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THE 



JOHNS HOPKINS HOSPITAL 



BULLETIN 



VOLUME XXV 



BALTIMORl 

I III JOHNS IK >PKINS PR] SS 

1014 








Zfye £oro (gaUimovt (prcee 

BALTIMORE, MD., U. 8. A. 



15 



BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered as Second-Class Matter at the Baltimore, Maryland, Postoffice. 



Vol. XXV.-No. 275. 



BALTIMORE, JANUARY, 19 14. 



[Price, 25 Cents 



CONTENTS. 

PAGE I p AQI 

The History of Medicine m a Subject of Teaching and Research. Notes and Newe . . ■>", 

By Dii. Akmii.d C. Ki.kiss 1 

_. _ ., , , , ,,, , Xotes on New Books 26 

John Hunter : His Life and Labors. (Illustrated.) 

liv C. W. <:. Roiiber, M. D 10 Books Received j:i 



THE HISTORY OF MEDICINE AS A SUBJECT OF TEACHING AND 

RESEARCH.* 

By Dr. Arnold C. Klebs, Lausanne. Switzerland. 



In this country no definite place in the scheme of medical 
education has yet been assigned to the history of our art and 
science. I shall endeavor to plead its cause in the light of 
past experience and present achievement. Having taken 
pains to study the subject during a prolonged residence in 
Europe, where it has received special attention. I shall try to 
bring out what seem to me the main features of the work and 
efforts there. I may state at the outset that, in doing bo, I do 
not wish to recommend blind imitation. <>n the contrary, 
I am convinced that in this country an altogether different 
course might be taken to great advantage and that experience 
gained abroad can only be used as a pathfinder. 

The value of medical history as a r] ature in med- 

ical education has nowhere been more strongly emphasized 
than here in America h\ l> Jc n Shaw Billings. He was 
no friend of "the languid swell who thinks it bad 

tie practical," but neither did he agree with th 
rho belittle, as interfering with practical effi 
any effort towards a broader culture, nowledge and 

a better understanding of the higher amis of their art and 
science. ~ to be s historian of mi 

in the technical sense of the term, although having done fine 
work in this as in so man;, other fields, he used the inspiration 
and the lessons of that history, which he mastered as few have 
r the solution of the problems then before him. The 
enormous share he has had in the upbuilding of a higher med- 
ical education in this country will only be fully appn 
when his quiet activity has become better known. The study 

* Read at a meeting of The Johns Hopkins Hospital Historical 
:iub, Dec. 8. 1913. 



of the history of medicine and its promotion as a distinct 
feature of medical education li. . recommended, dis- 

couraging, however, certain methods then advocated and pur- 
sued in this direction. In 1883, in addressing the U 
and Chirurgical Faculty of the State of Maryland, he urged 
the cultivation of local medical history of eity and - 
that body. Doctors and surgeons, lie recommended, would do 
well to keep historical books on their shelves, and might, with- 
out prejudice to their professional capacity, " read something 
else besides manuals and textbooks." Even a1 this early date 
he expr i if as follows: " It is to be hoped that the 

scheme of higher medical i which your univei 

about to organi/e will include instruction in bibliographical 
and hisl I as in those of the laboratory 

and clinic." 

The Late 1 1 I F. Cordell, in hi tial ad- 

e 105th an the same faculty, 

could Bhow how far this hope has mai ccellent 

work is being done at the Historical Club of The Johns Hop- 
kins Hospital, but that onlj three nniver Lvania, 
Maryland and M innesota, tuv a full con 
li ctures on historical medicine, whi< 

result. This address was commented upon in . 
torial in the " London I. 

■ d in favor of the .-tudv of medical history, and b 
ordell, that In- advice • 
more attention in the British Isles, where no univei 
teaching school of medicine dealt wi I in any way. 

Ten more 
we look around now it cannot he sa of the 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 21 



history of medicine has made very decided progress as a fea- 
d medical education. The number of academic courses 
on this subject is, however, no exact measure of the in- 
terest manifested in the subject itself. Their establishment 
depends largely upon personal and local opportunities, and, 
where the subject has become a feature, it cannot be said 
that it enjoys a very great popularity, here or abroad. I 
believe, however, that this is due more to an inadequate 
method of procedure than to a lack of interest. That such an 
interest is continually on the increase hardly needs demon- 
stration. While some years ago a historical consideration of 
a medical subject was practically never heard of, now we see 
articles appearing on every side which are evidence that a 
good deal of historical thinking and studying is in progress. 
In this relation it might be noted that while we find hidden 
in special journals and archives abroad masses of valuable and 
interesting data derived from historical research, similar arti- 
cles when intended for the profession and appearing in gen- 
eral journals have always to take a back seat and axe usually 
put at the end and in the smallest available type. This is in 
strong contrast to the procedure here and in England, where 
one sees not infrequently such historical essays appearing in 
the most prominent places. 

Although by no means all American and English writings 
can bear comparison with those of an Osier, it is nevertheless 
interesting, and applicable to a number of English essays, to 
note what the great German historian Sudhoff has said in the 
conclusion of a review of Osier's " Alabama Student " : " It 
seems to me that there is a more echt historischer Geist in 
these biographic essays by an English clinician than in many a 
learned medico-historical work of a German professional his- 
torian." ' It is just this truly historical spirit, recognized by 
Sudhoff and so brilliantly applied by himself and Neuburger, 
which is a common characteristic of the historical utterances 
of many of our physicians. It pervades the speeches and essays 
of Welch, Weir Mitchell, Abraham Jacobi, and many of their 
juniors, and it especially formed the quintessence of the 
gigantic life work of Billings. 

I believe there is ground for congratulation and that we 
have a fertile soil, which, properly tilled and sown, will 
some day bring forth a bountiful harvest. The student 
abroad enters the medical school better prepared intellectually 
than he does here; this is what is being more and more rec- 
ognized by our educational authorities, and on the success of 
reform in this direction will depend to a large extent the ulti- 
mate, more general establishment of a higher medical educa- 
tion. Only on such a ground can historical medicine thrive 
and, in return, benefit medical education and medicine in gen- 
eral. The opportunism w-hich has so far characterised the 
attitude of medical education towards historical medicine will 
yield to a purposeful determinism as soon as a better prelimi- 
nary