously mentioned iron salt are added,
will often control the hemorrhage. Tampons of cotton dipped in the iron
solution may also be necessary. Gastric and intestinal hemorrhages are to be
combated by ice in combination with opium. Therapeutic requirements are,
however, rarely necessary, as the condition is infrequent. The same is true
of renal hemorrhages.
With symptoms of collapse, stimulants are to be used (wine, coffee with
brandy, champagne, camphor, ether). The application of heat may become
necessary (hot bottles, hot sand bags). In severe cases hypodermoclysis of
physiologic salt solution, to which oxygen has lately been added with success,
may be resorted to. iad
During convalescence the patient must be placed on a nourishing diet.
Residence in the country, by the sea, or in the mountains 1s advisable. Of
drugs, iron is the best. The urine is to be frequently examined even after the
actual disease has run its course, for sometimes in immediate sequence or a
33
498 THE HEMORRHAGIC DIATHESES
long time afterward (weeks and months) albuminuria may appear. Occasion-
ally this disappears with a stimulating diet and warm baths; in other cases it
remains and passes into a chronic (interstitial) nephritis. For the treatment
of this condition, the article upon renal disease may be consulted; but I may
remark here that, even in such cases, I have seen favorable results from cold
sea baths, though only in well-nourished and robust individuals.
THE ANIMAL PARASITES
THE ANIMAL PARASITES OF MAN
By E. PEIPER, Greirswatp
By “animal parasites of man” we mean the organisms which live tempo-
rarily or permanently on or in the body of man and derive their nourishment
from it. There is no difference, properly, between animals that live as para-
sites and those that live free. For, on the one hand, there are parasites—e. ¢.,
the ascaris nigrovenosa (this species, indeed, does not live on man)—which
produce mature offspring capable of living free, and, on the other hand, ani-
mals which usually live free may appear as parasites. Thus, the larve of
flies, which usually live on decaying organic substances, are found “ occasion-
ally” as parasites in man, either in the intestinal canal or in suppurating
wounds. These occasional parasites must not be classed with the so-called
“ pseudoparasites.” By the latter we generally mean foreign bodies of various
kinds and origin which are manifest per vias naturales.
As stated, we distinguish between a temporary and a permanent parasitism.
Fleas and bed-bugs infest man only transiently. The development of these
organisms is independent of the human body. Temporary parasites include
the ectoparasites (or epizoa) which inhabit the skin, the conjunctival sac, the
mouth, the nose and its accessory cavities. It is true, the ectoparasites also
include some permanent parasites. Most of the permanent or stationary para-
sites are found as entoparasites or entozoa in the internal organs: in the intes-
tinal canal and the glands belonging to it, in the lungs, in the heart, in the
brain, and in the muscles. But the permanent parasites are not all entopara-
sites, for many of them live also on the skin. lice and sarcoptes hominis
rarely leave the body of man upon which they develop from the ova and
multiply.
Many parasites, such as tenia, ascarides, and ankylostoma inhabit man
only when mature; others, such as the echinococcus, only during a certain
period of its development. Man, therefore, is either the actual host or only
the intermediate host. For many parasites, such as tenia solium and tenia
saginata, man has the doubtful honor of being the only host. But, man also
becomes the host of parasites which, as a rule, select another host animal.
Thus, the cysticercus cellulose occur not only in the pig, deer, and cat, but
by autoinfection also in man. Balantidium coli and echinorhyncus gigas are
specific parasites of the pig, but occasionally they are found in man.
Since remote times physicians and zoologists have attempted to ascertain
the origin of the parasites. As a rule, this has been easy with the ectopara-
sites; but exceedingly difficult with the entoparasites. For not only in the
501
502 THE ANIMAL PARASITES OF MAN
intestine, but in the organs of the human body that are beyond the reach of
external contact, parasites are found whose origin baffles conception, and most
remarkable suppositions and opinions have arisen regarding this origin. The
most simple and most natural explanation of this secret of nature was the
assumption of a generatio equivoca. It was believed that spontaneous gen-
eration, which was supposed to be common among the lower animals, occurred
also among the entoparasites. Endeavors were made to demonstrate that the
parasites developed from the intestinal mucus, from inspissated fecal masses,
and from decomposed blood. Step by step, the proof was slowly furnished
that not only highly organized animals, but also the lower were endowed with
sexual powers, and that the parasites developed only from fecundated ova. In-
vestigators have had to contend with one great difficulty, namely, the occur-
rence of young, asecual forms. But the transition of these into intermediate
hosts, their return to the specific host, and their development into mature forms
was finally established experimentally.
With certain exceptions, sexual maturity and parasitism coincide for those
entoparasites which are under discussion. The ova or embryos of the mature
parasites reach the outside world, and here, protected by a covering which is
very resistant to external influences, they continue their development, and
finally reach an intermediate host. Many exceptions occur. The embryos of
the trichina spiralis pass from the intestinal wall of the host immediately into
his tissues. Others, slipping from the sac of the ova, live free for some space
of time; still others migrate directly into the final host, there to reach their
maturity. Asexual forms first pass into an intermediate host, where they are
harbored and still further developed, until at last they reach their final host;
or, after the lapse of some time, they become subject to retrogressive changes.
Our knowledge of the distribution of the animal parasites in man is very
incomplete. It is certain that oxyuris, ascaris and trichocephalus, as well as
the ectoparasites, pediculus, cimex and pulex, are found throughout the world,
and are probably the most common animal parasites. Others, such as
echinococeus, ankylostoma, filaria, are observed only in certain countries, out-
side of these only sporadically, and then introduced from infected districts.
Precise statistical reports regarding the distribution of the parasites, which
might assist in the explanation of various questions, are very limited in
number.
Aside from the influence of climate and soil, the frequency of the occurrence
of parasites in man is due also to the customs and habits of a country, and,
no less, to the personal cleanliness of the individual inhabitants. I do not
refer merely to ordinary cleanliness of the body, which is of importance in the
transmission of the ectoparasite, but particularly to cleanliness in kitchen and
household. There can be no doubt that the majority of the parasites are trans-
mitted by food and drink, by ingestion from contaminated vessels, soiled
hands, ete. In countries where, as in Abyssinia, beef is eaten raw or at least
not sufficiently well cooked, the beef tape-worm is greatly disseminated. The
tenia solium is not rarely found in Central Germany, where raw or half-cooked
pork is often eaten. For the same reason endemics and epidemics of trichinosis
have not yet been completely exterminated in these districts. The intake of the
THE ANIMAL PARASITES OF MAN 503
flukes need not necessarily be with measly meat; it may be brought about by
secondary conditions. It is impossible to enumerate all the accidental ways by
which the flukes may be transmitted to food, especially in butcher shops and
restaurants in which proper cleanliness is lacking. The transmission of the
bothriocephalus latus occurs in a manner similar to that of the cysticerci, the
hooklets of which are shown to retain great vitality in smoked or frozen pike.
The rdle assumed by insects, especially the common house-fly, in the dis-
semination of parasites is very interesting. Grassi has shown that the ova
of the tenia solium, oxyuris vermicularis, and trichocephalus dispar, pass
through the intestine of the fly without change. But Stiles reports that the
ova of ascarides undergo further development in the intestinal canal of the fly.
Owing to the very general prevalence of flies and their habit of settling upon
various food-stuffs, on which they defecate, there can be no doubt that these
insects contribute materially to the distribution of the ova of the helminthes.
It is certain that vegetables of various kinds and sources, if not thoroughly
washed, or if eaten raw, may become the carriers, the same as meat if it has
but come in contact with the ova of helminthes.
We know, from the interesting observations of Lutz, how the ascarides de-
velop. The rural population especially, and, above all, the children by play-
ing upon infected soil, acquire the embryos of. the ascaris lumbricoides from
the soil, whereas the parasites are far less frequent among city-bred people,
even among the children. The affection is often transmitted by food con-
taminated with infected earth, often by means of the drinking-water into
which germs capable of development have lodged.
The réle of drinking-water in the distribution of the entoparasites is un-
doubtedly of great importance. I do not refer only to the transmission of
occasional parasites, but, above all, to the protozoa, the ova of ascaris and of
trichocephalus, especially the immature forms of the trematodes, which reach
the human intestinal canal by polluted drinking-water. Water has an influ-
ence also in the development and distribution of the ankylostoma duodenale,
as we shall see later. Since the investigations of Loos, it can no longer be
doubted that the last-named parasite is-able to force its way into the human
organism through the uninjured skin. A number of authors believe this true
also of the filiaria medinensis (guinea worm). So manifold are the ways in
which the young forms of the parasites, or the parasites themselves, migrate
into man that we cannot enter upon them here.
When we endeavor to ascertain whence the former originate, we note that
the majority of parasites are derived from animals, especially from our domes-
tic animals, dogs, cats, pigs, and cattle. I refer only to the group of the
cestodes, to the trichina, and to numerous epizoa. The more intimate the
relations between animal and man, the greater the danger of transmission.
Furthermore, man himself is often not only the carrier, but the disseminator
of the parasites. Not only does he infect his surroundings with the young,
but occasionally he infects himself, as shall be demonstrated later in the dis-
cussion of oxyuris vermicularis.
In regard to the symptomatology, there is perhaps no realm of pathology
in which so many contradictory opinions have been expressed as have been
504 THE ANIMAL PARASITES OF MAN
called forth by the animal parasites, especially by the entozoa. Formerly, when
certain morbid phenomena could not be explained, enigmatical symptoms were
ascribed to the accidental presence of one or several parasites, thus giving rise
to many vague conceptions; later there was an evident inclination to ascribe
little, or no, reaction upon the affected organism to animal parasites, espe-
cially to the entozoa. Undoubtedly, both tendencies were wrong. The phe-
nomena observed in many persons infected by parasites, especially the nervous
manifestations, cephalalgia, pruritus, disturbances of sight and hearing,
mydriasis, sensations of general weakness and lassitude, should not always be
regarded as the consequence of helminthiasis. The decision regarding the
causal connection depends also upon whether the symptoms have occurred only
after the appearance of the parasite and have ceased soon after the expulsion
of the unwelcome visitor. Thus, Cobbold and Davaine report a number of
cases in which various nervous symptoms disappeared after the expulsion of
a tape-worm. In a case of epilepsy which had persisted for three years Marx
saw a cure take place after the expulsion of tenia solium. In a patient who
suffered from tabetic phenomena, and in whom there was marked temporary
myosis and loss of the pupillary reaction, Denti noted that all symptoms were
cured by the expulsion of a tenia solium. Noticeable, too, are the frequent
reports of disturbances of the visual apparatus in helminthiasis. In short, it
is certain that considerable disturbance of health, sometimes even serious dan-
ger to life, may be caused by the presence of parasites.
It is obvious that delicate, nervous, anemic persons suffer much more from
the presence of parasites than robust individuals, whose power of resistance is
greater, and that the reaction in the former is much more violent. The with-
drawal of food-stuffs which are easily assimilated but which often cause the ex-
pulsion of the tape-worm chains, meters in length, or numerous ascarides from
the intestinal canal, must inevitably, apart from the local reaction, be fol-
lowed by injurious sequels, especially in weak persons and children. The
presence of hundreds, even thousands, of blood-sucking ankylostomata cannot
fail to produce serious disturbances. Parasites which have lodged in vital
organs, in the liver, lungs, heart and in the eyes, in the brain and the spinal
cord, even if relatively small, will certainly cause serious functional disturb-
ances and disease.
The investigations in the last decade by Reyher, Runeberg, Dehio, Scha-
piro, Schaumann, and others, have demonstrated that the animal parasites,
especially the bothriocephali, produce toxins which, taken into the blood, may
lead to the severe manifestations of pernicious anemia. The secretion of toxic
substances by other animal parasites, such as echinococci, ascaris lumbricoides,
ankylostoma duodenale, etc., is also probable. We do not as yet know the toxin
itself, but we recognize its deleterious effects.
The number of parasites occurring in man is very large. Every year fur-
nishes reports of the appearance of animal parasites until then unknown. In
the following I shall review the fauna of man. It seems most practicable to
discuss them in a systematic order. I begin, therefore, with those organ-
isms which can only with difficulty be separated from the lowest vegetable
organisms.
PROTOZOA 505
PROTOZOA
We designate as protozoa the primordial animals, those microscopically
small but living organisms which, as monocellular elements, singly or in colo-
nies, collectively represent the simplest animal type. The substance of the
body, sarcode, consists of a contractile, finely granulated protoplasm which is
mononuclear or polynuclear. The viscid, hyaline ectosare is capable of motion
by contraction and expansion, or by extension and retraction of pseudopodia,
by cilia and flagella. There can be no doubt that it is concerned in the Inges-
tion and excretion of food. Fissures and openings in the ectosarc take the
place in some protozoa of the functions of mouth and anus. The soft endo-
sarc serves for the digestion of the food consumed ; the contractile vacuoles,
occurring in many protozoa, are intended for the accumulation of fluids to be
excreted. Propagation takes place by segmentation, gemmation or sporulation.
We know that all three varieties of the protozoa, the rhizopoda, the sporozoa
and the infusoria, occur as parasites in man.
The rhizopoda, “ root-footed ” organisms, include the ameeba coli (Loesch),
discovered in 1875, the amceba coli felis of Quincke in 1893, the ameeba coli
mitis of Quincke, which is minutely described in the interesting treatise of
Hoppe-Seyler, “ Dysentery and Ameba Enteritis,”+ and the amceba coli vul-
garis of Quincke. The investigations of Quincke and Roos have proven that
the latter are not pathogenic either in man or in cats. The severe and well-
known dysenteric symptoms caused by the first-named ameha may be mate-
rially complicated by the supervention of liver abscesses. Cases of infection
by ameeba coli mitis are considerably milder, but of a distinctly chronic course.
For details regarding these parasites I refer to the previously mentioned article.
Amebex in man are not confined to the intestines. I have referred to their
occurrence in the pus of liver abscesses in dysentery. Jjima demonstrated
Fic. 26.—AMEBA AT Fig. 27.—AMEBA IN Fig. 28.—AmMEBA FLat-
Rest. MorTIon. TENED.
Fias. 26-28.—Leypenia Gemmipara. (After von Leyden-Schaudinn.)
n, nucleus; 7, vacuole; pv, pulsating vacuole.
amebe in pleuritic and peritoneal exudates. Gros and Sternberg have reported
the presence of amebzx in the tartar of the teeth. Flexner found amebe in an
abscess in the oral cavity, Kartulis in the pus and in an extracted portion of
1 See the chapter on Dysentery in volume, “Infectious Diseases.”
506 THE ANIMAL PARASITES OF MAN
the lower jaw. Baelz observed amebe in the urine, Jiirgens in the mucous
membrane of the bladder, Kartulis in a tumor of the bladder, Wijnhoff and
Zeehuisen in mucohemorrhagic urine, and their causal relation to the morbid.
phenomena is not yet explained. This detection of amebe is undoubtedly very
interesting, but a definite opinion regarding their significance cannot be
arrived at until the culture of amebe in pure culture has been accomplished.
Then we shall be able by experiments to estimate their true significance as
generators of disease.
v. Leyden and Schaudinn found in the ascitic fluid of two cases of carci-
noma structures of an irregular polygonal or globular form, which, in a con-
tracted condition, measured from 3 to 36 yw. Uncontracted, they possess the
power of ameboid movement, and send forth processes which are either hyaline
or lamellar or granular. The plasma is thickly studded with very refractive
granules of a yellowish luster. Several vacuoles for fluid, among them one
pulsating, are generally found, and one nucleus. Propagation occurs by
gemmation and segmentation. Similar structures were found by Lauenstein
and Behla in the ascitic fluid of patients with carcinoma. It is still unde-
cided whether the Leydenia gemmipara Schaudinn, 1896, has any relation
to carcinoma.
The second class of the protozoa, the sporozoa, includes parasites which
have also been discussed by the above-mentioned authors, such as the coccidium
oviforme, Leuckart, 1879, the coccidium perforans, Leuckart, 1879, and the
coccidium bigemimum, Stiles, 1891. These parasites are rarely found in man,
it is true, but, when present, they cause obstinate intestinal catarrhs which are
difficult to cure. Undoubted cases of coccidiosis of the kidneys and of the
ureters have also been described by Lindemann, Bland-Sutton, and Targeff.
In the case reported by Clarke numerous small, greenish-brown cysts contain-
ing the parasites in varying sizes were found in the renal pelvis, in the ureters,
and in the bladder.
Miescher’s or Rainey’s tubes, which became known from the microscopical
examination of pork, are of no pathogenic significance and are only rarely
found in man. Apart from the doubtful cases of Lindemann and Rosenberg,
such structures have been found in man only by Kartulis in the muscles of
the abdomen, and by Baraban and Saint-Remy in the muscles of the larynx.
The most important group of the sporozoa are the hemosporidia which
include, as is well known, the malarial parasites of man. The highly interest-
ing history of the development of these parasites, and also the pathological con-
dition produced by them, have been exhaustively discussed in the chapter on
Malaria (which see in volume “ Infectious Diseases ”’).
In concluding this study of the sporozoa, I desire to mention that in the
future we may possibly be able to attribute other parasitic affections of man to
the parasitic nature of the protozoa. Some well-known authors assume that
the pathogenic germs of carcinoma, sarcoma, scarlatina, measles, smallpox, per-
tussis, etc., are represented by certain protozoa yet to be found or to be inves-
tigated. Unfortunately, the researches undertaken up to the present have not
led to a positive, indisputable result.
The third class of the protozoa embraces the infusoria, which are structures
‘PROTOZOA 507
of more or less constant form, and covered with cilia in varying number and
arrangement. The infusoria include the flagellates and the ciliated parasites.
Of the flagellates, trichomonas vaginalis, Donné, 1837, is frequently found
in yellowish, markedly acid vaginal mucus, whereas the parasite is not pres-
ent in the normal secretion of the vagina. The
parasite, which is elliptical in shape, and 0.01
mm. in length, is elongated into a delicate process
at the anterior border of which there are usually
four long, slender, whip-like flagella. An undu-
lating membrane, the contracting wave of which
is continually directed anteroposteriorly, extends
spirally from the point of origin of the flagella.
The parasite was found in purulent urine by
Marchand, Miura and Dock; in human feces by
Janowski and Skaller; in the contents of the
stomach in carcinome cardie by Strube.. It also
appears that the flagella found by Davaine, Grassi,
Eckekrantz, Cunningham, Tham, Marchand, Zun-
ker, Epstein, May, Roos, Schuberg, Schiirmayer,
and others, which, following Davaine (1854), are
designated as trichomonas hominis, are not essen-
tially different from trichomonas vaginalis. Simi-
lar structures were also found in the sputum in
gangrene of the lungs by Kannenberg, Streng and
Schmidt, in serous pleural exudate by Litten, in
putrid pleurisy by Roos. It appears that the para- ye ere a achietig
site designated plagiomonas urinaria by Kiinstler, apLy ENtarcep. (After
In 1883, also belongs in this class. The cilia Kistler.)
observed by earlier authors were probably only
simulated by the continuous motion of the undulating membrane. The num-
ber of the flagella is by no means characteristic.
No positive statements can be made regarding the significance of the tricho-
monades as generators of disease. Yet it is quite conceivable that, if present
in enormous quantities, they might lead to long-continued suppuration and
catarrh of the intestine. As a rule, they are easily exterminated by repeated.
doses of 0.1-0.2 of calomel.
Megastoma entericum Grassi, 1881, and s. Lamblia intestinalis Lambl,
1859, are of the same significance. The exact description of this parasite
will be found in the chapter on Dysentery,! where it is also stated that the
parasite, if occurring in large numbers, may cause an intestinal catarrh which
is usually cured without difficulty unless complicated by carcinoma or tuber-
culosis.
Of other flagella, monas globulus, Dujardin; monas lens, Dujardin; monas
elongata, Dujardin; bodo intestinalis, Ehrenberg; cercomonas acuminata,
Dujardin; cercomonas globulus, Dujardin; cercomonas biflagellata, Stein-
1 Volume, “ Infectious Diseases.”
508 THE ANIMAL PARASITES OF MAN
berg; trichomonas elongata, Steinberg; trichomonas caudata, Steinberg; and
trichomonas flagellata, Steinberg, have been probably found as simple com-
mensals.
Of the cilia inhabiting man, cilia infusoria, we are most interested in the
balantidium coli, Malmsten, 1857, the pathogenic significance of which as the
generator of severe dysenteric intestinal catarrhs is also described in the chap-
ter on Dysentery. Stockvis has also found balantidia in the sputum of a sol-
dier who had returned from the Sunda Islands.
Jacoby and Schaudinn have recently found a new balantidium minutum
n. sp. in diarrheic stools, and also the nyctotherus faba n. sp., illustrations of
Fic. 30.—Bavantipium Minutum.
n, nucleus; cv, contractile vacuole. (After mi.n, micronucleus; ma.m, macronucleus.
Schaudinn.) (After Schaudinn.)
which follow. Vorticelli, which, according to Lindner, are said to infest man,
cannot yet be recognized as parasitic structures.
This embraces the principal protozoa which occur in man.
We now come to the more highly-organized class, the plathelminthes or
flat-worms. To this group, which embraces the two classes of trematodes, or
sucking-worms, and cestodes, or tape-worms, belong the “ vermes intestinalis ”
of the earlier authors or “ helminthes ” which—sit venia verbo—represent the
true intestinal worms.
TREMATODES
The tongue- or leaf-shaped trematodes include the amphistomum hominis,
Lewis and McConnell, 1876.
I wish to include this parasite for the sake of completeness. Observed
but a few times in the tropics, it possesses no actual interest for us, especially
since its significance as a parasite is by no means accurately determined.
Of greater importance is the distomum hepaticum, Linné, 1758.
The liver-fluke is found in the intestines and in the bile-ducts of a great
number of mammals, especially in the sheep. Rot or liver disease in many
districts creates great ravages among sheep. The parasite is also often noted
to occur sporadically. Its body is oblong, flat, leaf-like, with a proboscidiform
projection on the cone-shaped head. One of the two suctorial discs is situ-
ated at the point of the cone-like head, and contains the opening of the mouth.
The other suctorial disc belongs to the abdominal surface. The oval eggs are
TREMATODES 509
of a considerable size: Breadth 0.075 to 0.09 mm., length 0.14 to 0.15 mm.
The anterior pole is flatter and has a lid.
The development of the liver-fluke, explained by Leuckart and Thomas, is
a very complicated one. The ova are discharged with the feces. After a pro-
longed stay in water, the elongated miracidium develops
and after some time breaks the cover of the egg. By
means of its ciliary sac it floats about, and finally is
taken up by its first intermediary hosts, small water
snails, the limneus minutus and limneus cahuensis,
which are found in large numbers in small pools. In
this host the miracidia become transformed into sporo-
cysts, which are generally found in the respiratory cavity
of the snail. The sporocysts produce a second genera-
tion of germ tubules, redia, from which, finally, the true
young of the distoma develop in the form of caudate
cercaria. The cercaria then emerge, adhere to grass and
water plants and, with these, enter their final host in an
encysted form. From the intestine they migrate into the bile-ducts, where
they develop into mature animals:
It is obvious, in view of this mode of development, that man is but rarely
inhabited by distoma, and even then only by a small number. The entrance
of the cercaria into man occurs principally by their ingestion with polluted
drinking-water or with raw vegetables, salad, or water-cress, which have grown
in inundated places. In many other ways they may enter the body; we need
only consider how often children and even grown people put meadow-plants into
the mouth. ,
About 18 cases of disease of the liver in man from distoma have been re-
corded. As only very few parasites were present, no special symptoms were
caused in the majority of these cases. Yet the cases of Bostroem and Biermer,
in which the fatal outcome of the disease was due to the parasite, prove that
even a single parasite may produce severe phenomena.
It seems that the parasites remain latent for considerable time. The
general condition of the patient changes gradually for the worse, he ema-
ciates, obstinate jaundice and uncontrollable, sometimes hemorrhagic, diar-
rhea develop. Then follow vomiting, violent pains in the region of the
liver and general dropsy until, with progressing cachexia, death takes place.
The autopsy often shows numerous changes in the liver: Enormous dilata-
tion and occlusion of the bile-ducts with ulceration of the same; excessive
increase of the connective tissue in the area surrounding the focus of the para-
site; obliteration of the large bile-ducts, occlusion of the hepatic duct, ete.
If, therefore, the diagnosis should be difficult, an examination of the stools
will enable the physician to recognize the disease. Bostroem and Perroncito
succeeded in finding the ova of distomata in the stools. ;
Owing to the difficulty of the diagnosis, the treatment must always remain
symptomatic; but if the diagnosis be correctly made, the expulsion of the
liver-fluke may be attempted by the administration of mineral waters or other
remedies promoting the secretion of bile.
Fic. 32.—Distomum
Hepaticum, LInNs.
510 THE ANIMAL PARASITES OF MAN
Occasionally the liver-fluke may pass from the liver into other organs,
Duval found the parasite in the trunk of the portal vein, and Friedberger in
the portal vein. It was found in abscess cavities upon the plantar surface of
the foot by Giesker ; behind the ear, by Fox; in the right hypochondriac region,
by Dionis des Carriéres; and it was extracted from the shoulder region by
Malherbe. Raillet reports that a French officer in Rio coughed up a Senegal
liver-fluke.
The bile-ducts of various mammals contain, together with the distomum
hepaticum, the distomum lanceolatum, Rudolphi, 1803, which, like the dis-
tomum crassum Busk, 1850, has been found but rarely in man.
Besides these, I shall also mention the distomum heterophyes, v. Siebold,
1852, and the distomum ophthalmobium, Diesing, 1850, as they have been
rarely observed in man.
In Formosa, Korea, and, particularly, in Japan, the distomum Wester-
manni, Kerbert, 1878, is frequently found, and this is also designated dis-
tomum pulmonale, Baelz, 1883, distomum Ringeri, Cobbold, 1880.
This reddish-brown parasite, according to Baelz, attains a length of 8-10
mm., a breadth of 5-6 mm.; it is oval, slightly rounded at the ends; a cross
section is almost circular; the suctorial discs of the mouth and abdomen are
Fie. 33.—DistomMumM WESTERMANNI AND Fic. 34.—Distomum SPATHULATUM AND
Ovum. (After Katsurada.) Ovum. (After Katsurada.)
almost of equal size. The ova, thousands of which are often found in bloody
sputum, are of a brown color, 0.08 to 0.01 mm. long and 0.05 mm. broad,
thin-shelled, and showing a lid at the blunt end. Besides in man, the parasite
ta been found in the dog and also in animals of the cat family, especially in
apan.
Distomatosis is widely disseminated in Japan, and is the cause of an appar-
ently harmless hemoptysis. ‘The parasites are found in cavities; in one case
dissected by Baelz there were twenty specimens. These cavities contain a
reddish, pulpy mass consisting of mucus, red blood-corpuscles and numerous
distoma ova. The cavities are connected with the bronchi by sieve-like open-
ings through which the ova, sometimes in enormous numbers, reach the spu-
TREMATODES 511
tum. The patient’s general health is not materially impaired; but there is
danger of fatal hemorrhages. The diagnosis is determined by the demon-
stration ofthe ova. The ova of the distoma may, according to Yamagiva and
Otani, be carried to the brain, and there give rise to serious disease.
No special therapy is known as yet. But it seems advisable that persons
infected by distoma should leave the regions where these are found in order
to avoid further infection.
The distomum spathulatum, Leuckart, 1876, or distomum sinense, Cob-
bold, 1875, is very common in man, and also in the cat, in China and in
some parts of Japan.
This parasite is reddish, almost transparent, flat, 10-18 mm. long, with
pointed anterior and posterior ends; the skin is smooth. The suctorial disc
of the mouth is larger than that of the abdomen; the latter is situated at
the line of the first quarter of the body. The oval eggs, 0.028-0.03 mm. long
and 0.016—0.017 mm. broad, are encapsulated, and gradually become black.
The parasites are generally found in large numbers in the bile-ducts, but
rarely in the stomach and in the intestines. They produce severe clinical
disturbances. According to Baelz, the trouble begins with enlargement of the
liver, and a sensation of pressure and weight in its region; this is accom-
panied by a morbid appetite. After some years the nutrition becomes defec-
tive, and uncontrollable diarrheas make their appearance and later become
hemorrhagic. Gradually dropsy, ascites, and anasarca develop, and the pa-
tients finally succumb with severe cachectic phenomena. The autopsy shows
the walls of the gall-bladder and bile-duct studded with cyst-like sinuses the
size of a nut, which often contain numerous parasites. The sinuses communi-
cate with the bile-ducts. The liver is enormously enlarged but of normal
color. The tissue in the neighborhood of the parasitic foci is atrophied. The
ova of the parasites are always found in the feces. We know but little regard-
ing the development of the parasite, only that the ovum while in utero
develops a ciliated miracidium. The young forms of the parasite probably
live in mollusea. In later stages of development they must reach the intestinal
tract of man with raw vegetable, and possibly also with animal, food.
The distomum conjunctum, Cobbold, 1859, has been found, so far, only
twice, in individuals in India who had succumbed to severe dysentery.
Distomum felineum, Rivolta, 1885, sive distomum sibiricum, Winogradoff,
1892, deserves special mention.
According to its contractions, its length is 8-18 mm., and its breadth
1.5-2.5 mm. ‘The parasite, according to Braun, in fresh condition, is of a
reddish color, almost transparent, flattened, and pointed at the anterior end;
the skin is not weaponed. The suctorial discs are of almost equal size. The
pharynx is immediately adjacent to the suctorial disc of the mouth; the
esophagus is as long as the pharynx. The intestinal shanks, which do not
branch out, extend to the posterior end of the body, and are filled with dark
brown, granular masses. The eggs are oval, and have a lid which is sharply
defined ; the length is 0.02-0.03 mm., the breadth 0.011-0.015 mm. ;
The parasite Winogradoff, which until 1892 was only found in the cat, in
that year was noted to be a very frequent parasite of man, being present in
512 THE ANIMAL PARASITES OF MAN
the liver. In the nine cases observed by Winogradoff, death was not due to
the parasites. Yet the changes produced by it are quite considerable, viz.,
dilatation and inflammation of the bile-ducts, and foci of cirrhosis. In one
case there were small pus foci; jaundice and contraction of the liver existed
in five cases, ascites in three; the liver was twice found to be enlarged.
Braun’s assumption that, owing to the great dissemination of distomum
felineum among cats, it must also be present in man, was soon confirmed.
Askanazy reported such a case from East Prussia, in 1900. It occurred in
a man who had died of colloid carcinoma, which originated in the epithelium
of the bile-ducts. The microscopical examination revealed ova and about
100 specimens of distomum felineum in the regions not affected by the tumor.
The same author reported a second case, also from East Prussia.
Askanazy supposes the infection in man to be due, as in the cat, to ‘the
consumption of raw, or only partially cooked, fish.
Of great interest is another trematode, distomum hematobium, Bilharz,
1852, or the Bilharzia hematobia, Bilharz, 1852. The parasites live sexually
apart.. The male is thicker (up to 1 mm.) and
shorter (12-14 mm.) than the more slender (up
to 0.13 mm.) and longer female (16-18 mm.).
The anterior part of the body which contains the’
suctorial discs is flattened. The posterior part of
the body of the male, by a turning up of the
lateral borders, forms a tube (canalis gynzcopho-
rus) which serves for the reception of the female.
The surface of the male is covered with small
spiny warts, that of the female is smooth. The
ova, which are often found in large numbers in
the vagina, are slender and quite long, about 0.12
Fie. 35.—Ova or Disromum 2m. long and 0.04 mm. broad. They are pointed
Hemarcerus. at one end, or, more rarely, supplied with a
pointed side tooth. The shell of the ova is thin,
and there is no lid. The full grown parasites are found in man in the portal,
splenic and renal veins, also in the venous plexus of the urinary bladder, and
in the rectum. The ova lie in small, white masses in the various organs, espe-
cially in the urinary passages, in the vesicula seminalis, and in the mucosa
and submucosa of the large intestine. The primary seat of the ova is probably
the vascular system. The ova, deposited in the veins which are distended to
small diverticuli, enter the tissues only after rupture of the vessels.
The history of the development of the parasite which occurs mostly and
quite frequently in Africa, and especially in Egypt, is not yet clear. We know
only the following: The ova are discharged with the urine. Sometimes empty
sacs of ova are found in the urine synchronously with free embryos. Evidently
a miracidium, completely ciliated, escapes from the ovum in urine that is
greatly diluted with water and floats for some time in the water. It appears
likely that there is an intermediate host; but all attempts to infect mollusca,
crustacea, and fish have been fruitless. Loos doubts the transmission by an
intermediate host. The embryo, in the opinion of this author, enters directly
TREMATODES 513
into man, and develops into a sporocyst which then infects a patient with
its young.
It has been assumed that man becomes infected with the parasite by drink-
ing infected water. Yet the observations and the experimental investigations
of Loos make this assumption doubtful. Attempts to infect monkeys by
giving them infected water to drink did not prove successful. Brock and Loos
assume that the parasites gain access directly through the skin during bathing.
Men and boys are affected much more frequently than women and girls who
bathe but rarely. Brock found that the newly arrived in the Transvaal who
went bathing were soon infected, whereas others who did not bathe remained
free from the parasite. Loos rejects, however, the assumption of Harley and
Allen that the parasite finds entrance into the body through the urethra.
The incubation period, according to Loos, is four weeks; according to Brock,
four months.
In addition to the parasites at the points of predilection in the vascular
system, autopsies reveal the most marked changes in the bladder and in the
ureters. In freshly developed cases there is a marked catarrh of these organs
with a viscid, yellowish-red mucus in which, as also in the mucous membrane
itself, numbers of distoma eggs are found. In chronic cases the mucous
-membrane shows the signs of a severe chronic catarrh, and has a sandy ap-
pearance. Characteristic excrescences, from the size of a pea to that of a
bean, and having the appearance of hemorrhagic ecchymoses, are formed in
the swollen submucous tissue. The excrescences sometimes become encrusted,
and then represent stony polypi which are broken off and form the nuclei
of bladder stones. Pyelitis, nephritis and hydronephrosis follow in severe
cases. Kartulis, Albarran-Bernard and Harrison quote cases from their expe-
riences which show in the tissues permeated with distomata the tendency to
proliferation, that is, to formation of carcinoma. Not the parasites, but the
ova, cause the severe irritation. They are also found in the lungs, in the
liver, in the prostate gland and in the mesenteric glands.
Clinically we encounter at first the manifestations of a hematuria asso-
ciated with burning pain in the urethra. At first intermittent, it gradually
becomes permanent. The characteristic ova are found very early in the urine.
If the infected individual does not leave the country, the disturbance is aggra-
vated by affections of the renal pelvis and of the kidneys. Stones in the
bladder and in the kidneys develop frequently. We have mentioned the
tendency to the formation of carcinoma. Cole Madden describes a papilloma
of the vagina produced by the ova of distoma. The mucous membrane of the
rectum shows similar polypoid excrescences as the bladder. The nutrition
becomes defective and, finally, after a course lasting years, death occurs with
cachectic manifestations. It seems that severe cases are most frequent in
Egypt. In South Africa, after protracted intermittent attacks of hematuria
and cystitis, the disease often, at least apparently, ends in recovery. The
destruction of the parasite does not in itself lead to recovery. Sonsino esti-
mates the duration of its life at two to three years. If the changes have been
very extensive, the morbid symptoms continue to develop after the death of
‘the parasite.
34
514 THE ANIMAL PARASITES OF MAN
If the views of Loos are correct, the prophylactic measures are plainly
indicated. In the infected countries energetic measures must be taken to
prevent the urine of infected individuals from ever reaching the rivers. The
embryos will soon perish in closed sewers. The greatest precautions are neces-
sary in regard to bathing, especially in the neighborhood of habitations in
which infected persons are living.
A therapy directed to the expulsion of the worms will probably always
remain useless. Efforts to expel them by turpentine oil or extractum filicis
maris have been, according to the reports of Brock, unsuccessful. We are,
therefore, entirely restricted to symptomatic treatment.
I may mention another trematode, the
Monostomum lentis of Nordmann, 1832,
which was once found in an extracted lens; this form is probably identical
with the distomum oculi, Ammon, 1833.
Hexathyridium pinguicola, Treutler, 1793, and hexathyridium venarum
are also counted among the trematodes.
CESTODES
Cestodes, tape-worms, have been known from antiquity as parasites of
man. Following the definition of Leuckart, we understand by cestodes flat-
worms without mouth or intestine, which develop by generation and by gem-
mation upon a scolex, and remain united for some length of time in a ribbon-
like colony.
The scolex, known under the name “head of the tape-worm,” is supplied
with two to four suctorial discs, and generally also with hooks that are bent
like a claw.
The head serves as the adhesion apparatus. The flat, two-edged links of
the chain (proglottides) grow away from the point of junction. The smallest
links contain the ova in which develop the embryos (oncospheres), which in
the bothriocephali are ciliated. Only these, reaching the outside world, per-
forate the shell of the ovum, and swarm in the water until they finally reach
an intermediary host. The ova of the other cestodes emerge into the outside
world with the feces, or still enclosed in the proglottid, and are at last taken
up by a suitable host. The oncospheres, enclosed in small cysts or embedded
in closed cavities of the body, develop in the host into scolices which, subse-
quently, are taken up by the actual host and grow into tape-worms.
The best-known of the tape-worms parasitic in man are the tenia solium,
Rudolphi, 1810, and the tenia saginata, Goeze, 1782.
I may forego a detailed description of these two parasites, since they are
well known. I shall only briefly outline their differentio-diagnostic charac-
teristics.
Tenia solium is distinguished by a head which is supplied with a rostellum,
a double row of hooklets and four suctorial discs. The proglottides, number-
ing 800 to 900, contain the testicles and the easily recognizable uterus con-
sisting of a medial trunk and of seven to ten lateral branches upon either
side. The marginal sexual papille alternate quite regularly. The rounded
CESTODES 515
ova, the shells of which are radially striated, enclose the oncosphere which is
supplied with six hooklets.
Malformations are rarer than in the tenia saginata. I wish to mention
only the three-edged or prismatic tenia which is produced, not as was fre-
quently assumed from a twelve-hooked oncosphere, but by the coalescence of
two scolices with one-half of their dorsal surfaces, whereas the other two
halves remain free; it appears that the dorsal parts of the coalescent halves
are at the same time greatly retarded in growth.
The ascxual immature form is the cysticercus cellulose, the finn of swine,
which is found principally in the pig, but also in other mammals. The mode
of infection of the pig and of man is well known.
The cysticercus cellulose occasionally also shows malformations. Such
are the cysticercus (tenia) acanthotrias Weinland and the cysticercus race-
mosus which is formed like a bunch of grapes and possesses many branches;
the latter is found in the brain and in the heart. This upsets (according to
the views of Redon, Blanchard, Raillet and Braun) the hypothesis of a special
genus of tenia (cysticercus) acanthotrias.
The second variety, the tenia saginata, is more rounded and larger than
the tenia solium, and has the following characteristics: The head is larger,
the row of hooklets and the rostellum are absent; the suctorial discs are
markedly developed. The proglottides are supplied with irregularly alter-
Fig. 36.—Ova or Trenta Sourum. Fia. 37.—Ova or Trenta SAGINATA.
The enlargement is the same in Fig. 36 and Fig. 37.
nating sexual papille; they show a uterus with 20 to 30 or even more lateral
branches; the sexually mature members which are cast off spontaneously are
frequently found without ova, because the latter have been discharged prema-
turely owing to a lesion of the uterus. The ova are similar to those of the tenia
solium (see illustrations). Malformations in the chain of links occur more
frequently than in the former variety.
Cysticercus bovis, which is the young form of this parasite, is principally
found in cattle. Whereas the cysticercus cellulose is sometimes found in the
organs of man, particularly in the brain and in the eye, generally through
autoinfection, only four cases have been reported in which the cysticercus
bovis has been found in man. It is probable, however, that these four cases
were not due to the cysticercus bovis at all, but to malformations of the
ceysticercus cellulose.
Man is considered to be the only host of these two forms. Deffke suc-
ceeded recently, by feeding the cysticercus cellulose to three dogs, in obtaining
in two of the dogs small specimens of tenia solium. The delicate specimens
gave the impression that they were in the process of expulsion. oo,
Tenia solium has for several decades become steadily rarer. This is evi-
516 THE ANIMAL PARASITES OF MAN
dently due to meat inspection during which,.owing to its size, cysticercus
cellulose is less often overlooked than cysticercus bovis.
Tenia cucumerina, Bloch, 1786, sive elliptica Batsch, 1782, is also well
known.
This tape-worm is frequently found in large numbers in the dog and in
the cat. The small rhomboid head shows a club-like rostellum studded with
about sixty hooklets arranged in four rows. The cucumber-shaped proglot-
tides are easily detected in the feces of the dog.
The cysticercoid young form inhabits, according to Leuckart and Melni-
koff, the abdominal cavity of the dog-louse, of the dog-flea, and, more rarely,
of the human flea. The habit which dogs and cats have of swallowing the
parasites that infest their hairy skins sufficiently explains the frequency of
the infection. This tenia occurs rarely in man, and is only observed in small
children. Blanchard reported the infection of an adult who always shared
his resting place during the night with his dog. ,
Quite as rare, at least in Germany, is the following tenia:
Tenia nana, v. Siebold, 1852.
This small tenia, only 2.5 em. long and 0.5—-0.7 mm. broad, is characterized
by a globular head supplied with a rostellum and four suctorial discs. The
rostellum is covered with a row of 22-27 hooklets. The proglottides, amount-
ing to about 200, are of an extended oblong form, the lower 20-60 of a
yellowish color, well-filled with ova. The sexual papille are all on one side.
The ova are covered with three structureless, transparent shells which are far
apart from each other.
Nothing is as yet known regarding the origin and development of this
parasite.
Leuckart supposes the intermediate hosts to be insects. According to
Grassi, the parasite develops without an intermediate host, as does the tenia
murina (Dujardin), which by many was formerly considered identical with
the former. The anatomical differences between these tenis were recently
pointed out by v. Linstow.
The teniz live in the small intestine in colonies, burrow their way deeply
into the mucous membrane of the gut, and, according to Grassi, produce
important changes in it.
The parasite has been observed only four times in Germany, and in all
four cases Cologne appeared to be the infected locality. It may possibly often
be mistaken for the oxyuris vermicularis, owing to their similarity. The
parasite has been observed in Egypt, Russia, Servia, Italy, Japan and South
America.
Very few cases of the
Tema flavopunctata, Weinland, 1858,
have been reported. Its identity with tenia diminuta, Rudolphi, and tenia
leptocephala Crepl. is established. The very small head is club-shaped, with
a rudimentary unprotected rostellum. The proglottides, 2.5-3.5 mm. broad,
0.6—-0.7 mm. long, present in their center, posteriorly, a yellow area which
CESTODES 517
corresponds to the male sexual organs. The intermediate hosts are, according
to Grassi, small insects, such as akis spinoza, anisolabis annulipes, asopia
farinalis, scaurus striatus, by the accidental ingestion of which man may also
become infected. These observations were confirmed by infection experiments
in man and in rats. The parasite has been so far found only seven times in
man, and almost exclusively in children.
Quite as rare is the
Tenia madagascariensis, Davaine, 1869.
This tape-worm is about 25-30 cm. long, with about 660-700 segments.
The head is supplied with four large, circular suctorial discs, and a rostellum
with a row of 90 peculiarly formed hooklets. The mature proglottides are
2 mm. long, 1.4 mm. broad. The sexual openings are situated on one side.
Each proglottid contains 120-150 small round ova. We are ignorant of the
exact development of the parasite and only know that species similar to this
tenia dwell in birds. Only five cases of this kind have been observed so far
in the tropics, among them one in British Guiana (by Daniels).
It appears to be very doubtful whether the tenia marginata, Balsch, 1786,
the tenia serrata, Goeze, 1782, and the tenia crassicollis Rudolphi, 1810, or
their cysticerces, have been observed in man, but five unknown tenie occurring
in man have been reported, and have been called the
Tenia confusa, Ward, 1896.
Ward, in a preliminary report, has described a tenia found in man. Its
length was about five meters. The end proglottides measured 27-35 mm., the
breadth 3.5-5 mm. This tenia is considerably more slender than the tenia
saginata. The head has four suctorial discs, and a retractile rostellum with
six or seven rows of small hooks, those in the front row being the largest.
Fic. 39. Fia. 40.
Fics, 38-42.—Trnta conrusa Warp. (After Guyer.)
Fig. 38, a, b,c, d, Chain of proglottides. Fig. 39, a and b, Mature proglottides. Fig. 40, Female
sexual organs. Fig. 41, Male sexual organs. Fig. 42, Ovum of the tenia confusa.
The proglottid-chain is distinguished from tenia solium and tenia saginata
by continuous longitudinal musculature, by the presence of a vesicula seminalis
518 THE ANIMAL PARASITES OF MAN
and a well-developed receptaculum seminis, and of a vaginal sphincter. The
ovarian tube opens into the lateral wall of the uterus. Fourteen to eighteen
lateral branches issue from each side of the uterus but are not perpendicular
to the main trunk. The yellowish ova are of ovoid form.
Tenia africana, v. Linstow, 1900.
The German colonial possessions have given us the knowledge of a new
tenia. v. Linstow described a large tenia of man which Dr. Fiilleborn found
in a negro soldier at Lake Nyassa. The scolex is unprotected, and is smaller
than the following chain of segments. The proglottides, even the terminal
ones, which, besides the uterus filled with ova, contain no other sexual organs,
are broader than they are long. The uterus consists of a longitudinal trunk
extending in an antero-posterior direction with 15-24 transverse branches on
either side which radiate toward the center. The interior organization is
different from that of tenia saginata in all essen-
tial points. The suctorial discs are enclosed by
rounded projections from which rays extend to the
periphery.
c
Fic. 43.—a-d, Segment chains of the tenia africana ; e, scolex from the vertical plane; f, lumen
of a suctorial disc. (After v. Linstow.)
The length of the three fragments of a tenia was 1,375 mm.; whereas the
segments of the tenia africana which are two mm. long show full maturity;
there is no trace of sexual organs in the segments of the tenia saginata which
are 3.16 mm. long and 5.84 mm. broad. The ova are ovoid, 0.042 mm. long
and 0.034 mm. broad.
Tenia asiatica, v. Linstow, 1901.
_ von Linstow recently described a tenia of man which was found by Anger
in Aschabad. The specimen is 298 mm. long; the segments are broader than
they are long and their chain is narrow. The foremost proglottides have a
breadth of only 0.16 mm. with a length that cannot be estimated. Later they
increase in breadth from 0,.67—-1.78, and in length gradually to 0.99 mm. The
posterior border of the segments slightly overlaps the beginning of the follow-
mg one. Seven hundred and fifty proglottides were present; the scolex was
absent. The formation of the uterus, as well as that of the other sexual
organs, suggests that this variety belongs to the tenia madagascariensis,
CESTODES
519
Recently, in the Centralblatt f. Bact. und Parasit., 1902, Band xxxi, page
770, v. Linstow described a
Tenia hominis n. spr.
in the collection of helminthes of the Musée zoologique de Académie Im-
périal des sciences de St. Petersbourg. This tenia was found by Anger in a
girl in Aschabad.
The scolex was 2.01 mm. long, 1.34 mm. broad. The vertex contained a
rudimentary but not prominent rostellum, 0.24 mm. long, entering deeply
)
A
into the scolex, without hooks.
The lumen of the suctorial
discs extended antero-posteri-
orly, so that they formed
regular circles upon cross sec-
tions. A ring-shaped promi-
nence was noted behind the
suctorial discs.
Fig, 44.—Ternia asiatica. (After v. Linstow.)
4, Tenia asiatica, natural size; B and C, schematic cross sections: B, with male, C, with female,
sexual organs; g, vessel; n, nerve; h, testicles; va, vas deferens; c, cirrus bag; 0, ovary;
d, yolk sac; r, receptaculum seminis; v, vagina; D, cross section through a segment with
masses of ova.
The chain of the proglottides was 70 mm. long, 1.11 mm. broad behind
the scolex, 1.97 mm. posteriorly. The sexual organs were not developed.
Hymenolepis (drepanitotenia) lanceolata, Bloch,
a parasite found in many water-fowl, was re-
cently expelled in two specimens by a boy twelve
years old. The scolex was not found. The
length of the tenia is 85-99 mm., its greatest
breadth behind the center of the body length is
8.5-12 mm. The proglottides are all consider-
ably broader than long. The leaf-like thin stro-
bila slightly tapers toward the anterior end;
posteriorly it extends in uniform breadth and its
termination is rounded. The ova possess the
shells which are characteristic of the genus hy-
menolepis, being far apart from each other.
This parasite uses, as intermediate hosts,
fresh water crabs; the cercocysts are found espe-
Fic. 45.—CrrcocystT From Crp-
RinoTuS INCONGRUENS, 1900.
520 THE ANIMAL PARASITES OF MAN
cially in the cyclops serrulatus, Fischer, and diaptomus spinosus, Daday; and
since these are frequently found in stagnant waters, the occurrence of the
parasite in geese and ducks is quite
natural. The crabs, which are often
difficult to recognize, occasionally mi-
grate with the drinking-water into the
intestinal canal of man; the cercocyst
inhabiting the crabs develops into hy-
menolepis lanceolata.
Fie. 46. — Hymeno-
LEPIs LANCEOLATA, Fic. 47.— Heap, Fic. 48.—ProcGtorrip oF HYMENOLEPIS.
Biocu. Enlarged Greatty En- This preparation I owe to the kindness of Pro-
abouttwenty times. LARGED. fessor W. Miller of Greifswald.
The most familiar of the bothriocephali is the
Bothriocephalus latus, Bremser, 1819.
This broad bothriocephalus, called also the pit-head, measures 5-9 meters
and is the longest tape-worm of man. The club-shaped head shows on its
lateral border on each side an elongated, slit-like pit. The individual pro-
glottides, 3,000 to 4,200 in number, are remarkably broad in proportion to
their length. A grayish-blue centerpiece of rosette-like form bordered by
two narrower bands is distinctly visible upon both surfaces. On the ventral
surface are the male sexual opening and the mouth of the vagina. The
mature ova are ovoid in form and surrounded by a brownish shell with a lid.
The ova are rarely found in the last mature segments of the chain. Large
numbers of proglottides are often expelled at once. They are voided with the
feces, having been previously discharged from the uterus. If the ova reach
the water, ciliated embryos develop within them, which slip from the shell
of the ova and float for some time in the water. The ciliated covering perhaps
seeks the intermediary host, which, as we learn from Braun’s brilliant investi-
gations, was found to be the pike (esox lucius), the burbot (lota vulgaris),
the perch (perca fluviatilis), the trutta vulgaris and lacustris, the thymallus
vulgaris, and the onchorhynchus Perryi. It is still undecided whether this
list exhausts the number of intermediate hosts.
The young of the bothriocephalus, plerocercoides, dwell encapsulated in
various parts of the intestines and of the musculature, and usually in large
numbers.
Bothriocephali have been cultivated by feeding experiments with plero-_
cercoides in the dog, the cat, and also in man.
The transmission of the parasite undoubtedly occurs by means of fish. It
takes place frequently in infected districts where fish are eaten raw, half
cooked, or after any other mode of preparation which does not effect a destruc-
tion of the ova. It is remarkable that living ova have been demonstrated
even in fish that were frozen stiff.
CESTODES 521
The geographical distribution of the bothriocephalus is a limited one. It
has been frequently noted in the Russian Baltic provinces, in the northeastern
part of Sweden, in Denmark, East Prussia, Russia and Poland. Its presence
has also been determined in the coast districts of Belgium, Holland, northern
France, and in Ireland. It is remarkably common in the western parts of
Switzerland, on the shores of Lake Geneva and Lake Neufchatel, and in those
parts of France and Italy bordering upon Switzerland. The parasite is often
seen in Japan. It is found sporadically in Germany, in Rhenish Hesse, Berlin,
Nuremberg, Munich and Greifswald, and has been found in North America.
Of the other bothriocephali we find in man the
Bothriocephalus cordatus, Leuckart, 1862.
This variety is characterized by a short, broad, heart-shaped head which is
supplied with two suctorial disc-like pits. The parasite which is chiefly found
in various mammals in Greenland and in Iceland is occasionally also noted
in man.
The tape-worm described as
Bothriocephalus cristatus, Davaine, 1874,
may possibly represent only another form of the bothriocephalus latus, Its
head is characterized by two extremely long, helmet-like points.
Of another variety of bothriocephalus,
Bothriocephalus Mansoni, Cobbold, 1883,
only plerocercoides have as yet been observed, and these apparently wander in
the body of man. They finally reach the skin, and there cause abscess forma-
tions, or they enter the urinary passages whence they are discharged with the
urine.
Bothriocephalus grandis, Blanchard, 1894.
Tjima and Kurimoto have observed a bothriocephalus previously unknown,
which lacks a head portion. It measures in breadth, anteriorly, 1.5 mm., pos-
Fic. 49.—BorurioceruaLus GRANDIS. PrRoGLoTTiIp anp Ovum. (After Ijima and Kurimoto.)
teriorly, 25 mm. The proglottides are extremely short, and are supplied with
a double genital apparatus.
The ventral surface contains the genital pori, anteriorly the mouth of the
cirrus and that of the vagina, behind these that of the uterus. The ova possess
a lid, are thick-shelled and brown; their length is 0.063 mm., their breadth,
0.048 mm. They contain a mulberry-like mass of fine globules.
There can be no doubt that parasites infect some persons In whom no
deleterious influence upon the health is manifest. The patients in such cases
522 THE ANIMAL PARASITES OF MAN
are often unaware of the presence of their guest until they note the discharge
of proglottides. The distressing thought of being the host of such a guest
causes the carriers of the parasite to seek medical aid. Strong, robust persons,
owing to their good constitution, are often uninjured by the parasite. “A weak
constitution and sensibility, or other factors which are especially the cause of
disintegration of the blood leading to pernicious anemia, will produce symp-
toms in the affected individuals, sometimes even the most severe morbid
phenomena.
There are patients who harbor the parasite for years without presenting
the slightest sign of helminthiasis. On the other hand, in sensitive persons
the symptoms may be numerous. In all cases the most positive indication is
the passage of segments of the worm, which occurs at times spontaneously,
at other times with the feces. With tenia saginata the spontaneous discharge
of proglottides appears to be more frequent than with tenia solium. In the
case of the bothriocephalus segments in chains amounting to several meters in
length are passed.
Not infrequently the ingestion of very salty food, of blueberries, straw-
berries, salad, or of alcoholic drinks, causes the passage of segments. In very
rare cases, proglottides are vomited. By reason of abnormal protrusion of the
intestines or of the pelvic organs from the abdominal coverings, proglottides
occasionally appear externally.
Besides these symptoms the microscopic examination of the feces is of
especial importance in the diagnosis. This should never be neglected if the
presence of tape-worm is suspected. Very frequently by careful, oft repeated
examinations of fecal masses indistinct symptoms on the part of the digestive
apparatus, of the nervous system, or of the general nutrition, have been ex-
plained, and treatment directed into the proper channels. As the uterus of
the tenia has no exit, the eggs can only find egress when the uterus of the
mature proglottid is injured. In the case of tenia saginata, discharge of
the eggs is almost the rule. The proglottides which are discharged are usually
without eggs. The ova of the bothriocephalus are extruded into the feces from
the uterus which has an external mouth. These may readily be differentiated
from the eggs of tenis, whereas the eggs of tenia saginata and tenia solium
only differ by their variation in size.
Besides the ova, Charcot-Robin’s crystals are found in the feces as in the
case of other helminthiases.
Whereas the passage of ova and proglottides is the most positive, and
occasionally the only, symptom of an existing tape-worm, the other symptoms
of tenia permit us to recognize the presence of a tape-worm with but slight
probability. In some patients there are disturbances of the digestive apparatus.
I shall only mention here pyrosis, bulimia, nausea, a longing for spicy food,
etc., symptoms which, as is well known, are grossly exaggerated in the pam-
phlets of quacks to attract the attention of patients. In others there are
colicky pains which are occasionally more severe after taking sour food, and
better after fluids. It is evident that the tape-worm acts as a foreign body
in the intestinal canal, and may exert a powerful irritation in the region it
inhabits, Probably the hooklets which some tenim possess may share in this
CESTODES 523
irritant action. If the tape-worm is only seen after it has been expelled, or
after it has died, it is difficult to understand what energy and motility the
parasite possesses under normal circumstances in the warm intestine of its
host, and how greatly it may irritate the intestinal mucous membrane. This
may be noted sometimes as pain, at other times as a digestive disturbance.
Intestinal catarrh, constipation, marked irregularity of the bowels are, in
fact, very frequent accompaniments of tape-worm disease. We have repeat-
edly noted the disappearance of all these symptoms after the removal of the
parasite.
Besides these local symptoms, in a number of patients suffering from
tape-worm there are also general phenomena and so-called reflex symptoms,
existing alone or together with the gastric phenomena. It is quite certain
that formerly in investigating these symptoms, as the result of incorrect views
and on account of erroneous pathological deductions, diagnoses have been
made which would not bear strict critical analysis. To deny them utterly
would, however, not be correct. There are to be mentioned: Vertigo, and
attacks of syncope, headache, stubborn singultus, pupillary differences, rapid
change of color in the face, pruritus, spasmodic attacks which occasionally
have the characteristics of epilepsy. According to the observations of Grassi,
in the case of tenia nana epileptic attacks are especially frequent. In deciding
upon the connection of phenomena of this kind, it will aid us in every case
to note whether they persist after the disappearance of the worm, and are
therefore to be looked upon as a purely reflex condition. If this be the case
they are, of course, only an accidental complication.
How far the symptoms on the part of the nervous system are to be regarded
as reflex, cannot always be immediately decided. We must first exclude those
cases in which cysticercus invasion has to be considered, as in the case of tenia
solium. We know positively from autopsies that the brain is the seat by pref-
erence of cysticerci. On the contrary, it must be questioned whether the
central nervous organs are not under the influence of toxic substances produced
by the parasite. It is more than likely that these animal parasites engender
toxic products which have a particularly deleterious effect upon the nervous
system as well as upon blood formation.
Reyher, Runeberg, Schapiro, Dehio and others have called attention to the
fact that the severe anemic conditions occurring in persons affected with
the bothriocephalus may assume the character of pernicious anemia and run
a course as such. These symptoms may certainly be referred to the presence
of the parasite. There is no longer any doubt of the etiologic connection.
The circumstance that the majority of infected persons are not anemic sug-
gests the thought that the poison is found only under special circumstances
as, for instance, the illness or death of the worm, or the presence of the para-
site for a considerable time. Lately Schaumann and Talqvist fed dogs with
segments of the bothriocephalus taken from a case of pernicious anemia, and
produced undoubted dissolution of blood in the dog. The forms of bothrio-
cephalus which do not produce anemia also contain the hematogenous poison.
Occasionally this is present in other tenia. Eisenlohr soon effected a cure of
a case of severe anemia by expulsion of a tenia saginata.
524 THE ANIMAL PARASITES OF MAN
In conclusion I must mention the fact that persons who have previously
been the hosts of parasites, and even persons who have never been affected
by tape-worm, but who have read or heard of the symptoms of helminthiasis,
occasionally suffer from hypochondria verminosa or teniaphobia. Nervous
disturbances which appear incidentally are referred to the presence of a tape-
worm. That hysterical or hypochondriacal individuals are particularly pre-
disposed to these conditions is so obvious that it need not be especially dwelt
upon.
‘ On account of the great number of local and general symptoms caused by
the presence of this parasite, considerable experience must have been acquired
to make one suspect the presence of a tape-worm. Certain symptoms which
are occasionally present in helminthiasis arouse this suspicion. Among these
are the complaints that the symptoms are most distressing when the stomach
is empty, and that the disturbances are less on taking sweet food, but are
increased by salty or acid food. However, I never begin a tape-worm treat-
ment until after the presence of the parasite has been proven by the passage
of proglottides or the eggs in the feces. In examining these the physician
must be careful not to confound remnants of undigested food, mucus casts,
and shreds of tendons, often mistaken by the laity for proglottides, and thus
make an erroneous diagnosis. Dry proglottides after being soaked in water
soon assume their characteristic form. As a rule, the microscopic determina-
tion of the eggs of the tenia enable us to make the diagnosis earlier and
with greater certainty than by the macroscopic proglottides. The encapsulated
eggs of the bothriocephalus are readily recognized, but, as has already been
mentioned, the differentiation between the eggs of tenia solium and tenia
saginata is more difficult.
To recognize from the shape of the proglottid which variety is present
it is advisable to fix this between two glass slides. The proglottid of the
tenia solium is more delicate and more transparent than the tougher segments
of the tenia saginata. In the former the structure of the branching uterus
is more plump, the number of lateral twigs only amounts to from 7 to 10,
while the uterus of the tenia saginata shows from 20 to 50 and more lateral
twigs. For the recognition of the less frequent parasites special text-books
on the subject must be consulted.
PROGNOSIS
The prognosis is generally favorable. Even in cases of severe bothrioceph-
alus anemia cure has generally taken place after the removal of the parasite.
Parasitism with the tenia solium necessitates special care on account of the
danger of autoinfection with the hooklets. It is particularly apt to occur
from the appearance of ripe proglottides in the stomach as the result of anti-
peristaltic movements. Prolonged presence of the proglottides in the stomach
explains why, in some persons, the cysticercus is found with such extraordi-
nary frequency in the brain and in the musculature. Even in the eye occa-
sionally more than one cysticercus is found. The host of the tenia solium
is also a certain menace to those about him. By insufficient cleanliness,
hy careless handling of the proglottides which have been passed, and by
CESTODES 525
contact with fecal masses, the possessor of a tenia solium may spread the
infection.
THERAPY
Prophylactic measures are based on the history of the development of these
parasites. In the first place the spread of cysticercus disease among animals
used for food must be prevented, and not only the tape-worms which are
voided, but also the feces of the patient with tape-worm disease should be
effectually destroyed, best by fire. All who harbor the parasites should be
placed under treatment as soon as possible, particularly such persons as come
in contact with animals used for food. The patients must be instructed
never to defecate in the open air.
The dissemination of tape-worm is actively combated by the erection of
abattoirs and the introduction of compulsory meat inspection. It is true this
protection is not absolute, for even with experienced meat inspectors some
cysticerci which are deeply hidden in the muscles may be overlooked. I refer
particularly to the small cysticerci which are few in number, as in the case
of the tenia saginata. Cleanliness in the kitchen and in the household, espe-
cially in handling raw meat, is absolutely necessary. Vessels in which raw
meat is kept should not be used for other food substances. Thorough boiling
kills the cysticercus as well as corning, with or without subsequent smoking.
The process of smoking, alone, by no means prevents the development of the
eysticerci. The heat in the inner parts of the meat to be smoked certainly
does not reach 50° C. and an absolute protection is therefore not obtained.
The removal of the tape-worm in delicate children, in the aged, during the
course of acute diseases, particularly severe intestinal diseases, and during
menstruation and pregnancy, is usually contraindicated.
I carry out the treatment in the course of a day in which I may personally
superintend it. For a long time the actual treatment is preceded by a prepara-
" tory one. I have been unable to convince myself of the value of a prolonged
preparation. On the day before the treatment is begun, I give milk, and
prohibit food containing sugar, so that the worm will have no favorable nutri-
tive material. After the midday meal, if at all possible, I give only coffee;
in the evening, bouillon, eggs, a little wheat bread, perhaps some red wine
diluted with water. At night the patient is given a tablespoonful of castor
oil or an enema.
Among numerous vermifuges, which I do not intend to enumerate here,
I prefer radix filices or the ethereal extract of male fern, and order extr.
fil. mar. eth. 5.0-6.0—7.5-10.0, syr. simpl. 40.0, M.D.S., to be taken within
ten minutes. Children receive a correspondingly smaller dose. The tape-worm
is to be stupefied by the remedy, and to be subsequently exposed to its action.
If nausea or vomiting occur, I give small pellets of ice, some brandy, or a
little lemonade. I am also quite fond of employing Helfenberg’s T'ape-worm
Remedy, which consists in the administration of eight capsules that contain
one gram of fil. mar. and 2 grams of castor oil. According to the patient,
I give 6 or 8 capsules at once, and, after an hour, 7 capsules which contain the
castor oil. I will briefly describe my method of treatment.
526 THE ANIMAL PARASITES OF MAN
The patient is required to go to bed. A bed-pan, irrigator, lukewarm
water and a black pus basin are to be ready at hand. The remedy must be
given in the morning before food is taken. To prevent nausea and vomiting,
small pellets of ice, brandy, or lemonade are taken. After an hour, one or
two tablespoonfuls of castor oil are administered. If, after one or two hours;
the worm has not been passed, an attempt should be made by the injection of
a large amount of lukewarm water into the rectum, to expel the parasite, which,
very frequently, has only been stunned. These injections are absolutely neces-
sary if large portions of the parasite are passed, as they readily break upon
manual extraction. If the head of the worm remain in the intestine, an
attempt must be made to expel this by the injection of a larger amount of
water.
This treatment may be regarded as successful when the head, or, more cor-
rectly, the heads, have been found. The search for the head, which is often
detached, is facilitated by placing the worm which has been passed in the flat
black basin. In spite of the greatest vigilance, it is occasionally impossible to
find the head. The result of the treatment is then questionable. It should,
however, only be repeated if, after eight to ten weeks, new proglottides are
passed, showing that the previous treatment has been unsuccessful.
ECHINOCOCCUS DISEASE
Echinococcus disease in the human subject is of increasing importance,
many cases having come under observation. I shall here consider the subject
as briefly as is consistent with accuracy.
The echinococcus polymorphus is the encysted cysticercus of the tenia
echinococeus discovered by v. Siebold in 1853, and is found chiefly in the
small intestine of the dog, the jackal and the wolf. The assumption that the
fox also may be a carrier and distributer of the tenia echinococcus has not yet
been proven.
The tape-worm has a length of from 4 to 5 mm. The head is armed with
a rostellum and a double row of hooklets. The number of joints is only three;
immediately after the last joint is desquamated a new portion forms. The
last joint, which contains the mature eggs, comprises almost two-thirds of the
entire length of the worm; it is of extremely delicate texture, and is easily
lacerated.
If parts of the infective proglottides reach the stomach of man and of cer-
tain animals, the tissue of these undergoes digestion by the gastric juice, but
the eggs which have been set free are not digested, nor is the embryo. This
has six hooklets which, emerging from the egg, penetrate the intestinal wall,
and thence in a more or less direct way reach the point where they later develop.
It is quite probable that many of the eggs and embryos perish on account of
the digestive power of the gastric juice, and are eliminated with the fecal
masses, for, otherwise, multiple echinococci would not be so exceedingly rare
—much rarer than the solitary form. According to van Beneden and Leuck-
‘art, the embryos forcibly penetrate the walls of the intestine, and finally reach
the blood and lymph-vessels, in which they are carried onward. The fact that
ECHINOCOCCUS DISEASE 527
they breed in the capillaries of the portal circulation explains the frequent
implication of the liver. Often the embryos lodge permanently in the mesen-
teric glands. Others, by means of the lymph-vessels, or by various avenues
of communication, invade the peritoneal and pleural cavities; others enter the
thoracic duct, thence find their way into the jugular vein and to the right
heart, and are retained in the lung or are distributed to near or even distant
organs.
After the echinococcus embryo has reached its destination it develops very
slowly; we would digress too far if we described the individual phases of its
development.
After the lapse of weeks or months, we again find the echinococcus in a
round white cyst which gradually increases in size. Its walls are composed
of a characteristically layered cuticula and a parenchymatous layer. After a
certain time the latter shows upon its inner surface the so-called breeding
capsules, which hang upon a short pedicle from the parenchymatous layer, and
are surrounded by a transparent fluid not containing albumin. Some of the
breeding capsules develop internally, some externally,
producing echinococcus heads, the so-called scolices.
Fie. 50.—Tenta Ecutnococcus. Fie. 51.—Heap or tHe Ecutnococcus:
Greatly enlarged. a, with projected, and b, with retracted, head.
In many cases daughter-cysts are formed. These originate from embryos
which probably represent original parts of the parenchymatous layer, but have
remained intralamellar. They lead to cyst formation surrounded by its own
cuticula. Gradually bulging inward, they finally reach the cyst cavity. We
then speak of echinococcus hydatidosus or endogenus. This endogenous
daughter-cyst development is opposed by the exogenous, which occurs mostly
among our animals used for food, but may even occur in man. The daughter-
cysts may later form other cysts. The contents of the cyst are colorless and
clear, or slightly opalescent. The fluid contains albumins which are not pre-
cipitated by boiling, also common salt, succinic acid and sugar; occasionally
inosite, leucin and tyrosin. :
The echinococcus cyst at any stage of its development may become sterile ;
i.e., the formation of scolices (acephalocysts) ceases. Not rarely the echino-
coccus worm becomes diseased and dies. The fluid becomes turbid, the walls
of the cyst collapse, the parenchymatous layer softens and fatty degeneration
528 THE ANIMAL PARASITES OF MAN
takes place. The head falls off, is partly destroyed or undergoes more or less
change, and swims about in the fluid. The contents thicken. A considerable
deposit of calcium salts occurs and the shrunken sac may finally be represented
by a single calcified nodule. ,
The echinococcus multilocularis, which in form so strongly resembles an
alveolar colloid of the liver that hitherto its original nature has often been
entirely misunderstood, must next be mentioned. It is found chiefly in the
liver, but also occasionally in the brain, the heart, the diaphragm, and the
pleural cavity; in the psoas muscle, the lung, the gall-bladder, the kidney, and
the adrenals; in the uterus and anterior wall of the chest; in the duodenum ;
in the portal and peribronchial lymph-glands and in the bones. The multi-
locular or alveolar echinococcus is characterized by small irregularly formed
cysts which are separated from one another by masses of connective tissue
enclosing a gelatinous plug. In section we recognize a honeycomb-like struc-
ture. All the cysts possess the properties of echinococcus cysts except for slight
deviations. Upon the inner surface there are frequently layers of granular
fatty material or pigment, besides balls with radiating stripes which consist of
an organic base impregnated with calcium salts. Not rarely needle-shaped
or sheaf-like crystals and hematoidin crystals are also noted. Scolices are
often absent,
The limits of the tumor are quite sharply circumscribed. Now and then
smaller isolated tumors are found adjacent. Virchow saw strands resembling
a pearl necklace, the parts of which projected like processes. The capsule is
invariably of a cartilaginous hardness, and adherent to the surrounding tissues.
This echinococeus was for a long time held to be only a variation in the
form of the cystoid echinococcus, due to its growth in the blood-vessels, lymph-
vessels, and biliary channels.
Its characteristic alveolar structure, as well as the conspicuous variation in
its geographic distribution, has raised doubts as to the identity of the multi-
locular with the hydatid forms. To decide this question, experiments in
feeding dogs with the echinococcus multilocularis were undertaken. Klemm,
Vogler, Mangold, and Miiller raised tenize which in the form of their hook-
lets, as well as in the position of the eggs in the terminal section, differed
from the tenia of the cystoid form. Mangold also succeeded, by feeding with
a tenia which he had raised, in developing two tumor foci in the liver of a pig;
these were recognized as echinococcus multilocularis. The occurrence of mul-
tilocular echinococcus in certain geographical regions is well known. Accord-
ing to Vierordt, it is found frequently in Wiirttemberg, Switzerland, Bavaria,
also in Austria and Russia, occasionally in Prussia, Baden and North America.
Recently Posselt has called attention to a previously unknown region of dis-
tribution in the Tyrol; Pichler described a case of echinococcus multilocularis
in Karnten. It is especially interesting to note that in the “classical coun-
tries” of the hydatid echinococcus, Iceland, Australia, Mecklenburg and New
Pomerania, Dalmatia and Argentina, the echinococcus multilocularis does not
occur at all or has been very rarely observed. On the other hand, in the specific
regions of distribution of the multilocular echinococcus, in Bavaria, Wiirt-
temberg, and Northern Switzerland, the hydatid form is quite rare. In conse-
ECHINOCOCCUS DISEASE 529
quence of Posselt’s very interesting investigations, I incline more and more
to the view that there are two forms of tenia echinococcus.
I should like here to refer to the fact that bone echinococci, which in their
distribution show great similarity to the multilocular echinococeus, are fre-
quently identified with these. In bone echinococcus we are dealing with the
exogenous proliferation of small and very small cysts deposited close beside
each other; but, besides these, there are also larger cysts with encapsulated
daughter-cysts in the surrounding soft parts. Now such larger cysts with
daughter-cyst formation are a characteristic of the hydatid form in which it
differs markedly from the multilocular form. For this reason it cannot be-
assumed that every osseous echinococcus belongs to the multilocular form.
Besides being found in man, the echinococcus has been noted particularly
in the lung and the liver of sheep, in cattle, and in pigs; more rarely in the
dog, the cat, the mule, the horse, the zebra, the dromedary, the camel, the
giraffe, etc.
Since it has been demonstrated with certainty that the echinococcus cysti-
cercus occurring in man and his domestic animals represents one and the same
tape-worm, there can no longer be any question as to the propagation of echino-
coccus disease in animal and man—that the dog takes up the grown cysticerci
which develop in the domestic animals. The possible modes of dissemination
of echinococcus disease in any country will therefore depend upon the number
of its domestic animals, and the distribution of the echinococcus pest among
them. Asa matter of fact, those countries, such as Iceland, Victoria, Mecklen-
burg and New Pomerania, in which the echinococcus occurs most frequently,
are noted for an excessively large number of animals, particularly cattle. A
number of years ago I endeavored to investigate the distribution of this para-
sitic disease, and from the reports of 52 slaughter-houses I decided that the
echinococcus occurs, upon the average, in 10.79 per cent. of cattle, in 9.83 per
cent. of sheep, and in 6.47 per cent. of pigs. Pomerania and Mecklenburg in
Germany are first in the frequency of the echinococcus disease. In Greifswald
the dissemination of the pest is enormous. In one period of six months 68.58
per cent. of cattle, 51.02 per cent. of sheep, and 4.93 per cent. of pigs were
found diseased. The conditions are similar in Mecklenburg. From my pre-
vious investigations I have concluded that the prevalence of the echinococcus
infection in the inhabitants of a country is in proportion to the distribution of
the echinococcus pest among its domestic animals. ;
In man, as well as in domestic animals, the dog is the usual, if not the
only, transmitter of the infectious germ. The greater the number of dogs
in any infected country, the greater the danger of contagion. In my own
vicinity, the number of dogs, particularly in the rural districts, is very great.
Apart from hunting dogs and shepherd dogs, almost every family possesses
a house dog. He accompanies his master as he works about the farm, espe-
cially when milking cows, which in the summer occurs twice during the day,
hence he has repeated opportunities to visit the grazing cattle, and to deposit
his feces upon the field. Here, on the small grazing places, the focus of infec-
tion must be sought for the grazing cattle, which remain here for months, by
day and by night.
35
530 THE ANIMAL PARASITES OF MAN
But how does the dog become infected? Every one who has made observa-
tions in the rural districts knows perfectly well. The butchers as well as the
shepherds—the latter, as a rule, performing the duty of slaughter in the coun-
try—are familiar with the danger of the echinococcus. Any one who has been
in a farming country at slaughter time knows that the parts of the meat which
are unsuitable for human food, among these frequently the liver and the lungs
which are permeated with echinococci, are used as food for the dogs. Where
there is careful management, organs of this kind are buried, but rarely so deep
that the dog who sniffs about cannot finally reach them. A vicious circle is
formed: the infected cattle, sheep and swine furnish the scolices to the dog;
the dog furnishes the ova of the tenia.
If we observe the frequently intimate relation of children as well as adults
with dogs, and how the dog will lick the face and the hands, we can scarcely
doubt that in this way, as well as by kissing, infection can be conveyed. Dogs
of every species sniff at their own ani as well as at those of other dogs; often
they carry around upon their noses collections of mature proglottides without
these being noticed on account of their diminutive size. Toys which small
children often lick, pieces of bread scattered about in different corners of the
nursery, may readily become contaminated by the mature eggs of the tenia.
The dogs probably discharge the mature proglottides with the feces. In the
feces of other dogs they are fond of sniffing around. Thus the dog’s nose
becomes contaminated, and the transmission of the ova of the tenia may occur.
Frequently the dog’s feces are discharged in the vicinity of pumps and wells.
The proglottides and their ova continue to live for a long time on account of
the moisture here constantly present, so that they reach the human stomach
with the drinking-water as a still germinating brood. The tenis may also be
readily distributed by means of vegetables that are eaten raw, such as lettuce,
cabbage, berries and fruits which grow upon the earth. The number of ways
in which an infected material, or the eggs of the tenia, finally reach the intes-
tinal tract of man is infinitely great, and it is unnecessary to presuppose an
intimate association of the infected individual with dogs.
The number of children infected appears very small when we consider the
fact that at this period of life, in consequence of close association with dogs,
they are particularly endangered. This observation is confirmed by all statis-
tics. In the Pomeranian investigation, among 139 patients only 13 were under
fifteen years of age. The majority of infections occur between the twentieth
and fortieth years of life. Probably in consequence of the slow development
of the echinococcus in the human organism, the germs acquired in youth, as
a rule, produce definite symptoms only in later years. That the course may
be chronic is shown by my collection of cases. Among others, a midwife, aged
sixty, from her twenty-fifth year (therefore for thirty-five years) had period-
ically coughed up echinococci. A farmer, aged forty, mentioned as the prob-
able period of invasion the time from his ninth to his twelfth year, since
during this period he always slept in a bed with several dogs. He had suf-
fered since his thirty-fifth year with frequent and repeated attacks of irrita-
tive cough with expectoration that contained echinococcus cysts.
It is difficult to find proof from the statistics of Mecklenburg and Pome-
ECHINOCOCCUS DISEASE 531
rania that certain customs and habits of the people, their sex, social condition
and occupation, their residence in the city or in the country, create a special
predisposition to acquire the parasites. Echinococcus disease represents a
slow, often insidious process, running its course for several decades, and the
occasional cause, the place and time of infection, cannot be determined.
In the majority of cases only one organ is attacked. Unilocular echino-
coccus disease most frequently has its seat in the liver. If several organs are
attacked—echinococcus multiplex—the liver is found to be one of the organs
affected.
Several series of statistics have been compiled with regard to the frequency
of “dog tape-worm.” These indicate clearly that the liver is the organ most
frequently affected; in the Mecklenburg investigation there were 69 per cent.
of such cases, in that of Pomerania, 67.33 per cent. As the next organ to
be implicated, the lung may be mentioned, showing 11.9 per cent. and 10.6 per
cent., following this the kidneys with 3.5 per cent. and 4.6 per cent.
The abdominal cavity, skin, and musculature .are also quite frequently
attacked, that is, in about 6 per cent. of cases; but, in fact, any organ may
be the seat of an echinococcus cyst. The view that traumatism favors the
accumulation of the infectious agents may probably be due to the fact that
after injuries the echinococci, which until then have been latent, manifest clin-
ical symptoms. The conditions are certainly different with the appearance of
multiple echinococci, especially in the abdominal cavity. The opinion that the
simultaneous invasion of many organisms may here be the cause will often
prove correct. But another mode of development may also be observed ;
namely, autosemination after puncture or rupture of an echinococcus sac.
Since v. Volkmann first called attention to this danger, I have observed it
clinically in many cases. The colonizing and propagation of cysts in the
abdominal cavity has been absolutely proven by the experiments of Riemann
under the direction of Garré. Similar experiments undertaken by other inves-
tigators and by myself failed of success, for some unknown reason. Either on
account of the danger of disseminating the echinococcus parasite, or because
of the toxicity of the echinococcus fluid, exploratory puncture has fallen into
disuse.
The danger that the subsequent oozing of the echinococcus fluid from the
point of puncture may bring about serious accidents and even death has been
demonstrated by numerous observations. The appearance of urticaria after
aspiration is a not infrequent occurrence. In a patient in Mosler’s clinic, a
few hours after the aspiration of an echinococcus of the liver, an eruption
of urticaria appeared, soon followed by cyanosis and dyspnea. Only after the
lapse of several hours did the threatening symptoms disappear. Other authors
report the appearance of fever, singultus, nausea, arthritic pains, ete. A
patient of Jenkins’s died with these symptoms; Martineau and Bryant report
similar cases. Experimental investigations also confirm the view that the
echinococcic fluid may have a toxic action. Brieger, for instance, isolated
among other substances one which he obtained in the form of salt of platinum,
and, after separating it from the metal, he injected it in solution into mice
with rapidly fatal result. Aspiration is not advisable, unless the radical oper-
532 THE ANIMAL PARASITES OF MAN
ation be performed immediately after the exploratory puncture; indeed, it is a
question whether aspiration should be performed at all.
Echinococcus disease is not always easy to diagnosticate. Frequently at
the autopsy, in the liver or other organs, cysts the size of a child’s head and
even larger are found which had not produced the slightest symptoms during
the life of the patient. The gravity of the disease depends upon the location
of the cyst, the size, the effect upon neighboring organs, and, possibly, the
purulent character of the contents of the cyst. Should it suppurate, small
echinococcus cysts in the brain and spinal cord may cause severe symptoms;
on the contrary, occasionally, large sacs which have no deleterious effect upon
the surrounding area exist for a long time without giving rise to serious symp-
toms. In general, the symptomatology may be described as follows:
SYMPTOMS
The embryo which has entered the body causes a reaction of the tissue
which leads to the formation of the wall of a cyst. With continued growth
the effect of pressure upon the neighboring tissue becomes apparent, and
decided disturbances in circulation, secretion and excretion are manifest.
Particularly dangerous is the development of the echinococcus in cavities
where the growing tumor cannot fail to cause serious disturbance, as for in-
stance in the pelvis, by compression of the organs situated in this region.
When the development of the echinococci occurs in the respiratory tract, the
symptoms there are also severe. The symptoms, however, become especially
threatening if suppuration supervene, or the contents of the cyst should per-
forate its walls. If the contents of the cyst be emptied into the abdominal or
thoracic cavities, fatal disease usually follows. When there is adhesion among
neighboring organs, after penetrating the wall of the cyst the parasite enters
these, and permeates them in the same way as the organs primarily affected.
Thus the parasite traverses remarkably great distances. The course is most
favorable when perforation occurs through the skin. Discharge into the
stomach and intestine and into the pelvis of the kidney, into the bladder or
into the vagina is relatively favorable. A cyst of this kind may very readily
become the starting point of a fatal pyemia. Perforation into the trachea,
into the bronchi, and particularly into the circulatory system is always most
serious. Echinococcus of the superficial organs runs a less dangerous course.
The general condition of the patient is usually most affected when the
echinococcus exerts an influence upon the neighboring organs by its size, or
when suppuration occurs. Only after attention has been thus called to the
affection does the patient seek professional aid. A number of conspicuous
phenomena, such as the slow, steady, painless growth of the tumor, the absence
of cachexia, the uniform roundness of the tumor, the smooth surface, the
absence of fever, the elasticity, the presence of fluctuation, and the possible
demonstration of a hydatid thrill, in general favor the existence of an echino-
coccus sac. By a hydatid thrill we mean that sensation which the tumor con-
veys to the percussing finger or to the palpating hand, a sensation similar to
that obtained by pressing upon a cushion with springs. The cause of the hyda-
ECHINOCOCCUS DISEASE 533
tid thrill appears to be the waves of the fluid contents of the cyst; it is, there-
fore, to a certain extent only a distinct fluctuation. This condition also occurs
in cysts of the ovaries, in ascites, ete. Santini and Rovighi have observed
that the echinococcus cysts, besides the hydatid thrill, convey also, upon simul-
taneous percussion and auscultation, a characteristic, deep, sonorous tone, the
so-called hydatid resonance. This phenomenon is said not to be present in
deep seated cysts with thickening and degenerating walls. The size and extent
of the cyst, as was demonstrated by Manasse in a case of renal echinococcus,
may be determined by the Rontgen rays. Confusion of the echinococcus cyst
with other tumors or abscesses, such as cystic degeneration of the kidneys,
ovarian cysts, tumors of the uterus, tumors of the omentum, of the pancreas,
subphrenic abscesses, etc., can, of course, never be entirely avoided. In spite
of the most minute examination of the history, of the results of inspection,
of palpation, and of percussion, and of the relation of the tumor to neighbor-
ing organs, the diagnosis in some cases cannot be made with absolute certainty
unless some definite points of support are obtained by rupture of the cyst
and an admixture of its contents with the sputum, with the vomitus, with
the contents of the intestines, and with the urine. In cases which offer great
diagnostic difficulty, an exploratory puncture may at once clear the entire
clinical picture by the recognition of a fluid which is non-albuminous, and
which contains scolices or hooklets. But the danger of this process will cer-
tainly always limit its use in diagnosis.
The prognosis depends upon the location, the size, and the relation of the
echinococcus cyst to its surroundings. Although a benign tumor in itself,
it may, particularly by suppuration, lead to phenomena which endanger life.
In multiple echinococci the prognosis is correspondingly more unfavorable.
TREATMENT
Prophylactic measures must be premised with a caution, which cannot be
too emphatically expressed, against intimate association with dogs. In infected
regions their number should be limited as much as possible. Whether methodic
tape-worm cures, on account of the perhaps brief parasitism of the tenia in
the dog, are of any use, is doubtful. On the contrary, the important point
in prophylaxis, it appears to me, is to protect the dogs from acquiring the
tenia echinococcus. This may be best attained by the introduction of the
compulsory inspection of meat. All organs infected with echinococci must be
destroyed by cremation. Meat inspection in the country districts among cattle
raisers is not likely to find favor when they learn that annually in Prussia
about 880 cattle directly succumb to the echinococcus pest. The indirect harm
arising from this is that animals infested with echinococcus suffer in their
nutrition, and are prematurely slaughtered, and this may be an important point
in agriculture. a
Internal treatment is ineffectual, and successive punctures with aspiration
of the contents as well as injections of medicated fluids should he rejected
for the above-mentioned reasons. ere
On principle I am opposed to the method introduced by Baccelli of injec-
534 THE ANIMAL PARASITES OF MAN
tions of corrosive sublimate, although a number of cases have been reported
with favorable results. The process consists in aspiration of the cyst contents
with a succeeding injection of a 1-1,000 corrosive sublimate solution. I have
seen recovery occur after puncture, even without injection of drugs, but much
more frequently suppuration followed and finally made laparotomy necessary.
Recovery through surgical means can only take place by the removal of the
echinococcus sac.
The seat of the diseases is usually the liver. For this reason I should like
briefly to describe the treatment of echinococcus of the liver. Madelung de-
fines extirpation of the cyst including the capsule as the unquestioned “ ideal ”
method of treatment. If of moderate size, with a superficial seat, and there
is no suppuration, this operation will bring about the best results. In the
majority of cases, the choice between a radical operation or one performed at
two different times comes into question. If danger is present, the single or’
less radical operation is to be preferred on account of its greater rapidity.
This is also recommended if the cyst is insufficiently exposed in the field of
operation, or if, with multiple cysts, after the removal of one cyst the others
are more easily reached. The method also by which an incision is made has
the advantage of being less dangerous. As a rule, this method is resorted to
if there are no special indications for more rapid interference.
Multilocular echinococcus has in only a few cases been treated by opera-
tion; namely, by Brunner, Terillon and Bruns: The latter advises cuneiform
excision. Only the smaller multilocular echinococci can be successfully re-
moved by operation.
ECHINOCOCCI OF VARIOUS ORGANS
I shall briefly review the echinococci found in different organs:
Echinococci of the brain are rare. Davaine mentions 32, Neisser 68 cases.
Upon the whole about 90 cases are known, and among these is one case of
multilocular echinococcus. Usually the parasite is solitary. It is generally
of moderate size. The cysts are situated in the white as well as in the gray
substance, and are surrounded by connective tissue capsules; the neighboring
cerebral substance is anemic, partly atrophic. After a fairly prolonged time
of growth a hemisphere may resemble a cac with thick walls. Several times
after penetrating the skull, growth and discharge externally through the nose,
ear, etc., have taken place. Westphal observed a case in which about 90 cysts
were discharged. The seat and the size of the tumor determine the symp-
toms. General cerebral and focal phenomena appear until we have the symp-
toms of cerebral tumor. The diagnosis of the nature of the tumor will be
possible only when echinococcus disease of another organ is present, or if, in
the course of the disease, external perforation occurs. If the nature of the
tumor and the localization of its seat are determined, surgical treatment may
be successful. In the main the prognosis is unfavorable.
Echinococcus of the spinal cord is even rarer than that of the brain. About
#2 cases in all are known. Usually the parasite is found between the dura
and the vertebra, more rarely in the dural sac; or it may develop in the verte-
ECHINOCOCCUS DISEASE 535
bra itself, penetrating externally or internally. In some cases the parasite grows
outwardly into the vertebral canal. Maguire mentions two cases in which the
parasite developed in the spinal cord itself.
The symptoms are those of compression. The first phenomena frequently
arise from disease of the vertebra, and from compression of the nerve trunks,
The symptoms develop gradually, and resemble those of a compression myelitis.
The entire absence of pain and the free movability of the vertebral column are
conspicuous; this, however, may also be the case in tumors. Diagnosis be-
comes possible when the parasite appears. The prognosis has usually been
unfavorable. In the case reported by Szkekeres, operation was attempted after
a piece of bone one-half a centimeter in length had been exfoliated.
Echinococcus of the orbit. Echinococcus of the eye-ball has as yet not
been determined with certainty, and echinococcus of the orbit is also rare.
Kramer has collected 68 and Golowin 93 observations. To these may be added
the cases of Ziegler, Wagenmann and Blaschek. It is noteworthy that, accord-
ing to Kramer, the disease occurs three times as frequently in men as in women.
In two-thirds of the cases the patients were between the eleventh and twenty-
first years of life. As a rule, the echinococcus develops primarily in the orbit,
in rarer cases it finds it way into neighboring organs after destruction of the
wall of the orbit. The parasite is found in both orbits with about the same
frequency, and almost always in the base; rarely in the anterior lateral parts.
The development is usually insidious, seldom fulminant. The first symptoms
are commonly pain and the development of an exophthalmos. The conjunc-
tiva and lids become inflamed. Decrease in motion of the bulbus oculi, dis-
turbances of vision, and loss of sight in varying grades appear gradually.
Suppuration is not rare. In cases in which no operation is performed, early
atrophy of the optic nerve, necrosis of the cornea, and panophthalmia occur.
The diagnosis is often very difficult. Confusion with malignant neoplasms
has several times led to enucleation. Kramer cautions us against exploratory
puncture on account of the danger of confounding the condition with that pro-
duced by an encephalocele. The slow development of a tumor in the orbit
without fever, severe pain deep in the orbital cavity, a tumor with distinct
or indistinct fluctuation, and the early appearance of disturbances of sight are
all strongly indicative of echinococcus. The treatment is surgical.
The echinococcus has been twice observed in the frontal sinus, which had
ruptured into the orbit.
In the nose, in the oral cavity, in the tongue, in the gums, in the pharynz
and in the parotid the echinococcus has also occasionally been observed.
Echinococcus in the neck is a rare occurrence. Giiterbock has collected
26 cases of this kind. Besides these J found cases recently published by Reich,
Jiirgens, Thévenot and Steinbriick. The parasite generally chooses as its seat
the region of the external border of the sternocleidomastoid; this without
doubt accounts for its originating in the sheaths of the large vessels of the
neck. The echinococcus sac slowly raises the sternocleidomastoid and appears
at the internal border of the muscle as a small tumor, while the larger portion
of the sac is situated upon the external border. The connection of both tumors
is proven by the continuance of the fluctuation. Later, with increased growth,
536 THE ANIMAL PARASITES IN MAN
the characteristic lobulated tumor disappears. Decided displacements of the
organs of the neck may develop in such cases. Confusions may arise from
echinococci which are situated in the muscle itself or that have developed in
the thyreoid gland. In three cases after successful extirpation death resulted
from secondary hemorrhage.
Echinococcus of the thyreoid gland is rare. Henle reports 18 cases; in
three other cases the diagnosis is questionable. Vitrac has collected 21 re-
ports of echinococcus of the thyreoid. Another case is reported by Posadac.
The echinococcus is usually unilocular and may attain the size of a fist. In-
creasing growth causes atrophic conditions of the glandular tissue. The con-
sequences of displacement, that is, compression, of the neighboring organs,
in which particularly the trachea, the esophagus and the recurrent laryngeal
nerve are to be considered, may be serious. Suppuration of the cyst is fre-
quent. The sac surrounding the echinococcus becomes adherent by inflamma-
tion to the adjacent areas, and these are to a certain extent involved in the echi-
nococcus sac, so that this represents only a part of the echinococcus. This
enlargement, results in increased erosion of the surrounding areas in which the
trachea particularly may be implicated. Adhesions to the muscles and the
skin are less frequent. The echinococcus grows very slowly. Its form is usu-
ally globular. The difficulty in respiration which occurs, to which difficulty
in deglutition and paralysis of the recurrent laryngeal nerve may be added,
causes the patient to consult aphysician. The diagnosis can rarely be made
with certainty. Early operation improves the prognosis decidedly. Accord-
ing to Henle wide opening of the sac is most frequently advisable, as enuclea-
tion is often very difficult. If this operation be attempted, it is not always
possible to spare the recurrent laryngeal nerve which may be situated in the
wall of the sac.
A case of echinococcus of the larynx has been described by Schiissler.
Primary echinococcus of the pleura is rare. Maydl and Winzerling have
collected 30 cases from literature. In these the echinococcus was situated
either between the pleura pulmonalis and the costal pleura, in the pleural cav-
ity, or external to the pleura costalis. Much more frequent are secondary
pleural echinococci which have ruptured into the pleural cavity from neigh-
boring organs.
The echinococcus is usually found upon the right side, surrounded by a thin
wall of connective tissue. It generally attains great dimensions. In the
main the symptoms differ but little from those of a pleurisy with effusion.
The patients complain of stitch in the side and an irritative cough, accom-
panied by scant mucus expectoration. Fever is absent. If the echinococcus
is large it leads to dilatation of the affected side of the thorax, frequently giving
a flaring shape to the lower part of the thorax, with retardation or immobility
im respiration. Percussion reveals a more or less extensive area of dulness,
frequently bow-shaped. Absence or diminution of the respiratory murmur
and of fremitus is noted; occasionally bronchial respiration is present. In
small cysts egophony and bronchophony are observed. Neisser quite prop-
erly emphasizes as characteristic the conspicuous proximity of normal and
abnormal auscultatory phenomena. In right-sided disease, the liver is dis-
ECHINOCOCCUS DISEASE 537
placed downward and the heart to the left. Left-sided echinococci lead to
dislocation of the spleen and kidney. In bilateral echinococcus the heart is
forced into the mediastinal space. If the echinococcus has a tendency to grow
outwardly it forces its way through the intercostal spaces, leads to erosion of
the ribs, and appears as a semiglobular tumor beneath the skin. The skin is
usually movable over the tumor, but occasionally adheres to it, and shows
decided inflammation. Secondary pleurisy is said to be invariably absent.
In the main, the echinococcus shows but slight tendency to perforation. If
rupture occurs, it usually takes place through the bronchi.
The diagnosis is mostly difficult. Differentiation from solid tumor is, how-
ever, generally possible. If a collection of fluid can be detected, the question
arises whether this is situated above or below the diaphragm. In favor of a
subdiaphragmatic seat is the bell-shaped prominence of the lower parts of the
thorax, and the absence of the respiratory displacement of the liver downward.
On account of atrophic paralysis of the diaphragm the upper bow-shaped
line of dulness prevents the recognition of respiratory displacement. Besides,
the history usually points to a disease of the liver. Yet in many cases a
positive diagnosis is almost impossible. To distinguish echinococcus from
pleurisy with effusion is important. The latter is accompanied by more
marked constitutional and local phenomena, chills, fever, cough, stitch in the
side and dyspnea. Later the dyspnea is less marked, while in the case of
echinococcus it is one of the most prominent and troublesome symptoms.
Pleural exudates lead to a uniform bulging, pleural echinococcus to a pro-
tuberance, of the lower aperture of the thorax. In pleurisy the line of dulness
follows the well-known characteristics, while in echinococcus the line of dul-
ness shows irregularities. The demonstration of another tumor in the liver
is not without importance. The course of pleurisy is much more rapid than
that of the slowly growing echinococcus. Exploratory puncture is not advis-
able on account of the danger associated with it, unless an immediate opera-
tion is to follow. ;
Echinococcus of the lung is next in frequency to that of the liver. Ac-
cording to Madelung 11.9 per cent. of all cases occurred in the lungs, and
according to the Pomeranian statistics, 10.6 per cent. The parasite may de-
velop in any part of the lung; most frequently, however, it is met with in the
right lower lobe. The latter circumstance is explained by the frequent simul-
taneous affection of the liver. The thinness of the walls of its capsule, as
elsewhere, and the yielding of the pulmonary tissue make the decided growth
of the echinococcus possible, and it not rarely fills the pleural cavity, leading
to displacement of the heart, of the diaphragm, the liver and the spleen. Symp-
toms of chronic inflammation, of hepatization, of atrophy, or of gangrene, may
develop and complicate the pathology. Erosion of the bronchi and of the
pulmonary vessels, and rupture into the pleural cavity, are not infrequent. As
the result of destruction of larger blood-vessels, severe, often fatal, attacks of
hemoptysis occur. ; :
The passage of daughter-cysts into the blood-vessels with the formation of
emboli has been observed. Upon opening into the bronchi, gangrenous sputum
appears in which daughter-cysts, scolices or shreds of membrane are found.
538 THE ANIMAL PARASITES OF MAN
In other cases the symptoms of pyopneumothorax develop. Not rarely rup-
ture into the diaphragm occurs, and thus the echinococcus finds entrance into
the parenchyma of the liver. Rupture into the intestine and into the walls of
the abdomen etc., has also been observed. Secondary pulmonary echinococci
are rarer than primary ones. Usually originating in the liver, they penetrate
the diaphragm and the pleural cavity and enter the lung. Rupture into the,
bronchi or into the pleural cavity produces severe symptoms. The simul-
taneous perforation of the biliary passages and the intestine has been repeat-
edly observed.
The symptoms for a long time may be indefinite and point only to an
affection of the respiratory organs. With increasing growth a very trouble-
some cough and attacks of dyspnea usually occur. As
the first symptom I have repeatedly observed hemop-
tysis with cough, so that the clinical picture resembled
phthisis pulmonum. Severe paroxysms of cough may
cause perforation by the echinococcus, mostly unilocu-
lar, into the bronchi, and the discharge of cysts, large,
rolled-up masses of membrane or shreds of membrane
and scolices. The seat of the disease, and sometimes
even the side which is affected by the disease, may be
Fic, 52.—ExpPrcToraTeD difficult to recognize, if the cyst is centrally situated
Ecuinococcus Mrm- ss : i
Suan: or is surrounded by a thick layer of pulmonary tissue
containing air. Not rarely, prior to rupture, suppura-
tion or putrefaction of the contents of the cyst occurs, and this always takes
place after rupture of the cyst.
If the seat of the echinococcus is at the periphery of the lung, especially
if it has attacked an upper lobe, the symptoms resemble chronic pulmonary
tuberculosis; but the fair condition of nutrition, in spite of repeated hemop-
tysis, and the absence of the characteristic expectoration are opposed to this
view. Occasionally a complication with tuberculosis is present. Even when
the disease attacks a lower lobe, no signs are usually manifest other than
those of a pleural effusion. The nature of the affection is frequently deter-
mined only by exploratory puncture, which is performed with the expectation
of finding a pleural exudate or an empyema.
The prognosis of pulmonary echinococcus is serious, but by no means abso-
lutely unfavorable. In the Pomeranian statistics, among 16 cases spontane-
ous discharge of the cyst was followed by recovery in eight, and two were
cured by operative treatment. Death resulted from exhaustion in two cases.
One that was operated upon died. In another, pulmonary echinococcus was
only an accidental autopsy finding. Surgical interference appears to be
advisable in all cases in which physical examination reveals suppuration and
putrefaction in the cyst.
Echinococcus of the mediastinum is uncommon. About six cases only are
on record. On account of the proximity to the heart and lungs, the echino-
coccus here causes grave danger.
Echinococcus disease of the circulatory apparatus is rare. According to
Huber about 40 cases have been observed. T'o these may be added the cases
ECHINOCOCCUS DISEASE 539
of Demantke, Lehne and Klehmet. The echinococcus is usually unilocular.
The right heart is more frequently implicated than the left. The seat of the
parasite is the heart muscle, and here it attains its growth. For the most
part its course is marked by no symptoms, at least of parasitism. The condi-
tions are different, however, if the distended cyst grows into the cardiac
cavities and bursts its sac. The symptoms of cesto-embolism in this case
do not differ decidedly from emboli as the result of thrombi. According to
the size and extent of the embolus, according to its benign or malignant
(putrid) composition, and according as the smaller or larger vessels are ob-
structed, the disturbances due to emboli of cestodens show varying charac-
teristics. We should digress too far if we further discussed these extremely
complicated conditions. Death often results suddenly without preceding symp-
toms. In some cases there are antecedent signs of disease of the heart and
of the lungs; in other cases death takes place after a long illness with com-
plications such as perforation and embolism of daughter-cysts.
In emboli into the greater circulation the perforating cyst is usually situ-
ated in the left heart, or the cysts develop from a pulmonary echinococcus
which has burrowed into the pulmonary vein. Death, as a rule, occurs sud-
denly. It may be readily understood that such cases as these are rarely
under clinical observation for a long time; the disease is found at the autopsy
in cases where death has occurred suddenly.
Echinococcus of the blood-vessels and lymph-vessels as well as of the pert-
cardium is extremely rare.
Echinococcus of the liver is the form most frequently met with. In the
Mecklenburg statistics they amounted to 69 per cent. of all observed cases,
in the Pomeranian statistics to 67.33 per cent. They are for the most part
unilocular, rarely multiple. They are found in all parts of the liver, but
most frequently in the right lobe. When centrally situated the cyst grows
but slowly, while echinococci peripherally situated give rise to great enlarge-
ment of the organ, even to six or seven times its normal size. The liver
substance is ruptured, and the cyst appears with single and multiple semi-
globular elevations upon the surface. If the echinococcus develops upon the
convex surface it forces the diaphragm far up into the pleural cavity, and
causes compression of the lung and displacement of the heart.
Occasionally the echinococeus penetrates the diaphragm and extends into,
or perforates into, the pleural cavity or the bronchi. When the cyst spreads
into the abdominal cavity, it causes displacement of the stomach and intes-
tines. It occasionally adheres to these organs, and, finally, ruptures into
them; or, in the absence of adhesions, it may perforate the abdominal cavity.
This is, however, rare. In such cases fatal peritonitis is the immediate con-
sequence, while with rupture into the stomach, intestines, etc., ultimate recov-
ery is possible. The paths which the echinococci may make for themselves
are numerous.
Echinococci of smaller size often produce no symptoms, or, at least, not
for a long time. Usually only with increasing growth does the parasite mani-
fest its presence. Symptoms are at first local, such as a sense of pressure,
of heaviness, or occasionally pain. Frequently echinococei of considerable size
540 THE ANIMAL PARASITES OF MAN
are seen which have grown almost without symptoms. They finally, however,
lead to displacement of adjacent organs, particularly of the lung and the
heart, and a prominence appears in the hepatic region and in the lower parts
of the thorax. Protuberances from the size of an apple to that of a child’s
head are not rare, and they may be recognized by inspection and palpation.
Palpation is almost always painless. Hydatid thrill, a symptom which has
been mentioned so often, is occasionally present. I have only rarely been
able to elicit it. Jaundice is by no means frequent. As the size of the tumor
increases it gives rise particularly to gastric difficulty: disturbance of appetite,
nausea, a tendency to vomit, constipation. Dyspnea, cough, attacks of fear,
cardiac palpitation, etc., also occur.
While the course has previously been afebrile, when suppuration of the
cyst occurs high fever, chills, and great pain appear, and, if suppuration be
long-continued, pyemic phenomena in the lungs, spleen and kidneys may bring
a threatening change. Rupture into the pleural cavity, into the lungs, and
into the abdominal cavity may also give rise to a condition of collapse, pyo-
pneumothorax, peritonitis, etc., and may seriously endanger the life of the
patient, Or perforation into the stomach or intestine may lead to vomiting
or discharge of the characteristic contents of the cyst. Rupture into the
biliary passages we have several times known to cause the discharge of bile-
stained cysts or shreds of membrane with the symptoms of a colitis hepatica.
In rare cases the echinococcus is felt beneath the abdominal walls far
removed from its original seat, and here finally leads to rupture.
The course described is not invariable in echinococcus disease. Fortu-
nately, the echinococcus not seldom develops to only moderate size. It dies,
the sac contracts, and the contents are absorbed. Calcareous nodes and broken
cheesy masses in which portions of the echinococcus may be recognized are
occasional autopsy findings. In the Pomeranian report, compiled by Wiede-
mann at my instigation, and including more than 153 cases, echinococcus
of the liver occurred 34 times = 33.01 per cent. as an accidental autopsy
finding.
The same compilation gives data concerning the prognosis of echinococcus
cases. In 28 instances there was no operative treatment. Twelve patients
died of chronic invalidism. Spontaneous recovery by perforation into the
lung and intestine occurred in 8 patients. In 8 other cases the further course
was unknown. In 41 operative cases recovery followed in 34 = 82.92 per
cent. Improvement occurred in 4 = 9.75 per cent.; 3 died = 7.31 per cent.
In the differential diagnosis, besides amyloid fatty liver and hypertrophic
cirrhosis—diseases which are sufficiently characterized by the accompanying
symptoms—we must consider: Hepatic abscess, cancer of the liver, syphilis
of the liver, dropsy of the gall-bladder, hydronephrosis, ete.
Lennhof calls attention to a symptom he observed in cysts of the lower
part of the liver—an “inspiratory furrow.” Upon deep inspiration, accord-
ing to his observation, the prominence of the abdomen due to the tumor moves
downward while the skin retracts above this, and between the arch of the
ribs and the prominence a flat furrow is formed.
Abscess of the liver usually develops acutely, and is accompanied by a chill,
ECHINOCOCCUS DISEASE 541
by decided pain and rapid loss of strength. Differentiation between hepatic
abscess and a suppurating echinococcus cyst is frequently very difficult.
Neither is differentiation between a cyst and a soft cancer nodule easy, for
such nodules may frequently produce the signs of fluctuation. Confusion
with dropsy of the gall-bladder may readily be avoided, as its position remote
‘from the liver, the form of the tumor, and the anemia will point out the
correct diagnosis.
The oval form of hydronephrosis, the immobility in respiration, its posi-
tion in relation to the colon, palpation in the knee-elbow position, and an
examination of the urine will prevent us from confounding echinococcus with
hydronephrosis.
Multilocular echinococcus also frequently exists for a long time without
symptoms, and then the sensation of fulness and heaviness in the epigastrium
and stubborn jaundice appear. Bulging in the hepatic region constantly in-
creases as the result of the decided enlargement of the organ. Palpation
reveals a tumor of hard consistence like cartilage; the surface is smooth and
nodulated. Fluctuation at first is limited to individual parts. The spleen
is usually enlarged. Nutrition gradually suffers; ascites, anasarca and at-
tacks of fever occur. Death results after one or several years, accompanied
by the symptoms of marasmus.
In form and size, and in the hardness of the liver, multilocular echinococcus
resembles hepatic cancer. But the course of the disease is slower, and nutritive
disturbances develop only in the advanced stages. Syphilis of the liver pre-
sents other forms and degrees of enlargement. The chills and marked jaun-
dice which usually occur in abscess of the liver will differentiate this affection
from multilocular echinococcus. Hepatic cirrhosis and amyloid liver will, as
a rule, be easily differentiated from the hydatid. The prognosis has usually
been considered absolutely unfavorable. We have already called attention to
the results recently obtained by operation.
Echinococcus of the pancreas has been described by Subboitic, Pericic and
Salis.
Echinococcus of the spleen is rare; according to the Pomeranian statistics
it occurred in 4 per cent. of the cases, in the Mecklenburg statistics in only
1.96 per cent. The parasite finds a favorable medium for its growth in the
soft splenic tissue. In the main, the symptoms of splenic echinococcus resem- .
ble those of hepatic echinococcus, but with the difference that the formation
of tumor is only upon the left side. Splenic echinococcus is not rarely com-
plicated by echinococcus of other organs.
Echinococcus of the kidney, which in the Mecklenburg statistics consti-
tutes 3.5 per cent. of the cases, and in the Pomeranian 4.58 per cent., usually
develops in the cortical substance. Renal echinococci for the most part are
unilateral. As it grows all parts of the kidney may be implicated in the
disease, and the kidney be transformed into a large echinococcus cyst. This
cyst extends into the abdominal cavity, and leads to dislocations and to adhe-
sions to neighboring organs. Diseases of the most varied kind may thus
be simulated. Small tumors produce no symptoms; larger ones cause pressure
phenomena, difficulty in respiration, ete. After years the symptoms of maras-
542 THE ANIMAL PARASITES OF MAN
mus develop, provided rupture into the pelvis of the kidney and discharge of
the cysts have not occurred. The urine which may be voided prior to, with,
or after, the discharge of the cyst is turbid, occasionally of a soapy-alkaline,
milky, or turbid appearance, and in the sediment the characteristic contents of
the cyst are found. After discharge the palpable tumor disappears, to recur
after some time. The affection may last for many years. Occasionally the
echinococcus takes other roads; perforation into the pleural cavity and abdom-
inal cavity has repeatedly been observed.
Renal echinococcus differs from cysts of the liver and of the spleen by the
immobility at its base, by its outlines which may be determined by percussion
from the borders of these organs, and by dislocation of the colon. The differ-
ential diagnosis between renal echinococcus and hydronephrosis is very diffi-
cult. The history of the development of the tumor, the proof of a hindrance
to the discharge of urine, the previous presence of renal calculi or of a stasis
pyelitis, point to the presence of hydronephrosis.
The prognosis of renal echinococci is considered by most authors to be very
grave. Fortunately, with the advance of modern surgery, operative treatment
gives better results than formerly.
In the adrenals only one case each of the cystic and of the multilocular
form has up to the present been found.
Echinococcus of the urinary bladder has been reported by Hinsworth and
Schonfeld.
Winterberg has described a case of echinococcus of the prostate gland.
Echinococct in the abdominal cavity. Primary cysts of the peritoneum
appear to be rare. They are always multiple. Their origin may be referred
to a profound general infection or to an autoinfection. The parasite is
usually found simultaneously in other organs. Numerous adhesions may fre-
quently preclude the determination of the point of origin. The symptoms
which result are due to the pressure exerted upon the abdominal organs.
Perforation is rare.
Primary retroperitoneal echinococci are not often found except in the
connective tissue of the pelvis and in the female genitalia, where the cysts
are situated subserously. In the Pomeranian statistics we find only one case
of this kind described by Bitter. Karewski recently published two cases. The
. symptomatology is usually obscure, and when suppuration takes place it points
to a perinephritic abscess. On account of the pressure of the thick layers of
muscles and of the bones of the trunk, held by tense fascia, the echinococcus
finds but little room for growth, and is forced to develop from the surface
by daughter- and granddaughter-cysts of exogenous growth. Conspicuous
symptoms appear only when suppuration occurs. To facilitate the diagnosis,
Karewski advises exploratory puncture, all danger being obviated by the extra-
peritoneal position.
Echinococet of the mesentery are somewhat infrequent, and their diagnosis
is not easy. In regard to their differentiation from cysts of the omentum,
Hahn states that the latter can come into question only when fixed loops of
intestine can be determined between the tumor and the abdominal wall, or in
the surroundings of the tumor, or in the limits which may be defined by
ECHINOCOCCUS DISEASE 548
palpation or by adhesions. If the intestine is in front the tympanitic note
of the latter is the most important diagnostic symptom.
Echinococcus of the omentum is rarely unilocular. Cases of this kind have
been published by Griinig and Liitkemiiller.
Echinococcus of the true pelvis and of the genitalia. In the male, echino-
cocci in the true pelvis develop in the space between the rectum and the blad-
der. Their growth leads to disturbances of function of the rectum and bladder.
Now and then perforation into the rectum occurs.
In the female we find echinococcus in the uterus, in the ovaries, in the
ligamenta lata, in the anterior and posterior halves of the pelvis.
In the uterus the echinococcus usually develops in the submucous tissue.
Scanzer’s view that the embryo in its wanderings reaches the abdominal open-
ing of the Fallopian tube grasped by the fimbriew, enters the cavity of the
uterus, and develops fully there, is quite properly rejected by Schatz for the
majority of cases. The submucous seat is explained by Schatz from the cir-
cumstance that the embryo, owing to greater strength of the blood current
in that direction, particularly at the time of menstruation, is forced against
the interior muscular layer near the mucosa. It evidently develops in the
muscles, and finally, when labor pains occur, enters the cavity of the uterus
through the muscles which have gradually become atrophic. The hydatid has
also been found in a subserous position.
The echinococcus lodged in the wall of the uterus is commonly mistaken
for a myoma, if echinococci have not appeared in other organs. The circum-
stance that the wall of the uterus, which in the case of myoma is usually
decidedly hypertrophied, is not found so in the case of echinococcus
(Schatz) may be utilized in the diagnosis. Subserous myomata develop
only a moderate muscular hypertrophy; their consistence is not character-
istic. Thirteen cases are mentioned in literature in which the echinococcus
sac was an impediment at birth (Schmidt, “Ueber Ech. in weibl. Becken,”
Diss, 1893).
Echinococci of the ovaries and ligamenta lata are rare. Schultze could
collect from literature only eleven cases of echinococcus of the ovary, to which
he added two cases that came under his own observation. Schatz remarks
concerning the diagnosis that a tumor of about the size of an orange, very
deeply seated near the uterus, should cause us to suspect echinococcus. Later
a group of such tumors, of equal size and closely situated, forms an important
diagnostic symptom. Extrauterine pregnancy on account of its rapid progress,
and disease of the tubes on account of the characteristic form of the enlarge-
ment, can scarcely be confounded with echinococcus. Beowit recently saw
both tubes transformed into echinococcus sacs.
Echinococcus of the cellular tissue of the pelvis is in the majority of cases
found upon the inner surface of the posterior wall, less frequently upon the
anterior. The diagnosis is greatly facilitated by the ease with which the
diseased area may be reached. Echinococcus of the pelvis may be suspected
if one or several smooth, tense, elastic but slightly movable tumors, not painful
upon pressure, are found, and the ovaries may be distinctly determined. In
many cases the cyst is situated between the uterus and the rectum. Fever
544 THE ANIMAL PARASITES OF MAN
and cachexia are.absent. The simultaneous presence of the parasite in other
organs facilitates the diagnosis.
Echinococci of the scrotum, the epididymis and the tunica vaginalis have
been observed in a few cases.
Echinococcus of the bones is rare. In the Pomeranian statistics not a
single case is mentioned.
The parasite is found more frequently in the long bones than in the
short bones. In the cases collected by Poppe, the frequency with which differ-.
ent bones were affected was as follows: Humerus 23 per cent., pelvis and tibia
18 per cent., vertebral column and femur 13 per cent., frontal bone 5 per cent.,
sphenoidal bone, scapula, index finger, sternum, and ribs each 1 case.
The parasite develops in the medullary cavity, i.e., in the spongy sub-
stance, and is at first entirely latent. Only with increasing growth do char-
acteristic changes occur. In the long tubular bones the medullary cavity
dilates, the wall of the bones becomes eroded, the external wall thin. Often
there is severe pain. Slight trauma leads to spontaneous fracture without
any previous symptom of disease of the bone. The fracture does not heal, a
fact which usually enables us to recognize the nature of the affection. Schnitz-
ler’s case proves that occasionally, even in echinococcus of the long tubular
bones, decided changes in form and circumference of the bones may take
place.
NEMATODA, THREAD-WORMS
The nematoda are slender, cylindrical, curved, thread-like or tubular
worms. Their surface is smooth and curled, occasionally supplied with hook-
lets, hairs, or bristlets. The anterior end of the body in which the mouth
cavity is situated is somewhat slender, the posterior end is pointed or rounded.
The anus is usually found upon the ventral surface. The nematoda, at least
those which are parasitic in man, are of different sexes. The males, as a
rule, are shorter and more slender than the females. In the males the posterior
end of the trunk is usually curved, while in the female it shows a straight
elongation. In the male the sexual opening and the anus are one, while
in the female the former is usually found at about the center of the body.
Of the nematoda which are parasitic in man I shall briefly mention:
Rhabditis terricole, Dujardin, 1845, which was once found in the cadaver.
Rhabditis pellio, Schneider, 1866, was found in acid urine containing albu-
min, blood and pus. I believe that I once saw this parasite with Westphal.
Rhabditis Niellyi, Blanchard, 1885, in a cabin boy produced an itching
skin eruption.
Anguillula putrefaciens, Kiihn, 1879, was once observed in vomitus. The
parasite was evidently taken into the stomach of the affected individual with
onions, and then had produced vomiting.
Of decidedly greater interest is:
Anguillula intestinalis et stercoralis, Bavay, 1877.
In 1876 Normand, a French marine surgeon, found, in the feces of a
soldier who suffered from the so-called Cochin-China diarrhea, anguillula which
NEMATODA, THREAD-WORMS 545
were designated by Bavay as anguillula stercoralis, Another parasite soon
afterward found by Normand in patients of this kind was described by Bavay
as anguillula intestinalis. By the investigations of Leuckart, Grassi, and
Leichtenstern, the relations of these parasites have been determined with cer-
tainty. For purposes of study, I may refer to the investigations of the
previously mentioned authors as well as to those of Askanazy and Zinn.
According to these investigations the development occurs in the following
manner: the hermaphroditic mother animal of the anguillula intestinalis,
according to Askanazy, lodges in the intestinal wall, chiefly in the mucous
membrane, and frequently bores its way into the epithelium of the gland,
there to take up nutritive products. The females at the same time deposit
their eggs here. The ova are transformed into embryos which then enter
the intestinal cavity. These are met with in fresh feces, often in great num-
bers, and, according to Zinn, in about twelve hours are transformed into filaria-
like larve. These again enter the intestinal canal of man, and are here
formed into parasitic anguillula. This process is called direct metamorphosis.
Other embryos of anguillula intestinalis develop outside the body in about
two to three days into sexually ripe male and female animals (rhabditis ster-
coralis). The direct descendants of these are the embryos of the rhabditis
stercoralis, from which the filaria-like larve are again formed. The latter
wander into the intestinal canal of man, and grow into mother animals of the
parasitic anguillula intestinalis. This mode of development is designated by
Leuckart as heterogeny. This heterogeny, as was first emphasized by Leich-
tenstern, does not occur in the majority of cases, particularly in those of
European origin.
Anguilluliasis occurs not only in southeastern Asia, Martinique and Bra-
zil, but was met with in 1878 and 1879 by Grassi and Parona in Italy, simul-
taneously with anchylostomiasis. Lately Askanazy found them in a game-
keeper in East Prussia who had never left his home, and who never came
in contact with Rhenish brickmakers.
The parasites live in the juices of the small intestines. Askanazy also
found them in the tissues of the mucosa, sometimes stretched out or rolled
together. They distribute themselves in the muscularis mucosa, and are met
with in great numbers in the region of Lieberkiihn’s glands. The parasite
enters the walls of the intestines to partake of the chyle. Here, according
to Askanazy, the eggs are deposited, and the parasite goes through its stages
of development. Teissier has observed that the embryos occasionally enter the
circulation. Askanazy seems to favor the view that the parasites are to be
regarded as no more than simple commensals.
Of special interest is the:
Filaria medinensis Velsch, 1674.
The females attain a length of from 60 to 80 em. and in form and appear-
ance resemble a catgut string. The male, according to Charles, has also
recently been found. It is only 4 cm. in length. Dracontiasis, as the path-
ologic phenomena produced by the parasite were called by Galen, is due to
the fact that the worm penetrates the human organism, and may remain for
36
546 THE ANIMAL PARASITES OF MAN
a long time under the skin of the connective tissue entirely latent. Only after
completing its full growth—the period of incubation appears to be from eight
to ten months—does it leave the papillary bodies of the corium by the forma-
tion of an abscess.
The medina worm is most frequently found in tropical countries, particu-
larly in the Old World: in Arabia, around the Persian Gulf, upon the Ganges,
the Caspian Sea, in Upper Egypt, Abyssinia and Guinea, It has also been
carried to South America.
The filaria embryos enclosed in the uterus can only secure their freedom
by rupture of the mother animal. How their further dissemination in the
human organism takes place has not yet been definitely determined. It has
been thought that the embryo finds ingress through the skin. Some authors
assume that infection is conveyed by drinking-water. Probably the worm
finds a hold around the lower extremities, especially about the malleoli. It is
much more rarely found upon the upper parts of the body.
The symptoms resemble the formation of a furuncle, at the base of which
the parasite is seen. Upon extraction of the worm, rupture of the parasite
should be avoided, and care should be taken to leave no fragments behind,
for, otherwise, decided inflammation soon appears.
A more delicate and smaller parasite is:
Filaria loa Guyot, 1778,
which lodges between the conjunctiva and bulbus oculi, and gives rise to abscess
formation in this region. The parasite is found chiefly in negroes upon the
west coast of Africa, also in South America and in the Antilles,
The other filariz are not of special interest. Among these I may mention
the filaria lentis, Diesing, 1851, the filaria hominis bronchialis, Rudolphi, 1819,
the filaria labialis, Pane, 1864, the filaria inermis, Grassi, 1887, the filaria
immitis, Leidy, 1856, the filaria rectiformis, Leidy, 1880, the filaria hominis
oris, Leidy, 1850, the strongylus subtilis, Loos, 1895, and the filaria volvulus,
Leuckart, 1893.
Filaria Bancrofti, Cobbold, 1887.
The embryos of this parasite were found in the fluid of a hydrocele by
Demarquay in 1863 in a Havanese. They were found later in the blood,
the urine, and in the chyle in so-called lymph-scrotum and in elephantiasis.
Bancroft and Lewis found the mature sexual forms in the lymph-vessels. The
females bear living young, which enter the blood with the lymph-stream. Ac-
cording to Manson they enter the blood only after sunset; after midnight
their number again decreases. If the patient sleep during the day, the em-
bryos appear in the blood during the daytime.
This periodic appearance is explained by v. Linstow by the circumstance
that the peripheral cutaneous vessels dilate during sleep, and thereby permit
the entrance of the embryos, which otherwise would only ‘be present in the
larger vessels. Manson states that the appearance of the embryos is simul-
taneous with the swarming of mosquitoes, which suck the blood of the affected
person, and are then filled with embryos. A part of the young brood develop
NEMATODA, THREAD-WORMS 547
with the mosquitoes, and a part are destroyed. The female mosquitoes die
after depositing their eggs in water. But the mature filaria, meanwhile, have
acquired the power of living for a time in water. With the water they, enter
the human host and there, chiefly in the lymph-vessel system, they become
sexually mature animals.
The male parasite is about 83 mm. in length, and has the thickness of a
hair of the head, while the female is 155 mm. in length and 0.7 mm. in
Fie. 53.—Fivaria EmsBryos.
This preparation I owe to the kindness of Professor Magathdes of Rio de Janeiro.
breadth. The posterior end of the male is pointed, and rolled in a spiral.
The sexual opening of the female is close to the head. In fresh blood the
embryo shows active movements of both ends; it is perfectly transparent, and
only in the middle of a parasite may a few granule clumps be recognized.
Scheube found them upon the average 0.216 mm. long and 0.004 mm. broad.
The home of the filaria is tropical Asia, Africa, America, and Australia.
Besides the filarie of Bancroft and Cobbold, other blood filariz are also
found. The filaria Magathdesi must first be mentioned. It is decidedly larger
than those previously named, and in Brazil lives in the heart of man. Fur-
thermore, Manson has described the filaria sanguinis hominis major—the
filaria diurna, Manson; the filaria sanguinis minor—the filiaria perstans, Man-
son; the filaria, Demarquayi; the filaria, Ozzardi. The sexually ripe form has
not yet been found, and v. Linstow believes these filaria to be developmental
phases of one and the same embryonic larval form.
The filaria produce marked symptoms in the lymphatic system, the walls
of which show inflammatory changes. Thrombosis and cicatricial closure of
the lymphatics cause varicose dilatation of the peripheral vessels and the forma-
tion of lymph-cysts. These rupture and their contents are set free in the
urinary bladder, under the cutis, or in other tissues. The perilymphatic con-
nective tissue is also inflamed. Finally symptoms are produced which resem-
ble elephantiasis.
548 THE ANIMAL PARASITES OF MAN
The filaria embryos appear to circulate for a long time in the blood before
they produce symptoms. Gradually general malaise develops, also pain in the
small of the back and renal region, and in the scrotum, followed by an inter-
mittent hematochyluria. Fever and enlargement of the spleen often accom-
pany the symptoms. After continuing for days and weeks these phenomena
cease, to reappear at the end of a certain period. During the attack the urine
is of a peach-red color. Blood and blood coaguli are found in the sediment,
while the urine above this is turbid, whitish, and has a tint of yellow not
unlike diluted cream. Upon the surface a cream-like fatty layer may fre-
quently be noticed. Sugar and peptone are absent; cholesterin, lecithin,
neutral fats, and fatty acids are present. Besides the embryos, red and white
corpuscles and large and small fat globules-are found. Gradually the lymph-
glands enlarge, in the males the scrotum, in the female the labia. The symp-
toms disappear, to return in a short time in an exaggerated form. Elephan-
tiasis-like swellings form upon the lower, and later upon the upper, extremities.
The disease finally causes death, after running a course for years with the
symptoms of marasmus. ;
Whether recovery, which occasionally is spontaneous, is due to remedies
or not is very questionable. Drugs appear to have no influence upon the para-
site. Surgical interference has been frequently attempted, but, according to
Scheube, does not prevent relapses. The utmost stress is to be laid upon
prophylaxis, and in this the question of drinking-water is of special impor-
tance. The habit of drinking unfiltered water from ditches and cisterns in
the tropics is undoubtedly a cause of the distribution of the parasite. Physi-
cians living in these regions strenuously advise that only filtered water, or
drinking-water from closed conduits, be used.
It is evident that our knowledge of filariasis is far from complete, and it
is hoped that future investigations may shed light upon some of its dark prob-
lems. For example, John O’Neill observed a filaria which produced prurigi-
nous vesicles and nodules upon the fingers and elbows with severe itching, and
of this parasite nothing further has been heard.
Among the most frequent human parasites are the ascaris lumbricoides,
Linné, 1758, trichocephalus dispar, Rudolphi, 1801, and the oxyuris vermicu-
laris, Linné, 1767.
A zoologic description of these parasites is unnecessary as they are well
known.
The ascaris lumbricoides resembles the rain-worm, and is unquestionably
the most common parasite of man. Its embryology was first clearly described
by Grassi in the year 1887, and he proved that it does not require an inter-
mediary host. The fact of direct infection with embryo-containing ova has
been confirmed by the further investigations of Lutz and Epstein.
Besides the ascaris lumbricoides, the ascaris mystax, Zeder (the nematode
of the cat or dog), has also been occasionally found in man. This parasite
is much smaller than that of man; and upon the end containing the head
two wing-like processes are situated which at once distinguish this worm from
those mentioned above.
NEMATODA, THREAD-WORMS 549
Ascaris maritima, Leuckart, 1876, has up to this time been found only
once—in Greenland.
Wherever ascarides hosts, including swine and cattle, distribute the ova in
the vicinity of human habitations, man, whose habits and customs bring him
into close contact with the foci of infection, acquires the ova of the nema-
tode. The agricultural population, in particular, by their occupation, and,
above all, the children, by playing in the infected earth take up the embryo.
Children in cities are much more rarely contaminated. By the slaughter of
pigs and cattle at home or inthe immediate vicinity, the infectious germs are
widely distributed about the house and in the garden, which is the ordinary
playground of the children. In the first and second years children are much
more rarely attacked than in the third year and upward. In later life ascarides
are more rarely met with but no age is exempt. Often infection occurs
through drinking-water or food, such as fruit, vegetables, and the like.
The. usual seat of the parasite is the small intestine. A single parasite is
rarely found; usually they collect in numbers.
The parasites frequently produce no symptoms, and their accidental dis-
charge betrays their presence. When the parasites are numerous, they pro-
duce more or less decided disturbance. In the milder cases only gastric symp-
toms appear: Anorexia, nausea, salivation, irregular bowel action. In children
there is frequently a slightly swollen appearance, deeply sunken eyes, itching
of the nose, nocturnal grinding of the teeth. Various nervous symptoms, such
as convulsions, epileptiform attacks, headache, pain in the back of the neck,
etc., may occur, although these are less frequent. Demme saw cases of severe
anemia due to the presence of numerous nematodes; Baelz also believes that
ascaris may occasionally produce severe anemia. lLeichtenstern saw severe
anemia, and in another case larval malaria with enlargement of the spleen,
improve after expulsion of the ascarides. These, as well as many other obser-
vations, do not permit us to regard this nematode as the harmless guest which
it is usually assumed to be. The severe nervous symptoms have, for the most
part, been looked upon as reflex. The observations of Huber, v. Linstow and
others have shown that this nematode contains a poison which may give rise
to urticaria and conjunctivitis. It has a sharp odor, manifest even on handling
of the parasite. As I have explained elsewhere it is quite possible to look
upon the nervous symptoms which accompany infection by nematodes not as
reflex but as toxic.
Decided local disturbances may also appear when numerous ascarides are
present. Sometimes, rarely it is true, the worms may form a ball so that the
symptoms of intestinal occlusion may arise. Leichtenstern questions this,
but from the observations of Mosler, Pelczynski, Stepp, Sperling and others,
it may be considered as proven. The view that nematodes may perforate the
intact mucous membrane has not yet been positively demonstrated by investi-
gation, but if ulcer formation is present it is quite possible that the parasites
may perforate the ulcerated surface.
It is a remarkable fact that at certain times, especially in serious febrile
diseases, ascarides leave their usual seat, the small intestine, and begin to wan-
der. Either they enter the large intestine, are voided from this independently,
550 THE ANIMAL PARASITES OF MAN
and are later found rolled up in the bed, or they are voided with the fecal
masses. In other cases they enter the stomach, thence the esophagus, and find
their exit by means of the mouth and nose. If they effect an entrance into
the larynx, severe suffocative phenomena are produced which may cause death.
Not rarely they find ingress to the excretory ducts of the large abdominal
glands, particularly the common gall duct, and thence reach the gall-bladder
or the liver and here produce serious lesions. More rarely they invade the
pancreatic duct or the vermiform appendix. The tendency of ascarides to
lodge in preformed foramina explains their occurrence in the abdominal cavity
after perforation of the intestine. If nematodes are capable of thus penetrat-
ing into intra- or extra-peritoneal abscesses, in their further course they may
be found in very remote situations. Thus, nematodes have been discharged
from the bladder, from the uterus, and from abscesses of the abdominal cavity.
If there is a suspicion of helminthiasis, the microscopical investigation of
the feces and the finding of the characteristic ova will, as a rule, enable us to
make a positive diagnosis.
The prognosis is generally favorable; only exceptionally, by the wandering
of the parasites, are threatening symptoms produced.
The administration of santonin will generally lead to the expulsion of the
parasite. This drug should never be given upon an empty stomach, however,
as rapid absorption permits its toxic properties to appear before its anthel-
mintic. As is well known, the symptoms of santonin poisoning consist of
yellow sight, yellow discoloration of the urine, general malaise, vomiting and
spasms, which may readily become dangerous in delicate children. Laxatives
soon cause the discharge of the poison.
Santonin is given to children in doses of 0.025-0.05, to adults in doses
of 0.1. Lozenges which usually contain 0.025—-0.05 of santonin may be ob-
tained in pharmacies, and one of these should be taken two or three times
daily. Upon the third day a laxative is administered, and frequently the
worms, which have been only stupefied, are discharged.
The ozyuris vermicularis, Linné, 1767, is also a parasite that is well known.
The direct development of the oxyuris without intermediary host, which was
indicated by the investigations of Leuckart, is generally accepted. By the
swallowing of oxyuric ova, Leuckart, Grassi and others have directly infected
themselves.
It does not appear to me to be sufficiently recognized that the ova are not
deposited in the intestine of man, but that the mature females leave the intes-
tine independently or with the feces. We can never conclude from the absence
of oxyurisova in the feces that this parasite is not present in the intestine. Only
outside of the intestinal canal does the female discharge its ova in the fecal
masses. Frequently the surroundings of the anus are thickly covered with oxy-
uris ova which have been deposited there by female parasites which have been in-
dependently discharged. In the ova an embryo soon develops which, however,
does not extrude from its sac until after retransportation to the human intes-
tinal tract. Unpared fruit, fresh vegetables, berries and other fruits which
have come into the slightest contact with infected feces often bring about this
infection, In other cases transmission is brought about by clothing which is
NEMATODA, THREAD-WORMS ddl
used in common, or by various utensils which may be contaminated with ova.
Ova have been repeatedly found in the dirt of the finger nails of oxyuris hosts.
This observation sufficiently explains why oxyuris hosts are rarely found iso-
lated in families, pensions, ete., and the same finding also explains the well-
known tenacity of the affection, which has been known to physicians for a
long time. The oxyuris host evidently infects himself anew almost daily, or
even every night.
The embryos which have been set free in the stomach develop to sexual
maturity in the small intestine. The impregnated females enter the cecum,
and there await the time for depositing their ova. When this period has
arrived, they wander toward the rectum, or beyond this, and are discharged.
No age is exempt from the parasite, but it is particularly frequent in
children. Great uncleanliness, huddling together, and sleeping with infected
persons favor contagion. The expulsion of parasites is so constant because of
their rapid increase that opportunity for the entrance of new ova may be long
delayed, and it is, therefore, not rare for persons to harbor a parasite for a
great many years.
If the number of parasites is small, they betray their presence only now
and then by itching and burning in the rectum. In sensitive individuals, after
passing through the anus, a few parasites only may cause a number of symp-
toms. These disturbances are decidedly increased by the presence of consid-
erable numbers of the oxyuris. By their serpentine movements in the lower
portion of the intestine they produce intense itching in the anus. This is par-
ticularly marked as soon as the patients go to bed. Sleep is prevented or is
interrupted. The periodicity of these symptoms is conspicuous, and as yet
no sufficient cause for this has been assigned. Large numbers of oxyuris cause
marked catarrhal irritation of the intestinal mucous membrane, perhaps also
erosions, which are brought about by the active boring movements of the head
extremity of the animals. The venous vessels dilate as in the case of hemor-
thoids. Frequently oxyuriasis is complicated with hemorrhoidal conditions
and chronic catarrh of the rectum. In consequence of this the bowels not
rarely become irregular and diarrheic, and the symptoms of tenesmus appear.
A number of consensual symptoms may also develop, which in children readily
lead to onanism. Oxyuris may cause pruritus; in the vagina in girls a leukor-
thea, in the prepuce in boys a balanitis. Marro found in a pus cyst well-pre-
served ova of oxyuris vermicularis.
Reflex symptoms of the most varied kinds, due to oxyuris, are said to occur
with particular frequency in neuropathically predisposed individuals; I have
gathered a number of observations of this kind. At all events, the presence
of numerous parasites is not without an influence on the affected organism.
In feeble persons, particularly in children, we note that the nutrition suffers,
the patient becomes weak and anemic, and there is loss of weight. After
expulsion of the parasite, however, the entire condition of the carrier often
improves suddenly. Occasionally the oxyuris wanders into the stomach, from
here to the esophagus, to the mouth or to the nose. Hartmann saw the fre-
quent expulsion of oxyuris from the nose. It was accompanied by the most
severe irritative symptoms, epileptiform attacks, and psychical disturbances.
552 THE ANIMAL PARASITES OF MAN
These were actually produced by the parasite, for after its destruction by in-
jections into the nose of corrosive sublimate solution and the internal admin-
istration of antipyrin, these nervous symptoms at once disappeared.
The diagnosis where oxyuriasis is suspected depends upon investigation of
the feces, or examination of the anus and its surroundings. If the finding
is negative, the patient is told to use a small enema of cold water immediately
upon the appearance of the symptoms. In the return flow of the water, the
parasites, if present, will be readily recognized. The microscopic examination
of the soiled parts around the anus readily reveals eggs if present. Ova are
found in the feces only if simultaneously also the macroscopically recognizable
female oxyuris is present.
The removal of oxyuriasis often requires great patience. In the first
place it is necessary to prevent the importation of ova by all tendencies and
habits which favor this. The sleeping together of well and sick children, the
common use of clothing, sponges, towels is to be prohibited. Frequent
change of bedding and cleanliness of the finger nails, etc., are to be advised.
Moreover, the parasites which are present in the small intestine, and particularly
in the cecum, must be expelled by purgatives, such as castor oil, rhubarb, com-
pound infusion of senna, etc. At the same time I employ santonin. But the
simultaneous employment of intestinal infusions is absolutely necessary in
order to expel the oxyuris which have entered the large intestine. In severe
cases I add to the water one to two teaspoonfuls of chlorin water, vinegar,
0.2 to 1 per cent. of medicated soap. As a common household remedy garlic
is also employed.
Among the most frequent and also, as a rule, most harmless intestinal para-
sites is the
Trichocephalus dispar, Rudolphi, 1801.
This organism is well known, and therefore a zoologic description is un-
necessary.
The parasite does not require an intermediary host. We have little knowl-
edge of the method by which it enters the human intestinal tract. Its long
period of development and the great resistance of the ova to external influ-
ences evidently favor the invasion. Dried and pulverized to dust, they are
readily consumed with raw fruit, vegetables or drinking-water, and thus enter
the human organism. After the young embryos have left the membrane of the
ovum, they attain their development in the small intestine, and finally lodge
in the cecum. The parasite is usually found in but few specimens. If found
numerously the signs of chronic catarrh may develop in that part of the intes-
tinal tract which they inhabit. The parasite adheres to the mucous mem-
brane in such a way that the anterior end of the head, which is curled in sev-
eral folds, surrounds the individual parts of the mucous membrane. In other
cases it has been proven that the entire anterior thin portion of the body—more
than two-thirds of the worm—penetrates the surface of the intestinal mucous
membrane. Accordingly it is often very difficult to loosen the parasite from
its hold in the mucous membrane.
In regard to the symptoms, in general little is known. In many cases,
NEMATODA, THREAD-WORMS 553
perhaps in the majority, there are apparently no symptoms. Only when a
massive collection becomes lodged in the cecum or in the colon, local difficulty
may result from the irritation which the worms produce by boring their way
deep into the mucous membrane. Moosbrugger, Burchard, Federolf have seen
severe symptoms due to trichocephales: Extreme anemia, enteritis with pro-
fuse hemorrhagic stools, emaciation and loss of strength. Since Askanazy has
shown that the trichocephalus invariably has an iron-containing pigment in
its intestinal epithelium, the origin of which is the hemoglobin of the blood,
this form of helminthiasis will evoke much greater interest.
The diagnosis may readily be made by the microscopic demonstration of the
characteristic ova, thick-shelled brown eggs, at both poles of which there is a
knob-like elevation.
The trichocephales cannot readily be expelled, but the combined adminis-
tration of anthelmintics and purgatives will give the best results. Besides
santonin, we have employed successfully the ethereal extract of male fern.
From the basis of his experience, Lutz advises thymol.
Among the nematodes which are of great pathogenic importance belong
the trichina spiralis, Owen, 1835, and the anchylostoma duodenale, Dubini.
1843. Ishall first describe
Trichina spiralis,
the appearance of which in the musculature of man was observed by Peacock
in 1828, and by J. Hilton in 1833. These and other findings, which were
looked upon only as interesting secondary findings at autopsies, attained their
true importance in 1860 through v. Zenker. In a case observed by this author,
of a girl who was dying from symptoms resembling enteric fever, numerous
recently entered trichine were found in the muscles, as well as many in the
intestine, while no other possible cause for her disease was evident. The same
author ascertained that in the district in which the patient had lived a num-
ber of milder affections had occurred. Sausages and hams which were still
there permitted the detection of massive encapsulated trichina. From this
time, the attention of physicians was directed to trichiniasis. It was soon pos-
sible, even during the life of the patient, to demonstrate the cause of the
disease in the musculature. Abundant material was furnished by the “ tri-
china epidemics” which appeared, particularly in Middle Germany; and the
study of these rapidly added to our knowledge of the previously absolutely
unknown disease, both clinically and pathologically, and enabled us to reach
definite conclusions.
But not only in Germany was trichinosis observed; its existence was soon
demonstrated in Switzerland, England, Denmark, Sweden, Russia, France,
Italy, India, Syria, America and Australia. Wherever the cause could be ascer-
tained, a connection with the ingestion of pork containing trichina was proven.
With the determination of this fact the question arose as to the source of
trichina for the swine. The theory that pigs were infected by the ingestion
of rain-worms, frogs and moles containing trichine was soon shown to be
erroneous. lLeuckart’s view, promulgated in 1862, that rats were the actual
source of infection for the pig was of far-reaching importance. We are also
554 THE ANIMAL PARASITES OF MAN
indebted to v. Zenker whose labors have proven that rats become infected by
the ingestion of other animals containing trichina. Contagion occurs in pigs,
as a rule, by “eating trichina-containing meat of other pigs.’ As is well
known, some parts of the meat are often utilized for feeding swine, particu-
larly during slaughter time in the country, and when. animals are skinned offal
containing trichine is often given to pigs. In such localities it is obvious that
sufficient waste material remains to infect at the same time the entire colony
of rats that are present. The latter continue to be for years a further source
of infection for the pigs, who are usually expert rat catchers, and who often
eat the enemy which they have killed. Wherever pigs infected with trichina
are slaughtered without the complete destruction of their cadavers, there is
danger of distribution of trichina. Mature trichine are found in the small
intestine of the rat, the wild boar, the fox, the polecat, the marten, the raccoon
and the cat, as well as in man and in swine. Man infects himself almost
exclusively by the ingestion of raw or insufficiently cooked pork, which con-
tains the so-called muscle trichina in a condition capable of development.
Thorough boiling or frying will kill the trichina, provided the temperature
in the inner portions of the meat is 50° to 55° R. Neither decomposition nor
cold diminishes the property of life in the trichina. Muscle trichine retain .
their power of development for many years (up to 31). Thorough salting de-
stroys the life of the trichina, but it is certainly not destroyed by cold smoking
nor in the so-called rapid smoking process.
The encapsulated trichine found in the musculature appear as small gray
nodules, rarely over 1 mm. in length, and consist of a capsule which, as in the
case of man, after the lapse of years becomes calcified. The capsule encloses
the trichina. This is a spiral worm of 0.6-1 mm. in length and 0.01-0.03 mm.
in breadth; the head is pointed, the tail is rounded ; upon the head is the mouth
opening, upon the tail the anus. If parts of muscles permeated with living
trichine reach the stomach of man, of the pig or of any other suitable animal,
the gastric juice dissolves the capsule; in from two to three days the para-
sites which have entered the intestine attain their sexual maturity. Soon
after copulation the males die, while the females, according to the observations
of Askanazy, actively bore into the intestinal mucous membrane, and seven
to nine days after infection has taken place produce living young. This act of
bringing forth takes place usually in the tissue of the intestinal mucous mem-
brane, that is, close to the central chyle vessels of the villi. Probably the
majority of the embryos enter the circulation directly through the chyle and
lymph-vessels ; carried by the blood-stream they wander into the transverse
striped muscles. Up to this time the usual mode of distribution has been
assumed to be migration, i. e., by boring through the intestinal walls, the para-
sites enter the peritoneal cavity, and thence the connective tissue parts of the
musculature ; or the path has been traced through the submucosa, through the
mesentery, and the retroperitoneal connective tissue. According to Askanazy,
distribution of the parasites by active wandering is only secondary. About
the ninth or the tenth day after infection, the first influx of parasites reaches
the musculature. The female is so immensely reproductive that, for about
seven weeks, new groups of parasites constantly find their way there.
NEMATODA, THREAD-WORMS 555
The young embryos have a length of 0.1 mm., a breadth of 0.006 mm. The
anterior end of the body is thicker than the posterior. After entering the mus-
cle, they penetrate still more deeply into its interstitial tissue, in a longi-
tudinal direction, toward the insertions of the tendons. Their path through
the fibers causes a number of changes in them. The trichina has a destructive
action upon the finer constituents of the fibers. These lose their transverse
strie and are changed into a fine granular mass. Without doubt the embryo
is nourished by the decomposed muscular substance. I do not wish to be
wearisome with the finer histologic details, and shall emphasize only the fol-
lowing points in the development of the muscle trichina: The development
occurs in about fourteen days. The muscle trichina gradually grows to a
length of 0.12-0.16 mm., simultaneously rolling itself into a spiral. The
sarcolemma distributes itself about the embryo, and thickens. In the inter-
stitial tissue, as well as in the muscular substance, such an increase of the mus-
cle nuclei occurs that the trichina appears completely embedded in them, and
surrounding it is an areola of granular material which stains more intensely
than the remaining contents of the nodule. After about four weeks the con-
tents of the nodule permeated by nuclei enter upon a process of reconstruction,
which, beginning at both ends, rapidly reduces these ends to thin threads.
Around the spiral swelling, as well as around the threads, is a gelatinous
sheath which Leuckart recognized as thickened sarcolemma. Outside of this
is a zone of inflammatory connective tissue richly supplied with connective
tissue corpuscles and leukocytes. Later the disorganized muscular mass in
the region of the thread-like processes disappears. The connection with the
material surrounding the trichina is interrupted. The formation of a clearly
defined trichina capsule now begins; starting from the surrounding con-
nective tissue cells, probably in the course of the old gelatinous sheath, the
new and firmer cyst is separated from the encroaching connective tissue cells.
Fat cells develop at the poles of the capsules. At about the sixth month the
capsule begins to calcify owing to a deposit of calcium carbonate. This cal-
cification may also affect the enclosed trichina. According to Langerhans, the
trichine as well as their capsules are capable of retrogression and may
finally, although only after many years, be completely eliminated from
the body.
In man, the source of infection is almost exclusively the pig, very rarely
the wild boar and the bear. The danger of transmission of trichine capable
of development from the ingestion of infected pork depends upon the prepara-
tion of the meat. People who partake of infected pork raw or insufficiently
cooked show the most severe symptoms. Raw meat in the form of so-called
hash, boiled fresh pork from a newly killed pig, roast sausage or German
sausage (Knackwurst) in the preparation of which the heating is insufficient
to insure the destruction of the trichina appear to be especially dangerous.
The ingestion of meat of this kind, which is particularly common in Middle
and North Germany, causes the frequent appearance of the disease in endemics
and epidemics. In the sixth decade of the last century severe epidemics of this
kind were observed in Plauen, Hettstadt, Hedersleben. In South Germany,
and in other countries, France, England, Belgium, America, ete., this custom
556 THE ANIMAL PARASITES OF MAN
does not prevail; pork is either well cooked or boiled or smoked, and trichina
epidemics are rare. The question is much discussed, whether infection may
be brought about by the importation into Germany of American ham and
bacon. According to Billings trichinosis is met with in American pork in
45.7 per cent., but the above question. has been answered in the negative by a
majority of authors. Some observers, however, hold a directly contrary opin-
ion. Caution is therefore enjoined. Nevertheless, sporadic cases may and
will occur everywhere in the future.
No age, no sex is exempt; all who partake of infected meat, either raw
or in a half-cooked state, are attacked. The severity of the disease depends
upon the amount of meat and the number of trichine consumed. Man
appears capable of harboring a certain number of muscle trichine without
symptoms. This is, at least, indicated by the accidental finding of muscle
trichine at the autopsy of individuals who during life had shown no
symptoms.
The symptoms produced by trichinosis correspond to the phases of develop-
ment of the trichine. Frequently, a few hours after the ingestion of meat
containing trichine, severe gastric and intestinal symptoms appear: Nausea,
vomiting, cardialgia, vertigo, headache, heaviness in the limbs, constipation
or diarrhea. If the infection be severe the symptoms often increase and simu-
late a severe intestinal catarrh, which in isolated cases may run its course
with choleraic symptoms. With increasing lassitude a more or less decided
fever develops. The patients become bedridden. v. Linstow quite properly
regards the severe initial intestinal symptoms as toxic, due to the toxic
products which have been set free by the dissolution of the capsules. The
presence of intestinal trichine in the dejecta has up to the present been rarely -
demonstrated.
In many cases, initial intestinal symptoms are wholly absent, and it is
therefore impossible to determine the period at which infection occurred.
There are indistinct symptoms; rheumatic pains in the limbs and fever; indi-
vidual muscles begin to swell and become edematous. Briefly, the symptoms
are those of myositis. Simon, Kratz and Rupprecht mention as characteristic,
even from the first days of the disease, the so-called “ sympathetic muscle lame-
ness.” This consists in a drawing sensation in the limbs, tension and tender-
ness In the muscles, such as is observed otherwise only after unusual muscular
exertion. The flexors, the muscles of the nape of the neck, and those of the
lumbar region are particularly involved. Sometimes in the first, more fre-
quently in the second, week, Kratz observed neuralgic pains in the abdomen
which, recurring at irregular periods, sometimes as often as six times in the
twenty-four hours, resembled a neuralgia cceliaca.
The gastric and intestinal disturbances are frequently accompanied by fever.
Only in mild cases is this absent during the second half of the second week,
and it is decidedly increased when the muscular symptoms become manifest.
Chilliness frequently accompanies the fever, though marked chills are rare.
The maximum rise of temperature (104° to 105.8° F.) is usually observed from
the ninth to the eleventh day after the beginning of the malady. At first con-
tinuous, the temperature finally shows a remittent type. The return to nor-
NEMATODA, THREAD-WORMS 557
mal is extraordinarily slow. This is markedly different from the temperature
course of enteric fever. In mild cases, even during the third week, the temper-
ature falls to normal, while severe cases continue to show a febrile range from
four to seven weeks. ‘The pulse frequency corresponds to the height of the
fever.
In the course of the second week, edema of the face, particularly of the
eyelids, is characteristic. After several days this may disappear, but it often
returns in the later stages. The affection of the muscles is accompanied by
marked edema; the genital region often remains free.
Usually from the ninth or tenth day—sometimes earlier or later—with the
entrance of the embryo into the muscles, symptoms occur there. The affected
muscles are tensely swollen, as hard as wood, and very sensitive to touch or
pressure. In mild cases only the sensation of painful tension is felt, and the
patients are still able to walk about. In severe cases the slightest movement
is accompanied by the most intense pain; locomotion and standing are im-
‘possible. As a rule, the muscles of the extremities and particularly the flexors
are the most painful. In‘order to relax their muscles as much as possible the
‘severe cases assume a characteristic position: Permanent dorsal decubitus with
an acute angle contracture in the shoulder, elbow and wrist joint; stiffness
and muscular rigidity are observed in the masseters, in the muscles of the
‘neck and of the upper extremities. Implication of the muscles of deglutition
and of the tongue often causes great difficulty in swallowing. Hoarseness and
aphonia result from the involvement of the muscles of the larynx; and in
severe cases pain in the muscles of the eye is rarely absent. The mobility of
the eye-balls is affected, and this gives to the face a conspicuously rigid appear-
ance. In severe cases, the masses of trichine cause difficulty in respiration ;
extreme dyspneic conditions may develop with very severe asthmatic attacks,
and may be a direct cause of death.
Even at the beginning of the second week Kratz noted inactivity of the
diaphragm upon inspiration. The condition noted by Askanazy is very inter-
esting. This author found under the pleura pulmonalis and in the lung sev-
eral disseminated red flakes or points which closely resembled the punctiform
ecchymoses upon the human pleura. These were demonstrated to be young
trichinee which had formed emboli.
Changes in the skin are not rare. Besides edema, pruritus, measle-like
exanthems, and in the later stages acne, furunculosis, herpes, etc., appear.
The sweats which occur in the mild as well as the severe cases are particularly
annoying. Desquamation of the skin takes place in convalescence. Formica-
tion and cutaneous anesthesia have been observed in isolated cases.
Stubborn bronchial catarrh develops early. In the later stages hypostatic
and catarrhal pulmonary inflammations occur. In debilitated patients these
not infrequently cause death. a3
In general there are no characteristic changes in the cardiac activity. In
severe cases and in the later course of the affection thromboses develop, par-
ticularly in the lower extremities. The appearance of decided leukocytosis with
a conspicuous increase of the eosinophiles, which show an increase of from
30 per cent. to 60 per cent., is interesting. This demonstration has repeatedly
558 THE ANIMAL PARASITES OF MAN
aroused a suspicion of trichinosis which has been later confirmed. Perhaps
the eosinophilic cells originate from the polymorphonuclear neutrophilic cells
of the diseased musculature.
Lately, in isolated cases, the temporary absence of the patella tendon reflex
as well as anomalies of the electric contractility of the muscles has been deter-
mined.
The urine shows the usual characteristics of fever urine. Nonne and
Hopfner have recently called attention to the not infrequent occurrence of
parenchymatous nephritis. Menstrual irregularities are common in some
epidemics. In pregnant women abortion is not rare.
Insomnia is one of the chief complaints of the patient. The mind, as a
tule, is perfectly clear; only in severe cases associated with high fever does
delirium occur.
It is obvious that the nutrition must suffer, particularly in grave cases.
In mild cases the coursE of the disease is from one to two weeks; in all
other cases one to two months intervene before recovery takes place. Death
is not rare. The mortality varies in different epidemics. In Hedersleben the
mortality amounted to 29.8 per cent., in Calbe 21 per cent., in Burg 20 per
cent., in Klein-Quenstedt 14 per cent. In children a favorable course of the
affection is frequent; recovery often takes place at the end of the third week.
Complications are rare. The slight predisposition of children to trichinosis
may be accounted for, first, by the lesser activity of their gastric juice, and
secondly, by their more frequent fecal movements in consequence of which
large portions of meat containing trichine may be discharged.
At the aurorsy the intestines reveal but slight changes, and these consist
principally in a catarrhal condition of the small intestine. Swelling of the
solitary glands, of Peyer’s patches, and of the mesenteric glands is observed.
In the intestinal mucus, up to the seventh week, intestinal trichinz are found.
Spleen is normal or enlarged. Fatty liver is frequent. Heart muscles and
kidneys often show granular opacity. Fatty-liver and nephritis, according to
v. Linstow and Askanazy, are due to the toxic products of metabolism of the
trichine. The lungs usually reveal the signs of a marked bronchitis. The
bronchial mucous membrane is intensely reddened, and has a tenacious mucus
coating. In the lower posterior portions lobular hepatization is revealed;
rarely hemorrhagic infarcts or metastatic abscesses. The color of the muscles
often resembles “smoked goose breast”; the smaller muscles are much paler
and “wax-colored.” From the end of the fifth week macroscopic changes in
the form of pale gray strie of from } to 1 cm. in length may be recognized.
Upon microscopic examination these are seen to be dark, granular, detritus-
like masses. Granular and fatty degeneration, sometimes also waxy degen-
eration, are found in the surrounding muscle fibers. Not rarely giant cell-
like structures are noted. Nonne and Hopfner describe the appearance of
vacuoles in the muscle fibers. In the later stages this musculature dis-
appears to a great extent and is pale. The number of muscle trichine
may be enormous. The most intense permeation, according to Cohnheini,
is found in the diaphragm, in the intercostals, in the muscles of the neck,
of the larynx and of the eyes, of the biceps and triceps. In milder cases
NEMATODA, THREAD-WORMS 559
the presence of a single trichina may be demonstrated only after a search
of hours.
The PROGNOSIS cannot be determined in the early stages of the disease.
Severe, fulminant phenomena, especially on the part of the digestive appa-
ratus, are not necessarily followed by a severe course, as the diarrheal dis-
charges remove a portion of the infectious material. Cases which appear mild
at the onset may subsequently become very severe. After a course of three to
four weeks, those cases in which the patient retains a good appetite and the
ability to sleep, as well as the integrity of the respiratory organs and of the
heart, permit the hope of a favorable outcome. In children the prognosis is
more favorable than in adults from the onset.
During the prevalence of epidemics, the priaGNosis is more readily made
than in sporadic cases. :
Mild cases may simulate gastric catarrh and muscular rheumatism ; severe
cases resemble acute gastro-intestinal catarrh, and in their further course may
be looked upon as acute articular rheumatism. The edema, the painfulness
of the affected muscle groups, the impairment of respiration, are important
in diagnosis. The differentiation from acute progressive polymyositis is not
always easy. In doubtful cases it is well to search the dejecta, particularly
the intestinal mucus, for intestinal trichine. In severer infections the tri-
chine may certainly be determined by the excision of small portions of mus-
cle, which are best taken from the lower end of the biceps. Direct excision is
decidedly preferable to the formerly practised harpooning.
The aim of the PROPHYLAXIS should be the prevention of trichinosis in the
pig. Stall feeding of swine gives in this respect a certain protection, espe-
cially if care is taken never to feed them with uncooked offal. In regions
where trichinosis frequently occurs a thorough inspection and radical destruc-
tion of meat containing trichine should be obligatory. The keeping and fat-
tening of swine in slaughter-houses should be prohibited.
Man is best protected from the disease by eating only thoroughly boiled
or well-fried pork. The most intense smoking or pickling will kill the para-
site, but these precautionary measures are not everywhere taken. There may
-be exposure to infection, for example, upon a journey. The most important
preventive measure, therefore, is the erection of slaughter-houses and the
introduction of compulsory meat inspection. The microscopic demonstration
of muscle trichine is not difficult, and this may be carried out by thoroughly
competent meat inspectors. Absolute protection, naturally, cannot be con-
ferred by meat inspection if only a few muscle trichine are present. It is
well, therefore, to carefully abstain from partaking of any but thoroughly
cooked or highly pickled or smoked pork. ;
We are very rarely in a position to begin treatment soon after infection has
taken place, but, when this is possible, emetics and purgatives are advisable.
Theoretically, an attempt should be made to expel the infectious masses by the
‘administration of castor oil, calomel, etc. Experimentally, it is true, no re-
markable results have followed this or any other method of treatment. Neither
potassium, nor sodium picronitrate, nor oil of turpentine, camala, extract of
male fern, glycerin, etc., has prevented infection.
560 THE ANIMAL PARASITES OF MAN
Mosler, upon the basis of experimental investigation, has advised benzine:
B Benzolisccicvisvssesaciaaee gives ecew ines 6.0,
Mucil. gummi arab...... cece eee eee eee 25.0,
Succi Niquits +1. c.senereeeieceee eweue cee. 8.0,
Aqua menth, pip.......... ee eee eee eee eee 120.0.
M.D.S. Well shaken, a tablespoonful every hour or two.
Besides this Mosler advises daily for several days an enema to which is added
three to eight grams of benzine. In the main the treatment is symptomatic.
For the sake of completeness I shall mention among other nematodes the
eustrongylus gigas, Rudolphi, 1802, a parasite which is found in the renal
pelvis of the dog, the wolf, the fox, the horse, the marten, the otter, etc., and
has been observed in man in about nine different cases. The parasite has fre-
quently been confounded with other nematodes, with coagula of blood, or with
mucus. According to experiments conducted in the dog, the eustrongylus
causes severe difficulty in urination. The ova of the parasite may be recognized
in the urine. The strongylus paradoxus, Mehlis, 1831, has been even less fre-
quently observed in man.
Gnathostoma siamense, Levinsen, 1889, has up to the present been seen
‘by Levinsen only as one female specimen in a Siamese and in two other persons.
ANKYLOSTOMIASIS—UNCINARIASIS
One of the most important entozoa of man is the
Ankylostoma duodenale, Dubini, 1843.
The parasite was first Giscovered by Dubini in 1838 in Milan in a human
cadaver. Soon its occurrence was also noted by Pruner, Bilharz and Griesin-
ger in Egypt. The parasite was recognized by Bilharz and Griesinger on
account of its hematophagous properties as the actual cause of “ Egyptian
chlorosis,” which is so extraordinarily prevalent in Egypt.
Wucherer, in 1866,.recognized the parasite as the cause of “ tropical chloro-
sis.’ Its presence was soon afterward determined in the anemia of brick-
makers, which had been known for a long time in Italy. Parona, Perroncito,
Bozzolo found the parasite associated with the anemia which attacked the
workmen engaged in constructing the Saint Gothard tunnel, and looked upon’
it as the causal factor. Soon the proof of its connection with anemia mon-
tana which occurred in the Belgian, Sardinian and French mines in 1882 was
established. The occurrence of the parasite was recognized by Mencke in the
brickmakers in the neighborhood of Bonn, and a few weeks later by Leichten-
stern among the workmen in the brick fields at Cologne.
Since that time its occurrence has also been proven in the miners of the
Rhine provinces, Westphalia and Silesia, sometimes in wide distribution.
The male parasite is usually of a white, the females of a whitish yellow,
brownish-red, or reddish color. The length of the male averages from 7-11.2
mm., the thickness 0.46 mm.; the females are 16.5 mm. long and 0.63 mm. in
ANKYLOSTOMIASIS—UNCINARIASIS 561
thickness. The parasite tapers toward the anterior extremity. The intestinal
tract begins with a wide slanting mouth, turned toward the back and having
six papille ; it has a bell-like mouth capsule, upon the border of which are six
tooth-like chitin ridges. The posterior end of the body of the female termi-
nates in a short ten-pin-like point; that of the male is somewhat bent, termi-
nating in a broad umbrella-like ribbed bursa copulatrix, upon which frequently
two long spicula of about 2 mm. in length protrude. The bursa copulatrix
serves, on account of its contractile parenchyma ribs, as an apparatus, by
means of which the males attach themselves to the body of the female during
copulation. The female sexual opening is close behind the middle of the body,
and is continued as a short vagina. The parts next to the vagina contain the
impregnated ova. These have an oval shape and a smooth surface. Their
length is 0.063 and their thickness from 0.036-0.04 mm. They are present
in enormous numbers in the human dejecta and, according to the time in
which they have remained in the intestinal canal, 2 or
4-8 segmentation globules may be recognized. Further
development occurs only outside of the human organism.
For this development the ova require a temperature of
from 25° to 30° C., moderate moisture, and a surface
distribution. Under these circum-
stances, after three to four days at
the latest the embryo may be recog-
nized. After twenty-four to forty-
eight hours more, it finds its way
through the pole of the ova, and
shows active movements.
LISQ
La
cate
a
b
Fie. 54. — ANKYLOSTO- Fie. 55.—Ova oF THE ANKYLOSTOMA Fie. 56.— Larva oF
MA DvUODENALE: a, DvuopENALE IN Various STAGES OF ANKYLOsToMa Dvo-
male; b, female. DEVELOPMENT. DENALE.
The young larva is 0.2-0.25 mm. in length and 0.015—0.017 mm. in thick-
ness. The posterior end of the body gradually tapers anteriorly to a pouch-
like point. The short and narrow opening of the mouth, the spindle-shaped
pharynx, and the globular stomach may be distinctly recognized ; in the latter
a Y-shaped figure, composed of the three pharyngeal teeth, is found in active
movement. The intestine terminates in a fine tube, the anus. The embryo
soon begins to grow, and after having attained a length of 0.7-0.8 mm. it
encapsulates itself. The larva finally lies in a transparent sheath which uni-
formly surrounds it. The sheath protects the embryo from external damage,
so that for months in this encysted state it may retain its power of further
development. Introduced into the human intestine, after dissolution of its
chitin capsule in the small intestine, the parasite develops to maturity. Five
37°
562 THE ANIMAL PARASITES OF MAN
to six weeks after infection has taken place the first ova appear in the human
dejecta.
The parasites, as well as the symptoms which are included under the name
ankylostomiasis, have been found exclusively in those persons who labor in
any way in the earth; miners, tunnel workmen, brickmakers, laborers upon
fortifications, ete. The dejecta voided by an ankylostoma host are exceed-
ingly rich in ova, as shown by the interesting observations of Leichtenstern
in the brick fields of Cologne, and they are the source of infection for other
workmen. The fecal masses deposited in the outskirts of the brick fields, with
the gradual advance of the work contaminate the layers of clay and become
mixed with the water. Thus there is abundant opportunity for the importa-
tion of encysted larve. The workmen eat their meals with dirty clay-cov-
ered hands, and in their various manipulations of the clay and earthworks,
in cleaning their tools, in the use of drinking-water and water for other pur-
poses, there are numerous opportunities for the encysted ankylostoma to find
their way into the human organism. Miners and tunnel laborers, and espe-
cially the country population in Egypt, Brazil and other countries, infect
themselves in a similar manner. In the country, particularly, with its limi-
tations and the absence of systematic hygiene, there are numerous favorable
conditions for the propagation of the parasites. In a damp, flat country
where the earth is only slightly permeable and there is an absence of suitable
latrines, discharge of the dejecta filled with ova in the immediate vicinity of
laborers and living places must, under any circumstances, convey the germs to
the inhabitants and laborers. Loos recently called attention to the fact that
the young embryo may enter the human organism by means of the skin.
The number of parasites is frequently very great: One hundred, 500, 1,000
and more have been found in the small intestine. They are blood-suckers,
cat é€oxyv; and when we consider that their duration of life is. relatively
long-—Leichtenstern estimates the maximum at five years—and that repeated
infection in one and the same individual in infected regions is probably the
rule, we can clearly understand the effects of this parasite, which is a blood-
sucker.
Three to four weeks after infection the first symptoms appear. Besides
dyspeptic difficulties, these consist especially of colic, diarrhea, increasing
lassitude, disinclination to work, pallor of the face. Tinnitus aurium, ver-
tigo and cardiac palpitation are added. The continuous withdrawal of blood
in the course of weeks or months leads gradually to the most extreme symp-
toms of anemia. Edema, dyspnea, and attacks of syncope develop upon the
slightest bodily exertion. The dejecta, often even five to six weeks after infec-
tion, have a hemorrhagic appearance; they are grayish red, brownish red or
black. Usually the first hemorrhagi¢ diarrheic discharges occur from five to
six weeks after invasion of the larvae; during a time, therefore, in which the
parasites frequently change their situation for the purpose of copulation. In
the later course of the affection symptoms of extreme anemia develop in the
patients who have become bedridden.
The pulse is rapid and thready. The carotids show active pulsation. In
the heart, which is frequently enlarged to percussion, there are systolic mur-
ANKYLOSTOMIASIS—UNCINARIASIS 563
murs ; over the jugular vein distinct nun’s murmurs may he recognized. Oc-
casionally an organic cardiac affection develops. As a rule, there is a diminu-
tion in the number of red blood-corpuscles, the amount of hemoglobin is
decidedly. reduced; sometimes there is leukocytosis. The lungs are usually
normal, provided accidental complications are not present. The microscopic
examination of the feces shows, besides more or less altered blood cells, the
presence of countless ova which, as a rule, are uniformly distributed through
the entire fecal mass. Almost invariably Charcot-Leyden crystals are found.
The parasite itself is generally only detected in the feces after the administra-
tion of anthelmintics.
With increasing severity of the disease the patients show the distinct symp-
toms of progressive anemia. Edema develops in the extremities and in the
face, and to this are added frequent attacks of fever. Changes in the eye-
ground, edema of the papilla, and effusions of blood into the retina have
frequently been observed. In some cases bone pains are noted; Leichten-
stern in such a case observed simultaneously a decided enlargement of the
spleen.
The majority of the severe anemic phenomena may probably be explained
by the blood-absorbing properties of the parasite. The ankylostoma are, as it
were, luxurious blood-absorbers, since they nourish themselves only from the
blood-plasma, while the red blood-corpuscles leave the intestinal canal of the
parasite in an unchanged condition. The loss of blood by secondary hemor-
rhage from the wounds, particularly during the time in which the parasites
frequently change their position for the purpose of copulation, is perhaps
even greater than the amount of blood absorbed. lLussano, by very interesting
investigations, believes he has proven that the ankylostoma give off like other
entozoa toxic products of metabolism which have a deleterious effect upon
the blood. Ervant, Arstan, Verdun, Zinn and Jacoby and others have ex-
pressed the opinion that, besides a blood-sucking activity, there is probably a
toxic effect upon the blood which is an important factor in the origin of ane-
mia. Bohland has determined an abnormally great decomposition of albumin
in ankylostoma patients.
If the disease is not recognized, if there is no relief, the debilitated patient
suffers for weeks and months, and finally succumbs with the symptoms of
general marasmus; or intercurrent affections terminate life. Only rarely
does a change of climate and of the mode of life bring about a spontaneous
recovery. ;
The cadavers of patients who die of ankylostomiasis are usually but little
emaciated, provided the cases have been uncomplicated, but they are invariably
pale and waxy-yellow. The panniculus adiposus, the fat in the mesentery,
in the heart, and in the mediastinum, is often decidedly increased. The mus-
cles are pale; general dropsical phenomena, including hydrothorax and
hydropericardium, are common. There is marked anemia of all organs.
The heart muscle is often dilated, hypertrophied, pale or grayish-brown. The
liver and spleen are more or less atrophic, and occasionally show amyloid de-
generation. Similar changes are often noted in the kidneys. The small intes-
tine is in some cases decidedly narrowed, the colon sometimes shows signs of
564 THE ANIMAL PARASITES OF MAN
chronic catarrh. In the duodenum, but especially in the jejunum and the
upper portion of the ileum, there are numerous small punctiform ecchymoses.
If the necropsy is carefully conducted, an extraordinary number of red-stained
ankylostoma are occasionally found. These ankylostoma have gained en-
trance into the mucosa, and cannot be removed without a certain amount of
force. At the point of adherence the mucosa reveals ecchymosed red plaques
of a punctated, dappled appearance which vary in size from a five-cent piece
to a half-dollar. It is more difficult, as a rule, to find the males than the
females, because the former have a more delicate structure, and are therefore
less noticeable in the mucus. The mesenteric glands are sometimes enlarged.
Masius and Francotte found that the bone-marrow of the long tubular bones
was grayish red; occasionally it is rich in fat and is, therefore, more yellow.
Numerous medullary cells and nucleated red corpuscles are found upon micro-
scopic examination.
Secondarily other entozoa have been found: Among them anguillula in-
testinalis and stercoralis ascaris lumbricoides, oxyuris vermicularis and tenia
saginata.
The aim of prophylaxis is, first, to prevent the entrance of the parasite
into regions not yet affected, and, secondly, to limit its spread in the infected
areas. To attain the first object, in the future no workmen should be em-
ployed in brickyards, in mines, in tunnels, and other earthworks until their
state of health has been carefully investigated, and their feces microscopically
examined for the presence of ankylostoma ova. Furthermore, the workmen
should be taught that if necessary care is exercised in constructing privies
the contamination of working places with infected dejecta from an accumula-
tion of feces can be entirely prevented. Those who know the habits of labor-
ers and their carelessness as to where they discharge their feces, will under-
stand that even most stringent hygienic rules will be imperfectly carried out.
The best prophylaxis, therefore, consists in employing only healthy workmen,
i.e., those not infected with ankylostomiasis.
If ankylostomiasis has been diagnosticated by examination of the feces,
the patient must enter the hospital, and undergo treatment for the expulsion
of the parasite. Leichtenstern, who has probably had the largest experience
in Germany in the treatment of ankylostomiasis, advises the administration,
without preliminary treatment, of the ethereal extract of felix mas which he
gives in a dose of ten grams. The drug is given after breakfast. From one
to two hours later a suitable dose of castor oil is administered to the patient.
The entozoa voided with the dejecta will have been killed. If, in the course
of a few days, ankylostoma ova are still found in the feces, the same treatment
must be repeated, a second or even a third time, until the ova are no longer
detected in the feces. Bozzola advises thymol (2 to 10 grams per day) ; other
authors also look upon this drug as a useful anthelmintic. It is evident that,
on acccount of the extreme anemia, a symptomatic treatment for this condition
must in many cases be employed during convalescence.
v. Linstow recently described a representative of the genus physaloptera,
physaloptera caucasica n. spr., as a parasite of man. This was found by v.
Linstow in the previously mentioned helminthic collection.
ARTHROPODA 565
Blanchard recently called the attention of physicians to the occurrence of
some varieties of gordius—small, elongated, thin worms having the shape of
filarie—as occasional parasites of man. He spoke particularly of the gordius
aquaticus, gordius argillaceus and gordius medinensis, which live in fresh
water, notably in the springs of mountainous regions. They are introduced
into the human intestinal tract by drinking-water, as well as by the ingestion
of fruit, and are finally voided. In all about seven transmissions have been
observed.
Almost as rare in man is the occurrence of the acanthocephala, a nematode-
like parasite without intestines whose anterior end is armed with a proboscis.
The echinorhynchus gigas, Goeze, 1782, is found in great numbers in the
small intestine of swine. According to Leuckart its presence in man has been
proven in a few cases. Lambl once observed the echinorhyncus hominis. It
has been shown by artificial infection experiments that echinorhyncus monili-
formis, Bremser, 1819, may occur in man.
Hirudines have been observed as occasional parasites of man, and may be
transmitted to man. Even now they are frequently used for medicinal pur-
poses. Among them have been noticed: Hirudo medicinalis, Linné, 1758,
Hirudo troctina, Johnston, 1816, Hirudo ceylonica Bl., Limnatis nilotica,
Savigny, 1820. These are found upon the skin or in the oral cavity of man,
and soon begin their blood-sucking activity.
ARTHROPODA
The arthropoda, particularly the arachnoids, the spiders and the insects,
are found in great numbers as parasites of man. Owing to their manner of
life they appear chiefly as ectoparasites. To these belong the
Leptus autumnalis, Shaw, 1790.
The so-called gooseberry or harvest acarus, which is 0.3-0.5 mm. long,
and of a reddish color, lives in great numbers through the summer in immature
forms on grass and shrubs, and occasionally as parasites upon man and other
mammals. The ova of the trombidium holosericum, which are conspicuous
in many gardens by their red color, are deposited in June or July. From these
a larva develops which we recognize as the leptus autumnalis. This larva bores
into the skin with its head and produces a severe cutaneous inflammation with
itching which may be relieved by washing with soap, by inunctions with bal-
sam of Peru, or 5 per cent. of carbolic solution or benzine.
Similar varieties of acarus such as tetranychus molestissimus, Weyen-
bergh, 1886, pediculoides ventricosus, Newport, 1850, tarsonemus intectus,
Karpelles, 1885, pygmephorus uncinatus, Flemming, 1884, have been found in
workmen who had handled Indian, Bulgarian or Russian grain, and suffered
from an itching skin eruption. Other varieties of acarus cheyletus eruditus
(Schrank, 1781), and tydeus molestus (Monig) which are found in rags,
stables, and tobacco stores, also attack man and give rise to distressing itching.
The dermanyssus avium (Dugés, 1834), the bird acarus, is better known.
It occurs in chickens, pigeons and in our song birds when kept in cages; it
566 THE ANIMAL PARASITES OF MAN
occasionally becomes parasitic in man, and produces very intense itching,
erythema and eczema. The acarus which is found in swallows, dermanyssus
hirudinis, Hermann, 1804, also occasionally becomes parasitic in man.
Of the ticks the ixodes ricinus Linné, 1758, is parasitic in man. The para-
site lives upon low bushes and generally attacks sheep, cattle, dogs, cats, and,
not rarely, also man. The female bores with its proboscis deeply into the
skin to suck blood. It is necessary to exercise caution in removing the insect,
as the proboscis tears readily, and if left in the wound causes inflammation.
The application of benzine, petroleum, or oil of turpentine readily removes the
parasite.
Not quite so harmless is the bite of the argas reflexus, Fabricius, 1794.
It lives in woodwork or masonry, and in some regions attacks pigeons. It
occasionally becomes parasitic in man. The parasite produces local inflamma-
tion and also certain general symptoms, among which are nausea, pyfosis, diar-
thea, irregular heart action and dyspnea. The poison is said to be contained
in the powerfully developed salivary glands. The bite of the argas persicus,
Fischer de Waldheim, 1824, and of the argas tholozani, Laboulbéne et Még-
nin, 1882, which live in Persia, is said to be dangerous. In the tropics still
other members of the family of argas are known (such as the argas turicata
Dugés, argas chincha, Gervais, etc.), which occasionally attack man and pro-
duce disagreeable symptoms. Of the family of the tyroglyphides only the
tyroglyphus farine, de Geer, and the tyroglyphus siro, Linné, the tyroglyphus
longior, Gervais, are to be mentioned as occasionally parasitic in man. More
important, on account of the extent of its distribution, is the family of sar-
coptes : m
Sarcoptes scabiet, Linné, 1748.
The knowledge of scabies dates back to antiquity. Aristotle was appar-
ently acquainted with the organism. But although the insect was familiarly
known for centuries, its natural history having been correctly described and
depicted, its parasitic character was not recognized, and the itch was looked
upon as a disease produced by an acrimonia sanguinis. This opinion became
the prevalent one. It was not until 1834, when the completely forgotten art
of catching the acarus was revived, that the pathology of the itch was recon-
structed, and the acarus generally recognized as the cause of the affection. It
is hardly necessary to give here a description of the acarus. A microscopic
preparation of the acarus may readily be obtained; in a patient with the itch
we look for a large pit which may frequently be seen with the naked eye.
This pit is seen upon the hands as a blackish line, and upon the trunk as a
whitish punctated line. At the end of this groove, where a whitish discolored
point may be recognized, the epidermis should be carefully removed with a
cataract needle, and the insect, which has been laid bare, can be extracted and
put upon a slide.
We can easily recognize upon the head the scissors-like jaw feelers with
which the impregnated female cuts or bores its way into the epidermis. Grad-
ually it’ penetrates the deeper layers of the rete Malpighii. The bite is fol-
lowed by the deposit of an exudate between the cutis and the newest epidermis
ARTHROPODA 567
layer from which the acarus is extracted; decided itching immediately arises,
perhaps in consequence of the discharge of an irritating fluid. Boring its way
transversely from without inward to deposit its eggs, the acarus makes a pas-
sage parallel with the first to the surface of the skin. From the eggs, about
50 in number, deposited in this passage an embryo develops, which after from
four to seven days makes its own opening to the external skin. After a short
time it again bores its way into the skin to pass through a desquamation proc-
ess, which is repeated several times, and about fourteen days later it appears
as a mature insect upon the skin. The male does not bore its own opening,
but only hollows out a funnel-like groove in which it lives.
The transmission of the acarus from man to man occurs occasionally by
means of clothing, but, as a rule, by intimate contact with the diseased skin,
and in almost every case by sleeping with a scabies patient. Among the
poorer classes, therefore, a scabies patient is likely soon to infect the entire
family. The disease is often spread by prostitutes.
The acarus is apt to attack the flexor surfaces of the joints of the hand
and fingers, the interdigital folds, the lateral surfaces of the fingers; in chil-
dren with a delicate skin the palm of the hand, the surroundings of the elhow-
joint, the anterior axillary fold; and in women the nipple. The navel, the
skin of the penis and scrotum, the trochanter region, the flexor of the knee
and the internal border of the foot are attacked. The acarus also prefers all
those portions of the body upon which the underclothing is tight. The face
and hairy scalp are rarely attacked. Samisch has described a case in which
scabies gave rise to severe inflammation of the eyes (“ keratitis,’ “ Biischel-
form ’’).
The irritation from the itching which the parasite produces by its burrow-
ing in the skin is very acute, especially at night, for at this time, stimulated
by the warmth of the bed, the mite nourishes itself. The affected individual
attempts to relieve the irritation by vigorous scratching. Not only are the
small nodular efflorescences produced by the parasites irritated by this scratch-
ing, but, in addition, new papular elevations are formed at the exit of the hair
follicles, and small vesicles like millet seeds with purulent contents. Contin-
ued scratching causes new eruptions, while the older ones are torn away, and
become covered with striew-like blood crusts, from which finally ulcers covered
with eschars develop. Marked pustular eruptions often follow even in young
people and eczema develops in all those who suffer for a long time from the
disease. The diagnosis of scabies may readily be made from the localiza-
tion of the excoriations, as eczema upon the nipple, upon the fold of the axilla,
upon the penis, ete.
A peculiar picture resembling the mange of animals is produced by scabies
norvegica s. crustosa. This shows a thick, dirty-gray induration composed of
deposits of epidermis upon the palm of the hand, on the sole of the foot, on
the elbows, on the face and the hairy scalp. These indurations contain the
parasites and their ova often in enormous numbers. According to Fiirsten-
berg this form of scabies is due to the smaller sarcoptes scabiei crustose,
Fiirstenberg.
The disease usually develops typically in one and a half to three months
568 THE ANIMAL PARASITES OF MAN
after infection. The eczema due to scratching has by this time spread over
the entire body; the longer the disease lasts the more marked it becomes.
Aside from the irritation and the loss of sleep due to this, no further symptoms
arise.
Spontaneous recovery does not result, but recovery from scabies in the
course of concurrent febrile diseases is noted as the consequence of the death
of the parasite. The ova, however, do not always die. Therefore, after recov-
ery from the disease, the itch frequently reappears.
The piacnosis is easy. The location of the efflorescences is particularly
characteristic. We can hardly err in making a diagnosis of the itch when
a markedly itching cutaneous eruption is characterized by the presence of
isolated nodules, particularly upon the anterior surface of the trunk and ex-
tremities, of small vesicles upon the fingers and interdigital folds, in the palm
of the hand and on the sole of the foot, with pustules upon the fingers, espe-
cially in young people, in whom eczema shows itself chiefly in those areas
between the nipple and the knees for which the parasite shows a preference,
The diagnosis becomes certain by the discovery of the acarus grooves, or of
the parasite itself. In all doubtful cases microscopic investigation is necessary.
Prurigo and scabies are often confounded. Leaving out of consideration
the time and place of development of the first prurigo efflorescences, prurigo
differs essentially by the localization of the eruption. This is found chiefly
upon the lower extremities, especially upon the extensor surfaces of the trunk,
but never upon the flexor surfaces of the joints.
After scabies has been recognized in an individual, it is wise to examine
carefully all other members of the family, and to treat simultaneously all
who are affected. ' The aim is to kill the parasite and heal the eczema. In
former times, when the parasitic nature of the itch was not yet understood,
the disease was looked upon as almost incurable; we can to-day rapidly cure
the affection by a number of remedies such as sulphur, tar, naphthol, balsam
of Peru, styrax, petroleum, ete.
It is sufficient to mention a few among the great number of prescriptions:
F Florum sulphuris, ) _-
Olei fae, t aa Pee ene 20.0
Saponis viridis, Pe
Axungie porcine, BA eo etlanl a se eoe Runs 40.0
UTeue Alle oe uceuseumer weet ere eeee 15.0
or B Styracis liquidi, 2
Paras nines ¢ Bis. W Ws WR ae een lava lacece 20.0
BONIS CIM cso oe Guay wdouww@rwedur cece 40.0
Vaselini, pe
Crete albe, t ee arn 10.0
or B B-Naphtholi, baa
Crete albe, BOS soa shes 6 69 ok ears wi Ss MER OR 10.0
MAMOMIS “VIE 4 rx seid eieke ease tiseeean 50.0
AZUMI POTN. rsciscreasvsseceecenas 100.0
ARTHROPODA 569
or i Siyraeig Mowidds vacsscesesweeevwvanre ccs 25.0
SPINS YIN see ve hui ung deweaneeiay 10.0
let “GL yeriiieyaio ed evens wie oancbar eau 65.0
When there is no eczema the best results will be obtained with inunctions
of balsam of Peru. The patient takes a bath in which he rubs himself briskly
with green soap. After an hour, when the skin has become entirely dry,
balsam of Peru is rubbed into the entire surface of the body. About ten grams
are sufficient for this purpose. The next day the same process is repeated.
After forty-eight hours the patient takes another bath, which completes the
process.
In the majority of cases it is well to give a bath to soften the epidermis
before beginning the actual treatment. In private practice I prefer, as a rem-
edy for scabies, the above-mentioned naphthol salve, which on the first day is
twice rubbed into the body and completely allays the itching during the suc-
ceeding night. If the itching should return, a third inunction is given upon
the second day. The patient is able to follow his ordinary occupation. It
is best for him to wear woolen underwear as the salve will less readily adhere
to this. Upon the sixth day a bath completes the antiscabies treatment. If
there is eczema this necessitates further therapeutic measures upon which I
cannot here enter.
The “rapid cures” were formerly much in vogue. In this treatment the
patient is put in a warm bath and is rubbed with black soap. The bath should
last an hour and a half and be followed by an inunction of
JF} Sulphuris citrini......... cece eee eee eee 10.0
Potassee subcarbonati........ ccc cece wees 1.0
ASUN SID e204 eee Oren eae hee ose RIS 40.0
This finishes the treatment. Sensitive persons readily react to this, as well
as to other rapid cures, by an eruption of eczema.
Certain forms of scabies occur in various domestic and wild animals, in
the horse, the sheep, the goat, the camel, the llama, the pig, the dog, the fox
and the lion. These parasites occasionally attack man.
According to Carron du Villards, there are two varieties of acarus in the
Antilles which may infect the eye. Fischer saw a decided inflammation of
the eye produced by a chicken louse (lipeurus variabilis, Nitzsch) which had
found its way into the conjunctival sac. According to Mégnin, another acarus,
the holothyrus coccinella, Gervais, produces in birds a dangerous disease,
which, when transmitted to man, causes itching of the skin and inflammation.
Another acarus, called by the inhabitants of the Antilles the arador, burrows
into the skin of the eyelids, forming brown, tortuous furrows which may be
recognized with the naked eye. Its presence produces severe itching.
An acarus nephrophages sanguinarius has been found by Miyake and
Scriba in the hemorrhagic urine of a Japanese. How important this acarus,
which is said most closely to resemble the dermatocopter communis, may be,
cannot at present be determined. The significance of the
Demodez folliculorum, Simon, 1842,
570 THE ANIMAL PARASITES OF MAN
is still debated. This acarus lives in the hair follicles in comedones and in
the glands of Meibomius in the skin of the face of man. In the dog, the pig,
the cat, and in cattle, hair follicle acari have been observed and are said to be
varieties of the parasite of man. The views of authors are divided as to the
importance of this parasite as a causative agent of disease. We incline more
and more to the opinion that it is one of the harmless parasites, and that its
occurrence in acne pustules is of no pathogenic significance. Nevertheless,
it is found with extraordinary frequency—according to Hunsche even in 92.5
per cent.—in the sebaceous glands of perfectly healthy individuals. The clin-
ical conception formulated by Raelmann of blepharitis acarica can no longer
be maintained. The acarus is found with great regularity in the ciliary folli-
cles of normal, as well as of abnormal, eyelids.
Of the linguatula, or tongue worms, which are elongated, vermiform, flat-
tened or cylindrically curled worms whose head is armed with an elliptical
chitin mouth and two retractile claws, one is parasitic in man. This is the
Pentastoma tentoides, Rudolpht, 1810.
The sexually mature parasite lives in the nasal cavity, the forehead bones
and jaw of the dog, the wolf, the horse, the mule, the goat, and, occasionally, also
in man. The eggs discharged with the nasal mucus contain embryos which
reach the open air where they are taken up by such animals as rabbits, hares,
cattle, horses, etc., and also sometimes by man. They penetrate the intestinal
wall, and reach the liver where they become encysted. For a long time the
larva pentastoma denticulatum, Rudolphi, was taken for an independent para-
site. After a certain time the larve may wander further, and in this way
reach the respiratory tract, especially the nose. In other cases infected organs
are eaten by carnivora. The larve which reach the intestinal tract finally
find their way to their preferred points of lodgment. Man unquestionably
infects himself in a similar manner. The pentastoma either accidentally
Su the nose or is introduced into the intestinal canal by contaminated
ood.
The sexually mature form is rarely met with in man. Laudon found the
parasite in a locksmith, who suffered for years from jaundice and gastric dis-
turbance, and later from epistaxis. Usually the larva (the pentastoma den-
ticulatum), when observed in man, is found particularly in the liver, the lung,
the spleen and small intestine, the peritoneum, the heart muscle and the
kidneys. Special symptoms are not present in these cases. The pentas-
toma can be diagnosticated only when they give rise to irritative symptoms
in the nose or its auxiliary cavities or when their ova are found in the
nasal secretion.
Pruner was the first to find in the liver of two negroes the
Pentastoma constrictum, v. Siebold, 1852.
Observations regarding the occurrence of this parasite are very scanty.
Tt appears that when present in great numbers it may be the cause of fatal
peritonitis.
Ve
ARTHROPODA 571
In conclusion I must mention the
INSECTS
which are parasitic in man, and I should first like to consider the réle which
they play in the transmission of infectious diseases. The reports concerning
this are scanty and widely scattered.
From the interesting investigations of Nutall it appears that it is only
rarely that anthrax, chicken cholera and mouse septicemia are transmitted by
bed-bugs and fleas, probably because the insects which absorb the microérgan-
isms with their sting, soon rid themselves of them. It cannot, however, be
denied that by crushing the sucking animals which contain these microérgan-
isms in their blood, and by scratching at the point of the bite, these germs may
be conveyed to man. But it must be remembered that the infectious germs
which are present in the dejecta of bed-bugs and fleas lose their toxic proper-
ties very rapidly. This is especially noticeable in fleas.
Plague bacilli, transmitted to bed-bugs and fleas, appear to die in the
intestinal canal of these insects. The danger lies in the fact that if any one
crushes an insect thus infected, and the bite is then rubbed or scratched, the
bacilli may be transmitted. It is certain from the experiments or Simmond
that flies which have fed upon the dejecta or the bodies of cholera patients take
up cholera germs, and transmit them to food. Relapsing fever spirilli taken
into the intestine of -bed-bugs appear to die with relative rapidity. The imme-
diate inoculation of apes with bed-bugs that have sucked themselves full and
have been crushed, has been followed by positive results. Typhoid bacilli may
apparently be carried by flies. It has been further proven that flies may take
tubercle bacilli into the intestinal tract. The bacilli have been found in the
dejecta (fly specks) upon walls, in closets, and on doors. It is not unlikely
that in regions where leprosy exists it is transmitted by means of sarcoptes.
The bubo disease, Egyptian ophthalmia, and conjunctivitis blennorrhoica may
be transmitted by flies. Favus and impetigo are said to be transmitted by lice.
That infectious diseases are transmitted to man by means of the ixodes is more
than doubtful. The rdle played by the ixodes bovis, Riley, 1869, or the bodph-
ilus bovis, Curtis, 1890, and by the tsetse fly in Texas fever, the tsetse fly
disease, has not come within the range of our observation.
Of the parasitic insects I shall only refer briefly to the head louse (pedicu-
lus capitis, de Geer). This parasite is distributed over the entire world. It
generally lives upon the hairy scalp, but in cases of great uncleanliness also
infects other parts of the body. The ova of the head louse are rarely found
in the cilia. From the excrement of the lice which is conveyed to the con-
junctival sac by the hands, conjunctivitis and blepharitis may apparently be
produced. In cases of stubborn head eczema, especially in children, the pres-
ence of lice should invariably be looked for. It is known that plica polonica
usually develops from a preceding pediculosis capitis with accompanying
eczema. The plica polonica (Polish plait) must be removed with the scissors.
To exterminate lice, washings with vinegar, petroleum, or corrosive sublimate
(1-1,000) and combing the hair by means of a fine comb are advisable. The
scalp should then be painted twice daily with Ziett-Lassar zinnober salve:
572 THE ANIMAL PARASITES OF MAN
BR Hydrargyri sulfurati rubri...........-eee eee 1.0
Sulfuris sublimati ......... eee ee ee eee 24.0
Olei bergamotte: ..... ec cece e eee eee ee tenes gtt. xxv
Vaselini flavi, ads... cece cece cee cee eect e eres 100
In children, Joseph advises:
Be Acidi salicylict ...... 0. cece ee eee eee eee teens 1.0
Tincturse benZ0eS..... 0.6 cee eee eee eee eens 2.0
Vaselini flavi, ad..... 0... cece cee cee erences 50.0
to be rubbed into the scalp twice daily.
The clothes louse, pediculus vestimenti, Burmeister, lives upon the throat,
neck, and trunk of man. The eggs are deposited in the lanugo hair of the
skin, as well as in the underclothing. The bite of the louse causes severe
itching, and by scratching strie-like wounds are produced. If the condition
exists for a long time, open wounds and ulcers of various kinds appear, and
finally a permanent pigmentation of the skin which is particularly noticeable
in those areas in which the clothes are worn close to the body. So-called lousi-
ness is produced by the abundance of the clothes louse. Cleansing the clothes
and disinfecting the same, and washing the body with vinegar or petroleum
will rapidly remove the disease.
The body louse (phthirius inguinalis, Redi, 1668) is most frequently found
in the hair surrounding the pubes. Thence it is distributed over the trunk
to the axillary cavity, into the beard, into the cilia and into the eye-brows,
but is very rarely found upon the hairy scalp. The exanthem produced by
scratching is usually found in corresponding places. The macule cerulee,
composed of reddish brown flakes, which are found upon the anterior lateral
aspect of the thorax, on the upper thighs and buttocks, are of a peculiar char-
acter, and are probably produced by a poison contained in the salivary gland.
The parasite may be removed by inunctions of gray salve followed by a bath.
Inunctions with balsam of Peru or white precipitate salve will also rapidly
remove the parasites. The phenomena produced by bed-bugs (cimex lectu-
larius, Merrett, 1667, cimex ciliatus, Eversmann, 1841, cimex rotundatus, Sig-
noret, 1851) and those produced by the flea, pulex irritans, Linné, 1758, are
sufficiently well known.
The sand-flea (sarcopsylla penetrans, Linné, 1758) has lately become of
more interest to Germany on account of its appearance in the colonies. Carried
from its home in South America to West Africa, the parasite has gradually
spread itself from west to east, until it reached German East Africa. By
1897 it became a land plague in Uhehe.
After the female (the male lives independently) has bored its way under
the toe-nail, it appears on the first day as a small harmless point, and may
easily be removed without pain. Early removal is the only protection from
serious consequences ; it is therefore advisable to inspect the feet daily, and this
is the more necessary in infected regions, as the sand-flea at first causes no
symptoms. :
ARTHROPODA 573
In eight to fourteen days the posterior portion of the abdomen of the para-
site swells to the size of a pea. It contains from 60 to 100 eggs. After depos-
iting the eggs the parasite dies. By incautious manipulation in its removal
or by other trauma which affect the toes and cause the abdomen of the para-
Vic. 57.—SarcoPpsyLLa PENETRANS, Sanp- Fig. 58.—SarcopsyLLa PENETRANS, REMOVED
FLEA, PRIoR TO ITS ENTRANCE UNDER THE FROM A WOUND OF THE NAIL.
Nai or THE Tor.
site to rupture, the ova are liberated, and stubborn ulcers develop which, if
neglected, cause the loss of the toes. Wound infection not rarely complicates
the further course. The parasite should be removed by carefully lifting it
out with a dull forceps.
FLY LARVZ (Maggots)
Fly larvee are occasionally observed as parasites in man. The mother ani-
mals belong to the family of cestrides or of the muscides, the actual flies. The
clinical picture produced by larve is known as myiosis externa or interna s.
intestinalis.
In Europe myiosis externa is mostly produced by the larva of the muscides,
more rarely by the larva of cestrides. For the latter the larva of the hypo-
derma bovis, de Geer, or hypoderma diana, Brauer, are responsible. In the
tropics the gadfly boil of man is due to the dermatobia noxialis, Brauer, or the
ochromyia anthropophaga. As soon as the eggs of these flies have been depos-
ited upon the skin, the larve pour forth, bore into the skin, and in the course
of a few months cause the affection which is known as the “ gadfly boil” of
cattle, of the stag and of the roe. In cattle larve are taken up by the mouth
and finally find their way under the skin; whether the same course is followed
in man has not yet been proven. Recovery occurs spontaneously, by the
egress of the parasites, or by surgical opening and extraction of the larve
from the carbuncle-like cutaneous swelling. Krautner observed a dipteren
larva in an isolated location. He extracted a larva of the hypoderma bovis
from the anterior chamber of the eye.
The occurrence of cestrus larve in the digestive apparatus of man has not
574 THE ANIMAL PARASITES OF MAN
yet been determined with certainty. Some authors, however have thought
that they produce another disease, the “ creeping disease.”
In the hot summer months it is noticed—the number of cases observed is
still limited—that upon the uncovered portions of the body irregular, serpen-
tine, linear elevations appear, which never branch, and these give rise to itching
and burning, and cause a red elevation, slightly raised above the skin. The
line is elongated, and tapers rapidly to a point (1-15 cm. in twenty-four
hours). Occasionally at intervals of from 1-2 cm. small nodules are notice-
able, which have been declared to be the fecal mass discharged by this insect.
That the disease is caused by an animal parasite is certain. The parasite itself,
which has been thought to be a gastrophilus larva, has not yet been zoologically
and definitely determined.
The majority of affections of myiosis externa are caused by muscides
larve. In Europe it is particularly the sarcophila Wohlfart, Portschinsky,
1875, in America the lucilia macellaria, Fabricius, 1794. Those persons are
most endangered who sleep in the open air and who suffer from any purulent
process: Pus from the ear, nose, or similar affections. The fly is otherwise
extremely timid and never enters living rooms, but is attracted by pus and
deposits its eggs. The larve, which soon come forth, cause remarkable de-
struction by their enormous appetite. Entering the auditory passages, they
eat the external covering, penetrate the tympanic cavity, and pass through
the Eustachian tube into the pharynx. Great destruction is wrought in
the nose and its auxiliary cavities, where ulcers and purulent wounds are
produced. Autopsy findings confirm the extraordinary virulence of these
parasites.
In the conjunctiva, in the oral cavity, even in the urethra and the bladder,
maggots have occasionally been observed. Formerly, before the introduction of
antiseptic surgery, maggots in wounds were not very uncommon; to-day they
appear only in such as are grossly neglected. Besides the parasites mentioned
above, in man larve of calliphora vomitoria Robineau-Desvoidy, cimex limen-
sis, sarcophaga carnaria, Meigen, musca cadaverina, musca domestica, musca
stabulans, and others have been observed.
I should like to say here that numerous occasional parasites, such as gal-
leria mellonella, dermestes lardarius, geophilus sodalis, geophilus hortensis,
thousand-leggers, have been removed by physicians from the nose. Laboulbéne
mentions a case in which the gammarus pulex was vomited. This by no means
exhausts the number of the occasional parasites.
For their removal, corrosive sublimate injections and chloroform or turpen-
tine mixtures are advised.
The myiosis intestinalis is a much-debated parasite. Although numerous
well-observed cases of this kind are on record, the presence of the larvae of flies
in the digestive apparatus is still doubted. We shall touch lightly on these
doubts which are nowise justified. Those that have been observed up to now
are the larva of musca vomitoria, musca domestica, musca nigra, musca cor-
vina, musca pendula, musca meteorica, calobata cibaria, hydrothorea meteorica,
sarcophaga affinis, sarcophaga carnaria, sarcophaga hemorrhoidalis, sarcoph-
aga hematodes, anthomyia canicularis, anthomyia scalaris, etc.
ARTHROPODA 575
On account of the myriads of flies about our houses and their habit of
resting preferably upon food where they deposit their eggs and on account of
the great production of fly larvee in water, it is quite remarkable that larve
of flies do not more frequently reach the gastro-intestinal canal of man. There
are many avenues by which the larve of the anthomyia varieties which de-
posit their ova in salad, radishes, berries, etc., may reach the intestinal canal.
Many of the larve are destroyed in the digestive tract, or do not find the condi-
tions suitable for their existence, but they generally possess such extraordinary
resistance as to be able to withstand the digestive process.
There is no specific symptomatology. In the history of these patients
complaints of nausea, tendency to vomit, vomiting, sour eructations, more or
less severe pain in the epigastrium, and attacks of colic may appear. At one
time there is constipation, at another time diarrhea, with or without blood.
Severe spasmodic attacks, cramps, sensations of fear are observed, which cease
at once when the larve are passed. There are no sequels, however, as the ex-
istence of the parasite is so brief. The larve are voided per anum with the
stools or by the mouth in vomitus; sometimes more than one hundred larve
are discharged.
As soon as the discharge of larve has been recognized, an attempt should
be made by therapeutic measures to effect the speedy removal of the parasite.
If the larvee are still present chiefly in the stomach, they may be removed
by lavage. In naphtholin (0.5-1.0 in single doses, up to 5.0 as a daily dose
for adults) we no doubt possess a remedy which causes the death of the larva,
that is, brings about their rapid removal.
Besides those mentioned, there are a number of other insects which are “ oc-
casional” parasites of man. I need mention here only the different varieties
of flies, mosquitoes, wasps, bees, hornets, ete., which occasionally attack man,
and by their sting cause marked pain. G. Braun has lately reported the bite of
poisonous spiders (Latodectus lagubris) which may bring about serious symp-
toms. The bite of the tarantula is harmless, but that of scorpions causes
severe inflammatory cutaneous symptoms. In conclusion, it must be men-
tioned that various caterpillars supplied with hairs containing retroserrates
and spinules may cause severe irritative phenomena upon the skin, the con-
nective tissue, the corium and iris. Gray or grayish yellow nodules the size
of a lentil, being round or oval, form in the iris and subconjunctival cellular
tissue. Laudon mentions that in girls inflammation of the sexual apparatus,
swelling of the labia and leukorrhea may be caused by the hairs of caterpillars,
and also that the toxic substances contained in the cavities of the hairs of
caterpillars may, by penetrating or tearing the human skin, produce severe
irritative phenomena.
For the relief of the bites or stings of insects, painting with sal am-
moniac, ichthyol, or ichthyol salve or the application of ichthyol plaster, is
advised.
The severe affections of the eye produced by the hairs of caterpillars re-
quire the extraction of the hairs which have entered; in iritis, atropin and
warm compresses. Unfortunately, the prognosis is not favorable. The cuta-
neous irritation may be lessened by vaselin or inunctions with lanolin.
576 THE ANIMAL PARASITES OF MAN
LITERATURE
R. Leuckart: ‘Die Parasiten des Menschen,” II. Aufl., Leipzig, 1886-91.
Braun: “ Die thierischen Parasiten des Menschen,” II. Aufl., Wurzburg, 1895.
Huber: “ Bibliographie der klinischen Helminthologie,” Jena.
Mosler und Peiper: ‘‘Thierische Parasiten.” ‘‘ Nothnagel’s specielle Path. u. Ther.,”’
VI. Bd., Wien, 1894.
E. Peiper: Ergebnisse der allgemeinen Pathologie und pathologischen Anatomie,
III. Jahrg. ‘Thierische Parasiten des Menschen.”
E. Peiper: “ Die Verbreitung der Echinokokkenkrankheit in Vorpommern,” Stuttgart,
1894.
E. Peiper: ‘Fliegenlarven als gelegentliche Parasiten des Menschen,” Berlin, 1900.
38
TOXICOLOGY
IMPORTANT POISONS AND THEIR TREATMENT
By R. v. JAKSCH, Pracuz
Ir is a difficult undertaking to confine within the limits of an article all
the data of importance in the study of the poisons with which the practising
physician is likely to come into contact.
In modern clinical medicine, the conception of poisoning must be very
widely extended. The amount of material to be considered is enormous, be-
cause every pathogenic agent which finds entrance into the human organism,
including also every contagium vivum, may produce toxic action. This great
group of poisons, the endogenous toxicoses, we shall not here consider, but
shall content ourselves with the discussion of the exogenous toxicoses which
are most important to the physician.
In the definition of the word poison, we are at once confronted with diffi-
culties which need not be further dwelt upon. Our object is to consider a
number of symptoms; and the treatment of a series of diseases all of which
are due to the introduction within the body of certain well-known chemical
agents from without. These agents include the acids, the alkalies, the metal-
loids, the metallic salts, gases, bodies that belong to organic chemistry, such
as the fat derivatives, bodies of the aromatic group, the camphors and balsams,
the alkaloids, the glucosides, bitter and indifferent bodies, the toxalbumins
and, finally, vegetable and animal poisons, the composition of which is only
partially known to us.
From this almost endless series it is apparent that we cannot describe all
of the pathologic pictures produced by these poisons, but it will be our object
to take, as an example, an important representative of each of the previously
mentioned groups, and describe its effects.
We will first direct our attention to the acids. The pathologic processes
produced by these poisons may very properly be designated as acidosis. The
differences between these acids and in their composition, if we include the
organic and inorganic varieties, are parallel with the difference in the clinical
picture which develops after their introduction into the human organism.
As the type of acidosis, I shall consider inorganic acid, sulphuric acid, and
shall discuss the important symptoms of this poison as acidosis. I may re-
mark that I choose this particular acid for the reason that this acid toxicosis
is observed with relative frequency by the physician.
There can be no doubt that by the introduction of large amounts of acids,
nervous symptoms may be produced; but symptoms of this kind are rarely
observed at the bedside, as the local symptoms produced by the acid toxicosis
579
580 IMPORTANT POISONS AND THEIR TREATMENT
completely dominate the scene. Those acids whose corrosive effects are less
prominent, as, for example, hydrochloric acid, may show nervous symptoms
which can be referred to the acid, but even this is relatively rare. If an indi-
vidual takes large quantities of free acid, e. g., sulphuric acid, what symptoms
are produced? The deeply invading eschars which cover all parts of the
mucous membrane are characteristic, particularly in those areas which are
brought in contact with the acid in deglutition. Severe retching and the
vomiting of brown pulpy masses, excessive pain in the gastric region, intense
burning in the esophagus, and marked salivation, are the immediate conse-
quences of such a toxicosis. The vomited material has an acid reaction;
within a few hours the symptoms of marked renal irritation develop.
If the amount of acid which has reached the stomach is relatively large,
and the acid is concentrated with the continuance of vomiting, symptoms of
perforative peritonitis soon appear, due to the erosion of the walls of the stom-
ach by the acid, and the patient succumbs in a short time, often within a few
hours. But even if the amount of acid swallowed was not large, days, even
weeks, must elapse before the eschars heal. Dysphagia, salivation, pain on
deglutition continue, and often fever follows, the wounds which have been
produced by the acid becoming the point of entrance by which pyogenic organ-
isms find their way into the body. An important fact is that all poisonings
with corrosive acids, even in cases which apparently run a mild course, may
lead to stricture of the esophagus; indeed this is an almost invariable result.
Of course the frequency of stricture depends on the variety of the acid. Poi-
soning by sulphuric acid almost always produces this symptom, nitric acid
less frequently, hydrochloric acid relatively seldom, but there can be no doubt
that strictures also occur from hydrochloric acid toxicosis. They are less often
seen after poisoning with organic acids, such as acetic acid, ete., perhaps be-
cause poisoning with concentrated solution of these acids is relatively rare.
An important symptom which must be discussed is renal irritation caused
by acid toxicosis, which, in my experience, often leads to the typical signs of
acute toxic nephritis. Acid nephritis may occur in all acid toxicoses; most
frequently, however, we meet with it after poisoning with sulphuric acid.
The symptoms are exactly the same as in acute nephritis due to other causes,
but I must emphasize the fact that edema does not accompany this form of
nephritis, and, furthermore, that dissolved hemoglobin frequently appears in
the urine.
The prognosis in poisoning with acids should always be considered grave,
as, even in the mildest cases, it can never be asserted at the onset that stricture
of the esophagus, which is invariably so dangerous, may not develop. Even
with judicious treatment, stricture may result in under-nutrition, or in actual
starvation with all its consequences.
In regard to the diagnosis, the fact that an acid toxicosis is present may
be readily determined from the markedly acid composition of the vomited
material, and from the previously described eschars. We must determine with
which acid we are dealing by a testing for the presence of that acid to which
the pathologic picture points. If, for example, the eschars are yellow or yel-
lowish, it may be presumed that nitric acid was the toxic agent. If the mucous
ACIDS’ 581
membrane looks as though it had been scalded, hydrochloric acid should be
thought of ; deeply invading, leather-like eschars are peculiar to sulphuric acid
toxicosis, white eschars are peculiar to tartaric acid, ete. The presence of the
special acids must, however, be proven by chemical analysis, the consideration
of which is not permissible within the scope of this article. Examinations of
this kind should, if possible, be made by each physician for himself, But we
cannot demand that the practising physician make these tests for himself be-
cause complicated chemical apparatus is necessary, and therefore I limit myself
in this article to a few general indications. Certain inorganic acids, such as sul-
phuric acid and nitric acid, may be very readily determined; the proof of the
presence of hydrochloric acid is more difficult, since it is normally present in
all stomach contents. But in most cases it is sufficient to demonstrate by
titration with an alkali a large amount of free acid in the vomited material.
Regarding the therapy, our sovereign remedy is milk, which possesses in a
high degree the power of acid neutralization; if this is not immediately at
hand (for rapidity of action is the most important and first requisite in the
treatment of acid toxicosis) then soap suds is to be administered; solutions
of albumin are also advisable; of drugs as antidotes, magnesia usta in water
is advisable, also lime water. The severe pain which these poisonings cause
justifies the use of opiates, morphin and cocain. Unfortunately, painting the
mucous membranes with the last-named remedies has repeatedly proved disap-
pointing to me.
Lavage of the stomach in such cases necessitates great care; lavage of the
stomach in poisoning from sulphuric acid, particularly, involves certain dan-
ger to the patient, for it cannot be denied that by such a process a gastric
perforation may be produced. It must also be remembered that even the act
of washing out the stomach in such patients produces severe pain, and other
forms of distress.
I must briefly describe those acid intoxications which, on account of their
not infrequent occurrence and their clinical picture, occupy a special position,
and, therefore, have certain interest for the physician. These are poisoning
by oxalic and prussic acids.
We shall first describe oXALIC ACID ToXIcosIs. Oxalic acid itself, above
all its salts, which are used for polishing metal ware, and to remove ink spots
from the skin, is in common use, and is a frequent cause of this toxicosis.
Oxalic acid and its salts produce like.mineral acids a corrosive effect upon
the mucous membranes which is shortly followed by a considerable reaction
and subsequent inflammation in the surrounding area; there results a picture
which more closely resembles poison by alkalies than by acids (see below).
The nervous symptoms which invariably appear in the course of poisoning
from this acid, such as convulsions, trismus, and tetanic attacks, are quite
noteworthy. In other cases, however, very threatening symptoms, oliguria and
anuria, become prominent as signs of severe acute toxic renal insufficiency
due to infarction of the kidney with calcium oxalate. _
The prognosis in this form of poisoning is always serious; and in all cases
a threatening clinical picture results. The diagnosis may be made from the
symptoms sketched above, and is usually easy. It becomes certain, however,
582 IMPORTANT POISONS AND THEIR TREATMENT
only when it is possible to demonstrate oxalic acid or its salts in the excre-
tions, above all, in the vomited material. In cases of poisoning, in which we
have the relatively slight corrosive effects which oxalic acid produces, energetic
gastric lavage, best of all with lime water, which changes oxalic acid and its
soluble salts into insoluble calcium oxalate, may be resorted to; lime water
may also be given internally. The use of sucrate of lime has been especially
praised.
As with oxalic acid toxicosis, a special position has been assigned to poi-
-soning with Prussic acip. In concentrated solution it is one of the most vio-
lent poisons known, and in the course of a few minutes causes death. With
a loud cry, the person poisoned collapses, the respiratory frequency rises enor-
mously, convulsions occur, and in a few minutes death results; so rapid is the
course that the physician rarely has an opportunity of attempting relief. If
there is time, immediate washing out of the stomach, with the addition of
hydrogen peroxid, is, at all events, in place; subcutaneous injections of atro-
pin, etc., have been advised, but, in the main, we are compelled to say that in
severe cases of poisoning therapy is ineffectual, and only in the mild cases may
we count upon success.
We now turn to the second group of poisons, that of the alkalies, salts of
alkaline metals, and metalloids. We shall describe only three forms of poi-
soning, namely: 1, Lye toxicosis; 2, poisoning with potassium chlorate; 3, poi-
soning with salts of barium.
Next to poisoning with sulphuric acid, unquestionably poisoning with LYE
is undoubtedly most often observed by the physician. We never get poisoning
by pure caustic soda, or pure caustic potash, but with mixtures which contain,
besides these bodies, potassium carbonate and other salts, i. e., with fluids which
are called in commerce soda solution and caustic soda.
What symptoms follow the introduction of these substances by the mouth?
In a short time vomiting of glassy, smeary, soap-like masses occurs and
may continue for hours, or even days; the vomited material has an intensely
alkaline reaction, and later often assumes a brown to brownish-red color due
to decomposed hemoglobin. The patient is tortured by great pain, particu-
larly upon deglutition, the areas of the mucous membrane which have come in
contact with the caustic substance appear softened, oozing, swollen, and cov-
ered with pseudo-membranes which desquamate in a few days, and then cause
the dreaded formation of strictures, particularly in the esophagus. Peritonitis,
due to perforation of the stomach by the corrosive action of the alkali upon
its walls, may also appear. The result of poisoning of this kind is always
serious, and in apparently mild cases the possible sequel of stricture of the
esophagus renders the prognosis unfavorable. I may add that alkalies, ceteris
paribus, give rise to stricture in decidedly slighter concentration than acids.
_ The treatment consists in the immediate neutralization of the alkali, which
is best accomplished by a lemonade containing tartaric acid. Prompt gastric
lavage is contraindicated on account of the danger of perforation of the
stomach; on the other hand, on account of the severe pain, the use of mor-
phin and other opiates will be necessary. Cocain has here been as ineffective
as in the treatment of acid toxicosis,
ALKALIES, SALTS OF ALKALINE METALS, AND METALLOIDS 583
Of special importance in this group of poisons is poTasstuM CHLORATE ;
hence we shall briefly consider it. The drug is of special significance for the
physician, as poisoning by its medicinal use has been frequently observed in
the last few years. The quantity of the salt necessary to bring about this
condition varies very widely in different individuals. The lethal dose in chil-
dren is from 5 to 6 grams and in adults 15 grams or more.
This toxicosis differs particularly from poisoning by alkalies in that there
are no local corrosive effects.
Such patients, however, show extreme cyanosis, they complain of a sense
of burning and oppression in the chest, the skin assumes a yellowish hue,
hemoglobin (hematin) appears in the urine without any other sign of nephritis.
In the further course of the affection there are severe nervous symptoms, such
as clonic and tonic spasms followed by delirium and then by deep coma; in
this condition the patient succumbs. Moreover, there are undoubted cases of
poisoning in which the typical symptoms of acute nephritis appear, and the
patient dies of uremia.
The prognosis is always dubious; but recovery may occur even in the
severest cases.
The diagnosis is made more certain by the demonstration of methemoglobin
in the blood, and proof positive is the presence of the salt in the fluid obtained
by gastric lavage. If the amounts introduced were very large, the character-
istic vapors of chlorin gas are at once given off upon the addition of hydro-
chloric acid. The treatment requires immediate and thorough washing of the
stomach, and the avoidance of the introduction of acids, for the latter generate
in the stomach a very dangerous chlorin gas. The use of enemata is also indi-
cated to eliminate the poison which perhaps may already be present in the
lower portions of the intestine.
A few words in regard to the COMBINATIONS OF BARIUM.
All of the soluble salts of barium are very poisonous! Even the insoluble
barium carbonate may be changed in the stomach into the soluble barium
chlorid, and then have a toxic effect.
The principal symptoms are: Severe pain in the abdomen, profuse diar-
thea, signs of acute nephritis and an entire host of nervous phenomena.
The therapy consists in immediate gastric lavage and in the administration
of magnesium sulphate and sodium sulphate.
The prognosis is very grave!
I have included this form of poisoning because the barium salts are reme-
dies which enormously increase blood pressure, and therefore barium chlorid
has been employed in place of calomel in disturbances of cardiac compensation.
The severe symptoms of this poisoning, I might say the absolute impossi-
bility of relying upon the action of these salts, forces me to advise against
their use, even should these salts, as heart tonics, find eulogists in the future.
We now proceed to another group of poisonous agents, the metalloids.
The first to be considered are chlorin, bromin and iodin, with their combina-
tions. Only two of the CHLORIN COMBINATIONS are of practical importance,
namely, chloral hydrate and chloroform. The first is used as a hypnotic ;
but it is not a harmless remedy, since upon long-continued use it may give rise
584 -IMPORTANT POISONS AND THEIR TREATMENT
to psychical depression, and according to all appearances, to progressive paral-
ysis ; and, moreover, in persons affected with disease of the heart, even in rela-
tively small doses (2 to 3 grams) it may cause death. We should, therefore,
be most cautious in the use of this remedy, sometimes so necessary, for exam-
ple, in the treatment of certain forms of delirium tremens! In cardiac dis-
eases, particularly, the use of chloral hydrate is contraindicated !
The second remedy to be discussed is chloroform. Every one knows the
blessing of its effect, and it is to be hoped that the physician may be spared
any exhibition of its deleterious action during his professional career!
Chloroform is a potent cardiac poison, and the sudden deaths in narcosis which
occur from time to time may be referred to this circumstance. There can be
no doubt that chloroform narcosis may produce permanent damage to the
organism, such as fatty degeneration of the heart and of the liver, and for
this reason our motto must be: Be cautious in the use of chloroform, whether
employed as an anesthetic or internally! JI shall not detail the symptoms.
These are generally known. Fatalities can never be entirely prevented in
chloroform anesthesia, but careful, minute investigation of the heart of the
patient who is to be anesthetized with chloroform will certainly limit them to a
great extent. We must hope that the time is not far distant when less dan-
gerous anesthetics will be substituted for chloroform narcosis. A beginning
has already been made in this direction by Schleich’s infiltration anesthesia.
In the second halogen, the BRoMIN saLTs shall be briefly mentioned ; these
are extensively used in medicine, and thus cause the development of that
pathologic picture which we appropriately designate as bromism. Although
we cannot avoid using the salts of bromin in the treatment of epilepsy, and
although recent observations have shown that the administration of the salts
of bromin in food free from chlorin or, at least, almost free from it, is rela-
tively well borne, on the other hand we cannot deny that, particularly in pre-
disposed individuals, even the therapeutic use of bromin may cause serious
symptoms of bromism. It is possible that the administration of bromin in
sesame oil may mitigate these symptoms, but it cannot be expected to prevent
their appearance entirely. The symptoms are anorexia, metallic taste, dys-
pepsia, decided emaciation, dermatoses of many varieties; also a series of
psychical and nervous disturbances, particularly loss of memory, and these
may lead to the development of the severest psychical symptoms. The sALTs
OF I0DIN act in a similar manner, except that here, as a rule, emaciation,
I might say all the somatic symptoms, take precedence of the psychical
element.
We now turn to another of this group of poisons, to PHosPHORUS, which,
at least in Austria, assumes uncommonly great importance, for, in certain
cities—especially in Prague, next in Vienna, less frequently in the country—
the number of poisonings by this agent, which, in the course of the year, come
under the observation of the physician, is an unusually large one. Almost
exclusively the cases are suicidal, although the poison is often taken to bring
about abortion. But the clinical picture of poisoning by phosphorus has
additional interest from the fact that a number of other toxicoses, even a num-
ber of diseases for the most part infectious, present or may present a picture
METALLOIDS 585
resembling poisoning from phosphorus. Mushroom poisoning (which see)
is an example of such toxicosis, and, of other diseases, acute yellow atrophy of
the liver.
What symptoms are produced by poisoning with sticks of phosphorus?
A few hours after the ingestion of the poison, nausea and a tendency to vomit,
more rarely actual vomiting, appears; the patient is uncommonly restless;
jaundice, which may occur upon the first or the second day after the poison-
ing, indicates the severity of the intoxication. Usually we see decided enlarge-
ment of the liver, which may even appear a few hours after the poisoning.
The evidences of the hemorrhagic diathesis and fever are added to this, and
in a few days the patient succumbs from his suffering. In the majority of
cases of poisoning with phosphorus it is fatty degeneration of the heart which
causes death. The later jaundice appears, the more favorable the prognosis;
a good appetite, or even a sensation of hunger, is a favorable sign in the course
of phosphorus toxicosis. In the severe cases the urine contains: Biliary col-
oring matter and albumin; not rarely, if large amounts of grape sugar be
administered to the patient, sugar is also present; that is, an alimentary glyco-
suria arises, a symptom which, according to my experience, is intimately con-
nected with the changes produced in the liver by this toxicosis.
What is the best treatment for phosphorus poisoning? I know of but
one reliable remedy: Thorough gastric lavage performed at once. The earlier
and the more actively this is carried out the more certain the result; never-
theless, even cases in which enormous amounts, up to 0.7 gram, of phos-
phorus have been taken may terminate in recovery, as is shown by a case of
my own. I also use sulphate of copper, solutions of old oil of turpentine,
hydrogen peroxid, and potassium permanganate, and I must admit that these
agents produce certain favorable effects, but, as a sovereign remedy in the
treatment of poisoning from phosphorus, they do not equal gastric lavage, in
which 30 to 40 liters of water may be used, and this should be continued until
the fluid no longer has the faintest smell of phosphorus. The chemical proof of
phosphorus in the vomited material or in the feces is very easy: Two pieces of
filter paper are moistened, one with a solution of nitrate of silver, the other
with a solution of lead acetate; both are then dipped in the material to be
tested. If the silver nitrate portion, owing to the reduction of salt of silver,
shows a black discoloration, this proves that phosphorus is present. When
the lead portion becomes black the result is uncertain, for then the reaction
may have been brought about by hydrogen sulphid, and this is particularly
prone to occur if the feces are examined. If the test is positive, i.e., if the
lead portion is not blackened, certain proof is furnished that poisoning by
phosphorus is present. I must remark here that a positive result in the test
of the feces always renders the prognosis unfavorable, for this reaction shows
that the phosphorus has passed through the entire intestine, and so has in all
probability been taken up into the organism. In such cases we must endeavor
to eliminate the phosphorus from the intestine as rapidly as possible, the best
means being by the administration of an infusion of senna. Much that is
interesting regarding phosphorus poisoning might still be mentioned, such as
the relations between poisoning by phosphorus and acute yellow atrophy of
586 IMPORTANT POISONS AND THEIR TREATMENT
the liver and certain forms of mushroom poisoning, but, unfortunately, these
are beyond the limits of this article.
Some reference must be made to chronic phosphorus poisoning which is
the terror of the workman in the manufacture of phosphorus matches; and
presents itself in the form of a phosphorus necrosis of the lower jaw. In
Austria, on account of the excellent hygienic measures enforced by the super-
vision of the Government, this form of the disease has become a rarity.
We now turn to another agent, suLPHUR and its combinations, of- which
poisoning by sulphureted hydrogen and carbon bisulphid are the most im-
portant.
Poisoning with sulphureted hydrogen is rare, but occurs most frequently
in chemical laboratories and among workmen in latrines. If the gas is pres-
ent in great amounts, and the air is, therefore, relatively deficient in oxygen,
the affected individual soon shows the severest symptoms, and rapidly perishes.
In less severe cases there is debility, weakness and vomiting occur, followed
by fibrillary muscular contractions, ete. Generally this form of poisoning is
of slight importance. On the other hand, poisoning by carbon bisulphid
occurs more frequently, and leads to very interesting changes in the retina
which until recently have been but little studied.
We now turn to a very important toxicosis, that of aRsENIC and its com-
binations.
All soluble combinations of arsenic are poisonous! The symptoms vary
according to the amount of the poison ingested, the ready solubility or insol-
ubility of the substance, and the state of the stomach; if taken on a full
stomach the phenomena appear less rapidly than on an empty stomach.
In the severest form, asphyxia arsenicalis, symptoms arise which very
closely resemble the clinical picture of cholera Asiatica and in a few hours may
cause death. I refer to such symptoms as vomiting, diarrhea, rice-water-like
stools, and cramps in the calves of the legs; in less severe cases the same symp-
tom-complex is produced—although less rapidly—and the symptoms of toxic
enteritis (purulent stools, tenesmus, etc.) are more prominent.
A positive diagnosis can only be made when arsenic is found in the vom-
ited material and in the excretions, for which purpose it is necessary to de-
termine the presence of arsenic by positive methods, and to isolate it: If
arsenious acid has been employed, an accurate microscopic investigation will
occasionally demonstrate that this substance is present: The white particles
are extracted with a forceps from the vomited material, rinsed with water,
and dissolved in hot water; upon cooling, the characteristic small octahedra
of arsenious acid are found as crystals.
_ What must be done in the treatment of this condition? The answer is
this: Immediate and thorough lavage of the stomach, administration of cal-
cined magnesium in water, also washing out the stomach with this preparation
and the administration of Bunsen’s remedy, namely, hydrated oxid of iron;
if at hand, lime water may be employed ; by frequent and copious enemata, the
intestine must be emptied, and the poison thus expelled from the bowel.
Chronic arsenic poisoning is very interesting on account of the extreme
cachexia, the severe nervous disturbances such as polyneuritis, etc., and the
METALLIC SALTS 587
very peculiar cutaneous melanoses to which these conditions lead and which
have lately been much studied. The therapy must be strictly adapted to each
individual case. It is impossible to enter into its details.
Poisoning by arseniureted hydrogen must be briefly referred to. This
is, of late, not rare in chemical laboratories and in chemical factories. The
cases Tun a severe course, but frequently terminate favorably. Jaundice,
hematuria, various spasms form the most important symptoms, i. e., the course
is entirely different from that of poisoning with the salts of arsenic! The
therapy consists only in strict prophylaxis: Avoidance of all chemical proc-
esses in open spaces in which arseniureted hydrogen can possibly develop.
We now turn to another form of toxicoses: Poisoning with metallic salts,
metallism. From the enormous number of metallic salts which could be men-
tioned here, I shall only emphasize poisoning with lead and mercury as of
practical importance.
Acute poisoning with salts of lead is, upon the whole, of comparatively
slight interest, but much more important are the chronic LEAD TOXICOSES.
Regarding the former, a metallic taste, a sensation of dryness and burning
in the mouth and throat, and severe colic-like pains are the most important
symptoms; later obstinate vomiting occurs, and the vomited material often
shows a hemorrhagic discoloration. A diagnosis of acute poisoning with the
salt of lead cannot be certainly made from these symptoms, but the presence
of lead salts in the vomited material, the history, the corpus delicti, i.e., the
investigation of the salt which may be at hand, the fluid, etc., render the
diagnosis of acute lead poisoning possible. The immediate administration of
milk, of solutions of albumin, of sodium sulphate and magnesium sulphate
which reduce lead combinations to an insoluble lead sulphate, is recommended.
It is most important for the physician to recognize chronic lead poisoning,
partly because of the frequency of its occurrence, and partly because it mani-
fests itself in such various ways.
Lead poisoning from occupation, as in type-setters, painters, gas-fitters,
etc., is usually preceded by symptoms of lead colic: The patients are seized
with paroxysms of severe cutting pains in the abdomen, an attack in its great-
est intensity rarely lasting longer than a quarter of an hour, and after a
shorter or longer interval the severe paroxysms of pain set in anew. The
abdomen is retracted, there is constipation, the pulse is slow. The physician
must act at once. A lukewarm bath will often relieve the paroxysms of pain
in the briefest time; but the patient should not be allowed to suffer, and if
this is not effective, morphin subcutaneously should be employed; 0.005 gram,
certainly 0.01 gram, hypodermically employed, will in a short time relieve
the attack. But the serious symptoms of chronic lead toxicosis can only be
averted if the patient, in the future, carefully avoids contact with combina-
tions of lead or working with salts of lead. If he fail to do this, the first
attack is succeeded by a second, a third, etc., and the serious tragedy of chronic
lead poisoning begins. Bs Se
Sometimes, besides the pale appearance, the excruciating pains i the
joints (arthralgia), paresthesia, various disturbances of sensation torment the
patient; in many cases he is spared these symptoms, but weakness in the
588 IMPORTANT POISONS AND THEIR TREATMENT
hands occurs, the hands are moved with difficulty, or, finally, can no longer
be extended: The unfortunate condition of bilateral radial paralysis develops
(wrist-drop). Sometimes the havoc ceases there; no other symptoms appear ;
but radial paralysis renders the patient incapable of working for a long time,
and frequently for life.
The condition becomes more serious if there is evidence of grave cere-
bral disease; symptoms of encephalitis, epilepsy, mania, briefly, mental dis-
turbances of all kinds, indicate how seriously this poison influences the brain.
Because of these disturbances the prognosis is very serious; and unless dis-
ease of another organ, consequent upon this toxicosis, particularly the lead
kidney, terminates the life of the unfortunate patient, the insane asylum is
likely to be his final resort.
The terrible nature of lead poison is thus apparent, and yet I have men-
tioned but a few signs of this toxicosis. It must be added that metabolism is
most unfavorably influenced by lead, in that it leads to an increased forma-
tion and excretion of uric acid, and thus produces symptoms which are also
observed in arthritis urica (gout).
What remedial agents does therapy furnish with which to combat these
conditions, and what treatment must be adopted if the phenomena described
have already appeared? Regarding the first point, only a careful prophylaxis
is in order. Workmen in lead who have once recovered from lead colic must
always change their occupation; the dangers to which they are subjected
must be fully explained to them, and they should be induced to seek other
means of support which do not bring them into contact with combinations
of lead. If, however, the unfortunate symptoms are present, i.e., radial
paralysis, we may attempt to improve the condition by the employment of
electricity, massage, particularly vibratory massage, also by the administra-
tion of preparations of iodin, such as sodium iodid, iodipin (10 per cent.
solution), and furthermore, by the use of baths. In the main we must admit
that in radial paralysis, encephalitis, epilepsy, ete., due to lead toxicosis, we are
almost powerless.
A word regarding the diagnosis. In the characteristic “lead line,’ the
peculiar bluish discloration of the mucous membrane of the mouth in those
areas in which the teeth are implanted in the jaws, we have a cardinal symp-
tom of lead toxicosis. It is true this symptom may be explained in many
ways, since various factors, for example, tooth powder which contains wood
charcoal, chronic mercury poisoning in workmen in iron and iron salts, may
produce a symptom which sometimes very closely resembles this. Hence a
diagnosis should never be made from the lead line alone. If, however, other
symptoms, particularly colic, favor the view that we are dealing with lead
toxicosis, the presence of the lead line may be considered to confirm this diag-
nosis, the more so as the chemical proof of lead in the secretions, for example,
: the urine, is frequently negative, particularly in the late stages of the
isease.
In practical importance mercurial poisoning may be placed side by side
with saturnine poisoning. Since the soluble combinations of mercury have
been utilized as antiseptics in therapy, the number of cases of acute as well as
METALLIC SALTS 589
chronic poisoning by mercury has been enormously increased, although re-
cently, since the recognition of the danger in this antisepsis, the number has
been lessened by a more judicious use of mercury.
All salts of MERCURY are poisonous! It is true the number of poisonings
which have been observed, for example, with mercuric sulphate, with mer-
curic iodid, ete., are exceedingly small in comparison with the number of
poisonings with corrosive sublimate, the hydrargyrum bichloratum corrosivum
(mercuric chlorid). These should not be confounded with mercurous chlorid,
calomel, which, in much smaller doses, also has a toxic effect. I saw a case in
which six grams had been taken with suicidal intent, yet it was followed by
recovery in a few days. The lethal dose of chlorid of mercury in our popula-
tion is about 0.2 gram; I say in our population, because the opium smokers
in China can bear enormous doses of corrosive sublimate.
In acute toxicosis with mercury, therefore, we shall discuss only the clin-
ical symptoms produced by corrosive sublimate. In the chronic form we shall
concern ourselves more or less with all of the salts, and metallic mercury,
even the fumes of mercury, will be taken into consideration.
What are the symptoms of poisoning by corrosive sublimate?
If the poison—as in the majority of cases—is introduced through the
mouth, widely distributed eschars at once appear upon those areas of the
mucous membrane which have come in contact with the poison. Violent vom-
iting appears; the vomitus is admixed with blood, and later with shreds of
mucous membrane. Colicky pains and profuse diarrhea follow, there is sup-
pression of urine or else but a small amount of hemorrhagic urine is voided.
Even at this stage a fatal termination may ensue; the subnormal temperature
and the small pulse with low tension indicate the approaching end. Usually,
however, the sufferings of the patient are decidedly prolonged. The deeply
penetrating eschars cause agonizing pain. Ulcerative stomatitis, parotitis,
annoying salivation increase the distress. Gastritis and ulcerative enteritis
with all of their consequences supervene. The symptoms on the part of the
kidney become more intense. The scanty urine shows the characteristics of
acute nephritis. After days of misery the patient succumbs to uremic
toxicosis.
In all cases of poisoning with corrosive sublimate the prognosis is serious.
Even apparently mild cases may develop acute nephritis and terminate fatally.
For certainty in diagnosis the presence of mercury must be proven in the
vomited material, in the urine, and perhaps in the feces. In a number of
cases the history and the typical symptoms will at once indicate the correct
diagnosis.
The therapy consists in immediate and thorough lavage of the stomach
with milk and solutions of albumin. Table salt increases the solubility of
corrosive sublimate and therefore cannot be employed. Stomatitis is to be
treated with solutions of potassium chlorate, the anuria with lukewarm baths
and by venesection. The severe pain necessitates the use of opiates.
We now turn to chronic mercurial poisoning. This occurs most commonly
among workers in certain industries.
I should like here to emphasize the fact that mercurial treatment care-
590 IMPORTANT POISONS AND THEIR TREATMENT
fully conducted and based upon a correct diagnosis has never produced in any
patient the symptoms of chronic mercury toxicosis!
The symptoms in the beginning resemble those of lead poisoning: pallor,
dyspepsia, the appearance of a black line upon the gums (see p. 588), but the
typical colic of lead poisoning is absent. The patient emaciates. Diarrhea,
stomatitis and salivation, and various dermatoses, such as erythema, eczema,
furunculosis, and ulcers of the skin, appear. Nervous symptoms, such as
tremor and polyneuritis, follow. These are the signs of increased psychical
irritability (erethismus mercurialis), and finally, severe psychical depression
(coma). All this makes the life of the patient miserable, and may shorten
it. But a greater danger consists in the fact that the kidney may be attacked,
and after years of invalidism the patients often succumb to the symptoms of
contracted kidney or of chronic nephritis, and even without nephritic symp-
toms some patients may succumb to marasmus preecox relatively early in life.
The prognosis in the first stages, in case no nephritic symptoms are pres-
ent, is not unfavorable; in the later stages, particularly if psychical disturb-
ances have appeared, it is always serious. In treatment, preparations of
iodin and bromin (sodium iodid, iodipin, etc.) are most efficacious. Sulphur
baths are also used. With intact kidneys, pilocarpin, in the form of subcu-
taneous injections, may render good service.
We now turn to another chapter: Poisoning with gases.
For the physician only CARBONIC OXID poisoning has acquired great im-
portance. This toxicosis offers a fruitful field, and it is necessary for him
to be acquainted with its pathology and therapy.
Illuminating gas, which contains from 7 per cent. to 10 per cent. of car-
bonic oxid gas, and the fumes of charcoal, which contain about 0.2 per cent.
to 0.4 per cent., are the sources of this poisoning, the former by the presence
of the gas in rooms where it is in use, the latter by the escape of charcoal fumes.
Danger may therefore arise from defective or misused gas fixtures and from
badly constructed stoves, and in case of fire.
Of the initial symptoms of the poisoning little is known. Vomiting occurs
frequently in this stage, and often, if the patient be unconscious, the entrance
of food or vomitus into the trachea may cause death by suffocation. In the
stage at which the physician usually arrives, the patient is unconscious, pro-
foundly asphyxiated. The temperature is low, cardiac action weak and irregu-
lar, the pulse quickening, and in a few hours death occurs. Elevations of
temperature up to 102.2° F., and nervous irritative symptoms, such as trismus,
tonic and clonic spasms, are not rare. Because of the anesthesia coincident with
coma, patients may be severely burned during treatment. The sequels which
may follow this toxicosis are particularly serious. These are chorea, polio-
myelitis, trophic disturbances of all kinds, gangrene, etc. Metabolism is also
seriously deranged ; alimentary glycosuria is an invariable symptom and spon-
taneous glycosuria frequently occurs.
The diagnosis is easy on account of the characteristic symptoms. For the
detection of carbonic oxid in the blood I advise the examination of blood
obtained by venesection. A portion should be diluted with about 20 times
as much water, and then boiled with caustic potash. If carbonic oxid be pres-
FAT BODIES 591
ent the solution becomes first turbid, then of a light red color. Normal blood
under these circumstances always assumes a dirty brownish hue. The pres-
ence of carbonic oxid hemoglobin in the blood, determined by the spectroscope,
may also facilitate the diagnosis.
The treatment of this condition may be considered as fairly established.
The sovereign remedy is profuse venesection with a subsequent normal saline
infusion. This is to be followed by a lukewarm bath with cold affusions.
I have rarely found it necessary to proceed to the latter measures, for since
I have treated every case of carbonic oxid toxicosis by venesection and
normal salt infusion—whether by accident or as an actual result of therapy
—in my hospital service I have lost no case of carbonic oxid toxicosis. In pri-
vate practice,“ however, I had two cases of carbonic oxid poison, illuminating
gas, which ran their course with very peculiar nervous symptoms and after a
duration of several days terminated fatally. Chronic carbonic oxid poisoning
is a result of inhaling for a long time an atmosphere which contains slight
amounts of carbonic oxid. Dyspepsia, anemia, jaundice, splenic tumor, and
various symptoms of a nervous nature form the interesting pathology of this
toxicosis.
We now proceed to the discussion of poisoning by those substances which
belong to the fat bodies—the methane derivatives.
The number of these derivatives is legion. Those interesting to the physi-
cian are few: namely, poisoning with ethyl alcohol, with sulphonal, trional and
tetronal.
ETHYL ALCOHOL is one of the most violent poisons. We may say that
there is no organ, no cell of the human organism, which is not subject to
deleterious influence from alcohol.
Even a single acute intoxication with alcohol, a debauch, may cause incal-
culable harm and lead to severe damage of the organism. It may give rise to
a long-continued gastric catarrh, to symptoms of polyneuritis and of renal
irritation—although thousands and thousands of cases of acute alcohol
intoxication do not produce such serious consequences. The symptoms of alco-
hol intoxication are: At first a stage of exaltation, with a series of nervous
symptoms, among which spasms, which are observed particularly in infancy,
must be emphasized. This is followed by deep coma, in which the patient
succumbs to the toxicosis. The greatest enemy of such patients is cold, and a
low external temperature not infrequently causes death.
The treatment of acute alcohol intoxication consists in the immediate
washing out of the stomach and the employment of lukewarm baths with cold
affusions. Cutaneous irritants, such as sinapisms, and even the subcutaneous
use of atropin, may be indicated.
A much more serious affection, and one peculiar to alcoholics, is delirium
tremens. This is an acute psychosis which in persons addicted to alcohol fre-
quently appears as an ominous and dangerous complication of acute diseases.
In the treatment of delirium trements chloral hydrate and opium in the
form of enemata are beneficial. ep eet ts
The symptoms of clironic alcoholism are of grave import. Primarily, it
is the kidney which is attacked, and with the result particularly of contracted
592 IMPORTANT POISONS AND THEIR TREATMENT
kidney. The abuse of alcohol at a relatively early age may produce arterio-
sclerosis also. Cutaneous changes of all kinds—acne, dilatation of the veins—
may be due to chronic alcoholism. The influence upon the liver is particu-
larly prominent and typical; alcoholic cirrhosis with ascites, caput Medusa,
the small, tough degenerated liver, form a clinical picture peculiar to this
disease. An entire array of nervous diseases as well, such as polyneuritis, etc.,
and apoplexy due to arteriosclerosis, threaten the alcoholic, who frequently
indeed betrays himself as such by the tremor of the hands.
The proper therapy of chronic alcoholism requires primarily the avoidance
of alcohol in any form. In such cases, however, this abstinence usually comes
too late, for alcohol has already produced irreparable organic changes. For
this reason all our efforts must be directed toward lessening -the abuse of
alcohol.
The modern movement against the use of alcohol is calculated to produce
a change in this direction. It will be long in taking deep root, but its prin-
ciple is correct. Only by an example of total abstinence may we hope to bring
about results. In writings and popular lectures, etc., this standpoint should
be defended, and finally it will enable us to combat tne dire consequences of
chronic alcoholism.
A word regarding SULPHONAL, TRIONAL and TETRONAL. All of these
remedies are useful hypnotics, but they are also poisons, and the prolonged,
continued use of them will lead to hematoporphyrinuria, a very serious dis-
turbance of metabolism. For this reason the greatest care is necessary in their
use, and the continued employment of them should be prohibited.
We shall now devote our attention to cases of poisoning produced by agents
of the aromatic group.
The fact that our modern antipyretics, also our modern antineuralgics,
belong to this category gives them special importance.
In this brief article, I can emphasize few symptoms, but must confine
myself to the discussion of some general phenomena of this poisoning.
Above all, I must reiterate the fact that all of these remedies are blood-
poisons; all have the property of forming methemoglobin in the blood, to
which we may probably attribute the cyanosis which intoxication with these
remedies produces. Furthermore, the majority of these agents are combined
with sulphuric acid or glycuronic acid in the organism, and are excreted from
the organism as combinations.
The symptoms of poisoning by NITRO-BENZOL (mirbane oil, artificial bitter
oil of almonds) and ANILIN are of unusual interest. There is extreme cyano-
sis. Loss of consciousness recurs repeatedly in paroxysms—a symptom due to
the changes in the blood produced by nitro-benzol toxicosis and peculiar to
such poisoning. Although these toxicoses show exceeedingly threatening
symptoms—for example, pulmonary edema—they may, nevertheless, run a
favorable course. Nitro-benzol poisoning and amido-benzol poisoning have
lately been observed frequently. They are incident to certain occupations,
and it is not too much to expect that since the danger which these industries
entail has been recognized proper prophylaxis will in future make such cases
of poisoning much more rare.
AROMATIC GROUP 593
Among the bodies of this group greatest interest is attached to PHENOL
(hydroxybenzol, carbolic acid), first, because, on account of the extensive medi-
cinal use of the drug, these cases of poisoning have become uncommonly fre-
quent, and secondly, because the course of this poisoning is similar in type to
that of poisoning by the hydroxylens of benzol.
Phenol in concentrated solution causes the formation of eschars upon the
skin and mucous membrane; even local necroses may be produced or stub-
born acute eczemas which may be distributed over the entire body. In spite
of this, however, the dangers would be slight if these were the only effects of
the poison. But, introduced into the organism in somewhat larger quantities,
it gives rise to headache, vertigo, spasms, mydriasis, tinnitus aurium, severe
cyanosis and cardiac collapse, to which the patient may succumb in a short
time. Even a 2 to 3 per cent. solution injected in large quantity into the
pleural cavity, into the rectum, etc., may produce this effect.
The diagnosis of pheno-toxicosis is easy. The characteristic odor of the
breath, the very dark, discolored urine, deficient in sulpho-sulphuric acid,
will at once identify the case.
In regard to treatment, if the poison has been taken through the mouth,
the stomach should be washed at once. This is best done with water and wine
vinegar in equal amounts. The comatose stage should be treated with luke-
warm baths and cold affusions. Sugar of lime and sodium sulphite should be
employed as antidotes.
The best practice is to be cautious in the use of carbolic acid and its
preparations for medical purposes, and the sale of unauthorized preparations
should be forbidden. Even dilute solutions should never be used for washing
out the cavities of the body.
Chronic carbolic toxicosis is an evil to which many physicians were par-
ticularly exposed at the time when operations were carried on under the car-
bolic spray, a method which has now been abandoned. Dermatoses of all
varieties, loss of memory, renal affections—briefly, a marasmus precox—are
the distressing symptoms of this toxicosis, which has now almost disappeared.
The prognosis is always serious. A number of physicians have succumbed
to this poisoning, but it is now rare.
Analogous affections are produced by other derivatives of the phenol group,
particularly by the dioxybenzoles. Picric acid (trinitrophenol) causes, as an
important symptom, a yellow discoloration of the skin which is not due to
biliary coloring matter.
Particular ‘stress must be laid upon poisoning with FREE SALICYLIC ACID,
as this has a highly corrosive effect upon the mucous membranes, and thus
gives rise to serious gastroenteritis. I emphasize this because, apparently
through ignorance of these facts, free salicylic acid is repeatedly advised
medicinally, and I desire to caution physicians against its use! The salicylates
are also poisons, although local irritative effects are not peculiar to them ;
taken in very large doses, or by individuals who are very susceptible to the
action of salicylic acid, they produce toxic phenomena consisting of transitory
amaurosis, difficulty in hearing, hematuria and hemoglobinuria. In contrast
with free salicylic acid, however, their effect is relatively slight:
39
594 IMPORTANT POISONS AND THEIR TREATMENT
Before leaving this group of poisons, I must refer to another remedy which,
on account of its extensive use in therapy, often gives rise to toxicosis. This
drug is ANTIPYRIN. Antipyrin, at one time the favorite and most extensively
employed antipyretic and antineuralgic, is also a poison which may cause severe
symptoms of intoxication; in particular, dermatoses of all kinds, the hemor-
thagic diathesis, and many cases of so-called hemorrhagic scarlatina which
are not due to the intensity of the disease, but to the intensity of the therapy
employed. There can be no doubt that antipyrin, besides producing exan-
thematous eruptions, also produces enanthemas of the most varied kinds. In
persons who show an idiosyncrasy to antipyrin—and such individuals are not
rare—even small doses may produce a variety of eruptions. It is true that
no serious phenomena have as yet been noted among the symptoms of antipyrin
toxicosis; nevertheless, the therapeutic employment of this remedy necessitates
care, all the more so as its continued use may give rise to the symptoms of
chronic antipyrin toxicosis. This is as yet but little known, and has been but
little studied, the condition running its course with dyspepsia and gastric and’
intestinal catarrh.
The group of camphors and terpins, ethereal oils, balsams and resins, we
shall mention but briefly. In the main but slight importance is to be attached
to them. Only Japanese camphor, commonly called simply caMPHorR, and
employed internally as the oil of camphor, is of importance to the physician.
There is no doubt that the introduction of large quantities of camphor into
the organism causes extreme cerebral irritation, delirium, spasms and convul-
sions, even albuminuria and severe renal irritation, and for this reason it is
not to be indiscriminately used. But also by the subcutaneous employment
of the oil of camphor—at least in certain affections, such as enteric fever—
local abscesses may be produced, even with the most cautious asepsis. I do
not deny the favorable effect of camphorated oil in cardiac collapse, but the
experience of recent years shows that particular care is necessary in the em-
ployment of even this oil!
Some remedies which are in common use, such as BALSAM OF COPAIBA and
GAMBOGE, belong to this group, and if indiscreetly employed may give rise to
toxic symptoms. Toxic nephritis and toxic enteritis may be produced by
these agents, and for this reason they are by no means to be looked upon as
indifferent substances. They are enumerated here only that I may recom-
mend care in their medicinal employment.
The next group of agents with which we shall concern ourselves is that
of the alkaloids. After prussic acid, this group contains the most violent poi-
sons for the human organism, poisons which, even in minimal doses, may. occa-
sion the severest symptoms. Chemically, the alkaloids are basic bodies which
contain a pyridin nucleus, and combine with acids. Their action is inde-
pendent of the nature of the acid, but depends upon the nature of the free
base, and, therefore, upon the nature of the alkaloid. All these agents are
characterized by the fact that they have only slight local action; they there-
fore rarely give rise to gastritis and enteritis, but they act intensely, even in
small doses, upon the heart and the brain, paralyzing the respiratory center,
and in this way rapidly cause death.
ALKALOIDS 595
A number of these alkaloids, such as ceaffein, thein, and nicotin, are con-
tained in substances which are in general use, such as tea leaves after steeping,
coffee grounds, and tobacco; therefore, chronic poisoning by these alkaloids
is commonly observed. The scope of this article does not permit me to enu-
merate all of the alkaloids familiar to us, to which additions are made from
year to year by the discovery of new alkaloids in the vegetable kingdom. I
shall cite the effects of only those alkaloids which are of medical importance.
such as nicotin, morphin, atropin, and cocain. The symptoms of all poison-
ings due to alkaloids is quite similar, and the therapy in the majority of cases
is in the main analogous.
Nicotin is the active alkaloid of tobacco leaves (nicotiana tabacum) and
the different products manufactured from them. Poisoning with this exceed-
ingly virulent free base rarely occurs, and, therefore, is of no practical impor-
tance. Most significant are those forms of poisoning by tobacco in which,
besides nicotin, other deleterious agents, such as the pyridin bases, carbonic
oxid and prussic acid, etc., collectively give rise to the conditions known as
acute and chronic nicotinism.
We shall first describe acute nicotinism.
I may be brief, for every one who has smoked knows the disagreeable conse-
quences of the first attempt, and has retained the effects in memory. Headache,
nausea, vomiting, diarrhea, great debility and weakness are the symptoms
with which the unaccustomed organism responds to the poisonous proper-
ties of tobacco. Baths with cold affusions and the administration of alcohol
will rapidly relieve the symptoms. Tannin and dilute lugol solution may also
be employed internally in severe cases. Usually, however, such poisoning runs
a favorable course in a few hours, and only a headache, which sometimes con-
tinues for days, may remain.
More important than acute nicotin poisoning due to the use of tobacco is
chronic nicotin poisoning which presents itself to the physician in a different
aspect. Tachycardia, arrhythmia, and cardiac weakness are the principal and
common symptoms in this toxicosis, though these symptoms are susceptible
of different explanations. How far severe anatomical changes of the heart
are related to chronic tobacco toxicosis I shall not attempt to decide; the possi-
bility of such an occurrence cannot be disputed. Other and very important
symptoms are disturbances on the part of the eyes; amblyopia, amaurosis,
miosis and spasm of accommodation. Weakness of memory and melancholic
conditions are also among the signs of chronic nicotinism.
The treatment consists only of prophylaxis, i. e., the moderate use of nico-
tin. Disturbances of sight are to be relieved by keeping the patient in a
darkened room, and by injections of pilocarpin and strychnin. :
The next alkaloid to be considered is morphin. Opium, the dried juice of
the papaver somniferum, contains a number of alkaloids, but the symptoms of
poisoning which it produces are all closely akin to those due to morphin, so
that we may consider collectively the symptoms which these agents produce.
Morphin and opium are two of the most valuable treasures of our materia
medica. By their judicious use, the physician has brought amelioration to
countless numbers of sufferers, but no less has their improper use caused in-
596 IMPORTANT POISONS AND THEIR TREATMENT
calculable damage. Opium is employed extensively in the Orient and slightly
in our country as an intoxicant in the form of smoking. Thus used it causes
severe chronic poisoning to which I shall later refer.
We shall first consider the consequences of the introduction into the body
of large quantities of opium or morphin. What constitutes a large quantity
is always relative: in a child a milligram of morphin may give rise to the
severest symptoms, while the morphinomaniac addicted to morphin may take
0.5 gram and more. At first sopor appears. This passes into deep sleep.
The temperature of the body falls, the respirations and the pulse become slow
and irregular, the pupils are narrowed, the sclere injected, and in a few
hours the adult patient succumbs in deepest coma. With children, as shown
by the observations of Eschle and myself, spasms are prominent, and the child
succumbs to paralysis of the respiratory center.
If the individual withstands the shock of the first few hours, or if, by
proper treatment, the dangerous stage has been fortunately passed after days
of coma, consciousness may return. The patient is, however, greatly debili-
tated; headache, vomiting, stypsis and dyspepsia continue, and frequently in
the period of convalescence death occurs suddenly from cardiac paralysis.
The urine frequently shows glycosuria, alimentary as well as spontaneous.
How is acute morphinism, or opium poisoning, to be treated ?
First, in all cases, the stomach is to be washed out, even though morphin
has been injected subcutaneously, for it is excreted into the stomach.
The sopor must be combated; a warm bath with cold affusions gives the
most certain results. If this procedure has no effect, venesection and the
inhalation of oxygen should be resorted to. In desperate cases tracheotomy is
also to be performed, and oxygen may be introduced through a tracheal can-
nula. If, as in the case of a child, respiratory disturbances are most promi-
nent, artificial respiration and even phrenic faradization is to be employed.
Threatening cardiac collapse is to be met with injections of camphorated oil
as well as hypodermics of strychnin.
So much, briefly, in regard to acute morphin poisoning.
A very important réle is played by CHRONIC MORPHIN TOXICosIS, which
is widely prevalent.
The diagnosis is not always easy, for often the patient makes every effort
to mislead the physician. Numerous deeply situated scars on the skin from
abscesses of the subcutaneous cellular tissue are suspicious. Dyspepsia, styp-
sis, also the symptoms of marasmus precox, increase the likelihood of the
diagnosis, but it becomes absolutely certain only when the patient confesses
that he uses morphin, or when solutions of morphin are found in his possession.
_ The treatment of chronic morphinism can be successfully carried out only
in a hospital or in sanatoria adapted to this purpose. A withdrawal treatment
must be more or less slow, according to the somatic condition of the individual.
Hitzig’s gastric lavage with Carlsbad water, and the simultaneous subcutaneous
injection daily of decreasing quantities of morphin, are advisable. The em-
ployment of so-called substitution methods, i.e., the substitution of alcohol,
cocain, ete., for morphin, has produced no good results.
If, under this withdrawal treatment, signs of collapse appear, the treatment
ALKALOIDS 597
is to be discontinued. Larger doses of morphin must be administered, or, if
cardiac weakness intervene, digitalis or subcutancous injections of camphor-
ated oil, etc., are to be employed.
We now turn to aTRorIn POISONING.
The cases of poisoning where atropin has been administered as medicine
are very rare. Poisoning by belladonna (atropa belladonna) is more frequent.
These cases of poisoning occur usually in children. The characteristic symp-
toms are dryness of the mouth, burning of the throat, and difficulty of deglu-
tition. There is also extreme psychical alteration. The cardinal symptom,
however, is maximal dilatation and absence of reaction of the pupils, accom-
panied by marked acceleration of the pulse. In cases terminating fatally, deep
coma supervenes, then paralyses of all kinds, and the patients succumb in a
few hours.
In all such forms of poisoning immediate gastric lavage is indicated, as
well as the employment of emetics, and subcutaneous injections of apomorphin.
The best antidote is morphin subcutaneously injected in doses of 0.02-0.03
gram.
Among the poisons of special interest to the physician is that of cocarn,
an alkaloid produced only within the last two decades of the last century, but
which has found employment in medicine to a great extent as a local anes-
thetic. Intradural injections of cocain have lately been advised, and, unless
the greatest care is exercised, these will soon increase the numbers of poison-
ings from this remedy.
The first symptom of cocain poisoning is local anesthesia of the areas of
the body coming in contact with the cocain, a symptom which the physician is
frequently desirous of producing. Unfortunately this symptom does not appear
alone, but the respiratory and pulse frequency are increased, arrhythmia of
cardiac action occurs, the pupils are dilated, there is cyanosis combined with
pallor, and the patient succumbs to cardiac collapse. Occasionally such cases
are characterized by the appearance of severe mental disturbance prior to the
final collapse ; not rarely, however, even after these very severe symptoms, final
recovery takes place. Treatment: Gastric lavage if there is severe collapse;
warm baths with cold affusions.
A disease which has only lately originated from the abuse of cocain is
cocainism, which, in its disastrous consequences, is scarcely less important than
chronic morphinism; the symptoms are generally referable to the nervous
system, and their number is legion; rapidly increasing marasmus causes the
early death of the patient.
In the group of the glucocides only one toxicosis plays a leading réle, and
this is poisoning from the leaves of DIGITALIS PURPUREA, which, as is well
known, contains two glucocides (digitalin, digitalein), besides digitonin. and
digitoxin, a soap-like substance.
The curative effects of infusion of digitalis and tincture of digitalis, etc.,
are known to all physicians—the increased diuresis, the stronger cardiac con-
traction, the slowing of the pulse. It is perhaps not so well known that in-
fusion of digitalis may become decomposed by the action of mold fungi and
bacteria and toxic substances appear in consequence,
598 IMPORTANT POISONS AND THEIR TREATMENT
In summer we should make it a rule to ascertain that an infusion of digi-
talis has not decomposed; but, besides this, digitalis in too large a dose, or in
too large a dose in a special case, may cause symptoms undesirable to both the
patient and the physician. Among these we may mention vomiting, gastric
oppression, marked diminution of the pulse frequency, slight muscular trem-
bling, symptoms of depression, irregular pulse, cold sweats, severe urticaria-
like exanthems. In the severest cases death occurs in collapse.
Mild cases run a favorable course in a few days without treatment, or by
simply stopping the administration of digitalis. The severe and most extreme
cases require active treatment. The stomach and intestines must be emptied,
caffein and theobromin given, and serpentaria virginica may be employed as
an antidote. If the signs of cardiac debility are threatening, strychnin and
atropin are to be subcutaneously injected.
I may remark that severe forms of digitalis poisoning are rarely observed
by the physician.
Of poisonings with bitters and indifferent agents, only ALoIN toxicosis need
be mentioned.
Employed in small doses (0.2-1.0 gram) aloes cause copious diarrheic
discharges. Very large doses give rise to gastritis, enteritis, and nephritis.
Treatment consists in the administration of opiates and mucilaginous drinks.
The best way to prevent poisoning of this kind is for the physician to refrain
from prescribing aloin in too large doses.
A word in regard to ARNICAN, the active constituent of the tincture of
arnica, from arnica montana. It was formerly medicinally employed, but is
no longer used. Its property of markedly irritating the skin, and, upon inter-
nal use, of producing stomatitis, gastritis and enteritis, has robbed it of its
usefulness, and I only mention it at this place to warn the physician against
its employment.
We must now refer to a long series of vegetable and animal poisons.
These are related partially to poisonous albumin bodies, such as toxalbu-
mins, phytalbumoses, etc., as, for example, in some poisonous toad-stools, in
snake poison, in spider poison. They are partly related also to bodies previ-
ously unknown which, sooner or later, will be assigned to one of the previously
described groups.
From the great number of poisonings by these agents I shall briefly men-
tion a few which are of special interest to the physician.
First we shall consider poisoning from ERGor (secale cornutum), the per-
manent mycelium of claviceps purpurea. The views of physicians are not yet
in accord as to the poisonous principle of this drug. According to Kobert,
sphacelinic acid, cornutin, according to Jacobi, sphacelotoxin is the toxic prin-
ciple. Poisoning, as a rule, simultaneously affects groups of persons who have
eaten food prepared with flour contaminated with ergot. The toxicosis may
Tun an acute or a chronic course.
Acute ergot poisoning runs its course with vomiting and abdominal pain,
pain in the epigastrium, the chest and extremities. There are various nervous
symptoms: above all, paresthesia and tonic contractures of the extremities,
as well as ataxia, epileptiform attacks, and severe psychical disturbances.
|
VEGETABLE AND ANIMAL POISONS 599
Cyanosis, diarrhea and fever may occur. In cases running an unfavorable
course, the temperature falls in the later stages, and severe syncope appears.
The patient succumbs in a few days, sometimes even after a few hours. The
prognosis of ergotin poisoning is always grave, as the sequele of such poi-
soning, even In cases running a favorable course, may be noticeable for years
afterward.
For a positive diagnosis of the affection, ergot must be found in the vom-
ited material, in the remains of the flour which has been ingested. For this
purpose we use the coloring matter contained in ergot—erythrosclerotin.
T'reatment.—As a primary measure the proper instruction of the public
should be enjoined. The treatment itself consists in washing out the stom-
ach, emptying the intestine by the employment of enemata or of purgatives
such as castor oil and calomel; as antidotes, tannin and chlorin water; for the
collapse, warm baths with cold affusions; in milder cases stimulants, such as
coffee, tea, alcohol. In severe cardiac collapse injections of camphorated oil
are recommended.
The phenomena of chronic ergotism relate particularly to the nervous sys-
tem. The most marked symptoms are the paresthesias, in consequence of
which the disease is still popularly called itching disease (Kribbelkrankheit).
First tonic, then clonic, spasms occur (convulsive ergotism) ; the patient ema-
ciates to an extreme; trophic disturbances of all kinds, such as furunculosis,
loss of hair, loss of the nails, etc., follow. The most dangerous form is that
known to the physician as gangrenous ergotism. Gangrene of an extremity
in a short time leads to septic infection to which the patient succumbs.
The treatment of the intestinal symptoms is the same as in acute ergotism.
The severe pains are relieved by sodium salicylate, bromids, and opiates, and
protracted lukewarm. baths are also beneficial; gangrene necessitates surgical
measures, although they are usually of no avail.
Following ergotism, we must consider PELLAGRA (mal de sol) due to the
ingestion of spoiled maize. Besides a number of dyspeptic difficulties, an
erythema presents itself particularly upon the exposed portions of the body
and recurs year after year in summer. The patient emaciates, nutrition suf-
fers greatly, and he becomes anemic. Nervous symptoms follow; pareses,
paralyses, atrophies of the musculature, ptosis, amaurosis, ete. The patient
improves in winter; but anemia, dropsy, and finally fever and delirium often
set in, and after suffering for years he succumbs, provided an intercurrent
affection such as tuberculosis or sepsis does not cause death before this.
The prognosis is exceedingly unfavorable, the treatment unfortunately in-
effectual, and only by a proper prophylaxis and the avoidance of spoiled maize
as food can we prevent the appearance of this dreaded plague. It is endemic
in Friaul and Upper Italy as well as in Bukowina.
Poisoning by TOAD-STOOLs is of practical interest. We will consider only
the amanita phalloides and the agaricus phalloides. These are often con-
founded with the field champignons which resemble them. The plum agaricus
is the most frequent cause of this form of poisoning. ;
The symptoms are profuse diarrhea, vomiting, anuria, spasms and col-
lapse, to which the patient may succumb even in the first stage. In the fur-
600 IMPORTANT POISONS AND THEIR TREATMENT
ther course of the affection, jaundice and nephritis occur. The disease is
very serious. Seventy-five per cent. of those attacked die. Treatment: Gas-
tric lavage, venesection with subsequent salt infusion, and subcutaneous injec-
tion of strychnin.
Poisoning with AGARICUS MUSCARIUS must also be considered. The symp-
toms are vomiting, hemorrhagic diarrhea, a condition resembling alcohol in-
toxication, followed by tonic and clonic spasms to which the patient may suc-
cumb in a few hours or a few days. The prognosis is decidedly more favorable
than in poisoning with agaricus phalloides. Treatment: Gastric lavage,
emetics, apomorphin, then tannin; perhaps also venesection and normal salt
infusion.
In poisoning with HEBELOMA, on account of the muscarin-like effect, injec-
tions of atropin are in place.
We must still refer to poisoning with mMusHRooms. The edible mushroom
is non-toxic. All poisonings of this kind are due to the toxic mushroom,
which greatly resembles it.
The symptoms are similar to those produced by amanita phalloides. But
the course is generally more favorable and briefer. The treatment is the same
as in poisoning with amanita phalloides.
It must be borne in mind that non-toxic mushrooms may also give rise
to poisoning, if they have decomposed. The best prophylaxis against mush-
room poisoning is proper instruction at school in the recognition of the poison-
ous mushrooms; the inspectors in markets should by strict supervision prevent
the sale of the toad-stool which so closely resembles the non-toxic mushroom.
In discussing FISH POISONING we may be brief. It is of but little conse-
quence. If the fish itself is non-poisonous, poisoning is only brought about
by the fact that it was already decomposed when eaten. Such poisoning will
be included under meat poisoning.
Fish, however, may be poisonous. For example, eel blood is poisonous, the
roe of the barbel and of the pike (esox lucius) contains toxic substances, and
this is also said to be true of the head of the sheat fish (silurus glanis). The
tetrodon varieties indigenous to Japan contain a poison resembling curare.
The ingestion of fish may also have a deleterious effect if the fish itself has
been diseased (bacillary infection, plasmodia, invasion of entozoa). The his-
tory will for the most part point to the diagnosis. The symptoms are mani-
fold; usually the signs of gastritis toxica dominate the situation, but nervous
phenomena such as pupillary symptoms, spasms and unconsciousness also
appear. The course of the disease is generally severe, and frequently the
termination is fatal.
The treatment consists in gastric lavage, the earlier performed. the better ;
but this should also be employed in the later stages if vomiting is present.
Toxic gastroenteritis is to be relieved by opiates and mucilaginous drinks.
OysTERS and MUSSELS may produce similar effects, if the bivalves were
themselves diseased, or had fed on poisonous substances,
In conclusion, we proceed to the discussion of MEAT POISONING.
Although the various forms of meat poisoning differ in their etiology.
there is but little difference in their pathology: ing
pathology; they may be due to eating
VEGETABLE AND ANIMAL POISONS 601
poisonous animal food or the meat of diseased animals. We shall investigate
particularly that form produced by the ingestion of decomposed meat of any
kind. This we usually designate as alantiasis or botulism. This form is the
most important, as it is the one most frequently observed by the physician.
We must distinguish three quite different clinical forms: (a) That form
which presents predominant paralytic symptoms; (b) that form running its
course with symptoms of atomatropin poisoning; (c) that form running its
course with symptoms of gastroenteritis. The ingestion of decomposed sausage,
in particular, causes the second form, while the ingestion of liver and kidney
causes the gastroenteritic symptoms.
The affection is always to be regarded as serious; the mortality is very high.
The treatment must be in accordance with the form of the intoxication.
In any case, the immediate washing out of the stomach is always in place.
The treatment of the second form is the same as that of fish poisoning, while
in the third form the treatment of gastroenteritis, repeatedly mentioned, is
here of the utmost importance. In conclusion it must be borne in mind that
other foods also, such as milk and cheese, may be the cause of similar poisoning,
and poisoning after the ingestion of foods containing vanillin may be included
in this category.
DIET TABLE!
Diet List, Showing the Nutritive Value per Ounce of Various Foodstuffs Expressed
in Calories, the Weight Required for a “Portion” of 100 Calories Each,
and the Number of Calories of Each Food Principle
in an Ordinary Serving of Food.
‘ |
e CaLortes Per Ounce. | | Catortes Servep.
2 | oe) a ‘
ap Foon. dq g 3 50S | & es o
Ss Bee) Cee ee ee ee ee
o% 2 & = | ee ane 2 1
3 Ay 2 | oa a =a | ©
a | a Ay
oO 2) |
1 {Almonds.:............ 24.5 |146.4 | 20.2 191.1 62) 7 | 38) 5
3} |Apples, Baked......... 6] 1.3 | 28.4 | 30.3 | 3.3] 2 4/ 94 | 1
5h |Apples, Fresh.......... 2.75) 7.15] 91.3 |101.1 98} 2 7| 91 | 1
6 |Apple Juice............ 0 0 17 17 5.8 | 0 0; 100 | 1
3% |Apple Sauce........... 3 .8 | 20.65, 21.78! 4.6 1 3| 71 2
3 |Apricots.............. 1.3] 0 15.6 | 16.9 | 6 4 0} 46 4
1? |Asparagus (cooked)....| 2.5 8.8 2.6 | 13.9 Cok 5 15 5 4
3} |Bananas.............. 1.5 1.6 | 25.7 | 28.8 3.47| 5 6 89 1
3} |Bananas, Baked....... 3.2 4.73) 32.37 40.3 2.5 8 11 81 1
6 |Barley Gruel.......... 1.5 .7| 10.2 | 12.4] 8.1] 9 4] 62 g
34 |Barley, Pearl.......... 2.97 .87| 27.24 31.08} 3.2 9 3 88 1
43 |Bean Broth........... 4.3} 3.2] 11.6} 19.1 5.2 | 22 16] 62 | 1
34 |Beans, Baked.......... 10 12.5 | 33.6 | 56 1.7 | 32 38 | 105 | 13
3+ |Beans, Baked (canned).| 8 6.6 | 22.9 | 37.5 2.6 | 27 22) 76 1}
3 |Beet Greens (cooked). ..| 2.6 9.1 3.7 | 15.4 6.5 8 30 12 4
2} |Beets (cooked)......... 2.7 3 8.6 | 11.6 8.6] 5 1 19 +
1} |Biscuit, Beaten........ 8.4 | 47.3 | 79.2 1134.9 .75| 10 61 | 104 1¢
24 |Biscuit, Cream......... 10.3 | 27.5 | 49.6 | 87.5 1.1 | 24 64 | 112 2
1 |Biscuit, Gluten........ 48.5 2.8 | 56.1 107.4 .93) 45 3 52 1
1 |Biscuit, Rice.......... 8.5 .9 | 96.6 106 .94| 7 1; 92 /1
3 |Blackberries........... 1.5 2.6 | 12.7‘ 16.8 6 4 8 38 4
34 |Blanc Mange (Chocolate)| 3.4 | 22.86] 16.25 42.52; 2.35) 12 81 57 14
5 |Blood Oranges.........] 9 5 | 13.5 | 14.9] 6.7] 4 2) 69 Z
42 |Bouillon, Tomato.......}| 3.62| 7.98 4.77, 16.37; 6.1 | 17 36 22 2
4% |Bouillon, Vegetable.....) 7 4.3) 7 | 18.3] 5.5 | 29 18 | 28 3
4 |Brazil Nuts............ 19.8 178.1 | 8.2 206.1 .48) 9 87 4 |
3 |Bread Custard Pudding.| 8.75| 46.08) 67.24 122.07 .81} 23 133 | 194 34
2 (Bread, Corn........... 8.5 |12.3|52 | 72.8| 1.3|17 | 25) 108 | 13
2 |Bread, Gluten......... 10.8 3.7 | 58.1 | 72.6 1.4 | 18 70 | 112 2
2 |Bread, Graham........ 10.4 | 4.8 | 60.8 | 76 1.3 | 20 9} 121 | 13
2 |Bread, Rye............ 10.5 1.6 | 62.1 | 74.2 1.3 | 21 3 | 126 14
2 |Bread, White..........| 9.3 3.7 | 63.4 | 76.4 1.3 | 18 7 | 125 13
2 |Bread, Whole Wheat.. .|11.3 2.4 | 58 71.7 1.4 | 24 5 | 121 14
43 |Broth, Bean...........| 4.39} 3.16) 11.58 19.13) 5.2 | 22 16 62 1
4% |Broth (Mock Chicken)..| 3.7 | 3.3 | 4.7 | 11.7 | 16 14 16 | 20 4
44 |Broth (Vegetable)......| 2.8 | 0 5 | 3.3] 30.3113.3; of 2.4] 2
} [Butter (Dairy)......... 1.2 |226.6| 0 227.8 4/1 | 99] 0 |1
1 From the diet list of the Battle Creek Sanitarium, Battle Creek, Michigan, J. H. Kellogg, Medical
Superintendent.
602 A
DIET TABLE—Continued
Catortes Per OUNCE, CALORIES SERVED. :
eo FI 3
a 24 ellis
5 4 ES) 380 a
‘ad 2 8 on, 2» ws
38 #| & | 2 °65) 8) 2) 2 |e
Og S Fy 3 s & ~ g moo
: ‘ g g.
‘ ics
6 |Buttermilk........-..- 3.5 1.3 + ae A a a 10 a :
4 |Cabbage, Boiled........ 8} 6.1 : : . :
7.6 | 40.9 | 66.8 |114.6 | 87 15 | 80 | 180 | 24
2 |Cake, Coffee........... : at iba g\oa | es ier LS
él Beh ees ea — 14.2 ae Pe aes a '
6 anteloupe 4 pera ‘ adn # F : ee
34 |Carrots, Creamed.. sb actane 2.01; 7.5 | 10.3 Hae ee a a :
3 Cauliflower, Steamed. . ae i bee a Oe ay ; : L
1 |Celery.........---055- ii. : : ‘ : aie
: Cheese, Cottage......-. aa oT cee aie re a a i
3 Cn Licneedeae 6.6 |134.9 | 32.5 |174 6 |132 269 8 8 34
8 |Corn Cake...........-- 13.9 | 28.8 | 52.8 | 95.6 1 - - “e aS :
2 Corn Flakes...... eee 1.4 | 91.3 103.5 : i
Corn, Green, Swee
(cooked).......... {3.6 | 2.9 | 22 | 28.5 a 10 se 58 2
Crackers, Graham...... 11.7 | 25.1 | 86.1 1122.9 ; Shae | ic
Cranberries (cooked)....| _.2 .7 | 47.8 | 48.7 re % a ae
PCreAM «cane y name scaae 2.9 | 49.3 | 5.3 | 57.5 7 a
| q| of | 86 | B | 26 are at 714
\Cucumbers Lig istitha ta AWS . ; 5 pa j
Currants, Red......... 1.8 ... | 14.9 | 16.7 Pe : ;
Custard, ua ..| 5.7 | 18 12.5 | 31.2 3 18 0
Dandelion reens :
(cooked).........--- 2.8 | 2.7 | 12.5 | 18 5.4) 8 : oe i
DateBaisnceis aan vans 25% 2.5) 7.5 | 91.5 101.5 |) 1 3 1 160 :
Egg Plant............- 6.63; 26.43} 37.9 | 71 1.4] 8 | 38 54 a
Eggs, Poached. . ..116.3 | 32 .... | 48.3 | 2.1 | 26 | 42 eee |
Eggnog, Milk. . ...{ 5.9 | 28 9 38 2.6 | 46 |183 71
Endive............--- 3.3) 1 4.93} 9.3) 10.7] 9 3 13 i
English Walnuts....... 19.4 |169.2 | 18.2 |206.8 .48) 9 82 9
LDC Vat: ee eee eee 2.6 .8 | 18 21.4) 4.7] 9.1) 2.8 63 3
ETS cscs. scenes 8 SH Aaa 5| 8 86.6 | 92.4] 1.1 1 16 | 173 q
4 |Filberts.............-- 18.2 |174.1 | 15.2 |207.5 48) 9 | 84 7
4 |French Salad Dressing. .| 0 198 2.85/200.9 5 0 99 1 1
1 |Gluten Biscuit, 40%... .|48.5 2.8 | 56.1 |107.4 .9 | 45 3 52 1
2} \Gooseberfies, Stewed...| .5 | .... | 18.9 | 19.4 | 5.15] 1 haa 49 $
33 |Grape Fruit........... 9 .6 [11.8 | 13.2] 7.6] 3 2 45 4
6 |Grape Juice........... 0 0 23.8 | 23.8 | 4.2] 0 0 | 150 | 14
5 |Grapes (Atwater)...... 1.16) 3.2 | 16.6) 20.9] 4.7] 5 | 16 79 | 1
6 |Gruel, Barley..........| 1.48 -7 | 10.2 | 12.39} 8.07) 9 4 62 3
6G} |Gruel, Corn Meal....... 8 A 6.8 8 12.5 5 3 42 4
6 |Gruel, Oatmeal........ 1.3 1.4] 5.8] 8.5] 11.7] 7 8 35 4
3: |Hash, Potatoes, and
Onions..............| 2.35} 10.79) 17.63] 30.7 3.25) 7 36 57
4} |Hominy.. Shai dades dle .5 | 20.7 | 23.8 | 4.2 | 11 2 87
12 |Honey.. datibrask sll 6 AO) ... | 94.7 | 95.2 1.05} 1 ... | 149
1 |Jelly, Currant.......... 1.2 ... | 90.1 ) 91.3 1.09) 1 hae 99
5 |)Kumyss.. .......{ 3.3 | 5.6] 6.3 | 15.2 | 6.6 | 16.5) 28 31.
5} Lemonade............. .. | 14.2) 14.2 | 7 nee 75
3 |Lentils (cooked)....... 8.5 .3 | 22.9 | 31.7) 3.1 | 25.5 .9) 68.
3 (Macaroni and Tomato. .| 5 3.86] 17.16] 26 3.8 | 15 11 49
2% ,Macaroni au Gratin.....|10.8 | 15.88) 17.85) 44.5 2.2 | 30 45 50
1 |Maple Sugar........... 0 0 96.6 | 96.6 1.1] 0 0 | 100
24 |Marmalade, Fig. . 2.8 4 | 48.7 | 51.9 1.9 6 1. | 118
1} Mayonnaise, Cooked... 6.87| 67.1 2.85, 76.8 1.3 9 88 3
602 B
o
DIET TABLE—Continued
% : Catories Per Ounce. CALORIES SERVED.
7 ,
g p : it
On % i BES a
op Foon. 7 a g eke a =
é4 a/2¢)3e/" |°8|3 |) ¢
3 |e | 8 = je | ae
ae) am 2 ard Ay a
8 a
o 16)
64 |Milk, Skimmed........ 4 8 6 10.8 9.3 | 26 5.2: 39
6 Milk Whole...... pee | 3.8 | 11 5.8 | 20.6 4.9 | 22.8} 66 34.8
4 |Nuts, Almonds......... 24.5 |146.4 | 20.2 /191.1 .52| 7 | 38 5
4 |Nuts, Hickory......... 18 -|179.7 | 18.3 |211 47 9 | 89.8} 6.
4} Oatmeal (Cooked).. 3.3 | 1.3 | 13.4 | 18 5.6 | 14 5 56
} |Olive Oil.............. 0 |264.1 | 0 |264.1 41 0 {100 0
14 |Olives, Ripe (7)........ 2 69.1 5 76.1 1.3 2 91 7
4, \Qmneleb..oicsacx sexes 14 59 1 74 1.4 | 56 |236 4
24 |Onions, Boiled.........| 1.13) 4.29} 5.1 | 10.52 9.5} 3 | 10 12
5 |Orange Juice.......... 0 0 15.1 | 15.1 6.6 0 0 75
5 |Oranges............--- 9 .6 | 13.5 | 14.9 6.7 4 2 69
3 |Parsnips, Mashed...... 1.7} 5.9] 9.5} 17.1] 5.8) 5 | 17 28
9} |Patties, Rice.........- 14.9 | 39.04] 77.24,131.2 .76| 37 97 191
4 |Peaches, Fresh......... 9 .3|11.6| 12.8] 7.8] 3 1 46
Z Peanuts. ipwaleate rem ge aes 30.1 |102.9 8.5 {161.5 .6 | 22.5) 77.1 6.
A |Pears..........----+--| .7] 1.3 | 16.5] 18.5] 5.4) 3 5 67
3 |Peas, Green..........- 7.8 | 9.1] 17.5 | 34.4] 3 23 «| 26 51
4 |Pie, ‘Apple cuatro che 7.5 | 18 37.2 | 62.7] 1.591 33 | 80 | 162
5 |Pie, Mince...........-- 15.09} 22.2 | 35.1 ; 72.39} 1.3 | 73 {108 169
5 |Pie, Pumpkin.......... 3.25| 7.26] 24.88] 35.4 2.8 | 36 71 168
4 |Pineapple,.Fresh....... 5 8] 11.3 | 12.6) 8 2 3 45
4. [PLUMS 5.065 ccs e aw ee sey 1.2] .... | 23.5 | 24.7] 4 5 238 95
4 |Popped Corn.......... 12.5 | 18.3 | 91.8 |117.6 .85} 5 5 40
3 |Potatoes, Baked....... 3.4 4 | 28.9 | 32.7 3 11 1 88
33 |Prunes (Cooked). . 8 .83 | 26.4 | 27.5 3.65] 3 1 96
24 |Pudding, Baked Indian.| 4.8 | 21.8 | 20 46.6 | 2.1] 13 | 58 54
24 \Pudding, Apple Tapioca] 4.5 | 17.58] 26.44) 48.5 2.07) 12 | 45 68
1 |Radishes............-- 1.5 3} 6.7 | 8.5} 11.7 1 as 5
1 |Raising............--- 3 8.8 | 88.8 |100.6 1 3 9 88
4 \Raspberries, Fresh .
Black... ..ccss 04 ce 4+ 2 2.6 | 14.7 | 19.3 5.2 8 10 57
3} \Raspberries, Fresh Red.| 1.2] .... | 14.7] 15.9] 6.3] 4 46
4 |Rice, Boiled........... 3.3 .8 | 28.5 | 32.1 3.1) 13 1 111
Salad, String Bean..... 7 | 61.7| 2.3] 54.7] 1.8) 2 | 93 5
Salad, Vegetable. . 4.3 | 4.8] 9.2/18.3] 5.5] 6 6 13
Soup, Bean... 94| 4 |24.7|38.1| 2.6] 25 |15 | 65
Soup, Clear Tomato. . 3.1 | 7 8.9 | 19 5.2} 17 | 36 47
. Soup, Split Pea.......-. 7.18} 1.85} 18.07] 27.1 | 3.6 | 34 8 83
Spinach. . iste anece || ISO L 4.93} 9.3 | 10.7 | 9 3 13
Squash, Baked......... 1.6 2.2 | 16 19.8 5 4 6 40
Strawberries, Fresh.. 1.2 1.6 8.6 | 11.4 8.5 5 7 38
+ |Sugar (Granulated)... 0 0 116.6 |116.6 91 0 0 25
Sweet Potatoes (Cooked) 3.5 5.6 | 49.1 | 58.2 1.7 | 12 19 169
Toast, Breakfast. . 1.4 | 27.5 | 86.2 {125.1 8 4 12 34
Toast, Cream........-- 4.15| 29.9 | 13.6 | 47.65) 2.1 | 18 143 64
Tomatoes, Sliced......- 1 1.1] 4.6] 6.7 | 16 4 4 17
Turnips, Mashed....... 6 2.8 2.7 6.1 | 16.4 2 12 11
Watercress.........--- 1.4 8| 3.4] 5.6)17.8] 2 1 7
Watermelon........-.- 5 5 | 7:8 | 8.8 | 1L4| 4 4 67
Wheat, Cracked.......- 3.3 1 22 26.3 3.8 ] 18 6 126
Whey........-2 22 e? 1.2 8 5.8 7.8 | 12.8 8.4} 5.6} 40
Whok -wheat Wafers or
oe bhi ete 11.4 | 26 84.5 |122.7 .81| 12 27 86
Zwieback.....----+0+° 11.4 | 26.4 | 85.8 |123.6 ‘8 | 11.4, 26.4| 85.8
[aD ee ft i
Portions Served.
oo wee et
LHR kone wo
—e
[all sent aunt mend = NwWNe
NH epee mo feo
Vote
aX
Plated tre
RR pt CS al
nw
mtb
ooh
we
tot etic
eee
“FLESH FOODS.
eb Gusanraa PER OUNCE. ad CaLories SERVED.
ae 235
2 a : o60 a - | wm
33 Foon. B ¢ [28] ¢ | #88) 2] « [a8] 38
Ba : f 122) 8 |das) 5] & | fe] 86
o8 ef) "jee & [ete 8° | oa
Beef Juice...........0.0.00008 5.42 1.71} 0 7.13) 14 19 6 0 4
a Beef, Roasted (Fat)............ 18.14} 136.85} 0 | 155.26 -65) 48 | 352; 0] 4
21 |Beef, Round (Boiled, Lean).....| 40.9 4.54, O| 45.6 2.2 | 90 10; O/; 1
6: [Bouillon 2c concscgc niece owen 3 nate! « 2.3 3] 3 3 33 23 1; 1] ¢
3} |Chicken (Broilers)............. 24.6 6.56} 0}; 31.16) 3.2; 79 | 21 O;1
SH Clam sic, css agave duty sa astua'aa thes 7.5 1.08} 0 8.58] 11.6 | 28 4/18); 4
5: i@od Hishiyes exis +04 wees sie ds aes 19.3 1.02! 0] 20.32) 4.9 | 95 5; O} 1
25 |GOOSEs g.igaepede she 5 satu we tae Tate & 18.1 95.4 0; 113.5 .88) 48 | 252 | 01 3
3 {Halibut (Steak)........% eet Ast 21.78) 13.9 0 35.68) 2.8 | 61 39 | OO] 1
2 |Lamb Chops (Boiled).......... 25.3 79.7 | O| 105 .96; 48 | 152 | 0] 2
34 |Lamb (Leg, Roast)............ 22.2 33.3 0 55.5 1.8} 80] 120] 0/2
3 {Liver (Veal)..............005. 21.78, 13.9 0, 35.68) 2.8] 61 39} O11
2 |Lobsters:s:siugigs yack eee 19 4.8 0} 23.82) 4.1 | 39 10; 1); 4
24 [Mutton (Leg, Boiled)...........| 29.1 54.1 0; 83.2 1.2/ 70} 30] Oj} 1
84 |Oysters....6 06 cranes cae se es 7.2 3.23 0 10.43) 6.8 | 24 12/ 14/ 43
1 |Pork (Bacon, Medium Eas 11.3 | 177.3 |. 0 | 188.6 .53] 12 | 188 0/2
2} |Pork (Ham, Boiled).. 25.4 65.4 0 90.3 1.1/ 56 | 144] 0} 2
3 |Pork (Loin, Chops)............ 18.5 84.5 0 | 103 .97| 54 | 246 0; 3
24 [Salmon (California) a eiastich acest 20.4 | 46.6 0! 66.6 1.5 | 45 | 105 | 0! 13
2a SMA oe ci eee Gcedi na aust Sine Beane 21.9 | 25.71; O| 47.61! 2.1] 46 54} 0.1
12 /Trout (Brook).. 22.2 | 55.5 0 77.7 3.6] 40/ 10} 0; 3
NS DUP CY cee xcesaistes 2 vata a ages oe gas 24.1 59.1 0) 83.2 1.2 | 29 71 0; 1
24 |Veal (hes, Boiled)............. 30.4 11.2 O|} 41.6 2.4 | 73 27 0.1
FOOD UNITS OR CALORIES PER OUNCE OF UNCOOKED FOODSTUFFS.
None served in the uncooked state.
Value given only for the purpose of comparison.
602 D
ne Car- Pro- | Car- ;
Foop | a 5, | Pats. a a Total. Foon. teina: Fats. aoe Total.
Asparagus....... 2.1 ms) 3.9 6.5!) Gluten Meal ee
Barley, Pearled.. 9.9 2.9 99.8} 103.6 per cent.).. 18.4 1.7 83.6] 103.7
Beans (dried).... 26.3 | 4.8) 69.5] 100.6||Hominy........ 9.7 1.6 | 92.2} 108.5
Beans, Butter | Lentils......... 30 2.7 69.1) 101.8
(green) Seeacnans £ il 1.6] 34 46.6 || Macaroni....... 3.5 | 4 18.4} 25.9
Beans, Lima(dried) 21.1 4 76.9} 102 Mushrooms..... 4.1 1.1 7.9) 13.1
Beets........... 1.9 3 11.3) 13.5]| Oatmeal. . 18.8 | 19.2 78.8) 116.8
Beans, String....| 2.7 8 8.6 12.1/| Onions........ 1.9 8 11.6} 14.3
Cabbage......... 1 19). .8 6.5} 9.2]| Parsnips........] 1.9 1.3 15.8) 19
Carrots.......... | 1.3 1.1 10.9) 13.3]} Peanuts........ 22.8 | 77.6 | 21.6] 122
Cauliflower. ...... 2.1 1.3 5.5 8.9 || Peas (dried).....) 28.7 RET 72.3) 100.7
Cocoa........... 25.2 | 77.1 44 146.3 || Peas, Green..... 8.2 1.3 19.7} 29.2
Corn, Green...... 3.65 2.9] 23 29.5 || Potatoes........] 2.6 3 21.5} 24.4
Cornmeal........ 10.7 5.1 87.9} 103.7 || Prunes......... 2.5 0 85.8} 88
Cornstarch. . sees (cee. | 105 | 105 Pumpkin....... 1.2 3 6.1) 7.6
Cranberries 6 1.6 11.5} 13.7]| Radishes....... 1.5 3 6.8 8.6
Egg Plant....... 1.4 8 6 8.2]| Rice........... 9 8 92 101.8
Flour, Corn...... 8.3 | 3.5 | 91.5] 103.3]|Spinach........ 2.5 8 3.7) 7
‘Flour, Graham.../ 15.5 | 5.9 | 83.3! 104.7 Squash 1.6] 1.3] 10.5) 18.4
Flour, Rye....... 7.9 2.4 91.8) 102.1]| Sweet Potatoes. . 2:1 1.9 32 36
Flour, Wheat (as Turnips........ 1.5 5 9.5) _ 11.5
tire Wheat)... 16.1 5.1 83.8] 105 Vegetable Oys- ;
Flour, Whea 6 ters or Salsify.| 1 5.3 4.1) 10.4
(Fine White).. 9.2 3.7 89.1] 102 Wheat, Cracked .| 13 4.5 88.1] 105.6
Flour Wheat ra.) 12.6 2.9 87.7! 103.2
INDEX OF
A
ABEL, 210.
ABELOUS, 205, 206.
Appison, 199, 200, 202, 205, 214.
AprIAN, C., 253, 259.
AJELLO, 459, 494.
ALBARRAN, 449, 513.
Axsu, 14, 40.
ALEXANDER, 209.
Auten, 513.
Ammann, E., 419.
Ammon, 514.
ANDERSON, 442.
ANDERSSON, 225.
AncerR, 518, 519.
Anscuttz, W., 246, 259.
ARCTANDER, 482.
ARNOLD, 235, 237, 327, 347.
ArsTAN, 563.
ASKANAZY, 347, 376, 386, 512, 545, 553, 554,
557, 558.
ATTLEE, 451.
Atwater, 20, 24.
Autp, 204.
AVERBECK, 214.
B
Bascock, 195.
Bases, 216, 394, 400, 429, 460.
BacceE.ut, 533.
Bacustrom, 397.
Baxruz, 506, 510, 511, 549.
Bauscu, 517.
BaMBERGER, 468, 476.
Bancrort, 546, 547.
Bane, 266, 267.
BaNNATYNE, 248, 255, 259.
AUTHORS
Bantt, 382, 383, 384, 386.
Bantine, 70, 72, 73, 74, 163, 164, 165, 166,
173, 175.
BaraBan, 506.
Barson, 257, 259.
Bartow, 485.
Barszewsky, 271.
Batrmann, 459.
Batscu, 516.
Bauer, 39.
Baumann, 2, 189, 190, 191.
BAuMuER, 248, 247.
Bavay, 544, 545.
Bazin, 143.
BECHTEREW, 246, 247, 259.
BrEcKLER, 397.
BEcQUEREL, 334, 341, 408.
Brer, 248, 259.
Beuua, 506.
Brnpa, C., 229.
vAN BENEDEN, 526.
BeEneEpIctT, 20, 24.
BenneckeE, R., 247.
Browirt, 543.
BeErent, W., 256, 260.
BERGELL, 18, 266.
BERNARD, CLAUDE, 111, 114, 115, 116.
BETTENCOURT, 189.
Bran, 263, 267, 269, 270, 271.
Bipper, 4, 10.
BieEDERT, 47.
Brepu, 208.
Bier, Aueust, 258, 259, 260.
BrermMer, 509.
Binwarz, 512, 560.
Biiiines, 495, 556.
BitiroTH, 378, 488.
Binet, 30.
Brrcn-HIRscureELpD, 433.
603
604
Bircuer, 188.
Biscuorr, E., 4, 56.
Bitter, 542.
BsreRRE, 89.
BLANCHARD, 515, 516, 521, 544, 564.
Buanp-Sutton, 506.
BuascuHex, 535.
BLAXALL, 255, 259.
BLEIBTREU, 56.
Biocu, 516, 519.
Buu, 189, 209, 226.
BLUMENTHAL, F., 262, 269.
Bosrizkt, 469.
Borr, 219.
BoERHAAVE, 162.
Bow.uanp, 563.
Bouncer, 415.
BonFits, 370, 386.
Bontexoer, 391.
Bornstein, 19, 20, 56, 57.
Borntracer, 394.
Bostrorm, 509.
Boucuarp, Cu., 22, 26, 33, 143, 243, 252,
255, 257, 260.
Bovursiger, 449.
Bozzoto, 560, 564.
BraMWELL, Byrom, 180, 185, 195.
BRANDENBURG, 286
Brat, 270.
Braver, 573.
Brawn, G., 511, 512, 515, 520, 575, 576.
Braun, Juius, 246, 260.
Breamer, 63.
BREISACcHER, 14.
BreirHavupt, 14.
Bremser, 520, 565.
Briscer, 531.
BRILLAT-SAVARIN, 170.
Brock, 513, 514.
Bropen, 25.
Broock, 454.
Brown, 303.
Brown-S&QuarD, 205, 206.
Bruce, 195.
Brunner, 534.
v. Bruns, 192, 198, 534.
Bryant, 531.
Buut, 433.
Bunnag, 153, 154, 155, 398, 410.
Bunsen, 586.
Burcwarp, 553.
BurRMEISTER, 572.
INDEX OF AUTHORS
Burresi, 216.
Busx, 510.
C
Cazot, 194, 195, 283, 366.
CaMERER, 36, 37.
CaNnarp, 286.
Cannstatt, 470.
CanTaNnI, 98, 164, 165.
CaPoRELLI, 271.
Caspar, 18, 20, 38, 51.
Casper, L., 451.
Cassirer, R., 248, 260.
Castan, 450.
pu CasTEL, 463.
Ceci, 460.
Crtsus, 175, 389.
CHALVET, 408.
CHamBeErs, Tuomas K., 163, 165.
Cuarcot, 140, 179, 243, 244, 245, 246, 248,
250, 522.
CHARLES, 545.
CHARRIER, 256.
CHaRRIN, 260.
CuHarrRon, 482.
CuELius, 415.
CHENZINSKY, 295.
Cuossat, 4.
CLarK, 335, 386.
CuarkgE, I. I., 247, 260, 506.
CoBBo.p, 504, 510, 511, 521, 546, 547.
Couen, G., 425, 435.
CoHNHEIM, J., 370, 386, 424, 558.
Cotomepinti, 271.
Contt, 394.
Corvus, 390.
Cornet, 296.
CrEMER, 18.
CuntgrR, 421.
CunniIncHAM, 190, 507.
Curscumann, H., 246, 260, 308.
Curtis, 571.
CYBULSKI, 205, 208.
v. Cron, 208.
Dapay, 520.
DaniEts, 517.
Dapper, 56, 73.
Dars, A., 277.
INDEX OF AUTHORS
Darier, 208.
Darwin, 418.
DavaIne, G., 244, 260, 504, 507, 517, 521,
534.
Davigs, Y., 194.
Dezove, 161.
Derrxke, 515.
Dexaio, 504, 523.
Devrecu, A., 126, 397.
DEMANTKE, 539.
Demarquay, 546, 547.
Demme, 460, 549.
Denys, 460.
Dent, 504.
Desnos, 451.
DeETTweEILeR, 63.
Deucuer, 46, 47, 48.
Dresine, 510, 546.
Dock, 507.
Dourn, 468.
DE DomeEnIcis, 205.
DonpeErs, 166.
Donvonzus, 390.
Donne, 507.
Doérine, 391.
Drawitz, 390.
DrecuHsEL, 189.
Drrzr, 208.
Dusini, 553, 560.
Ducuex, 408.
DuckwortH, Sir Dyce, 128.
Ducis, 565, 566.
Duurine, 479.
Dusarvin, 507, 516, 544.
Diinscumann, 40.
v. Duscu, 463, 480, 492, 493.
Duvau, 510.
E
Exstein, W., 56, 70, 72, 73, 74, 125, 151,
152, 167, 211, 355, 375, 386.
Ecurutus, 390.
Eckrexkrantz, 507.
Ecxuarp, 114, 115.
Epe., 225.
Epwarps, 313.
EHRENBERG, 507.
Exruarpt, 113.
Enrzicu, P., 293, 294, 295, 300, 304, 305,
319, 345, 346, 347, 351, 354, 355, 365,
375, 376, 377, 384, 387.
605
Ercunorst, 39.
EIsentone, 523.
Evter, J., 259, 260.
Enaet, C. 8., 286, 347.
Epstein, 507, 548.
Eps, 242.
Ersen, 47.
Ervant, 563.
Escuun, 596.
Evcatenus, 390, 391.
EVERSMANN, 572.
Ewa tp, C. A., 179, 180, 190, 193, 194, 212.
F
Fasricius, 566, 574.
Fauve, 396.
FEDEROLF, 553.
FErILCHENFELD, L., 269.
Ferris, 195.
FiscHer, Emin, 265.
Fiscuer, M., 416, 423, 435, 520, 569.
FLEINER, 216, 220.
FLEISCHER, 42, 353.
FLEISCHL, 277.
FLEMMING, 565.
Fuisscu, 239.
Fieury, 386.
FLEXNER, 505.
Fiopervus, 447.
Foa, 209, 219.
Forpyce, 437.
Forster, 8.
Fox, 510.
Francorte, 564.
Frank, Jonann Peter, 144, 160, 162.
FRANKEL, A., 130, 210, 233, 355.
FRAENKEL, 8., 189.
Frericus, 10.
FREUDWEILER, 376, 387.
FRIEDBERGER, 510.
FRIEDENTHAL, 266.
FULLEBORN, 518.
FURSTENBERG, 567.
vy. Fira, 210.
G
GAERTNER, 279.
GateEn, 545.
GaLLAND-GLEIZE, 449.
GarkRb, 531.
606
Garrop, 128, 132, 136, 146.
Garrop, ALFRED, 243, 255, 260, 398, 410.
GarRRoD, ARCHIBALD, 243, 257, 260.
G&Artie, H., 39.
GARTNER, 429, 486.
GauTHIER, 195.
Gavoy-Rirrer, 424.
Gayet, 441.
pvE Gesr, 566, 571, 573.
GEIGEL, 124.
GENDRE, 460.
GEPPERT, 8, 27, 34.
GERHARDT, 38.
GERHARDT, C., 253, 256, 260, 342,
Geruarpt, D., 110.
Gervais, 566, 569.
GissxerR, 510.
GiupertT, A., 144.
GinNARD, 460.
GIOVANNINI, 429, 460, 463, 489.
Gury, 187. ,
Gocut, 417, 432, 439, 440, 441, 455, 456.
Gorzz, 514, 517, 565.
GotpMann, 190.
GoLowin, 535.
GoTTLIEB, 190, 208.
GotTsTEIN, 195.
GRANDIDIER, 414, 415, 417, 422, 424, 452.
Grass!, 508, 507, 516, 517, 523, 545, 546,
548, 550.
GRASSMANN, 48.
GRATIOLET, 205.
Grawitz, E., 29, 320, 328, 387, 424.
Green, 463.
GREENFELD, 180.
GREENHOw, 214.
GRETSEL, 381, 387.
GRIESINGER, 381, 560.
GRIFFOUILLERES, 119.
GRISOLLE, 459.
Gros, 505.
GROSGLIK, 8., 444.
Gruser, 13.
Grunp, 266.
Grinie, 543.
GUBLER, 239.
GUELLIoT, 482.
GuLL, Sir Wo., 179.
GitrerBock, 535.
Gururig, 451.
Guyon, 450.
Guyot, 455, 546.
INDEX OF
AUTHORS
H
Haaser, 157, 158.
Haun, 542.
HALpAnge, 328.
Hamm, 245.
HAMMARSTEN, 265.
HAMMERSCHLAG, 284,
Hamonic, 449.
Hanav, 233, 239, 241.
Hanor, 460.
HANSEMANN, 239, 241.
Harwey, 205, 394, 513.
Harris, 445.
Harrison, 513.
Harrmann, 551.
Harvey, 70, 72, 163, 165.
Hayem, 465, 488.
HEBERDEN, 248.
Hepra, 470.
HEIDENHAIN, 347.
HEINSHEIMER, 180.
HELMHOLTZ, 2.
Hiémarp, 454.
HEN gE, 536.
HENNEBERG, 19.
Hennie, 190.
Henocu, 403, 404, 479, 481, 482, 485,
497.
HERMANN, 566.
HERTOGHE, 192, 194.
Hertwie, O., 418.
Herve, 482.
Herz, 251, 260.
Hevusner, 36, 47, 486.
HEwEs, 283.
HEYLAND, 424,
Hermann, R., 454.
Hitton, J., 553.
Hinswortu, 542.
Hippocrates, 147, 166, 389, 473.
Hirscu, Aveust, 389, 390, 391,
398.
Hirscu, Tu., 441.
HirscuFexp, F., 14, 40, 56, 70, 72, 73, 74,
174,
His, Jr., 130.
His, W., 243, 417, 418.
Hirzie, 596.
Hocus, 480.
Hopexin, 370.
Horsauer, 446.
397,
INDEX OF AUTHORS
Horr, 256, 260, 439, 455, 456.
HorrmMann, ALBIN, 88, 243, 253, 260,
424,
HorMEIster, 3 190, 196.
Home, 395.
Hooper, 423.
HOprner, 558.
Hopre-Sryier, 1, 8, 36, 49, 505.
Horsizy, 189.
Hos, 417.
v. Héssiin, 23, 48, 175, 176.
Huser, 538, 549, 576.
HULTGREN, 225.
Hun, 185.
HunpDHAUSEN, JOHANNES, 167.
Hounscue, 570.
Hurcuinson, Woops, 241.
Hyrtz, 152.
Isma, 505, 521.
ImMERMANN, 164, 406, 425, 427, 432.
IsraEL, J., 445, 446, 451.
IsRaEL, O., 234, 240.
Jackson, 394.
Jacos, 18, 266.
Jacosi, 207, 598.
JacoBy, 508, 563.
v. Jaxscu, R., 382, 387, 408, 579.
JANOWSKI, 507.
JANZEN, 120.
JaQuet, 34, 35, 190.
JASTROWITZ, 266, 269.
JENKINS, 531.
JoHNSTON, 565.
JOINVILLE, 390.
Joties, A., 374, 387.
Jongs, Lioyp, 334, 460.
JosEPH, 572.
JiRGcens, 216, 506, 535.
K
Kacuet, M., 249, 260.
v. Kanipen, 213, 216.
Kauter, 115.
607
Ka.invero, 216.
KatrTenspacn, 494,
KANNENBERG, 507.
Kapost, 479.
Karewsk1, 542.
Karpe.ies, 565.
Kartutis, 505, 506, 513.
Kasr, 186.
Karzenstein, 24, 27.
Kavurmann, 18.
Kayser, 18, 21.
DE KEERSMAECKER, 447,
Keurer, 435, 454.
Kersert, 510.
Kipp, 433.
Kiscu, 70, 72, 73, 74, 177.
KueLpau., 447.
Kieps, 235, 238, 408, 418, 460.
KLEHMET, 539.
Kiem, 528.
Kuemperer, G., 14, 31, 39, 40, 443, 451.
Knapp, 268.
Kosert, 598.
Kocu, Ropert, 275, 290, 292, 460, 461.
Kocu, W., 427, 428, 429, 430.
Kocurr, 187.
Kocuegr, Jr., 189.
KoruHiLerR, ARMIN, 462.
v. Koacrrer, 463, 464, 465, 488.
Kop, 489.
KG Liiker, 347, 418.
Konia, F., 432, 488, 439, 440, 455, 456.
K6ppe, 287.
Korxunorr, 10.
Kosseu, A., 265, 266.
Kramer, 391.
KRAMER, 535.
Kratz, 556, 557.
Kraus, FRr., 27, 28, 30, 33.
Krauss, 463.
Krautner, 573.
KREBEL, 392, 396.
Kremer, O., 256, 260.
Kretscuy, 408.
Krue, B., 15, 16, 17, 19, 56, 57, 61.
KRUKENBERG, 209.
Kinn, 544.
Kitz, 112, 268.
Kumacawa, 14.
Kunprat, 375, 387.
Kinstie, 39, 507.
Kurimoro, 521.
608
L
LaBanb, 262, 268.
LaBouLBeEne, 408, 574, 566.
Lamst, 507, 565.
LANCEREAUX, 243, 252, 257, 260.
Lanpavu, 197.
Lanpri-BeEavvals, 243, 260.
v. LANGER, 229, 230, 235, 238.
LaNnGERuHANS, 555.
Lane.ois, 205, 206.
Larrey, 151.
Lavupon, 570, 575.
LAvENSTEIN, 442, 506.
Laves, 28, 33.
Lavoisier, 2.
Lazarus, A., 275, 304, 319.
Lepreton, 460, 462, 468.
Leg, 397.
Le Genpre, 128, 460.
Lreae, Wickyam, 433, 453.
Leaurn, 442, 448.
Leumann, C. G, 10, 32.
LEHNE, 539.
LEICHTENSTERN, 29, 194, 545, 549, 560,
562, 563, 564.
Leipy, 546.
LrIsHMAN, 292, 296.
Letorr, 463, 464, 465, 488.
LENNANDER, 447.
Lennuor, 540.
Lzo, 28, 33.
Lion, 163.
Liépine, 262.
Letzericu, 460, 461.
von Leuss, 303, 344.
Leucxart, R., 506, 509, 510, 514, 516,
521, 526, 545, 549, 550, 558, 555, 565,
576.
LreurHo.p, 474, 479, 493.
Levinsen, 560.
Lrvy-Dorn, 195.
LewanpowskI, 208, 226.
Lewin, G., 214, 219.
Lewis, 508, 546.
v. LeypEn, 39, 40, 443, 506.
LIcHTENFELDT, 20.
LIEBERMEISTER, 25.
von Lizzie, Justus, 2, 3, 4, 50, 51, 398, 447.
Linp, 391.
LInDEMANN, 258, 260, 506.
Linpner, 508.
INDEX OF AUTHORS
Linné, 508, 548, 550, 565, 566, 572.
Linser, 440.
v. Linstow, 516, 518, 519, 546, 547, 549,
556, 558, 564.
Lipmann-Wutrr, 39.
Liston, 423.
Litten, M., 388, 465, 507.
Locxwoop, 461.
LorFrF_ER, 291.
Loxrscu, 505.
Lorw1, 51.
Lorwy, A., 25, 196, 286.
Loussz, 25.
Lonecorg, 365, 371.
Loos, 503, 512, 513, 514, 546, 562.
Lossgen, 415, 424.
Loumeau, 449.
Lowir, 356.
Ltcxsz, 172.
Lupwie, 1.
Lurr, 128.
Lussano, 563.
Lirnse, 16, 17, 18, 19, 21, 40, 41, 56, 57,
265.
LUrxKemMuier, 543.
Luz, 503, 548, 553.
Luzert, 460.
Masitie, 192.
Mason, 195.
MackeEnzig, 189.
Manpen, Cots, 513.
Maveuune, 534, 537.
Magnus, 390.
Maanus-Levy, A., 23, 27, 28, 29, 30, 33,
34, 35, 64, 130, 185, 192.
Macurre, 535.
Matiuuarp, L., 257, 260.
MALHERBE, 448, 510.
Matmsten, 508.
ManasseE, K., 209, 245, 261, 533.
Manco tp, 528.
Mann, 51.
Manson, 546, 547.
Maracuiano, 495.
Marcuanp, 206, 507.
Marran, 460.
Man, 394.
INDEX OF
Marz, Pierre, 229, 230, 232, 237, 238,
240, 241, 243, 244, 246, 256.
MaRINESCU, 237, 238.
MaRIScHLER, 43.
Marquarpsen, E., 167.
Marro, 551.
MartinEau, 5381.
Marx, 504.
Mastus, 564.
Matruss, M., 167.
Matuiev, 117, 468.
May, 30, 40, 507.
Mayopt, 536.
McConnez, 508.
McKenziz, D., 454, 463.
McLennan, 190.
McMounn, 209, 212.
Méentn, 566, 569.
Menus, 560.
Mricen, 574.
MEINERT, 323, 335.
MsziscHer, 277.
MeEuntikorr, 516.
Mencxe, 560.
MeENnDELSOHN, 261.
Menzer, 257, 260.
v. MERING, 24, 25, 48.
Merrett, 572.
Meyer, Fritz, 270, 271.
Meyer, R., 2, 33.
MixscHer, 506.
Mixuticz, 193.
Minter, 394.
MrtcHELL, 8S. Wetr, 58, 65, 66.
Miura, 507.
Miyake, 569.
Mos1vs, 64.
Moxorr, 347.
MO.tuER, 485.
Monie, 565.
Moors, 208.
MoossruceGErR, 553.
MorazewskI, 47.
Mosier, 531, 549, 560, 576.
Muutmann, 209.
Miuer, Fr., 29, 31, 39, 45, 46, 47, 61,
64, 266, 528.
Miizr, Jon., 246, 260.
Miier, W., 259, 260.
Murray, 189:
Murert, 393, 394.
MutTzENBECHER, 415.
40
AUTHORS 609
N
Nassg, 415.
Naunyn, B., 31, 39, 77, 265, 446.
NEALE, 411.
NEBELTHAU, 31.
Neuwrine, 27, 28, 33.
Netsser, 536.
Nerriesnip, 494.
NEvBERG, Car, 265, 266, 267, 268, 269.
Neumann, H., 265, 266, 267, 347, 354, 363,
461, 486, 487.
Neusser, 203, 220.
Newport, 565.
Nicuots, 454.
Nicoxarer, A., 148.
Niemeyer, Ferix, 340.
Nirzscu, 569.
Nott, 265.
Nowne, 558.
v. Noorpvgn, C., 15, 16, 28, 34, 35, 37, 38,
39, 40, 41, 42, 47, 54, 56, 68, 72, 73,
74, 194, 323, 334.
NorDENSKJOLD, 411.
Norpmann, 514.
Normanp, 544, 545.
NoTHNAGEL, 205, 213, 335.
Nutatu, 571.
O
Orrret, 56, 70, 72, 73, 74, 75, 174, 175,
425, 427, 432.
OESTREICH, 224.
Oxavs, 390.
Outver, THomas, 131, 207, 277.
O'NEILL, Joun, 548.
Oprtz, 408.
Orp, WILLIAM, 179, 184, 185.
Oster, WiLuiaM, 151, 283, 382, 383,
387.
OswaLp, 189, 190.
OranI, 511.
Orrr, 424.
Orro, 415.
Owen, 553.
OzaRKIEWICZ, 43.
Ozzarp, 547.
Pane, 546.
PaprENHEIM, 347.
610
Park, 196.
Parona, 545, 560.
Pastreav, 450.
Peirer, E., 501, 576.
Pet, 180, 375, 387.
Peuczynsxi, 549.
Penzoupt, 353, 408.
PrppPEr, 221.
Perricic, 541.
Prrroncito, 509, 560.
PEscHEL, 14.
Petrone, 460.
vy. Perrenxorer, 4, 7, 33, 36, 154, 352,
353.
Preirrer, E., 19, 248, 261.
Priicer, E., 1, 15, 16, 18, 19, 20, 22, 38,
41, 50, 57, 447.
PHILIPPEAUX, 205.
PicHipr, 528.
PickarptT, 226.
Picqut, 446.
Pinxvs, 375, 376. 377, 384, 387.
Puayrair, 58, 65, 66.
Puiny, 163, 389.
Porrizr, 446.
Poncet, A., 257, 261.
Ponrick, 186, 196, 242.
Popp, 544.
PortTscuinsky, 574.
Posapac, 536.
Posseit, 528, 529.
Potain, 224, 253, 261.
Porat, 257, 261.
Pousson, 446, 449.
PRIBRAM, 243, 244, 246, 251, 255, 256, 259,
261.
Proscuer, 290.
Provt, 96.
PruppeEn, 185.
Pruner, 560, 570.
Purinton, 208.
Putnam, James J., 314.
Q
Quénu, 195.
QuINncKE, 112, 341, 505.
R
RazinowitTsca, H., 251, 261.
RaxELMANN, 570.
INDEX OF AUTHORS
Ratruiet, 510, 515.
Rainey, 506.
Rayer, 470.
Raymonp, 214.
Reatez, 271.
v. RECKLINGHAUSEN, 427, 465.
Recuus, 195.
Repti, 572.
Repon, 515.
Rerep, Dorotuy, 371.
Reep, M., 387.
Reenier, 446.
ReEHER, 460.
Retcu, 535.
Rernpacu, 193.
REINHOLD, 195.
Reiss, L., 199.
Renavt, 213.
REVERDIN, 187.
Reyuwer, 504, 523.
Risor, 418.
RicutTer, 196.
RiEDER, 322, 347.
Regt, 213, 463, 464, 465, 488.
Riemann, 531.
Rietuus, 27, 30.
Rivey, 571.
v. RInDFLEISCH, 359.
Rirrer, 42.
Rivotta, 511.
Roperts, 127, 137.
Rosin, A., 30, 157, 164, 522.
Rosinson, 262.
Ropvrsr, 334, 341, 408.
Rosssg, 250, 261.
Roumann, 18.
RounstEIn, 319.
Roto, 87.
Roma, 257, 261.
RoMANowskEy, 292.
Rome, 271.
RonssEvs, 390.
Roos, 189, 505, 507.
Roque, 244, 256, 261.
Rosrmann, R., 42, 50.
RosEnBERG, 506.
RosENELL, 394.
Rosenaquist, 39.
Rosin, 262, 268.
Rosirzx1, 191.
Rost, 18. ,
Rovieu, 533.
INDEX OF AUTHORS
Rovsine, 447, 448,
RUBENSTEIN, 347, 365, 366.
Rusnzr, 2, 3, 4, 5, 6, 9, 12, 21, 28, 34, 36,
37, 44, 47, 98.
Rupo1n, 510, 514, 516, 517, 546, 548,
552, 560, 570.
Rurr, 264.
Runesere, 504, 523,
Ruprrecut, 556.
SABATIER, 442.
SaHul, 279, 425.
Saint-Remy, 506.
Sauis, 541.
Satkowsk1, E., 262, 263, 265, 266, 267
269, 272.
Satomon, 25.
SAmiscH, 567.
Santini, 533.
Savace, 180.
Savenzy, 419, 565.
Scanzgr, 543.
ScuArrr, 207.
Scuapiro, 111, 504, 523.
ScHATTENFROH, 25.
Scuarz, 543.
ScHAuDINN, 506, 508.
ScHauMann, 319, 504, 523.
Scursy-Bucu, 458, 477.
Scuepe, 442.
Scuruse, 547, 548.
Scurassr, B., 386, 387.
Scurrr, M., 187, 188, 205.
Scrip, Water, 379, 387.
ScHILLING, 225.
ScHLEICH, 584.
ScHLESINGER, 247, 261.
ScHMALTz, 284,
Scumipt, Ap., 4, 10, 45, 46, 47, 48, 507
543.
Scumipt, ALEX., 424.
ScHMIEDEBERG, 342.
Scumirz, 80, 81.
ScHMoLi, 42.
Scuneiwer, 408, 544.
Scunirzier, 544.
ScHouz, 29.
ScHONFELD, 542.
ScHONLEIN,
476, 477, 478, 479.
?
?
154, 457, 470, 473, 474, 475,
611
ScuRANK, 565.
Scurerper, E., 169.
Scurépr, 194,
ScHusBerc, 507.
ScHuBert, 43.
Scnucuarpr, 250, 261.
ScHULer, M,, 243, 244, 255, 261.
ScHULTZE, Max, 347, 543.
Scuiinmayen, 507.
Scuiisster, 536.
Scuwas, 459.
ScHwa.pe, 167,
ScHWENINGER, 70, 75.
Scuwimmer, 458.
Scripa, 569.
S&pan, 419.
SEGGEL, 407.
Senator, H., 115, 226, 243, 248, 261, 370,
387, 442, 443, 446, 447, 451.
Senn, 369.
SERRANO, 189.
SuHaw, 179, 565.
v. Stezoxp, 510, 516, 526, 570.
Sianoret, 572.
SILBERMANN, 462, 463, 464, 495.
Simmons, 371.
Simon, 556, 569.
Simon-Lecrarn, 460.
Siven, 14, 15.
SKALLER, 507.
Smit, 328.
SOENNECKEN, 276.
Sonven, 36, 37.
Sonsino, 513.
Speck, 25.
SPERLING, 549.
SPIETSCHKA, 495.
STaBeEL, 193.
STADELMANN,
STADTHAGEN,
STaHEL, 415.
STEINBACHER, J., 174.
STEINBERG, 508.
STEINBRUcK, 535.
STENGEL, 320.
Stepp, 549.
STERNBERG, 229, 230, 231, 233, 234, 235,
236, 239, 240, 241, 387, 505.
STEVEN, 366.
STEYSKAL, 47.
Stites, 503, 506.
Stockvis, 508.
34, 234.
353.
612 INDEX OF
StorRMER, 113.
SrrassBurRGER, J., 46, 48.
Strauss, H., 47, 112, 257, 261, 319, 361.
Strene, 507.
VAN DER STRICHT, CLAUS, 239.
Strocanow, 465, 488.
Strom, 482.
Struse, 507.
SrrRuBELL, 113, 120.
STRUMPELL, 39, 236, 246, 436.
Strive, 27, 28, 33.
Suspoitic, 541.
Suprecx, 251, 261.
SvENSON, 27, 32, 34.
SypenHAM, Tuomas, 126, 147, 340, 391.
SZKEKERES, 535.
Szymonowicz, 205, 208.
T
TALLERMANN, 258, 261.
TaLiquist, 21, 277, 523.
Tauma, 386, 387.
TamBacu, 189.
TAMBURINI, 239, 241.
Tarcerr, 506.
TépenaT, 449.
TEISSIER, 244, 256, 261, 545.
TERILLON, 534.
Terrier, 118.
Tuam, 507.
TuHirbseE, 460.
TuHévENoT, 535.
THIELE, 27, 28, 33.
THIERFELDER, 267.
Tuomas, 509.
THompson, 218.
TIGERSTEDT, 8, 36, 37.
Tizzon1, 205, 206, 429, 460, 463, 489.
TouLens, 127, 137, 142.
Traveg, L., 31, 39, 152, 474, 488, 493.
TREUTLER, 514.
TRoussEAU, 112, 126, 244, 261, 334.
TscHirKorr, 212.
Turek, 282, 283.
TURNER, 395.
Umber, 266.
Urnorr, 241.
AUTHORS
Veuicu, 208.
VetscuH, 545.
Vervun, 563.
VerRGA, 229, 238.
VERWORN, 52.
VESSALLE, 460.
Vipat, 245, 261.
Vieut, 417.
Vierorpvt, 528.
Vircnow, 204, 209, 240, 244, 329, 331, 338,
344, 347, 370, 377, 423, 425, 431, 432,
528.
Virrac, 536.
VoGEL, 42, 268.
VoaLeEr, 528.
v. Vort, 1, 4, 6, 7, 9, 10, 11, 13, 14, 15, 16,
18, 19, 20, 21, 22, 23, 33, 41, 44, 45,
50, 51, 56, 57, 352, 353.
VoLHARD, 46.
v. VoLKMANN, R., 243, 244, 246, 261, 319,
531.
VuLPIAN, 209.
Ww
Wapp, 163.
WaceEnmann, 535.
WaALDEYER, 231.
DE WALDHEIM, FiscHER, 566.
Watuacg, 80. )
Warp, 517.
WartTHIN, 369, 383.
WEICHSELBAUM, 250, 256, 261.
WEIGERT, 465.
Wei, Emin, 119, 144.
WEINLAND, 515, 516.
WEINTRAUD, 1, 28, 33, 47.
WELLs, GipEon, 190, 193, 195.
WENDELSTADT, 192.
Wertuor, 453, 457.
WESTPHAL, 124, 534, 544.
Wicumann, R., 256.
Wipat, 460.
Wiepemann, 540.
Wiervs, 390.
WIERUSZSKIJ, 394.
Wunuorr, 506.
WIKNER, 462.
Wiks, 370, 387.
Wian, 470.
Winoerapvorr, 511, 512.
WINTERBERG, 542.
INDEX OF AUTHORS
WINTERNITz, H., 25.
WINZERLING, 536.
Wirran, 479.
WoHLGEMUTH, 266.
Wouumann, 255, 259, 261.
Wo pert, 25.
Wricut, A. E., 292, 296, 398, 399.
Wucuerer, 560.
Wonver.icu, 330, 470.
Y
Yamaaiva, 511.
ZEDER, 548.
ZEEHUISEN, 506.
v. ZENKER, 553, 554.
ZENNER, 248.
ZIEGLER, 535.
ZIEMANN, 292.
v. ZIEMSSEN, 322, 379.
Zinn, 80, 81, 563, 545.
ZONDEK, 445.
ZUNKER, 507.
ZuNtTzZ, 8, 18, 22, 23, 24, 30, 32, 34, 35.
613
INDEX
A
Abdominal cavity, echinococcus in, 531.
lymphadenoids in, 375.
Abdominal lymph-channels, displaced, 383.
Abdominal sympathetic, disease of, 111.
Abortion causing thrombophlebitis, 478.
. Abscess of liver in dysentery, 505.
Absorption, increase of, by stasis, 259.
of food, disturbances of, 43.
of food, insufficient, 6.
Acanthocephala, 565.
Acarus, harvest, 565.
of birds, 565.
transmitted by prostitutes, 567.
Acetone reaction, 102.
Acetonuria, 91.
Achylia, 47.
gastrica, 313.
Acid, glycuronic, 262, 267.
Acid poisoning, diagnosis and prognosis of,
580.
Acidosis, 87, 90, 95, 97, 102, 579.
Acids, use of, in obesity, 178.
Acquired diseases, 414.
Acromegalia, 195, 229.
autopsy reports of, 230.
benign, 233.
bony enlargement in, 234.
combination of, with diabetes, 233.
development of jaw in, 235.
disproportion of bodily parts in, 230.
duration of, 234.
enlargement of soft parts in, 237.
etiology of, 230.
eye changes in, 232.
functional structures in, 236.
malignant, 233, 239, 241.
nervous phenomena caused by, 233.
pathological anatomy of, 237.
pathology of, 234.
photographs of cases of, 231.
Acromegalia, symptoms of, 231.
therapy of, 242.
Addison’s disease, 199.
aggravation and improvement of, 225.
atypical cases of, 218.
autopsy reports of, 214.
cardiac weakness in, 211.
cases of remission in, 225.
changes of the nervous system in, 215,
216.
clinical picture of, 200, 210, 215, 222.
course and duration of, 210.
cutaneous complications of, 202.
dependence of, upon tuberculosis, 221.
deviations from type of, 214.
diagnosis of, 222.
experimental investigation of, 206.
gastric and intestinal symptoms in, 211.
general cachexia, a cause of, 221.
general conditions in, 203, 221.
histology of, 222.
intestinal symptoms in, 218.
muscular weakness in, 200.
nature of, 210.
nervous and toxic theories of, 221.
nervous symptoms in, 201, 206.
operative cure of, 224.
pathologico-anatomical lesions of, 202.
pigmentation of skin in, 218.
recognition of, 222.
spontaneous course of, 226.
statistics of, 214.
treatment of, 223, 224, 228, 229.
urine in, 212.
Addison’s disease with fluctuating course,
223.
Addison’s disease without adrenal affection,
214.
without bronzing, 214.
Adenomata, malignant, 239.
Adipose tissue, development of, 54.
Adipose tissue, in anemia, 308.
615
616
Adipositas, 151.
Adolescents, chlorosis in, 320, 336.
obesity of, 68, 154.
Adrenal glands, tumors of, 219.
Adrenal insufficiency, 223.
Adrenal parenchyma, chemical investiga-
tions of, 209.
Adrenal tablets, 226.
Adrenal therapy, results of, 227. :
Adrenals, absence of function of, 228.
accessory, 206, 220.
anatomy and physiology of, 204.
animal, implantation of, 226.
ascending disease of, 220.
atrophy of, 202.
cessation of function of, 199, 222.
changes of, in Addison’s disease, 203.
chemistry -of, 222.
degeneration of, 214, 223.
disease of, 199, 202.
differing from typical Addison’s, 215,
220.
extirpation of, 205, 206, 219.
function of, 203, 207.
functional disturbance of, 218.
organic extract of, 197, 207, 226 (see
also Suprarenal).
inflammation surrounding, 203.
internal secretion of, 209.
malignant tumors of, 220.
nature of, 203.
necessity of, to life, 205.
neoplasms of, 202.
parenchyma of, 221.
physiologic function of, 205.
pigment in, 209.
protective functions of, 207.
supplementary, 206.
unchanged condition of, in Addison’s
disease, 219.
use of, in natural condition, 226.
Adrenalin to arrest bleeding, 454.
Adynamia, 200.
Affections of bones and joints in the obese,
69.
Agaricus poisoning, 599.
Aged, metabolism of the, 36.
Aglycosuria, 93, 95.
dietetic, 87.
Air, fresh, reduced consumption of, 333.
Albumin, absorption of, in the sick, 47.
accumulation of, 41.
INDEX
Albumin, circulating, 11, 57.
dead and living, 3.
decomposition of, 7, 11, 39.
in ankylostomiasis, 563.
deficiency and superfluity of, 11.
introduction of, 11.
nuclear, 52.
organic, 16, 43. -
reserve, 16, 41, 57.
splitting of, 13.
superfluous amounts of, 12.
toxogenous decomposition of, 39, 40.
Albumin and iron preparations, 341.
Albumin as a “working mass,” 16.
as basis of metabolic products, 2.
Albumin bodies, 10, 70.
Albumin deposition, 15.
Albumin in food, indispensability of, 10.
minimal amount of, 74.
Albumin in urine of diabetics, 121.
Albumin metabolism, 35.
Albumin minimum, 10, 13.
hygienic and physiologic, 11.
Albumin of body, 43, 55.
Albumin of the food, 43, 73.
action of, in nutrition, 71.
Albumin savers, 15, 40.
Albuminuria, 86.
in diabetes, 86.
in. leukemia, 353.
in morbus maculosus, 475, 498.
in purpura, 493.
Alcohol, energy carried by, 50.
excess in, a cause of diabetes, 119.
gout caused by, 127, 130.
in beer, 106.
premature indulgence in, 332.
use of, in the cure of obesity, 74.
in diabetes, 101.
Alcoholism, chronic, 591.
Aleuronat, 70, 167.
| Alkali tension, 286.
Alkalies, salts of, poisoning by, 582.
Alkalimeter, 286.
Alkaloids, poisoning from, 594.
Alloxur bodies, 374.
Aloin poisoning, 598.
Alopecia in gout, 143.
Amanita phalloides,.600.
Amebe, 505.
occurrence of, in various parts of body,
505, 506. .
INDEX 617
Ameboid movement, 346.
Amenorrhea in myxedema, 185.
American Pediatric Society’s investigation
of infantile scurvy, 393, 404, 485.
American remedy for gout, 135.
Amido-benzol poisoning, 592.
Amphistomum hominis, 508.
Amyloid degeneration, 250.
Anacidity of stomach, 47.
Anatomical changes in chronic articular
rheumatism, 248.
Anematosis, 221.
Anemia, 304.
absence of nervous symptoms in, 328.
ascarides, a cause of, 549.
blood changes in, 301, 306, 328.
blood examination in, 307, 309.
bothriocephalus, 311, 317.
caused by uncinaria, 318.
change of climate in, 310, 319.
clinical symptomatology of, 308.
cold applications in, 310.
combination of, with obesity, 156.
decreased metabolism in, 33.
destruction of tissue in, 39.
differentiation of simple from pernicious,
317.
excessive, 359.
fatty degeneration of, 308.
faulty nutrition a cause of, 306.
general metabolism of, 308.
general treatment of, 319.
hemorrhagic diathesis in, 308.
idiopathic, 306.
infantum pseudoleukemica, 382.
jaundice in, 312.
leukemia, caused by, 352, 357, 367.
lymphatica, 370.
lymphaticolienalis, 370.
montana, 560.
of brickmakers, 560.
pernicious, 47, 305, 314, 382.
post-malarial, 318.
profound, 203.
progressive pernicious, 305, 310, 563.
cardiac symptoms in, 313.
clinical picture of, 312.
course of, 317.
forms of, 314.
metabolism in, 313.
post mortem findings in, 314.
primary, 310.
Anemia, progressive pernicious, remission
in, 317.
symptoms of, 311.
tumor formation in, 315.
secondary or symptomatic, 305.
severe, 357, 358.
simple, 305.
cause of, 305.
diagnosis of, 309.
prognosis of, 309.
treatment of, 309.
chronic, 381.
splenic, 326, 381.
therapy of, 318.
variety of, indicated by blood changes,
312.
well-nourished appearance in, 313.
Anemia in Hodgkin’s disease, 373.
Anemia from tape-worm, 523.
Anemics with normal hemoglobin, 281.
Angina pectoris, 141.
Angina pectoris in diabetes, 85.
Angioneurosis, 448.
Anguillula, development of, 545.
intestinalis et stercoralis, Bavay, 544, 545.
putrefaciens, 544.
Anilin poisoning, 592.
- Animal economy, 4.
Animal poisons, 598.
Animal parasites of man, 501.
Animal protoplasm, decomposition of, 52.
Animals, echinococcus disease among, 529.
fattening of, 153.
parasites derived from, 503.
Ankle, sprain of, 146.
Ankylosis, 259.
fibrous, 250.
of bleeders, 438.
Ankylostoma, 501.
disturbances caused by, 504.
duodenale, 561.
Ankylostomiasis, 560.
autopsy findings of, 563.
prophylaxis and treatment of, 564.
symptoms of, 562.
Anorexia, 323.
in gout, 140.
Anthrax, 571.
Antifat cures, 72, 160, 170.
indication for, 69.
irrational, 55.
metabolism in, 56.
618
Antipyrin poisoning, 594.
Antirheumatics, in gout, 149.
Antitoxic action in adrenals, 221.
Anus, itching of, 551.
Aorta, aneurism of, 216.
chlorotica, 329.
of hemophiliacs, 431.
Apepsia. See Achylia.
gastrica, 47.
Apparatus, use of, in rheumatism, 259.
Appetite, 29.
caprices of, 60, 323, 428.
diminished by decreased fluid intake, 75.
enormous, in diabetes, 113.
Appetite in the healthy and the sick, 22.
Appetite of the obese, 157.
Arabinose, 267.
Argas reflexus, Fabricius, 566.
Argas, varieties of, 566.
Arnican poisoning, 598.
Arnica, tincture of, 598.
Aromatics, poisoning by, 592.
Arsenic, idiosyncrasy for, 319.
in treatment of anemia, 309.
chlorosis, 343.
gout, 149.
Hodgkin’s disease, 378.
myxedema, 192.
pseudo-leukemia, 386.
poisoning by, 586.
Arsenic atoxyl, 379.
Arsenious acid in Hodgkin’s disease, 379.
Artefacts, 356.
Arteries, atheromatous degeneration of, 157.
central, marantic thrombosis of, 358.
compression of, for hemorrhage, 454.
condition of, as indication of age, 81.
peripheral, pulsation of, 322.
pulsation of, in anemia, 313.
Arteriosclerosis, differentiation of, from dia-
betes, 121.
in diabetes, 85.
Arthritic gout, primary, 131.
Arthritis, 125, 493.
chronic, Heberden’s nodes in, 248.
deformans, 244, 246.
gouty, 125.
hereditary, 253.
in hemorrhagic diseases, 476.
pauperum, 253.
urica, 125.
Arthritisme, 252, 255,
INDEX
Arthropathies, hemophilic, 455.
Arthropoda, 565.
Articulation, sterno-clavicular, 322.
Ascarides, causing suffocation, 550.
expulsion of, by santonin, 550.
occurrence of, in various parts of body,
549, 550.
Ascaris, infection of children by, 549.
lumbricoides, Linné, 548.
maritima, Leuckart, 549.
mystax, Zeder, 548.
Ascites, nitrogen balance after, 43.
occurrence of, in pseudo-leukemia, 386.
Asphyxia arsenicalis, 586.
Assafetida, in diabetes, 122.
Assimilation, insufficient, 44.
Asthenia, in Addison’s disease, 210.
Asthma, 174.
Athyreoidism, 225.
Athyreosis chronica, 188.
Atomatropin, 601.
Atoxyl, 386.
Atrophy in a nursling, 47.
Atrophy of ganglion cells, 217.
Atropin, in diabetes, 123.
Atropin poisoning, 597.
Auscultatory phenomena, 536.
Austrian marine, scurvy in, 412.
Autointoxication, 199.
Autopsy findings in Addison’s disease, 203.
Azoturia, 22.
B
Babes, bacillus found by, 394.
Bachstrom’s theory of scurvy, 397,
Bacillus anthracis, 461.
hemorrhagicus Kolb, 490.
hemorrhagicus velenosus, 489.
of plague, 571.
of typhoid, 571.
producing scurvy, 399.
purpure, 460, 461, 467.
pyocyaneus 8, 461.
Balanitis of prepuce, 551.
Balantidium coli, 501.
minutum, 508.
Balsam of Peru, for scabies, 569.
Banting, cure for corpulence, 70, 72, 73, 74,
163, 164, 165, 166, 173, 175.
Banti’s disease, 370, 381.
clinical picture of, 381.
INDEX
Banti’s disease, lienal and splenic, 381.
urine in, 382.
Bandage, rubber, in rheumatism, 258.
Barium, poisoning by combinations of, 583.
Barlow’s disease, 396, 485, 486, 487.
increase of, in Berlin, 486.
Basedow’s disease, 64, 65, 198.
Graves’ disease.
Bath cure, 101, 148.
for gout, 135.
in diabetes, 101.
Baths, hot, for chlorotics, 341.
mud, 148.
peat, 148.
sulphur mud, 148.
sun, of Celsus, 175.
thermal, 148.
value of, in diabetes, 122.
with electric light, 258.
Bear’s paw of acromegalia, 234.
Bed-bugs, transmission of parasites by, 571.
varieties of, 572.
Beer, as preventive of scurvy, 411.
consumption of, in Munich, 130.
effects of, in diabetes, 100.
use of, in obesity, 170.
Beer glycosuria, 79.
Belles-lettres, influence of, on girls, 338..
Benzine, in trichinosis, 560.
Bernard, Claude, experiments of, 115, 116.
Bial’s reagent, 263.
tests for pentose, 267.
Bicycling, 67, 72.
in obesity, 176.
Bidder and Schmidt’s investigations in
metabolism, 4.
Bier’s hot air treatment, 259.
Bile, chemical composition of, 345.
stasis of, 46.
Bile-ducts, dilatation and inflammation of,
512.
Bilharzia hematobia, 512.
prevalence of, in Africa, 512.
Biliary passages, inflammation of, 140.
Biogen molecule, 52.
Bird acarus, 565.
Bites of insects, treatment of, 575.
Bitters, poisoning by, 598.
sugar contained in, 101.
Biuret reaction, 51.
Bladder, distoma infection in, 513.
echinococci of, 542,
See also
619
Bleeder families, 415, 416, 417.
Bleeder’s disease, 413. See also Hemophilia.
joint, 432, 439, 440.
Bleeders, marriage of, 452.
Blindness, color, 418.
night, 419.
transitory, 325.
Blood, abnormal composition of, 427.
abnormal distribution of,’ 281.
agglutination of, 290.
albumin in, 307, 312.
alkalinity of, 276, 286.
anemic composition of, 324, 336.
bacteriology of, 290.
changes of, in progressive pernicious
anemia, 311.
chlorotic, 326.
circulation of, 304.
coagulability of, 454.
coloring matter of, 325.
composition of, favoring hemophilia, 422.
in purpura, 494.
condition of, in hemophilia, 424.
in purpuric child, 495.
_ in scurvy, 408.
dilution of, 282.
diseases of, 273.
fixing methods of examination of, 292.
flooding of, with sugar, 79.
fluid constituents of, 327..
impoverished, 33.
injection of, 206.
inspissation of, 124.
insufficient coagulability of, 423.
intensity of color of, 277.
internal secretions in, 334.
leukemic, composition of, 344.
lymph-cell formation in, 361.
methemaglobin in, in poisoning, 583.
morphological alterations of, 311, 333.
pallor of, in chlorosis, 325.
pathology of, 345.
pigment originating in, 213.
processes for staining, 293, 294.
protective bodies of, 276.
regeneration of, 305.
shadow-corpuseles in, 495.
shadow formation in, 462.
solids of, 307, 312.
specific gravity of, 284, 307, 312.
spectroscopic examination of, 287.
the seat of chlorotic disease in, 333.
620
Blood, total solids in, 285.
transfusion of, 319.
uric acid in, 255.
Blood cell formation, infectious disturbance
of, 362.
Blood cells, 326.
acidophilic, 297.
anomalies of, 299.
circulating, 310.
eosinophilic, 297.
mononuclear, 346.
non-nucleated, 345.
nucleated, 326.
oxyphilic, 297.
red, counting of, 325.
reduction of, 327.
varying size of, 326.
Blood changes in Addison’s disease, 212.
Blood-corpuscles, 281.
condition of, in chlorosis, 325.
counting of, 281, 325.
normal numbers of, 283.
nucleated, 349.
percentage of, in anemia, 306.
pessary forms of, 496.
red, counting of, 325.
condition of, in anemia, 306.
formation of, 344.
reduction of, 312.
volume of, 287.
white, 283, 307. :
condition of, in leukemia, 360.
increase of, 344, 355.
number of, 300.
polymorphia of, 364.
Blood count in Addison’s disease, 204.
Blood-counting, apparatus for, 281.
Blood examination, 275.
in diseases of bone-marrow, 275.
in malaria, 291.
in parasitic diseases, 275.
method of, 276.
Blood-formation, anomaly of, 335.
embryonal type of, 310.
impairment of, 356.
morbidly active, 344.
pathological, 365.
peculiarity of, in anemia, 317.
Blood-kindred, intermarriage between, 421.
Blood plaques, 327.
recognition of, 293, 299.
Blood-poisons, 592.
INDEX
Blood preparations containing iron, 342.
Blood-pressure raised by adrenal therapy,
207, 209.
Blood serum, agglutination of, 289.
dilution of, 289.
investigation of, 285.
methods for testing, 289.
reduction of, 327.
total solids in, 327.
Blood-staining, by Chenzinsky’s method,
295.
by Ehrlich’s method, 293, 296.
universal method of, 296.
Blood tumors, 437.
Blood-vessel glands, 238.
Blood-vessels, echinococcus in, 537, 539.
rupture of, 431.
Blood volume, in hemophiliacs, 425.
Blushing of chlorotics, 325, 335.
Body, activity of, 5.
composition of, 11.
Body-albumin, 7.
Body landmarks, displacement of, in obesity,
159, 160.
Body nitrogen, increase of, 57.
Body-weight as a control in experiments, 7.
increase of, 59.
Boerhaave’s cases of obesity, 160, 162.
Bone-marrow, cell development in, 347, 348.
changes in, 351.
in anemia, 315.
condition of, in pseudo-leukemia, 371.
functional alteration in, 365.
insufficient function of, 360.
lymphoid hyperplasia of, 355.
pathological changes of, 333.
red, 345.
reduced function of, 362.
Bones, affection of, by gout, 139.
atrophy of, 251.
changes in, of hemophiliacs, 456.
condition of, in scurvy, 407, 408.
deformities of, in acromegalia, 232.
echinococcus of, 544.
enlargement of, in acromegalia, 234.
long, tumor in tract of, 485.
sensitiveness of, to pressure, 358.
X-ray examination of, 432.
Bothriocephalus anemia, prognosis of, 524.
treatment of, 318.
Bothriocephalus cordatus, Leuckart, 521.
cristatus, Davaine, 521.
INDEX
Bothriocephalus grandis, Blanchard, 521.
latus, Bremser, 520.
distribution of, 521.
Mansoni, Cobbold, 521.
passage of segments of, 522.
Botulism, 601.
Boys, chlorosis of, 320, 330.
gout in, 129.
Brain, distoma in, 511.
echinococci of, 534.
effusions of blood into, 158.
injury to, as cause of diabetes, 115.
Bread, casein, 170.
containing aleuronat or ergon, 168.
diabetic, 99.
rye, in obesity, 173.
wheat, for the obese, 168, 169.
Breithaupt and Cetti, the fasters, 14.
Brickmakers, disease of, 560.
Bright’s disease, 467, 468.
Brisement forcé, 456.
British Medical Association, Congress of,
179.
Bromin salts, poisoning by, 584.
Bromism, 584.
Bronchial catarrh in trichinosis, 557.
Bronzing in Addison’s disease, 201.
Bruit de diable, 322.
Bubo disease, 571.
Buffy coat, 431.
Bulimia in Addison's disease, 200.
Bunge’s theory of scurvy, 410.
Burns under X-ray treatment, 369, 381.
Bischel-form of keratitis, 567.
Cc
Cabot’s, researches in blood examination,
283.
Cachexia associated with pigmentation of
skin, 203.
from parasites, 511.
in Hodgkin’s disease, 373.
myxedematous, 191.
strumipriva, 187, 188.
thyreopriva, 187, 188.
tubercular, 221.
Cachexie pachydermique, 179.
Calculi, uratic, 157.
Calorimetry, direct, 9.
in man, 6.
621
Calory estimations, of Rubner, 44,
Calory requirement of body, 6, 7.
Calory supply, diminution of, 53.
Calves, cramps in, 128, 136.
Carhphor, in diabetes, 122.
Camphor poisoning, 594.
Cancer, hepatic, 541.
Cane-sugar, 78.
Cantani’s obesity cure, 165.
Capillaries, rupture of, 433.
Carbohydrates, absorption of, 48.
allowance of, in diabetes, 98.
in the diet, 74.
in feces, estimation of, amount of, 45.
percentage of, in beer, 106.
in food, tables of, 104.
in wines and spirits, 106.
tolerance of, 88.
value of, as albumin savers, 40.
Carbolic acid poisoning, 593.
Carbon balance, 7.
Carbon bisulphid, 586.
Carbonic acid, excretion of, 8.
Carbonic acid poisoning, 590.
chronic, 591.
Carcinoma, colloid, 512.
from parasitic infection, 513.
Carlsbad, treatment at, in diabetes, 101.
Casein, 70, 169.
Castor oil, in trichinosis, 559.
Castration, as a cause of obesity, 154.
Cataphoresis, 425.
Catarrh, intestinal, due to coccidia, 506.
tendency to, in obesity, 157.
Caterpillars, toxic effect of, 575.
Cattle, mortality among, from echinococ-
cus, 533.
Cautery, to control hemorrhage, 454.
Cell accumulations, lymphadenoid, 375.
Cell, protoplasm of, 3.
destruction of, 3.
Cells, chemical activity of, 3.
decomposition in, 3.
dwarf, 356.
growth energy of, 57.
katabolic activity of, 61.
nuclei of, disease of, 131.
parenchyma, 204.
regenerative energy of, 57.
Cerebral affections, due to gout, 142.
Cerebral diseases, polyuria in, 115.
Cerebral disturbances in myxedema, 184.
622
Cervical ganglia, neuritic disease in, 216.
Cestodes, 514.
Cesto-embolism, 539.
Cetti and Breithaupt, the fasters, 14, 32.
Chambers’s cure of corpulence, 163.
Champagne as cause of gouty attack, 135.
Charcoal in calorimetric investigations, 6.
Charcot on rheumatism, 244.
Charcot-Leyden crystals, 350, 563.
Cheese, in diet of diabetes, 100.
Chemical analysis, in case of poisoning, 581.
Chemical curative agents, 197.
Chemical processes as source of heat, 2.
Chemotactic stimulus, 344.
Chemotaxis, 365.
negative and positive, 302.
Cherry cure, 147.
Chicken cholera, 571.
Children, metabolism of, 36.
Chin, double, 159.
China, organotherapy in, 196.
Chiragra, 125.
Chlorin combinations, poisoning by, 583.
Chloroform poisoning, 584.
Chlorosis, 305, 320.
anatomical foundation of, 330.
appetite in, caprices of, 323.
blood changes in, 325, 327, 334.
blood examination in, 325, 328, 336.
body temperature in, 323.
cardiac murmurs in, 321.
cardiac palpitation in, 322.
causes of, 333.
changes of skin in, 320.
combination of, with obesity, 156.
complications of, 329.
course of, 337.
derangement of nervous system a cause
of, 335, 336.
development of, 339.
diagnosis of, 328, 336.
diet in, 341.
digestive symptoms in, 323.
diseased blood as a cause of, 334.
Egyptian, 560.
extreme pallor in, 336.
forms of, 337.
frequency of, in cities, 331, 333.
genesis of, 333.
gigantea, 154.
habitual, 330.
hereditary, 339.
INDEX
Chlorosis, independent symptoms of, 324,
latent, 329.
metabolism in, 33.
mode of life favoring, 339.
murmurs in, 321.
nervous disturbances of, 324, 325.
no specific treatment for, 340.
occurrence of, among servant girls, 332.
in boys, 320, 330.
in fat people, 320.
in men, 329.
in time of Hippocrates, 320.
pathological anatomy of, 329.
persistent, 330.
predisposing causes of, 331.
prognosis of, 329.
prophylaxis of, 343.
rapidity of pulse in, 322.
relapses of, 330.
relation of, to sex, 330.
respiratory apparatus in, 323.
sexual functions in, 323.
symptomatology of, 328.
tight lacing a cause of, 332:
treatment of, 339.
by suggestion, 342.
tropical, 560.
vagaries of appetite in, 323.
Cholelithiasis, 140.
Cholera Asiatica, simulated by arsenical
poisoning, 586.
Choleraic symptoms, in trichinosis, 556.
Chorea, thyreoid therapy in, 195.
Chronic articular rheumatism, 243. .
Chyle tracts, 48.
Cimex, varieties of, 572.
Circulatory apparatus, changes in, 329.
condition of, in chlorosis, 321.
echinococcus in, 538.
Circulatory disturbances as result of obesity,
69.
Circumcision, of hemophiliacs, 434, 452.
Cirrhosis, hepatic, 43, 382.
hypertrophic hepatic, 141.
of liver from parasitic changes, 512.
Claudicatio intermittens, 85. :
Climacterium, use of odphorin in, 197.
Climate, influence of, in producing scurvy,
397.
Clothing, use of, in common, 550.
Club finger tips, 256.
Club-foot, as sequence of scurvy, 409.
INDEX
Coal gas poisoning, 79.
Cocain poisoning, 597.
Cocainism, 597.
Coccidium, bigemimum, 506.
oviforme, 506.
perforans, 506.
Colchicum in gout, 149.
Cold and heat, effect of, in metabolism, 25.
Cold, extreme, a cause of diabetes insipidus,
119.
use of, in diabetes, 122.
Colic, lead, 587.
renal, 451.
Collapse, cardiac, 596.
treatment of, 497.
Colloid masses, excretion of, 204.
Color-blindness, 418.
Color-index, 283.
Coma, acid, 92.
diabetic, 80, 91, 102.
fatal, in anemia, 319.
in purpura, 483.
opium, 596.
Combustion, a source of energy and heat, 2.
increase and decrease of, 26.
Compensation, process of, 88.
Comptodactylie, 255.
Congress, British Medical Association, 179.
Forth French, for Urology, 1889, 448.
International Medical, at Paris, 126, 127.
Congress of Internal Medicine, 1885, 56.
Connective tissue, 348.
changes of, in acromegalia, 237.
Connective tissue hyperplasia, 237, 238.
Constipation in chlorosis, 323.
in gout, 140, 148.
in scurvy, 413.
obstinate, in the obese, 157.
stubborn, 172.
Consumption, occurrence of, in small eaters,
63.
Contractures of fingers and toes, 251.
Convalescence, abundance of food in, 40.
in morbus maculosus, 497.
Copaiba, balsam of, poisoning by, 594.
Coprostasis in chlorosis, 340.
Corium, pigmentation in deep layers of, 213.
Cornutin poisoning, 598.
Coronary artery, calcification of, 269.
Corpulence, 151. See also Obesity.
Wadd’s views on, 163.
Corrosive sublimate, tolerance of, 589.
623
Corrosive sublimate poisoning, symptoms of,
589.
Corsets, injurious effects of, 332.
Country life for chlorotics, 340.
Cramps in legs, 139.
Cream, in diet of diabetics, 100.
Creeping disease, 574.
Cremation of infected meat, 533.
Cretinism, 30, 187.
endemic, 188, 189.
sporadic, 187, 188.
Cretinoid state in women, 180.
Crick in the back, 139.
Crusades, scurvy during, 390.
Crystallose, 109.
Cure, Nature-healing, 60.
Oertel, 174.
of obesity, 177.
Cures, dietetic, 54.
mineral water, in diabetes, 92, 101.
weakening, 67.
Cyanosis in blood poison, 592.
Cyclops serrulatus, Fischer, 520.
Cyprinotus incongruens, 519.
Cystericus bovis, 115.
cellulose, 501, 515.
Cystoid echinococcus, 528.
D
Daltonism, hereditary, 415, 418.
Deafness from lymphatic nodules, 352.
Debove’s treatment of obesity, 161.
Decomposition, alterations of, 4.
nuclein, 52.
of food, 6.
Deformity, in chronic
matism, 246.
of bones in arthritis, 256.
Degeneration, amyloid, 47.
granular, 326.
hyaline, vascular, 466.
phenomena of, 326.
Deglutition, difficult, 373.
Delirium tremens, 591.
Demodex folliculorum, Simon, 569.
Dentition, a critical period in hemophiliacs,
434.
Depression, hypochondriac, 142.
paroxysms of, 143.
Dextro-rotary pentose, 267.
articular rheu-
624 INDEX
Dextrose, 77.
Dextrosuria, 77.
Diabéte azoturique, 113.
Diabetes, actual cure of, 82.
arteriosclerotic, 84.
arthriticus, 144.
cerebral causes of, 122.
chronic, 81.
coexistent with acromegalia, 233.
combination of, with pentosuria, 268.
decipiens, 144.
diet in, 33.
disease of the brain a cause of, 114.
drug treatment of, 122.
gastric disturbances in, 102.
hysterical, 117.
increased appetite in, 113.
insipidus, 110.
clinical picture of, 110.
constitutional condition in, 120.
diagnosis of, 121.
etiologic therapy of, 122.
etiology of, 112.
hereditary form of, 119.
idiopathic form of, 118. :
infectious diseases, followed by, 119.
low temperature in, 114.
normal, 117.
organic disease of brain, a cause of,
111.
over-nutrition in, 64.
prognosis of, 120.
psychical treatment of, 122.
special varieties of, 115.
symptoms and course of, 112.
typical cases of, 120.
mellitus, 77, 83, 167.
after scarlatina, 80.
combination of, with gout, 130.
hereditary, 82.
metabolism in, 32.
mild and severe forms of, 83.
occurrence of, in the young, 81.
over-nutrition in, 64.
practical therapy of, 92.
regulated diet for, 96.
theoretic treatment of, 87.
valuable foods in, 89.
various forms of, 83.
mild and severe, 83.
nutrition in, 113.
oceurrence of, in a chemist, 80.
Diabetes, occurrence of, in the aged and in
the young, 80, 81.
in the obese, 83.
organic, 81.
pancreatic, 81.
pure, 84.
quantitative diet in, 98.
relations of, to gout, 144.
saccharin, 115.
sugar excretion in, 52.
tables of foods in, 103.
thirst in, 113.
treatment of, 87, 101.
typical cases of, 94.
Diaceturia, 91.
Diaphragm, inactivity of, 557.
rupture into, 538.
Diaptomus spinosus, Daday, 520.
Diarrhea, fatty, 47.
in leukemia, 369.
in scurvy, 408.
Diatheses, hemorrhagic, 388.
Diathesis, gouty, 130.
hemorrhagic, in anemia, 308.
oxalate, 449.
uric acid, 126.
Didymin, 197.
Diet, amylaceous, 80.
antifat, grades of, 72.
calculation of nutrition and calory value
of, 107.
effect of, in metabolism, 44.
employment of, in chlorotics, 340, 341.
for the obese, 167.
in diabetes, 87, 96, 122.
in leukemia, 369.
maintenance, of the sick, 37.
mixed, 80.
nutrition and calory value of, 107.
preventive of scurvy, 411, 412.
quantitative regulation of, 96.
researches in, 48.
schemes, adherence to, 76.
tests in, 48.
vegetable, 61, 147.
Diet-tables of Chambers, 163.
Dietary for diabetics, 108.
of Banting, 72, 74.
of Chambers, 163.
of Dapper, 73.
of Ebstein, 72, 74.
of Harvey, 72.
INDEX
Dietary of Hirschfeld, 74.
of Kisch, 74.
of Oertel, 72, 74.
of v. Noorden, 74.
Dietetic cures, 54, 69.
Dietotherapy, 2, 39.
dangers of, 102.
Digestion, condition of, in Hodgkin’s dis-
ease, 381.
impaired by tape-worm, 522.
physiology of, 1.
vicarious intestinal, 47.
Digestive apparatus, disorders of, in dia-
betes, 114.
Digestive canal, catarrh of, 140.
disturbances of, in Addison’s disease,
200.
Digestive organs in anemia, 313.
Digestive tract, anemic changes in, 315.
Digitalis and its glucocides, poisoning by,
597.
Digitalis infusion, decomposition of, 597.
Dioptrics, 419.
Dioxybenzole poisoning, 593.
Diplobacilli, 490.
Distoma, 509, 510.
fatal disease caused by, 512.
occurrence of, in China, India, and Japan,
511.
Distomatosis, 510.
Distomum felineum, Rivolta, 511.
hematobium, Bilharz, 512.
hepaticum, Linné, 509.
pulmonale, Baelz, 1883, 510.
sibiricum, Winogradoff, 511.
spathulatum, Leuckart, 511.
Westermanni, 510.
Dog, as transmitter of echinococci, 529.
Dog tape-worm, 531.
Drinking-water as disseminator of para-
sites, 503.
Dropsy, oily, 151.
Drugs, production of hysterical polyuria by,
118.
Dupuytren’s contracture, 145.
Dwarf, acromegalic skeleton of, 231.
Dwarfs, prehistoric, 229.
Dysentery, distoma found in cases of, 511.
intercurrent, with scurvy, 408.
Dyspepsia, intestinal, 140.
nervous, 60.
Dyspnea, 352.
41
625
E
Ear, gouty processes in, 143.
gouty tophi in, 135.
Earth, diseases caused by working in, 562.
Ecchondroses of rheumatism, 246, 248.
Ecchymoses of purpura, 459, 470, 484,
488.
Echinococci, autosemination of, 531.
of various organs, 534.
Echinococcus, 501.
areas infected by, 529.
cysticercus, 529.
cysts of, 527, 532.
expectoration of membrane of, 538.
multilocular, 534.
multilocularis, 528.
multiplex, 531.
occurrence of, in bones, 529.
in female genital organs, 543.
in oral cavity, 535.
prevalence of, among animals, 526.
prevalence of infection of, 529.
propagation of, 527.
pulmonary, 538.
renal, 541.
toxicity of fluid of, 531.
transmission of, by dog, 529.
tumors of, 528.
Echinococcus disease, 526.
course and temperature in, 540.
prognosis of, 533, 540.
prophylaxis of, 533.
symptoms of, 532.
treatment of, 533.
unilocular, 531, 539.
with duration of thirty-five years, 530.
Echinococcus sac, an impediment at birth,
543.
Echinorhyncus gigas, Goeze, 501, 565.
Ectoparasites, 501, 565.
Edema in trichinosis, 557.
Edema of face, 341.
Effusion, hemorrhagic, 492.
in scurvy, 400.
into knee-joint, 455.
Effusions in gout, 134.
Eggs, in diet of diabetics, 100, 108.
Ehrlich eye-piece, 301.
Ebrlich-Pinkus formula, 376.
Ehrlich’s method of staining, 293, 294,
296.
626
Ehrlich’s investigations of the blood, 345,
351.
Electricity to spleen, 386.
Electricity, use of, in diabetes, 123.
Elephantiasis, swellings resembling, 548.
Emaciation, cure of, 161.
in diabetes insipidus, 120.
in rheumatism, 250.
significance of, 38, 39.
Emboli, from echinococcus cysts, 537.
in trichinosis, 557.
Embonpoint, 153, 155.
Emphysema, pulmonary, 142.
Endocardium involved in rheumatism, 251.
Enemata of benzine, 560.
Energy, law of conservation of, 2.
loss of, 48, 44.
transferrence of, 3, 11.
metabolism of, 5.
Energy requirement of body, 11.
of the healthy, 9.
English navy, absence of scurvy in, 411.
Enlargement, in acromegalia, 230.
glandular and multiple, 375.
Enteric fever in chlorotics, 339.
Entoparasites, 501.
Entozoa, 501.
Enuresis nocturna, 119.
Enzymes, action of, 13.
Eosinophiles, 347, 355.
in trichinosis, 557.
Eosinophilic leukocytosis, 365.
Epidemics of trichinosis, 553.
of scurvy, 390, 391, 392.
Epididymis, echinococci of, 544.
Epilepsy, 116.
from tenia solium, 504.
Epinephrin, 210.
Epinephrectomy in animals, 206.
Episcleritis, 252.
Epistaxis, occurrence of, in hemophiliacs,
454.
treatment of, 497.
Epizoa, 501.
Equilibrium, nitrogenous, 10.
Ergon in bread for the obese, 167.
Ergot, use of, in hemorrhages, 454.
Ergot poisoning, 598.
chronic, 599.
Ergotin, in diabetes, 123.
Ergotism, convulsive, 599.
gangrenous, 599.
INDEX
Eruption, itching, 544.
Erythema, nodosum, 473, 477.
Erythroblasts, 300.
in anemia, 311.
Erythrocytes, 307, 344.
decrease of, 349.
increased formation of, 283.
morphological changes in, 306.
normal proportions of, 345.
recurrence of, in chlorotic blood, 326.
stippling of, 292, 300, 312.
Erythrosclerotin, 599.
Eschars, from acid poisons, 580.
Esophagus, ascarides in, 550.
Ethyl alcohol, poisoning by, 591.
Eucalyptus, in pseudo-leukemia, 386.
Eucasin, 48.
Eustrongylus gigas, Rudolphi, 560.
Excretion by skin, stimulation of, 128.
Excretions, estimation of, 6.
Exercise, bodily, during antifat cures, 56.
muscular, in diabetes, 92.
in obesity, 175, 176.
in production of flesh, 58.
passive, 177.
Exercises, free, of German turners, 176.
Exophthalmic goiter, 64, 66, 193.
Exophthalmos in acromegalia, 233.
Expired air, estimation of, 6.
Extremities, neuralgia of, 314.
size of, in acromegalia, 230.
Eye, affections of, in rheumatism, 252.
changes of, in acromegalia, 232.
cysticercus in, 524.
disease of, from acarus, 569.
from caterpillars, 575.
specks before, 324.
Eye-ball, echinococcus of, 535.
Eye-ground in leukemia, 352.
Eyrich’s picture of purpura, 484.
F
Face, cyanosis of, 373.
edema of, 373.
Faradization, 66.
Fasters, professional, 14.
Fasting values, 9.
Fat, combustion of, 75.
danger of, in various diseases, 55.
development of, in prime of life, 55.
INDEX
Fat, divisibility of, 12.
estimation of, in feces, 45.
formation of, 12, 18, 21, 34.
excessive, 151, 159.
increase of, 55.
losses and accumulations of, 58.
mal-assimilation of, 46.
nausea caused by, 167.
necessity of, as a food, 166.
repugnance to, 40.
satiety caused by, 167.
significance of, 54.
splitting of, 46.
sugar formation from, 52.
tables of, in various foods, 103.
place of, in diet, 21, 74.
of the diabetic, 89.
value of, in diabetes, 100.
in various diseases, 55.
Fat of normal children, 153.
Fat absorption, decrease of, 46.
Fat-albumin diet, 175.
Fat bodies, poisoning by, 591.
Fat marrow changes in pernicious anemia,
316.
Fat metabolism, 75.
Fat-milk, Gartner’s, 486.
Fats, neutral, 46.
Fatigue, sensation of, in anemia, 308.
Fattening of animals, 153.
Fatty degeneration in progressive pernicious
anemia, 315.
Features, change of, in myxedema, 184.
Feces, albumin losses in, 47.
analysis of, 45.
calory value of, 44.
elementary analysis of, 4.
estimation of, 6.
fatty acids in, 46.
microscopic examination of, 522
parasites in, 507.
Feeding forced, 16, 19, 40, 56.
Female breast in obesity, 151.
Females, hemophilia occurring in, 414.
Fermentation test, 262, 264.
Ferratin, 342.
Ferrum carbonicum, 341.
Ferrum chloratum, 341.
Ferrum citricum, 341.
Ferrum oxydatum, 341.
Ferrum sesquichloratum, 341.
Ferrum sulphuricum, 341.
627
Fever, chronic relapsing, 375.
destruction of tissue in, 39.
gastric, 80.
intermittent, 494.
recurring, glandular, 375.
relapsing, pre-natal, transmission of, 429.
with glandular enlargement, 376.
Filaria Bancrofti, Cobbold, 546.
embryos, 547.
loa Guyot, 546.
Magathesi, 547.
medinensis Velsch, 545.
varieties of, 546.
Fingers, gout in, 138.
nodosities of, 255.
Finland, hemophilia in, 451.
Fischer's test, 77.
Fish in diabetes, 108.
Fish, raw, parasitic infection from, 512.
Fish poisoning, 600.
. Fixation, methylic alcohol, 293.
Flagellates, 507.
_ Flat-foot occurring in the gouty, 144, 158.
Flat-worms, 508.
Fleischl’s hemometer, 277, 278.
Flesh, increase of, 55.
Flesh production by stock raisers, 19.
Fluid in blood, increase of, 341.
Fluids, digestive, in metabolism, 4.
intake of, limited in diabetes, 124.
in obesity, 174.
simultaneous intake of, with solid food,
75.
Fly, as carrier of infection, 571.
Fly larve, 501, 573.
in remote parts of body, 574.
Follicles, destruction of, 186.
Food, albuminous, reduction of, 97.
assimilation of, 45.
changes in, ill effects of, 333.
consumption of, in the healthy, 4.
in tubercular disease, 38.
contamination of, by flies, 575.
decomposition of, 3, 49.
diminished consumption of, 32.
energy value of, 37.
faulty absorption of, 44.
fresh, as preventive of scurvy, 485.
indigestible, craving for, 323.
intake of, influence of, 23.
limitation of, in obesity, 154.
nature and quantity of, 21.
628
Food, necessity of, for maintenance, 59.
oxidation of, 3.
parasites disseminated by, 511.
passage of tape-worm caused by, 522.
repugnance for, 323.
source of energy in, 2.
sudden withdrawal of, 31.
unclean, as disseminator of parasites, 503.
uniform limitation of, 174.
Food molecule, as containing nitrogen, 51.
Food products, disintegration of, 2.
divisibility of, 12.
plastic, 2.
respiratory, 2.
Food requirement of the sick, 21.
Food surplus, 61.
Food values, compilative table of, 14.
standard, 8.
Foods, kinds of, for the obese, 167.
percentage of fat in, 103.
sugar-producing, 89.
Foot, gout in, 125.
Force, in living organism, 2.
Force, interchange of, 22, 37.
permutation of, 2.
Forced feeding, a cause of cardiac weak-
ness, 65.
in hysteria and neurasthenia, 65, 66.
in production of flesh, 58.
indications for, 62.
technic of, 70.
Fowler’s solution in Addison’s disease, 224.
in morbus maculosus, 497.
Fractures, treatment of, by thyreoid gland,
195.
Freiburg, prevalence of goiter in, 190.
Friction as source of heat, 2.
in chlorosis, 340.
Frontal sinus, echinococcus in, 535.
Fruits, 108.
carbohydrate contents of, 105.
dried, in diabetes, 99.
in diabetes, 99.
pentosan in, 268.
G
Gadfly boil, 573.
Gaertner’s hemophotograph, 279.
Galactose, 267.
Ganglia, semilunar, inflammation and de-
generation of, 216.
INDEX
Gangrene, of extremity, from ergotism, 599.
Garrod’s views of scurvy, 398, 410.
Gases, interchange of, 30, 36, 308.
interchange of, in obesity, 154.
respiratory, 8.
poisoning by, 590.
Gastric chemism, disturbance of, 47.
Gastric contents, examination of, 323, 340.
Gastric dyspepsia in gout, 140.
Gastric hunger, 60.
Gastric juice, action of, on echinococci, 526.
Gastrophilus larva, 574.
Gastroptosis, 323, 333.
Gelatin to control hemorrhage, 454.
Genital organs, echinococcus in, 543.
examination of, 337.
hypoplastic changes in, 330.
implication of, in acromegalia, 238.
German marine, scurvy in, 412.
Germany, parasitic disease in, 529.
Ghida, 125.
Giant growth, 195, 230.
Giant skull, pathologic, 229.
Giants, prehistoric, 229.
ticht. See Gout.
Gigantism, 234, 237.
Gigantoblasts, 300.
Gigantocytes, 299, 300.
Gingivitis, bacillus causing, 394.
Girls, neuroses appearing in, 336.
Glands, enlargement of, 371.
extirpation of, 380.
intestinal atrophy of, 47,
pain in, 376.
tuberculosis of, 375, 376.
Glandular disease caused by poison in blood,
378.
predisposition to, 378.
Glandular organs, in scurvy, 400.
Glaucoma in gout, 143.
Gliomata, 239.
Glucose, 77.
Glycogen deposit, 12, 16.
Glycogenic area of brain, 114.
Glycogenic center, 111.
Glycosuria, 77.
alimentary, 77, 78, 79.
in gout, 144.
combination of, with pentosuria, 269.
diabetic, 87.
e saccharo, 79.
experimental, 79.
Glycosuria, nature of processes in, 78.
physiologic, 77.
spontat.eous, 79, 81.
transitory, 81.
Glycosuria in morphin poisoning, 596.
Gnathostoma siamense, Levinsen, 560.
Goiter, occurrence of, in infants, 190.
massive, 238.
parenchymatous, 192.
Gonagra, 125.
Gonorrhea, 256, 478.
gouty, 142.
Gordius, varieties of, 565.
Gout, 125.
annual attack of, 139.
cachectic stage of, 149.
cancer, caused by, 143.
causes of, 126, 127.
cerebral affections in, 142.
clinical cases of, 128, 134.
clinical history of, 126.
combined with hematuria, 451.
condition of heart in, 141.
confounding of, with rheumatism, 243.
course of, 145.
curative resorts for, 148.
decreased metabolism in, 33.
diagnosis of, 146, 150.
diet in, 147.
edema in, 134.
exemption of women from, 147.
faulty action of kidney a cause of, 128.
fever in, 134.
foci of, 133.
Garrod’s views of, 136, 243.
Heberden’s nodes in, 248.
hereditary, 128, 144.
intermediate symptoms of, 133, 139.
“internal,’’ 145.
larval, 132, 149.
latent, 132.
location of, in extremities, 131, 145.
in right toe, 128.
lymphangitis in, 143.
materia peccaus in, 132.
metabolism in, 42.
occurrence of, in adolescents, 129.
in ancient times, 126.
in England, 130, 131.
in Munich, 130.
in upper and lower classes, 130.
pain in, 134.
INDEX
629
Gout, paralysis in, 143,
paroxysms of, 136.
pathogenesis of, 126.
predisposition to, 139.
premonitions of, 133, 139.
primary arthritic, 127, 138, 140.
treatment of, 146.
prognosis of, 145, 150.
prophylaxis of, 147.
relation of, to chronic arthritis, 255.
respiratory conditions in, 142.
retrocedent, 132.
skin affections in, 143.
specific treatment of, 148.
Sydenham’s description of, 126.
symptomatology of, 132, 133, 139.
treatment of, 146, 148, 150.
by “patience and cotton,” 149.
typical attack of, 131, 133.
visceral, 140.
Gowers’s hemoglobinometer, 277, 279.
Gram-Weigert process, 490.
Grandidier’s views of hemophilia, 415, 452.
Granular cells of epithelium, 239.
Grapes in diabetes, 99.
Grape cure, 148.
Grape-sugar, 12, 264, 270.
in the urine, 77, 78, 262.
Grasshopper plague in Russia, 397.
Graves’ disease, 28, 29, 38, 70, 193.
forced feeding in, 65.
Growth, excessive, in acromegalia, 230.
Gruber-Widal reaction, 289.
Gull, Sir Wm., on myxedema, 179.
Gummata of skin in diabetes, 121.
Gums, disease of, 413.
fetor of, 492.
gangrene of, 403.
in purpura, 459, 470.
lead line of, 588, 590.
scorbutic, 485.
spongy, 394.
the seat of scurvy, 402.
Gymnastics, 67, 176.
in obesity, 72.
H
Hair in acromegalia, 237.
in scurvy, 405.
Haller’s acid, 497.
in hemophilia, 453,
630
Hammerschlag’s method for testing specific
gravity of the blood, 284.
Hardening processes, 257.
Harvey’s cure of obesity, 70, 72, 163, 165.
Hayem’s solution, 281.
Head, weight of, in acromegalia, 235.
Health, calory requirement in, 35.
consumption of food in, 4.
energy-value of food in, 45.
Health resorts, advantages of, 339.
of Europe, 343.
Heart and vascular system in gout, 141.
Heart, defective development of, 329, 331.
dilatation of, 158.
in chlorosis, 322.
failure of, 75.
fatty, 152, 174.
fatty degeneration of, from phosphorus
poisoning, 585.
hypertrophy of, 121.
hypoplasia of, 329.
weakness of, in obesity, 176.
Heart muscle, degeneration of, 330.
disease of, 75.
Heart, hypoplasia of, 329.
Heat, independent sources of, 2.
loss of, in metabolism, 25.
production of, in metabolism, 36.
Heat and cold in metabolism of the sick, 25.
Heat equivalents, 44.
Hebeloma poisoning, 600.
Heberden’s nodes, 247, 248.
Helminthiasis, 504, 522.
distressing symptoms of, 524.
prognosis of, 550.
Hematoblasts, 345.
Hematogen, 342.
Hematokrit, 287.
Hematology, 304, 354.
Hematomata, 491.
diffuse, 437.
Hematopoietic apparatus of chlorotics, 329.
Hematopoietic function, 435.
Hematopoietic organs, 341.
affection of, 305.
Hematopoietic tissues, 363.
Hematuria, angioneurotic, 449.
caused by parasitic disease, 513.
essential, 448, 449.
gouty, 451.
hemophilic, 449.
idiopathic renal, 444.
INDEX
Hematuria, in leukemia, 353.
in pregnancy, 450.
unilateral, 446, 447.
Hemeralopia, 419.
transmission of, 419.
Hemoalkalimetric test of alkalinity of the
blood, 399.
Hemocytometer, 282.
Hemoglobin, 277.
absorption spectra of, 288.
consumption of, 305.
formation of, 305.
percentage of, in anemia, 306, 312.
in purpuric blood, 495. ;
reduction of, 288, 305, 306, 326, 327, 349.
in chlorosis, 325, 333.
remedies containing, 342.
Hemoglobin scale, 277.
Hemoglobinemia, 288.
Hemoglobinometer, 277, 325.
Hemometer, 277, 279.
Hemophilia, 413, 445, 446.
amount of blood loss in, 426.
autopsy findings in, 430, 433.
appearance of, after trauma, 429.
blood examination in, 423, 424.
blood-vessels unruptured in, 431.
causes of, unknown. 430.
congenital, 421, 428, 429.
course of, 434.
development of, by intermarriage, 421.
diagnosis of, 440.
discovery of, at operations, 434.
geographical distribution of, 422.
hereditary, 414, 415, 416, 417.
human, 429.
identity of, with scurvy, 427. °
joints in, 432, 439, 455.
local, 448.
origin of, 425.
prognosis of, 451.
prophylaxis of, 452, 455.
renal, 442.
revealed by accident, 434.
seat of hemorrhage in, 435.
stages of, 438.
statistics of, 415.
symptomatology of, 434.
three forms of, 440.
transmission of, in families by females,
414-417.
treatment of, 452, 453.
INDEX 631
Hemophilia as independent disease, 427.
as toxic infectious disease, 427, 428.
Hemophiliacs, capricious appetite of, 428.
care of, in childhood, 453.
choice of occupation for, 453.
diet of, 453.
early death of, 430, 434.
longevity of, 416.
remarkable blood finding in, 425.
Hemophotograph, 279, 280.
Hemoptysis in echinococcus disease, 537.
Hemorrhage, arrest of, 454.
arthritic, 435, 441.
conjunctival, 429.
control of, by zymo-plasma, 424.
cutaneous, 409, 466, 471, 476.
difficult control of, 437.
embolic, 477.
essential renal, 445, 447.
gastric, 451.
internal, 336, 494.
interstitial, 435, 436, 437:
leopard appearance of skin caused by,
466.
multiple capillary, 465.
occurrence of, after extraction of teeth,
452, 454.
in hemophilia, 423.
in progressive, pernicious anemia, 314.
in scurvy, 399, 401, 404, 409.
without external cause, 436.
prodromes of, 435.
pulmonary, 451, 494.
renal, 444, 447, 450, 451.
retinal, 308, 314, 478, 488, 494.
spontaneous, 414, 429, 430, 436.
superficial, 435, 436.
toxic, 429.
traumatic, 414, 429, 436, 437.
treatment of, 497.
Hemorrhages, local, upon a hemophilic
basis, 442.
strie-like, 472.
Hemorrhagic diathesis, 388, 477.
of leukemics, 353, 355.
of the newborn, 461.
Hemosodium-urate, 127.
Hemosporidia, 506.
Henoch’s purpura, 462, 479, 481, 482, 495.
Hereditary transmission of disease, 415, 416,
417.
Herpétisme, 252, 255.
Heterogeny, 545.
Hexathyridium, 514.
“Hexenschuss,”’ 139.
Hexose, oxidation of, 265.
Hippocrates, description of peliosis by, 473.
treatment of obesity by, 152.
Hirschfeld on antifat cures, 56.
Hirschfeld’s diet rules, 174.
Hirudines, 565.
History of gout, 126.
of scurvy, 388.
Hodgkin’s disease, 370.
clinical picture of, 372.
course, duration, and outcome of, 378.
diagnosis of, 375.
hereditary predisposition to, 377.
local symptoms of, 372.
therapy of, 378.
Hoppe-Seyler-Tigerstedt apparatus, 8.
Host, parasitic, autoinfection of, 551.
Hot-air bath, influence in metabolism, 25.
House-fly, as disseminator of parasites, 503.
Hunger cure, 161, 175.
Hurry of life, a cause of chlorosis, 333.
Hydatid echinococcus, 528.
resonance, 533.
thrill, 532, 540.
Hydrochloric acid, action on pentose, 265.
Hydrogen, arseniureted, poisoning by, 587.
sulphureted, poisoning by, 586.
Hydronephrosis, 541.
Hydrops tuberculosis fibrinosus, 439.
Hydrotherapy in diabetes, 122.
in obesity, 175, 176.
modern, 310.
Hygiene, errors in, 306.
general, 331.
ignorance of principles of, 343.
lack of, among earth workers, 562.
as cause of chlorosis, 333.
observance of, in Hodgkin’s disease, 380.
Hymenolepis (drepanitotenia) lanceolata,
Bloch, 519.
Hyperacidity of stomach, 47.
Hypercompensation, 88.
Hyperemia, 258.
Hyperglobulia, 283.
Hyperglycemia, diabetic, 78, 86.
Hyperglycosuria, 78.
Hyperhidrosis, 251.
Hyperleukocytosis, 302, 308. =
Hypernutrition. See Over-nutrition.
632
Hyperplasia, acromegalic, 240.
altruistic, 241.
Hypertrophy of soft parts in acromegalia,
237.
Hypnosis, as cause of hysterical polyuria,
118.
“Hypnotism, questionable use of, 122.
Hypochondria verminosa, 524.
Hypoderma bovis, 573.
Hypodermoclysis, saline, 497.
Hypoleukocytosis, 302.
Hyponutrition. See Under-nutrition.
Hypophysis, adenomata of, 240.
disease of, 195.
hypertrophy of, 195.
tumor of, 232, 233, 235.
Hypoplasia, inactivity, 331.
Hypoplasia of heart and vascular system,
329.
Hysteria, association of, with diabetes, 117.
combination of, with chlorosis, 338.
origin of, 335.
polyuria in, 116, 118.
stigmata of, 117, 119.
Sydenham’s views of, 340.
symptom-complex of, 336.
I
Tleus, causes of, 370.
Immermann-Oertel theory of hemophilia,
427, 437.
Inactivity of intestines, intervals of, 9.
Inanition, 148.
producing fever, 30.
Infarcts, hemorrhagic, 401.
Infection, conveyance of, by food, 509.
by mice, 571.
by water-cress, 509.
through wounds, 478.
leukemia caused by, 356.
morbus maculosus caused by, 459, 460,
461.
Inflammation, pulmonary, 339.
Influenza, a cause of gout, 127.
combined with scurvy, 396.
occurrence of, in chlorotics, 339.
Infusoria, 506.
Ingesta and excreta compared, 6.
Innervation apparatus, 205.
Inosite, 112.
INDEX
Insane, muscular action in the, 44.
Insects, parasitic, 571.
parasites propagated by, 503.
sting of, 575.
Insomnia, 324.
in trichinosis, 558.
Inspiratory furrow in liver, 540.
Intermarriage, debilitation by, 253.
influence of, among hemophiliacs, 415,
421.
of relatives favoring disease, 452.
Internal secretion, absence of, 199.
Intervertebral ganglia, disease of, 216.
Intestines, abnormal decomposition in,
335.
activity of, 323.
autointoxication from, 335.
paresis of, 219.
leukemic infiltration of, 351.
Intestinal canal, assimilation of food in,
45.
Intima, fatty degeneration of, 431.
Intoxication, acid, 399, 581.
Inunctions, splenic, 386.
Iodin, ingestion of, 42.
poisoning by, 584.
use of, in therapy of Hodgkin’s disease,
379. :
in therapy of leukemia, 368.
Todothyrin, 189.
Tridocyclitis, 252.
Tritis, 252.
Iron, food rich in, 309.
inorganic, 341.
use of, in anemia, 309.
in gout, 149.
in morbus maculosus, 497.
Tron chlorid, action of, on adrenals, 209.
in hemophilia, 453.
Iron springs of Europe, 343.
of Germany, 342, 343.
Iron therapy in chlorosis, 340, 341.
Ischiagra, 125.
Isodynamic action of carbohydrates and
fats, 51.
Isodynamics, law of, 5.
Isolation in treatment of diabetes, 124.
Israel’s case of acromegalia, 240.
Itch, eruption with, 565.
Itching disease, 599.
Itching, in scabies, 567.
Ixodes ricinus Linné, 566.
INDEX
J
Jaundice in phosphorus poisoning, 585.
Jaw, hyperplasia of, in acromegalia, 235,
236. »
periosteum of, in scurvy, 403.
Jecorin, 209.
Joint, hemophilic, 432, 439, 455.
Joint, of knee, puncture of, 455.
Joints, affection of, secondary, 478.
disease of, types of, 244,
+ effusions of, in scurvy, 399.
hemorrhages into, 429.
in rheumatism, 244.
inflammation of; 125.
puncture of, 456.
stiffness of, 247.
swellings of, in purpura, 471.
symptoms of, in gout, 132, 136.
tuberculosis of, 258.
K
Katherine of Arragon’s salad, 398.
Keratitis from scabies, 567.
Kidney, amyloid, simulating diabetes, 121.
circulation of, 123.
coccidiosis of, 506.
contracted, altered function of kidney in,
112.
differentiated from diabetes, 121.
echinococcus of, 541.
floating, 450.
functional disturbance of, 128.
genuine contracted, 142.
increased excretion of water by, 111.
insufficiency of, 132.
necrosis of, in gout, 142.
neoplasm of, 450.
normal, hemorrhage from, 446, 447.
parenchymatous inflammation of, 330.
Kisch’s cure for obesity, 177.
Knee, gouty attack in, 135.
stiff, from gout, 128.
Koch’s theory of hemophilia, 428.
Kolb’s views of purpura, 489.
Konig’s views of hemophilia, 438.
Koppe’s method of blood examination, 287.
Kreatinin 112.
Kribbelkrankheit, 599.
Krug’s experiments in feeding, 15, 17.
633
Kyphosis of acromegalia, 235.
of shoulder and hip, 246.
L
L-arabinose, 264.
L-xylose, 264.
Lactose, 78.
Lactosuria, 77.
Lancereaux’s views of rheumatism, 252.
Larrey, observations of, on obesity, 151.
Larynx, echinococcus of, 536.
gout in, 142.
Lavoisier’s study of chemical processes, 2.
Law of the conservation of energy, 2, 53.
of the development of the surface, 5.
of the permutation of forces, 2.
Lead acetate, in diabetes, 123.
Lead colic, 587.
Lead line, 588, 590.
Lead poisoning, 131, 587.
Lecithin in adrenals, 209.
Lemon cure, of gout, 148.
of hemophilia, 453.
Leontiasis ossea, 236.
Leprosy, 571.
Leptus autumnalis, Shaw, 565.
Leucin, 209.
Leukanemia, 357, 362.
Leukemia, 345.
acute, cutaneous hemorrhages in, 485.
autopsy reports of, 359.
blood-changes in, 348.
blood examinations in, 358, 360.
causes of, 357.
diagnosis of, 349, 364, 366.
fatal course of, 367.
fever in, 352.
leukocyte, 350, 354, 355.
local treatment of, 368.
lymphatic, 303, 350, 351, 354, 362.
myelogenous, 302, 350, 354, 356.
parasites found in, 356.
pathogenesis of, 363.
prognosis of, 367.
proportions of blood-corpuscles in, 366.
specific poison as cause of, 356.
splenic-medullary, 354.
symptoms of, 348.
true, 378.
treatment of, 367.
varieties of, 349.
634
Leukocytes, basophilic, 347.
condition of, in chlorotic blood, 326.
large mononuclear, 297.
mononuclear, 346, 356.
morphology of, 349.
neutrophilic polynuclear, 346.
normal proportion of, 349.
polynuclear neutrophilic, 297.
reduction of, 312.
Leukocytosis, 301, 302, 303, 344, 347.
Addison’s disease accompanied by, 204.
phenomenon of, 303.
post hemorrhagic, 328.
trichinosis accompanied by, 557.
varieties of, 364.
Leukopenia, 302, 385.
Leukorrhea from parasites, 551.
Levulose, 109.
Levulosuria, 77, 262.
Letzerich’s views of purpura, 460.
Leydenia gemmipara Schaudinn, 506.
Lice, of body, clothes, and head, 501, 571,
572.
Life insurance and obesity, 157, 160.
Life insurance and pentosuria, 271.
Life, mode of, as cause of disease, 333.
favoring chlorosis, 339.
unhygienic, 332.
process of, a mystery, 49.
Ligamenta lata, echinococcus in, 543.
Lind’s description of scurvy, 391.
Linguatula, 570.
Lip, hemorrhagic prominence of, 483.
Lipoma arborescens, 249.
Lipomatosis cordis, 152.
universalis, 152, 154.
Liver, abscess of, 540.
alcoholic, 383.
cirrhosis of, 43, 382.
coagulation necrosis of, 489.
condition of, in splenic pseudo-leukemia,
382.
echinococcus of, 530, 531, 534.
enlargement of, 351.
functional disturbance of, 140.
Liver, as food, forbidden in diabetes, 99.
Liver-fluke, 508.
in various parts of body, 510.
Living cell substance, 41.
Lithia, salts of, 257.
Lithium in gout, 148.
Léwit’s researches in leukemia, 356,
INDEX
Longevity of the obese, 157.
Lumbago in gout, 146.
Luxury consumption, 10, 53.
Lungs, echinococcus of, 537.
hemorrhagic edema in, 401.
hypostatic congestion of, 401.
Liithje’s experiments, 16.
Lymph-formation, anomalies of, 335.
Lymph-glands, adhesion of, 376.
enlargement of, 351, 370.
internal, enlargement of, 372.
lymphocyte production in. 348.
rupture of, 376.
Lymph-vessels, echinococcus of, 539.
Lymphadenoid proliferations, 375.
Lymphadenoma, 339.
Lymphangitis, 143.
Lymphatic trunks, displaced, 373.
Lymphemia, acute, 355. :
Lymphocytes, 293, 296, 302, 346, 382.
increase of, 361.
Lymphocythemia, 382.
Lymphocytosis, 365, 366.
Lymphomata, 384.
leukemic, 375.
Lymphomatosis, 372.
Lympho-sarcomatosis, 375, 377.
Lye, poisoning by, 582.
M
Macrocytes, 299.
Macroglossia in acromegalia, 236.
Maggots. See Fly-larve.
Magnus-Levy, experiments of, 23.
researches of, in metabolism, 34.
Maintenance of life, law of, 5.
on low nutrition, 53.
Mal de sol, 599.
Malaria, blood examination in, 291.
enlarged spleen in, 384.
melanotic discoloration from, 383.
Males, hemophilia in, 415.
Malnutrition, 161.
Malperforant, 85.
Maltose, 262.
Maltosuria, 271.
Mange of animals, 567.
Marasmus in cocainism, 597.
Marriage, of chlorotic girls, 338.
of hemophiliacs, 452.
INDEX
Massage, 66.
in chlorosis, 340, 341.
of spleen, 386.
Mast-cells, 298, 347, 355.
Meals, daily number of, 171.
Meat, compulsory inspection of, 533.
decomposed, poisoning from, 601.
fresh, a preventive of scurvy, 395.
kind and amount of, in diet of diabetics,
99, 108.
of poisonous animals, 601.
prevention of infection by, 525, 554.
salt, as cause of scurvy, 397, 398, 411.
value of, in diet, 74.
Mediastinum, echinococcus of, 538.
Medical Congress, Paris, 1900, 126, 127.
Medication in anemia, 309.
Medicine, Internal, Congress of, 56.
Medullin, 197. —
Megaloblasts, 300, 311.
in anemia, 311.
Megalocytes, 299, 300.
Melanotic discoloration, 383.
Memory, failure of, in anemia, 314.
Men, chlorosis in, 329, 330.
_ development of fat in, 159.
Meningitis, tubercular, in Addison’s disease,
225. :
Meningocele congenita, 428.
Menopause, hematuria accompanying, 450.
obesity, as caused by, 155.
occurrence of rheumatism during, 245.
use of odphorin in, 155, 196, 197.
Menstruation, abnormalities of, 333.
condition of, in chlorosis, 324.
in hemophiliacs, 435.
disorders of, use of odphorin in, 197.
Mental changes, in myxedema, 185.
Mentholglycuronic acid, 264.
Mercury, poisoning by, 587, 589.
Mesentery, echinococci of, 542.
Metabolism, Caspari’s investigations in,
51.
chemical processes of, 4.
condition of, in children, 36.
in chlorosis, 323.
in gout, 42.
in progressive pernicious anemia, 313.
diagram of, 35.
disturbance of, in myxedema, 185.
experiments in, of Kayser, 21.
from dynamic point of view, 49.
635
Metabolism, hereditary weakness of, 82.
increased, 192.
intermediary, 53.
Krug’s experiments in, 61.
limited labor of, in diabetes, 96.
modern laws of, 4.
perversion of, 32.
proportion of, to body surface, 5.
quantitative analysis of disturbances of,”
1, 4, 37.
quantitative estimation of, 8.
ratio of, in rest, 5.
researches in, of Bischoff, 56.
of Jaquet, 35.
of Liithje, 40, 41, 56.
of Rubner, 36.
of Sonden, 36, 37.
of Tigerstedt, 36, 37.
respiratory, 4, 25.
slowing of, 26, 31.
stimulation of, 343.
sugar, 267.
total energy of, 22.
toxic products of, 207.
Metachromasia, 298.
Metallic salts, poisoning by, 587.
Metalloids, poisoning by, 582, 583.
Metals, alkaline, poisoning by, 582.
Metamorphosis, direct, 545.
Methemoglobin, 287.
Microblasts, 307.
Microcytes, 299, 326.
Miescher’s tubes, 506.
Migraine in gout, 143.
Milk, condensed Swiss, for infants, 487.
Pasteurization of, 486.
value of, for chlorotics, 341.
in diet of diabetics, 100, 108.
in acid toxicosis, 581.
Milk-sugar, 78, 262.
Mineral spring cures, 148.
for Hodgkin’s disease, 379.
in rheumatism, 258.
Minute-kilo-values in metabolism, 34.
Mitchell, S. Weir, on treatment of neuras-
thenia and hysteria, 65.
Mode of life as cause of gout, 128.
Monkeys, experimental production of scurvy
in, 394.
Monoarthritis, senile, 256.
Monosodium urate, 127.
Monostomum lentis, Nordmann, 514.
636
Morbus maculosus Werlhofii, 414, 425, 457.
autointoxication a cause of, 459.
autopsy report of, 484.
bacteriology of, 489, 490.
composition of blood in, 494.
confounding of, with typhus, 482.
cutaneous hemorrhages accompanying,
464.
diagnosis of, 484.
distinction of, from scurvy, 458.
etiology of, 459, 477.
febrile phenomena in, 494.
frequency of, in youth, 480.
infectious, 459, 460, 461.
intestinal symptoms in, 492, 493.
nervous shock a cause of, 468.
occurrence of, after fright, 462.
pathological anatomy of, 487.
predisposing cause of, 480.
prognosis of, in children, 481.
prophylaxis of, 496.
relapses of, 461.
special symptomatology of, 481, 490.
stages of, 480.
temperature in, 472.
treatment of, 496.
Morphin habitués, 271.
Morphin, poisoning, acute and chronic, 595.
Morphinism, 271, 4438.
Motor disturbances in chlorosis, 324.
Mountain climbing, 67, 72.
Mouse septicemia, 571.
Mucous gland, tumor of, 238.
Mucous membrane, catarrh of, 140.
condition of, in scurvy, 400.
Mucous membrane of mouth, in Addison’s
disease, 201.
Mucous membrane of respiratory organs,
142.
Murmurs, anemic, 321.
functional, 321.
hemic, 321.
nun’s, 322.
organic, 321.
venous, 322.
Muscides larve, 574.
Muscle, accumulation of, 55.
increase of, 57.
Muscle lameness, sympathetic, 556.
Muscles, activity of, 53.
condition of, 54.
electric contractility of, 558.
INDEX
Muscles, excision of, in trichinosis, 559.
free movement of, 331.
loosening of, by scurvy, 400.
resemblance of, to smoked goose breast,
558.
swelling of, in trichinosis. 557.
work hypertrophy of, 57.
Muscular labor, forced, 52.
Muscular power, source of, 15, 51.
Muscular tension, effect of, 44.
Muscular tonus, 30.
Musculature, increase of, in acromegalia,
236.
trichine in, 554.
Mushroom poisoning, 585, 600.
Mussels, poisoning by, 600.
Myelin, 209.
Myelocytes, 300, 347.
production of, 360.
Myiosis, 573.
intestinalis, 574.
Myopathy, progressive, 195.
Myositis, acute fibrous, 248.
Myxedema, 30, 179, 188.
abortive, 192.
autopsy reports of, 186.
etiology of, 180.
infantile, 187.
pathology of, 186.
relapses of, 193.
sensations of cold in, 185.
substitution therapy in, 225.
symptoms of, 180.
temperature in, 185.
therapy of, 188. .
thyreoiodin in, 189, 193, 195.
““Myxcedéme fruste,” 191, 192.
N
Nansen Expedition, absence of scurvy in,
393, 411, 412.
Nasal cavity, inflammation of, 377.
Natural-Healer, 60.
Nature-cure institutions, 60.
Nausea caused by fat, 167.
Neck, echinococcus in, 535.
enlarged glands of, 371.
Necrosis of jaw in scurvy, 403.
Needle baths, 257.
Nematoda, 544.
INDEX
Nematodes, perforation of ulcers by, 549.
Nephrectomy, 447.
for renal hemophilia, 443.
Nephritis, 142, 451.
chronic, 337.
differentiated from diabetes, 121.
in rheumatism, 252.
interstitial, 498.
metabolism in, 41, 42.
parenchymatous, 449.
in trichinosis, 558.
unilateral, 445.
Nephrolithiasis, 449.
Nerve areas connected with adrenals, 222.
Nerve elements, 204.
Nervines in diabetes, 93.
Nervous symptoms in Addison’s disease,
200, 211, 218.
in chlorosis, 324.
Nervous system, central, 255.
disturbances of, 313.
in anemia, 315.
changes in, in Addison’s disease, 215.
condition of, in acromegalia, 238.
in gout, 142.
disease of, a cause of Addison’s disease,
213.
simulating adrenal disease, 219.
hereditary affection of, 426.
Neuenahr, treatment at, 101.
Neuralgia, gouty, 143.
intercostal, 324.
local pressure as cause of, 373.
occurrence of, in chlorosis, 324.
Neurasthenia, under-nutrition resulting in,
60.
value of fat in, 55.
Neurasthenic conditions, 142.
Neuritis, in gout, 143.
Neuropathic constitution, 115.
Neuropathic predisposition, 441.
Neuroses, combination of, with corpulence,
69.
functional, 116.
general, 142.
Neurosis of vasomotors, 336.
Neutral dyes, staining in, 297.
Neutrophiles, 355.
Neutrophilic leukocytosis, 365.
Neutrose, 48.
Newcastle-on-Tyne, lead poisoning at, 131.
Nicotin poisoning, acute and chronic, 595.
637
Night-blindness, etiology of, 419.
Nitro-benzol, poisoning by, 592.
Nitrogen, elimination of, 12, 42, 43,
estimations of, in feces, 45.
food substances free from, 71.
retention of, 17.
Nitrogen accumulation, 19.
Nitrogen-balance, 37.
Nitrogen equilibrium, 7, 20, 29.
Nitrogen excretion in the urine, 11.
Nodules, caused by filarice, 548.
Nodules, gouty, 137, 138.
lymphatic, 352.
No-fat cure, 163, 165.
Noorden-Dapper on antifat cures, 56.
Normal proportions of blood-corpuscles, 283,
284,
Normoblasts, 300, 307, 356.
shower of, in blood after hemorrhage,
328.
Normocytes, 299.
Nose, copper, in gout, 143.
echinococcus in, 535.
expulsion of oxyuris from, 551.
parasitic disease of, 574.
Nose bleed, 426.
Nostalgia as cause of chlorosis, 333.
Nourishment during antifat cures, 56.
Nuclein, atypical, 266.
food rich in, 137.
pancreatic, 267.
Nucleinic acid, 265, 267.
Nucleins, animal, 265.
Nucleo-proteids, 266.
Nursing, in morbus maculosus, 496.
of chlorotics, 340.
Nutrition, condition of, 54.
conducing to chlorosis, 332.
general disturbance of, 206.
individual standard of, 55.
laws of, 4.
in carnivora, 4.
medium state of, 55, 59.
optimum of, 66.
processes of, 50.
rational therapy of, 1.
Nutrition, in morbus maculosus, 496.
of convalescents, 31.
of fever patients, 31.
of the sick, 35.
Nutritive preparations, 70.
Nutrose, 70.
638
Nyctotherus faba, 508.
Nylander’s test, 262-
Obesity, 151.
after menopause, 155.
after pregnancy, 155.
alcohol, a cause of, 155.
association of, with gout and diahetes,
154.
Banting cure of, 70, 72, 73, 74, 163, 164,
165, 166, 173, 175.
calory requirement in, 35.
clinical cases of, 171.
combination of, with gout, 171.
complications of, 69, 156.
composition of urine in, 157.
constitutional, 35.
cure of, by thyreoiodin, 194.
dangers of rapid reduction of, 68.
Debove’s treatment of, 161.
degrees of, 68.
diagnosis of, 159.
diet in, 161.
economy of food material in, 34.
effect of, on life insurance, 158.
effect of perspiration in, 26.
etiology of, 62, 153.
example of, 151.
fluids unlimited in, 75.
functional, 156.
gout, as caused by, 130.
Harvey’s cure of, 70, 72, 163, 165.
in ancient times, 151, 152.
influence of, upon feminine fertility, 152.
on mental powers, 159.
metabolism in, 34.
muscular exercise in, 173.
occurrence of, in convalescence, 155.
of adolescents, 154.
of eunuchs, 154.
of people of Munich, 155.
of the healthy, 68.
over-nutrition a cause of, 57.
plethoric, 62, 177.
predisposition to, 153, 154.
prognosis in, 157.
relation of, to gout, 144.
slow reduction of, 170.
stages of, 155.
thirst in, 170.
INDEX
Obesity, treatment of, 160, 175, 176.
by depletion, 162.
under-nutrition in cure of, 59.
value of exercise in, 173.
various methods of cure of, 70, 163.
views of Ebstein and Oertel on reduction
of, 56.
Odor of scorbutic fluid and tissue, 403, 405.
Oertel obesity cure, 174, 175.
Oertel’s views of hemophilia, 425.
Oligeemia vera, 330.
Oligemia combined with chlorosis, 338.
Oligochromemia, 304, 326, 385.
Oligocythemia, 185, 250, 325, 385.
Oligoplasmia, 328.
Omagra, 125.
Omentum, echinococcus of, 543.
Onychia scorbutica, 405.
Odphorin, use of, during the menopause, 155,
196, 197.
for menstrual difficulties, 197.
Open air exercise, 67.
Ophthalmia, metastatic, 459.
Opium poisoning, acute and chronic, 595,
596.
Opium smokers of China, 589.
Opotherapy, 196.
Oral cavity, amebz in, 505.
bacilli in, 378, 294, 395.
echinococcus in, 535.
foul odor from, 408.
Orbit, echinococcus of, 535.
Orcin test, 263, 272.
Ord’s cases of myxedema, 179.
Organic diseases, 331.
Organism, process of life in, a mystery, 49.
waste in, 12.
Organotherapy, 189, 196, 224.
employment of, since antiquity, 196.
in acromegalia, 242.
in anemia, 319.
in leukemia, 368.
practice of, in China, 196.
review of, 197, 198.
Organs, blood-forming, 310.
Orthopedic treatment, 259.
Orthopnea, 352.
Osteoarthropathy, hypertrophic, 240.
Osteomyelitis, 257.
Ovarian extract, 155, 196, 197.
Ovarian therapy, 155, 196, 197.
Ovaries, echinococcus of, 543.
INDEX
Over-nutrition, 54.
accumulation of fat in, 59.
amount of food necessary for, 59.
best method of, 70.
combination of, with hard manual labor,
62.
with muscular exercise, 58.
consequences of, 61.
in Basedow’s disease, 65.
in chronic wasting diseases, 63.
in diabetes, 64.
in exophthalmic goiter, 64.
in functional nervous diseases, 65.
in pulmonary tuberculosis, 63.
in syphilis, 63.
indications for, 62, 66.
occurrence of, 61.
technic of, 69.
Oxalic acid toxicosis, 581.
Oxidation, changes in, in disease, 43.
deficient, in myxedema, 185.
degree of, 22.
after muscular labor, 24.
in fever, 30.
diminished, 34.
increase of, by hot water bath, 25.
secondary, 91.
Oxybutyric acid in urine, 91.
Oxygen, consumption of, 8.
inhalations of, in leukemia, 368.
intake of, 8.
treatment by, 497.
Oxyuriasis, diagnosis of, 552.
treatment of, 552.
Oxyuris host, 551.
vermicularis, Linné, 548, 550.
Oysters, poisoning by, 600.
P
Pain in Addison’s disease, 218.
in gout, 126.
Palate, gangrene of, 479.
Pallor, general, in chlorosis, 336.
Palpitation, cardiac, 322.
Pancreas, carcinoma of, 46.
cohdition of, in acromegalia, 238.
diseases of, as cause of diabetes, 82, 84.
echinococcus of, 541. ;
extirpation of, producing diabetes, 81.
relation of, to glycosuria, 196.
639
Pancreas proteid, 266.
Pancreatic juice, action of, 46.
occlusion of, 46, 47.
Panophthalmia, 535.
Parablasts, 417, 418.
Paracentesis, 43.
Paralyses in the obese, 69.
Paralysis, gouty, 143.
Parasites, anemia caused by, 309.
animal, distribution of, 502.
sexual maturity of, 502.
varieties of, 501.
asexual forms of, 502.
blood-sucking, 562.
development of, 502.
intestinal, 39.
health not injured by, 521.
occasional, 501, 575.
permanent, 501.
tenacity of life of, 520.
virulent form of, 574.
Parasites of man, 499.
amebee, 505.
balantidia, 508.
cilia, 508.
coccidia, 506.
distoma, 509.
flagella, 507.
helminthes, 508.
infusoria, 507.
megastoma entericum, 507.
plathelminthes, 508.
protozoa, 505.
rhizopoda, 505.
trichomonades, 507.
vorticelli, 508.
Parasitic disease, blood examination in,
275.
prevention of, 525.
symptomatology of, 503, 509.
Parenchymatous injections, 386.
Parotid, echinococcus in, 535.
Passive exudation, 363.
Pediculus capitis, de Geer, 571.
Peliosis cachecticorum, 476.
gonorrhoica, 479.
theumatica, 409, 469, 473, 474, 492.
autopsy findings of, 488.
Bamberger’s cases of, 476.
with a typical course, A76.
Schoenleinii, 457.
Pellagra, 599.
640
Pelvis, true, echinococcus of, 543.
Pentastoma constrictum, v. Siebold, 570.
tenioides, Rudolphi, 570.
Pentose, 77, 262.
combustion of, 265.
dextro-rotary, 272.
in animals, 266.
Pentosuria, 77, 262.
alimentary and chronic, 268.
caused by cherries, plums, beer, 77.
in morphin habitués, 271.
increase of, by starches, 264.
prognosis of, 271.
relation of, to diabetes, 271.
therapy of, 271.
typical cases of, 269.
Pentosuria and life insurance, 272.
Peptones, calories in, 13.
Pericardium, echinococcus of, 539.
Peripheral joints, gout in, 136.
Peripheral nerves, degeneration of, 216.
Peristalsis, intestinal, 207.
Peritonitis, tubercular, 47.
Perityphlitis, examination of blood in, 303.
Pernicious anemia, 39, 47, 305, 314, 382.
metabolism in, 33.
parasites as cause of, 504.
presence of tape-worms a cause of, 523.
toxic influence inducing, 316.
Perspiration, insensible, 26, 113, 184.
Perspiration, sensible, 26.
Pes varus congenitus, 428.
Petechie in scurvy, 404.
Pettenkofer respiratory apparatus, 154.
Peyer’s patches, in purpura, 487.
Pharmacodynamics, 197.
Phenol poisoning, 593.
Phenylhydrazin test, 262, 263, 264.
Phenylosazone, 265.
Phlegmons of gout, 134.
Phloridzin poisoning, 83.
Phloroglucin test, 263, 265.
Phosphorus in dejecta, chemical proof of,
585.
Phosphorus, retention of, 18.
Phosphorus poisoning, 584.
chronic, 586.
Photography in case of acromegalics, 231.
Phthirius inguinalis, Redi, 572.
Physaloptera caucasica n. spr., 564.
Physical exertion, influence of, on metabo-
lism, 24.
INDEX
Physical remedies, 257.
Picric acid poisoning, 593.
Pierre Marie’s study of acromegalia, 229.
Pigment in blood, 292.
Pigment, pathologic deposition of, 213.
Pigmentation of skin, 200.
Pilocarpin, in diabetes, 123.
Pimelosis, 152.
Piperazin in gout, 148.
Piperin in pseudo-leukemia, 386.
Pituitary body, 195.
in acromegalia, 238.
Placental area, diphtheria of, 478.
Plagiomonas urinaria, 507.
Plasma, accumulation of, in blood, 335.
Plasmon, 48, 70.
Plaster of Paris, for hemophilie joints,
456.
Playfair-Mitchell treatment of neurasthenia,
58, 65.
Plerocercoides, 520.
Plethora, 341.
hemorrhage as caused by, 487.
hydremic, 425.
serosa, 121.
vera seu sanguinea, 156.
Pleura, ecchymoses upon, 557.
echinococcus of, 536.
inflammation of, 373.
Pleural effusions, 373.
Plica polonica, 571.
Pliny on corpulence, 163.
Pliny’s rules for obesity, 152.
Pneumonia, central, 291.
followed by purpura, 482.
Poisoning, acid, 579, 581.
agaricus muscarius, 600.
alkaloid, 594.
anilin, 592.
animal, 598.
antipyrin, 594.
arnican, 598.
arsenical, 586.
atropin, 597.
balsam of copaiba, 594.
barium, 583.
bromin, 584
camphor, 594.
carbolic acid, 593.
carbonic oxid, 590.
chloral hydrate, 584.
chloroform, 584.
Poisoning, cocain, 597.
cornutin, 598.
digitalis, 597.
endogenous, 579.
ergot, 598.
ethyl alcohol, 591.
exogenous, 579.
fish, 600.
gas, 590.
iodin, 584.
lead, 587.
meat, 600.
mercurial, 587, 589.
morphin, 595, 596.
mushroom, 585, 600.
mussel, 600.
nicotin, 595.
nitro-benzol, 592.
opium, 595, 596.
oxalic acid, 581.
oyster, 600.
phenol, 593.
phloridzin, 79.
phosphorus, 584.
picric acid, 593.
prussic acid, 582.
salicylic acid, 593.
sulphonal, 591, 592.
sulphur, 586.
tetronal, 591, 592.
toad-stool, 599.
trional, 591, 592.
vegetable, 598.
Poisoning caused by alkalies, 582.
by antineuralgics and antipyretics, 592.
by arseniureted hydrogen, 587.
by caffein and thein, 595.
by chlorin combinations, 583.
by lye, 582.
by metallic salts, 587.
by metalloids, 582, 583.
by potassium chlorate, 583.
Pocket spectroscope, 287.
Podagra, 125, 140.
Poikilocytosis, 299, 306, 312, 326.
Polyuria, 111.
after trauma, 116.
hysterical, 116, 118.
permanent, 115, 119.
pure primary, 117, 118.
transitory, 115.
underlying cause of, 122.
42
INDEX 641
Polyarthritis, chronic, 253.
primary chronic progressive, 246,
sicca, 250.
villosa, 244,
Polychromatophilia, 326.
Polychromatophilie degeneration, 299, 307,
312.
Polycythemia, 185.
Polydipsia, 111.
Polynuclear leukocytosis, 365.
Polypionia infantum, 154.
Polyplasmia, 328.
Polysarcia, 155.
adiposa, 152.
Pork, containing trichina, 553.
Portal vein, disease of, 383.
Potassium, deficiency of, causing scurvy,
399.
acid vegetable, as preventive of scurvy,
410.
Potassium bromid, in diabetes, 122.
Potassium carbonate, in potatoes, 398.
Potassium chlorate, 583.
Potassium soap, 379, 380.
Potatoes, as preventive of scurvy, 397, 398.
Predisposition to diabetes, 80, 94.
to gout, 126, 139.
to hemophilia, 414.
to scurvy, 390, 396.
Pregnancy, diabetes insipidus occurring in,
120.
hematuria in, 450.
hemorrhages of, 454.
lactosuria in, 79.
psychical influences during, 421.
Priapism in leukemia, 352.
Pribram’s statistics of rheumatism, 243,
244.
Priessnitz pack, 258.
Progressive pernicious anemia, 305, 310,
359, 563.
cardiac symptoms of, 313.
course of, 317.
distinction of, from various diseases, 318.
fatality of, 317.
prognosis of, 317.
symptoms of, 311, 313.
Prophylaxis in diabetes, 93.
in hemophilia, 452.
Prostate gland, echinococci of, 542.
Proteid metabolism, 11, 39.
Proteid requirement for the sick, 37.
642
Proteids, identity of, 2.
Proteids in metabolism, 36.
Protein substances, 3.
Protoplasm, faulty composition of, 131.
general diseases of, 139, 154, 157.
granular, 346.
production of, 40.
Protozoa, 505.
Prurigo, 568.
Pruritis from oxyuris, 551.
Prussia, cattle disease in, 533.
Prussic acid, 582.
Pseudo-leukemia, 363, 370.
clinical picture of, 377.
lesions of, 371.
occurrence of, in children, 385.
treatment of, 385.
Pseudo-leukemia lienalis, 371.
lymphatica, 371.
lymphatico-lienalis, 371.
Pseudoparasites, 501.
Psoriasis, 143, 253.
linguez, 140.
Psychic functions in diabetes
114.
Psychical anomalies in chlorosis, 324.
in diabetes insipidus, 117.
Psychical causes of chlorosis, 332.
Psychical influences, symptoms of, 304.
Psychosis, acute, 591.
Ptomain poisoning, a cause of scurvy, 393,
394,
Puberty, chlorosis appearing at, 330.
Pulmonary artery, murmur over, in chlor-
osis, 321.
Pulse, in anemia, 321.
Pulse, tension changes in, 121.
Purpura, changes in the blood causing, 463.
changes in vessels causing, 463.
chilling of body a cause of, 468.
clinical picture of, 469.
distinction of, from various diseases, 458.
experimental production of, 461, 462.
Henoch’s, 462, 479, 481, 482.
idiopathic, 489.
mildest forms of, 471.
relapsing, 468, 471, 492.
remarkable case of, 483, 484.
spontaneous and primary, 467.
successive attacks of, 492.
toxic forms of, 459.
varieties of, 457, 469.
insipidus,
INDEX
Purpura, varieties of, abdominalis, 469, 479.
cachecticorum, 465.
dyspeptica, 469.
fulminans, 467, 481.
gonorrhoica, 469, 492.
hemorrhagica, 457, 469, 471, 472.
intestinalis, 471, 492.
rheumatica, 457, 465, 469, 471, 473, 492.
scorbutica, 471.
simplex, 457, 467, 469.
urticans, 457, 473. ;
Pyelitis, simulating diabetes, 121.
Pyemia from echinococcus, 532.
Pyrocatechin, 209.
Q
Quinin in leukemia, 368.
in pseudo-leukemia, 385.
R
Rachisagra, 125.
Rachitis, 459, 467, 485.
treatment of, by thyreoid gland, 195.
Radioscopy, 191.
Rags, parasites in, 565.
Rail-brace apparatus, 456.
Rainey’s tubes, 506.
Rape, attempted, causing morbus macu-
losus, 469.
Rats as source of trichina infection, 553.
Rectum, itching of, 551.
polypus of, 513.
Refrigeration as cause of purpura, 468.
Régime, antinervous, 340.
Relapsing fever, spirilli of, 291.
Renal diseases, associated with obesity, 69.
Renal echinococcus, 533.
Renal epithelium, 449.
Renal gout, primary, 132.
Renal hematuria, essential, 445.
Renal hemophilia, 442.
cases of, 443.
hereditary, 451.
Renal hemorrhage, hemophilic, treatment
of, 444.
congestive, 450.
forms of, 447.
Renal inflammation combined with gout,
137.
INDEX
Renal irritation from acid toxicosis, 580.
Resorts for treatment of diabetes, 101.
of gout, 148.
Respiration, difficult, in Hodgkin's disease,
373.
Respiration rate, acceleration of, 323.
Respiratory apparatus, 7.
of Hoppe-Seyler-Tigerstedt, 8.
of Zuntz and Geppert, 8.
Respiratory diseases in the obese, 69.
Respiratory metabolism, 28, 34.
Respiratory organs, inflammation of, in
gout, 142.
Respiratory passages, catarrh of, 352.
Respiratory quotient, 8.
Rest energy, 5.
Rest in bed for neurasthenia, 65.
Rest in treatment of chlorosis, 340.
Rest metabolism, 29.
Rest values in metabolism, 24, 27, 32.
tables for, 27.
Restlessness, influence of, in metabolism, 44.
Rete Malpighii, pigmentation in, 213.
Retina, serous infiltrations of, 325.
Retinal hemorrhages, 308, 314, 478, 488,
494.
Retinitis leukemica, 352.
Retinitis of Bright’s disease, 467.
Retroperitoneal echinococci, 542.
Rhabditis, varieties of, 544.
Rheumatism, 144.
acute, sweats of, 478.
acute articular, 244, 252.
with atypical course, 478.
articular, in a chorus girl, 248.
chronic, 244.
Rheumatism, chronic articular, 243, 246.
etiology of, 243.
joint implication in, 244.
pathology of, 248.
treatment of, 257.
combination of, with gout, 148.
gonorrheal, 475. |
internal treatment of, 257.
occurrence of, in hemophiliacs, 413, 416.
pseudo-articular, 256.
secondary chronic, 244.
simulation of, by trichinosis, 559.
Rheumatisme articulaire chronique pro-
gressif, 244.
déformant, 244.
goutteux, diathésique, 244.
643
Rheumatisme infectieux, 244.
noueux, 244,
Rheumatoid, acute, 256.
tuberculous, 256.
Rhinagra, 143.
Rickets and enlarged spleen, 384.
Robin’s obesity cure, 164.
Roborants in Hodgkin’s disease, 381.
Roborat, 48, 70, 169.
Romanowsky stains, 292, 296, 299, 307, 346.
Réntgen rays. See X-rays.
Rovsing, views of, on unilateral hematuria,
447,
Rowing, 72.
Rubner’s calculations in metabolism, 9.
calorimetric investigations, 5.
law of the conservation of energy, 2.
law of the development of the surface, 5
Ss)
Salicylic acid poisoning, 593.
Salines in hemophilia, 453.
Saliva, increased in scurvy, 403.
Salkowski’s case of pentosuria, 263.
discovery of pentosuria, 267.
Sanatoria, dietetics in, 71.
influence of life in, 67.
treatment of chlorosis in, 339.
Sand-flea, disease caused by, 572.
Santonin for expulsion of parasites, 550.
for oxyuriasis, 552.
Sarcomata, 239.
multiple, 433.
Sarcopsylla penetrans, 572.
Sarcoptes hominis, 501.
scabiei, Linné, 566.
Saturnine poisoning. See Lead.
Sausage poisoning, 601.
Scabies, diagnosis and treatment of, 568.
Scarlatina followed by purpura, 482.
Scharbock, 389.
Sciatica in diabetes insipidus, 114.
Schmaltz’s pycnometer, 284.
Schmaltz’s test for specific gravity of the
blood, 284.
Schmidt’s fermentation test, 45.
Schmidt’s test diet, 48.
Schénlein’s disease, 473.
Scleroderma, 213.
Scrofula, 63.
644 INDEX
Scrotum, echinococci of, 544. Sepsis, myxedema followed by, 186.
excessive development of, 151. severe, hemorrhages in, 485.
Scurvy, 388, 485. Septicemia, conveyed by mice, 571.
absence of, in Nansen Expedition, 393, | Serum of the blood, 285.
412. Serum, specific gravity of, 327.
American Collective Report on, 393, 404, | Servant girls, chlorosis among, 332.
485. Sexual disturbances, 334.
as an infectious disease, 399. Sexual functions in chlorosis, 323.
bacillus found in, 394. Sexual organs, anomalies of, 334.
constitutional phenomena of, 402. Siderosis, 314.
contraction of, by nurses, 395. Silbermann’s views of purpura, 464.
diagnosis of, 409. Silenus as type of obesity, 152, 156.
etiology of, 393. Siven, experiments of, 15.
experimental study of, 393. Skalotyrbé, 389, 390.
external signs of, 402, 409. Skin, affections of, in gout, 143.
fatal outcome of, 410. in rheumatism, 252.
faulty nutrition, a cause of, 397. bleaching of, in Addison’s disease, 201.
frequency of, in Alaska, 392. bronzing of, 212, 220, 226.
geographic distribution of, 391. changes of, in trichinosis, 557.
general and special treatment of, 413. condition of, in gouty attack, 134.
gums the chief seat of, 402. in myxedema, 179, 184.
hereditary predisposition to, 396. in rheumatism, 251.
Hirsch’s tabulations of, 391. discoloration of, 201.
history of, 388. doughy appearance of, 320.
infantile, 393, 395, 400, 404. edematous infiltration of, 320.
no known pathogenic agent of, 393. faded-yellow. in anemia, 312.
occurrence of, among seamen, 411, 412. greenish, 320, 336.
among Tartars, 395. hemorrhages of, 464.
among the wealthy, 397. itching of, in diabetes, 85.
among United States troops, 392. lymphadenoids in, 375.
during siege of Ladysmith, 399. marbling of, 483.
during siege of Paris, 397. metabolism stimulated from, 380.
in antiquity, 389. non-ulcerating nodes in, 352.
in Russia, 395. pallid, in anemia, 320.
in the tropics, 392. pigmentation of, 218.
pathological anatomy of, 399. trophic processes of, 194.
predisposition to, 396. uninjured, hemorrhage from, 426.
prevention of, in English marine, 411. Skull, changes of, in acromegalia, 235.
production of, in monkeys, 394. Sleepiness in chlorosis, 324.
prognosis of, 410. Smallpox, hemorrhagic, 484.
prophylaxis of, 395, 410. Sodium-biurate, 127.
rarity of severe forms of, 408. Sodium chlorid in diabetic urine, 112.
recovery from, 408. Sodium-quadriurate, 127.
symptomatology of, 401. Sodium urate, acid, 127.
treatment of, 410. Solar plexus, changes of, in Addison’s dis-
Sea-baths, in anemia, 310. ease, 216.
Seamen, scurvy among, 411. Soxhlet sterilizer, 486.
Sebaceous glands, parasites in, 570. Special sense, organs of, 325.
Semilunar ganglia, cauterization of, 219. Spectroscope, use of, 287.
extirpation of, 219. Speech in myxedema, 185.
Seneca’s views of gout, 147. Spermin, 197.
Sensuality awakened in the young, 332. Sphacelinic acid, poisoning by, 598.
INDEX 645
Sphacelotoxin, 598.
Sphygmogenin, 210.
Spices, use of, in diabetes, 109.
Spinal cord, changes of, in Addison’s dis-
ease, 216. _
echinococcus of, 534.
Spinal roots, neurotic processes in, 217.
Spirilli, relapsing fever, 571.
Splanchnic nerve, degeneration of, 216.
Splanchnomegalia, 237.
Spleen, cold applications to, 386.
echinococcus of, 541.
enlargement of, 350, 356, 370, 376, 383,
384,
idiopathic, 385.
in anemia, 313.
in Hodgkin’s disease, 372.
in pseudo-leukemia, 382.
hyperplasia of, 363, 383.
lymph-cell formation in, 361.
pappy softening of, 488.
Splenalgia, 324.
Splenectomy, 386.
in children, 386.
Splenica, 371.
Spleno-lymphatica, 371.
Spondylose rhizomélique, 246.
Spongiosa, 236.
Sporozoa, 506.
Sport, value of, in obesity, 176.
Springs, bromin-containing, 380.
iodin, 380.
sodium chlorid, 380.
Sputum, gangrenous, 537.
Staining process, of Ehrlich, 293.
Stains, neutral, 346.
tniacid, 346.
universal, 295.
Starvation, 21.
cure of, 161, 162.
losses in, 10, 11.
observations in, 14.
Stasis, circulatory, 352.
in disease of the heart, 48.
uric acid, 132.
Statistics of gout, 130.
Steinbacher’s cure of obesity, 174.
Stiffness of joints in rheumatism, 247.
Stippling, basophilic, 300.
Stomach, affection of, from gout, 140.
atony and displacement of, 335.
carcinoma of, 315.
Stomach, hyperacidity of, 47.
lavage of, 581, 597.
in opium poisoning, 596.
leukemic infiltrations in, 351.
perforation of, 581.
secretory activity of, 323.
Stomatite ulcéreuse, 389.
Stomatitis, aphthous and ulcerative, 403.
from arnica, 598.
in children, 403, 404.
Stomatokaké, 389, 390.
Stools, fatty, 46.
rice-water, 586.
Strawberry cure, 147.
Styptics, 454.
Substitutiontherapy, 188, 193.
Suffocation, from glandular swelling, 373.
Sugar, ingestion of, 78.
forbidden in diabetes, 109.
presence of, in urine, 44.
producers of, 78.
Suggestion, as cause of polyuria, 118.
effect of, 75.
Suggillations, enormous, in purpura, 483,
491.
scorbutic, 405.
Suicide by phosphorus poisoning, 584.
Sulphonal poisoning, 591, 592.
Sulphur, poisoning, 586.
Sulphuric acid, in morbus maculosus, 497.
Sun baths of Celsus, 175.
Sunstroke, a cause of diabetes insipidus,
119.
Suprarenals. See also Adrenals.
Suprarenal extract, action of, 208.
on central nervous system, 208.
in animals, 224.
vaso-constricting action of, 208.
Suprarenin, 210.
Surface, law of development of, 5.
Surgery, danger of, in bleeders, 452.
Sweat, exhaustive, 478.
reactive outbreak of, 341.
Sweat apparatus, 258.
Sweat baths, 341.
in diabetes, 123.
Sweat formation, 113.
Sweating, 29.
profuse, 44.
in leukemia, 352.
Sweetbreads, forbidden in diabetes, 99.
Switzerland, prevalence of goiter in, 190,
646
Sydenham’s views of gout, 147.
Sympathetic system, diseases of, 216, 218.
disorders of, 324.
neuritic disease of, 216.
Symptom-complex of gout, 132.
Syncope, in chlorosis, 324.
Synovial fluid, non-purulent in rheumatism,
249.
Syphilis, association of, with gout, 145, 148.
cerebral, 122.
diabetes as caused by, 120.
enlarged spleen in, 384.
hereditary, 384.
joint implication in, 145.
of brain, 115.
over-nutrition in, 63.
tertiary, 63.
Systolic murmurs, 321.
Systolic thrill, 321.
T
Tabes mesenterica, 47.
Table, comparative, of various diet schemes,
72.
of alcohol and carbohydrates in beer, 106.
of carbohydrates in fruits, 105.
in wines and spirits, 106.
of Dapper’s diet scheme, 73.
of energy metabolism per square meter
of body surface, 5.
of fatty foods and varieties of milk, 104.
of food values necessary for maintenance
of N-equilibrium, 14.
of percentage of carbohydrates in bread,
flour, vegetables, 104.
of fat in cheese, 104.
in eggs, 104.
in meat, 103.
in sausages and preserved meats, 104.
of rest values in different diseases, 27.
Tallqvist scale, 277.
Tamburini’s views of acromegalia, 241.
Tannin, in diabetes, 123.
Tape-worm, 514.
anemia as caused by, 318.
food causing passage of, 523.
presence of, without symptoms, 522.
reflex symptoms caused by, 523.
removal of, 525, 526.
Tape-worm disease, prognosis of, 524.
therapy of, 525,
INDEX
Tarantula, bite of, 575.
Taste, anomalies of, 325.
Technic of over-nutrition and under-nutri-
tion, 69.
Teeth, extraction of, in bleeders, 452, 454.
loosening of, 140, 485.
in scurvy, 403.
tartar of, containing amebe, 505.
Temperament, phlegmatic in the obese, 159.
Temperature in diabetes insipidus, 114.
in myxedema, 185.
in scurvy, 407.
in trichinosis, 556.
Tendon sheaths, nodules of, 251.
Tendons, stretching of, 146.
Tenia africana, v. Linstow, 518.
asiatica, v. Linstow, 518.
confusa, Ward, 517.
crassicollis, 517.
cucumerina, Bloch, 516.
echinococcus, 526.
transmitted by dog, 529, 530.
flavopunctata, Weinland, 516.
hominis n. spr., 519.
madagascariensis, Davaine, 517.
marginata, 517.
nana, v. Siebold, 516.
saginata, 501, 514, 515.
serrata, 517.
solium, 514.
characteristics of, 514.
prevalence of, in Germany, 502.
Teniaphobia, 524.
Tension, specific energy of, 5.
Tension energy, consumption of, 53.
Tension power, calculation of, 37.
Tetanus, thyreoid therapy in, 195.
Tetronal poisoning, 591. -
Therapy, dietetic, in anemia, 309.
of diabetes, 92.
physical, in anemia, 309.
suprarenal, 225, 226.
Thermal baths, 148.
Thirst, as symptom of diabetes, 113.
endurance of, in obesity, 170.
methods to relieve, 118.
Thirst cure, 174.
Thoma-Zeiss apparatus, 281, 283.
Thoracic organs, lymphadenoids in, 375.
Thread-worms, 544.
Thrombophlebitis suppurativa of pelvic
veins, 478.
INDEX
Thrombosis, as cause of purpura, 462, 463,
464, 465.
Thumb, exemption of, in rheumatism, 245.
Thymus gland in acromegalia, 238.
of hemophiliacs, 431.
Thymus preparations, 193.
Thyraden, 190.
Thyreo-antitoxin, 189.
Thyreoglobulin, 189.
Thyreoid cure of mental diseases, 195.
Thyreoid extract in myxedema, 180.
Thyreoid gland, absence of, 184.
administration of, 29.
atrophy of, 188.
degeneration of, 180.
echinococcus of, 536.
enlargement of, in acromegalia, 232, 238.
grafting of, 187.
internal secretory activity of, 334.
iodin contents of, 190.
strumous degeneration of, 186.
Thyreoid therapy, 188, 191.
toxic action of, 191.
Thyreoidectomy, 187.
in animals, 196.
Thyreoidin in obesity, 175, 176.
Thyreoiodin, 189, 193.
as cure for obesity, 194.
for skin affections, 194.
Thyreoidism, 189, 192.
Ticks, 566.
Tissue, consumption of, in diabetes, 90.
intoxication necrosis of, 40.
Tissue-building substance, unknown, 19.
Tissue changes in myxedema, 185.
Tissue decomposition in diabetes, 91.
Tissue destruction, 39.
Tissue hunger, 60.
Tissue irritation in gout, 143.
Tissue necrosis in gout, 133.
in scurvy, 400.
Tissue regeneration, 50.
Tissues, parablastic, 418.
Titration method of Liebig, 4.
Toad-stool poisoning, 599.
Tobacco poisoning, 595.
Toe, gout in, 136. ; :
Tongue, condition of, in Addison’s disease,
201.
enlargement of, in acromegalia, 236.
hyperplasia of, 236.
inky stain of, 201.
647
Tongue, muscular degeneration of, 236.
Tonics in rheumatism, 257.
Tophi, gouty, 135, 137, 1388, 146.
in burse mucose, 137.
Toxemia from presence of parasites, 523.
Tracheo-bronchial lymph-glands, swelling
of, 351.
Tracheo-bronchial mucous membrane, in-
flammation of, 377.
Tracheotomy in opium poisoning, 596.
Training, athletic, 161.
physical and mental, 331.
Transmission, pre-natal, of relapsing fever,
429.
Transactions XIIIth International Medical
Congress, 126, 127.
Transudates, effect of, in metabolism, 44.
Transvaal, distoma infection in, 513.
Trauma, as cause of diabetes, 115, 119.
Triacid solution for blood staining, 295.
Trichina spiralis, 553.
Trichine, development of, 554.
in pork, 553.
Trichinosis, autopsy reports of, 558.
distribution of, 553.
epidemics of, 555.
fever in, 556.
mortality of, 558.
muscle lameness in, 556.
origin of, 553, 554.
prognosis of, 559.
prophylaxis of, 559.
symptoms of, 556.
treatment of, 559.
Trichocephalus dispar, Rudolphi, 548, 552.
diagnosis of, 553.
Trichomonas, hominis, 507.
vaginalis, Donné, 507.
Trional poisoning, 591, 592.
Trombidium holosericum, 565.
Trommer’s test, 77, 78, 262.
Trophic tracts in Addison’s disease, 213.
Trophoneurosis, 142.
general, 221.
Trophoneuroses, infectious, 256.
Tropon, 48, 70.
Tsetse fly disease, 571.
Tubercular adenitis, 376.
Tuberculoid, rheumatic, 256.
Tuberculosis, adrenal, 219.
chronic, 202.
destruction of adrenals in, 220.
648
Tuberculosis, intestinal, 47.
mistaken for malaria, 293.
of glands, 375.
pulmonary, 31, 63, 337.
value of increased nutrition in, 60, 63.
Tumor, hypophysial, 239.
solid, 537.
splenic, direction of growth of, 350.
Tumors in Hodgkin’s disease, 372.
Tunica vaginalis, echinococeus of, 544.
Tiirck’s method of blood counting, 282.
Turpentinglycuronic acid, 264.
Typhoid bacilli, 291.
Tyroglyphides, varieties of, 566.
U
Ulcers, gouty, 137.
of scurvy, 405.
Uncinariasis, 560.
Under-nutrition, 54, 67.
consequences of, 59.
employment of, for the obese, 67.
in diabetes, 91.
indications for, 62.
occurrence of, 59.
prolonged, 38.
systematic, 59.
technic of, 69.
when obesity is complicated by other dis-
eases, 69.
Urates, 137.
monosodium, 137.
Uratica, 125.
Urea as measure of metabolism, 4.
excretion of, 42.
in diabetic urine, 112.
in leukemia, 353.
Urethra, distoma infection through, 518.
Uric acid as cause of gout, 126.
Uric acid, deposit of, 255.
condition of, in diabetic urine, 112.
in Hodgkin’s disease, 375.
in leukemia, 127.
excretion of, 131, 136.
in tissues, 127.
percentage of, in gout, 137.
Uric acid engorgement, 149.
Uricemia, 128.
Urina spastica, 117, 119.
Urinary organs, condition of, in gout, 141,
142.
INDEX
Urinary products, 44.
Urination, painful, from parasitic cause, 560.
Urine, changes in, in obesity, 157.
condition of, in diabetes, 84.
in diabetes insipidus, 64.
in hemophilia, 426.
in leukemia, 353.
in myxedema, 185.
in nephritis, 41.
decrease of, in fevers, 112.
dextro-rotary, 268.
elementary analysis of, 4.
estimation of excretion of, 6.
glycose in, 269.
increased excretion of, 110.
morning flood of, 112.
of herbivora, 264.
optically inactive, 270.
parasites in, 507.
pentose in, 262.
reducing substances in, 269, 270.
sugar in, in diabetes, 84.
Urohematoporphyrin, 212.
Urology, Fourth French Congress of, 448.
Urotropin in gout, 148.
Urticaria, 42, 143.
following echinococcus of liver, 531.
Uterus, echinococcus of, 543.
Vv
Vaccination of hemophiliacs, 434, 452.
Vagina, papilloma of, 513.
Vagrant’s disease, 203.
Valerian, in diabetes, 122, 123.
“Value”’ in blood counting, 283.
Value-estimation of blood, 283.
Valve, auriculoventricular, insufficiency of,
321.
Valvular disease, uncompensated, 48.
Vanillin poisoning, 601.
Varices in the obese, 69.
Vascular apparatus, capacity of, in hemo-
philia, 425. ;
Vascular disturbances of the obese, 158.
Vascular formation, deficiency of, 431.
retardation of, 431.
Vascular system, hypoplasia of, 330.
imperfect development of, 338.
structure of, 422, 423.
Vasomotor nerves, anomalous function of,
335.
INDEX
Vasomotor tracts in Addison’s disease, 213.
Vasomotors, neurosis of, 336.
Vegetable acid potash, deficiency of, 393.
Vegetable-albumin preparations, 169.
Vegetable poisons, 598.
Vegetable potassium, in various foods, 411.
Vegetables, fresh, as preventive of scurvy,
397.
in diet of diabetics, 99, 108, 122, 123.
of chlorotics, 341.
leguminous, for the obese, 170.
Veins, of neck, swelling of, 373.
pelvic, 478.
spermatic, 478.
Venesection, 341.
Venous thrombosis, 327.
Vermifuges, 525.
Vertebra, chronic rigidity of, 248.
Vertebral column, ankylosing disease of,
246.
Vertigo in chlorosis, 324.
in gout, 143.
Vesicles from filaria, 548.
miliarial, 491.
Vessels, dwarfed state of, 329.
Vestibulum malorum, 378.
pharyngis, 378.
Vibices, in scurvy, 404.
of purpura, 491.
Visceral complications in rheumatism, 251.
Vitality, increase of, 20.
Voit’s calorimetric method, 6, 7.
experiments, 4.
law of metabolism and nutrition, 11, 50.
Volkmann’s arthritis deformans, 246.
Vomiting of proglottides, 522.
v. Hoesslin on obesity, 175.
v. Kogerer’s views of purpura, 464.
Ww
Wadd’s views on corpulence, 163.
Wasting diseases, 63, 250.
Water, allowance of, in diabetes, 98.
cold, in treatment of rheumatism, 257.
demand of tissues for, 38.
excretion of, 17.
649
Water, loss of, in blood and tissues, 75.
precautions in use of, 548.
use of, in the cure of obesity, 74.
value of, in nutrition, 71.
Water-cress, infection conveyed by, 509.
Weakness, sensation of, in anemia, 308.
Weight, experimental demonstrations of, 4.
in regard to obesity, 158.
loss of, 34.
in diabetes, 84.
normally heavy, 158.
Weight of body, maintenance of, 37.
significance of, 38.
Werlhof’s disease, 457.
White blood corpuscles, table of, 299.
Widal’s reaction, 290, 291.
Wine in dietary of diabetics, 100.
Women, as conductors of hemophilia, 414.
diseases of, 155, 196, 197.
neuroses appearing in, 336.
Working cell substance, 16.
Worm, medina, 546.
Wounds, fly larvee in, 574.
infection of, 478.
x
X-rays, burns from treatment by, 369, 381.
examination by, of bleeder’s joint, 432.
treatment of leukemia by, 354, 369.
Xylose, 267.
Y
Yeast fermentation, 262.
Youth, chlorosis a disease of, 320, 330.
gout occurring in, 128.
hemophilia appearing in, 415.
life energy in, 36.
Z
Ziemann’s stain, 327.
Zipperlein. See Gout.
Zuntz’s researches in metabolism, 24.
Zymoplastic substance, 424.
(1)
PRACTICAL DIETETICS.
WITH SPECIAL REFERENCE TO DIET IN DISEASE.
By W. GILMAN THOMPSON, M.D.,
Professor of Medicine in the Cornell Medical College of the City of New York ; Visiting
Physician to the Presbyterian and Bellevue Hospitals, New York.
LARGE OCTAVO, EIGHT HUNDRED AND FOURTEEN
PAGES, ILLUSTRATED.
Cloth, $5.00.
Third Revised Edition. Sold only by Subscription.
“This is at once the best and most exhaustive book upon this subject with
which we are familiar. The best because, in the first place, it is written by a
teacher of therapeutics who knows the needs of the practicing physician, and
yet who has taught in previous years as a professor of physiology all that one
needs to know in regard to the principles of digestion and assimilation. For
this reason the author is unusually well qualified to prepare a useful manual, but
it is not until one has perused the volume that he thoroughly grasps the scope
and depth of the manner in which Dr. Thompson has treated his subject.”
—Therapeutic Gazette.
“The subject of the dietetic treatment of disease is not an attractive one.
This fact explains, no doubt, the comparatively little attention given it in college
curriculum and daily study. When one proceeds to examine the valuable con-
tributions to this subject, the scientific investigations which have been made by
the United States Department of Agriculture at various experiment stations in
all parts of the country, he is convinced that it is high time to look into the
matter pretty thoroughly. This book is of value for its summary of the latter
and its application of the knowledge to the treatment of the disease.”
—Brooklyn Medical Fournal.
“The portion of the work on diet in the various diseases must prove of much
value to the practitioner who has sought in vain in so-called ‘practices of medi-
cine’ for exhaustive discussion of diets for special pathological conditions. In
giving applicable diets few diseases are omitted, and the author not only gives
his own views, but quotes those of others, especially with regard to such con-
ditions as obesity, rheumatism, gout, and diabetes, in which proper feeding is of
such paramount importance. The volume contains nine full-page plates.”
—Medical Review of Reviews.
“In the seven years which have elapsed since the first appearance of this
standard text-book there have not been the many and important changes in
dietetics that other departments of our therapeutics have undergone. Never-
theless, Dr. Thompson has revised much that was published in the first edition,
and has introduced into this one the results of more recent studies in the
economic values of various dietaries. The general arrangement of the work is
unchanged.”—New York Medical Fournal.
D. APPLETON AND COMPANY, NEW YORK.
AUTHORITATIVE! PRACTICAL! ILLUSTRATED!
APPLETONS’
MEDICAL DICTIONARY.
A NEW ILLUSTRATED MEDICAL DICTIONARY.
An Illustrated Dictionary of Medicine and Allied Subjects in
which are given the derivation, accentuation, and definition of terms
used throughout the entire field of medical science.
EpiteD BY Frank P. Foster, M.D.
Numerous Illustrations. One volume, half leather, $10.00;
thumb indexed, $11.00.
‘This volume is large, very large, nearly two thousand pages, but it is a single volume,
and so its size can be forgiven. Asa dictionary the work has many excellencies. The pro-
nunciation is, as a rule, indicated only by accenting the title words, the derivations are given
briefly, and the French and German equivalents, and often the Greek, are inserted when they
differ materially from the English. In regard to orthography, we are glad to see that Dr.
Foster does not favor what he calls the fad of substituting the termination ‘ic’ for ‘ical,’ dis-
pensing with the final ‘e’ in such terminations as ‘ine’ and ‘ide,’ and suppressing diphthongs.
The definitions are clear and concise and, so far as we have been able to discover, accurate.
In fine, the only serious criticism of the work is its size, which might have been reduced by a
careful pruning and rejection of obsolete words; but this counts for little in view of the con-
venience of arrangement, the accuracy of definition, the completeness, and the beauty of
typography and binding.”—Vew York Medical Record, September 24, 1904.
‘*We see few dictionaries without errors or omissions ; in this book we have found none.”
—The Medical World, Philadelphia, Fa., November, 1904.
‘Probably the most complete and most exhaustive medical dictionary in existence. We
have tried in vain to think of a word which might be absent in this ponderous volume of
2,000 pages. Everything relating to medicine, pharmacy, chemistry, botany, etc., is there
and is explained clearly, concisely, and reliably.”
—New York Critic and Guide, October, 1904.
“Tt is accurate and up to date in most respects. . . . The work shows the result of careful
revision, as the most recent words are to be found in it.”
—The Fournal of the American Medical Association, Chicago, [1l., December 17, 1904.
“This volume before us, of nearly 2,000 pages, seems more of a dictionary and less of an
illustrated cyclopedia than almost any other upon the market. It represents conservatism
in lexicography, and is prepared on strict lexicological lines. . . . The definitions are excel-
lent and can be heartily praised.”
—folns Hopkins Hospital Bulletin, Baltimore, Md., January, 1905.
‘“We have looked over the volume carefully, and have sought for definitions of newer
subjects with interest, and in each instance we have not been disappointed. A number of
colored plates, as we!l as ordinary black-and-white illustrations, are employed to illustrate
the text. The plate upon malarial fever is an excellent one, and is far better executed than
most plates of this character; indeed, it is the best that we have seen since the publication
of Thayer and Hewetson’s plates some years ago.
_ ‘Although the number of medical dictionaries on the market to-day is very great, there
is always room for an A No. 1 book, and those that are already in existence will have to.
look to their laurels if they do not wish to be pushed aside by this very notable addition to
medical lexicography.”— The Therapeutic Gazette.
“T find it a handy, comprehensive, and scholarly work. I have tested it by looking for
useful terms recently introduced and thus far have not looked in vain, finding in each instance
a succinct, clear, and accurate definition.”—Solomon Solis-Cohen, M.D.
MAIL ORDERS PROMP7LY ATTENDED To.
D. APPLETON AND COMPANY, PUBLISHERS,
436 FirtH AVENUE, NEw York.
DISEASES OF THE HEART
AND ARTERIAL SYSTEM
By ROBERT H. BABCOCK, A.M., M.D.
Professor of Clinical Medicine and Diseases of the Chest, College of Physicians
and Surgeons (Medical Department of the Illinois State University),
Chicago ; Attending Physician to Cook County Hospital for
Consumptives ; Fellow and former President of the
American Climatological Association, etc.
Three Colored Plates and One Hundred and Thirty-nine
Illustrations in the Text. “8vo. Cloth, $6.00
SECOND EDITION
SOLD ONLY BY SUBSCRIPTION
“This treatise is evidently the result, not only of large clinical experience, but of
wide reading and careful reflection. The author disclaims any pretense of originality,
but it is open to question whether the conclusions and results of a ripe judgment, such
as are presented in this volume, are not worth quite as much as some academic so-
called original work. Certainly,a large amount of material, both clinical and literary,
has been worked out and presented in a most clear, succinct, and practical manner.
The author’s style is pleasing and without ambiguity, nor is the text over-loaded with
unnecessary technical terms. After a careful perusal of Dr. Babcock’s book there are
two features which strike the reader as characteristic and valuable. These are, on
the one hand, the case histories, and, on the other, the unusual number and value of
the pages devoted to the therapeutics of the subject. The narration of cases, although
at times in much detail, does not cause the usual weariness of flesh in the reading,
mainly because of the interesting manner in which they are written. They are
particularly well chosen to illustrate the manifold varieties of disease and the practical
wisdom required in the management of actual cases. Regarding the therapeutic side
of the work none but words of praise are required. So far as the reviewer’s reading
goes there isno more complete and reliable exposition of the treatment of circulatory
disease than that found in this volume. That this high commendation is deserved will
readily be admitted after reading chapters 16, 17, and 18 upon the treatment of valvular
heart disease. These chapters are distinguished by a fulness of detail and a variety of
therapeutic resource which cannot but prove of great value, not only to the young
practitioner, but, as well, to the clinician of years.
‘The book can be unhesitatingly recommended as a distinct acquisition to one’s
working library.’—‘Brooklyn Medical Journal.
‘*We commend to our readers this work of Babcock’s as a very desirable work
for both the specialist and the practitioner, and wish the author a most hearty wel-
come for his admirable literary endeavor.”—Medical News.
D. APPLETON AND COMPANY, NEW YORK.
OBSTETRICS.
A TEXT-BOOK FOR THE USE OF STUDENTS AND
PRACTITIONERS.
By J. WHITRIDGE WILLIAMS,
Professor of Obstetrics, Johns Hopkins University; Obstetrician-in-Chief to the Johns
Hopkins Hospital; Gynecologist to the Union Protestant Infirmary, Baltimore, Md.
SIX HUNDRED AND THIRTY ILLUSTRATIONS IN THE TEXT
AND EIGHT COLORED PLATES.
Cloth, $6.00; Half Leather, $6.50.
SOLD ONLY BY SUBSCRIPTION.
“The studies of the anatomy of the uterus and its adnexa are unique, and afford
the student opportunity for attractive occupation in the acquirement of completer
knowledge. The development of the ovum and placenta has never been set forth as
well in a work on obstetrics, according to our view, as by Williams. The illustrations
showing the structure of the placenta are admirable.
‘In the section on obstetric surgery, beginning with induction of abortion and ac-
couchement forcé, including forceps and version, Cesarean section and symphysiotomy,
destructive operations, and ending with operative procedures which do not aim at a
delivery, is found quite the most ample handling of operative obstetrics that has yet
been published in such a treatise. Here, again, illustrations supplement the text in an
instructive fashion. :
‘* Williams’s dealing with contracted and otherwise deformed pelves, and the man-
agement of labor in such conditions, is most satisfactory. Injuries of the birth canal,
infection, hemorrhage, and the puerperium are all prepared by one who understands the
greatest need of the student, and he tells him in the fewest and plainest words possible
what he must know to obtain success in the practice of obstetrics. It is a book made
by a clinician, which gives the most advanced exposition of the art and is a distinct
addition to obstetric literature.
‘*Much original work has been done in the way of illustration, as well as in the
preparation of the material of many chapters, and the whole subject-matter is presented
in an original manner. The book is a credit to both author and publisher.” —Buffalo
Medical Journal.
“At a certain examination the question was asked: ‘ Describe the management of a
face presentation in the M. D. P. position.” The examined men were like ‘ sheep before
the shearers’—i. e., dumb. An investigation showed that the popular text-book made
scant reference to the so-called ‘ undeliverable’ position.
‘Perhaps a knowledge of this fact led the reviewer of Dr. Whitridge Williams’s
work to consider, first, the description of the presentation in general, and, second, those
of the face in particular. The admirable methods employed in explanation and the
ample demonstrating drawings illustrating these fundamentals of obstetric knowledge
show that the author is that rare combination, a teacher and a student of students and
their requirements.
‘* Everything is detailed to the required minuteness, and beyond that nothing. The
cuts and engravings are many, novel and good. They fill a definite purpose, and that
purpose is not ‘padding.’ As one reads page after page the old-fashioned words,
* Pleasure and profit,’ recur to the mind.
“It has all the earmarks of success; it is crowded with hints of practical value, and
it shows what the trained hand and brain adopt as the best methods in overcoming the
obstacles of parturition. Surely, if conscientious work and real merit count, we may
expect to find this volume upon the lists of the colleges and treasured in private libra-
ries.".—New York State Journal of Medicine,
D. APPLETON AND COMPANY, NEW YORK.
CHEMICAL AND MICROSCOPICAL
DIAGNOSIS
By FRANCIS CARTER WOOD, M.D.
Adjunct Professor of Clinical Pathology, College of Physicians and Surgeons, Columbia
University, New York; Pathologist to St. Luke’s Hospital, New York
With One Hundred and Eighty-eight Illustrations in the Text and
Nine Colored Plates
8vo. Cloth, $5.00 net
‘‘No practitioner of medicine, whatever may be his special
work, can afford to be without some book of this sort, and the
present volume may frankly be recommended as satisfactory.”
—New York Medical Journal.
‘We regard this as one of the most important medical books
that have appeared of late, and venture the opinion that it will not
be long before it will be found in the hands of every laboratory
worker, whether teacher or pupil.”—Buffalo Medical Journal.
‘““The work at present before us may be unhesitatingly pro-
nounced one of the best.”—Medical Review of Reviews.
“It is unnecessary to emphasize, in the present state of medical
knowledge, the importance of microscopical and chemical exami-
nations of the blood and the secretions and excretions of the body
in the diagnosis of disease. Indeed, this has been so universally
appreciated within recent years that a distinct and increasing de-
mand has been created for works of reference on these and allied
subjects. Several such books already occupy honored positions in
this literature, and Dr. Wood’s book, the subject of this review, is
the latest addition'to the library of clinical pathology. Dr. Wood's
book is undoubtedly the most complete book of its kind that has
‘appeared in the English language.”
—California State Journal of Medicine.
D. APPLETON AND COMPANY, NEW YORK
THE DIAGNOSTICS OF
INTERNAL MEDICINE
A CLINICAL TREATISE UPON THE RECOGNIZED PRINCIPLES OF
MEDICAL DIAGNOSIS, PREPARED FOR THE USE OF
STUDENTS AND PRACTITIONERS OF MEDICINE
By GLENT WORTH REEVE BUTLER, A. M., M.D.
hi the Second Medical Division, Methodist Episcopal Hospital ; Attending Physician to
. os Brocklyn Hospital ; Consulting Physician to the Bushwick Central Hospital ; formerly
Associate Physician, Departments of Diseases of the Chest and Diseases of Children,
St. Mary’s Hospital, Brooklyn, N. Y.; Fellow of the New York Academy of
Medicine; Member of the Medical Society of the County of Kings, etc.
New Revised Edition, Rewritten and Enlarged
224 Illustrations, Five Plates, Twenty-two Charts. 8vo, 1061 pages
Cloth, $6.00
“ This is a valuable book upon an important subject. The general plan of the work, the
arrangement of subjects, the colored plates, the illustrations and diagrams, are alike excellent.
The book as a whole is, consequently, a reliable guide for students and practitioners in this
very important field of medical practice.”— Fournal of Medicine and Science.
“Works on diagnosis are comparatively numerous at the present time, but each new one
has its spec’al features of interest and value. The present volume covers the greater portion
of the field of internal medicine in a very satisfactory way, and undoubtedly will be found by
many more acceptable than other works. It is particularly strong in its illustrations; these
are generally very well selected to illustrate the text, which itself is clear and readable. It is
well worth a place in the physician's library "— Fournal of the American Medical Association,
Chicago.
‘This volume presents some unusual features, and will find many readers who will appre-
ciate the method by which the subject is treated. The great bulk of the work deals with the
evidences of disease, and does so in a most satisfactory manner. The student 1s taught how
to proceed in the examination of his patient, what routine questions are to be asked such as
would lead to « preliminary opinion which in turn would suggest certain examinations in
detail. ‘The author teaches not only what to do, but how to do it, and his advice and method
of diagnosis are to be highly recommended. The smaller details, which only acute observers
notice, are pointed out and their significance is weighed. It will be of service as a reference
book in suggesting explanations in cases where but one or few symptoms, not pathognomonic,
are presented for diagnosis—for each symptom is explained and the ordinary diseases in which
it occurs are mentioned, while in the latter part of the book the diseases are treated separately,
so that direct suggestions can be immediately considered without consulting another volume.
All the modern laboratory methods are well described, the chapters on the blood and stomach
contents being especially good, though brief. The thorough modernness of the instruction is
well instanced by drawings of the culex and anopheles genera of mosquitoes. The author is
evidently fully conversant with the clinical evidences of disease, for his treatment of the
chapters on the signs and symptoms which present themselves in the patient is unusually well
balanced with reference to their importance. The section on pain is very thorough; the
illustrations are profuse and particularly instructive.”—J/edzcal Record.
D. APPLETON AND COMPANY, NEW YORK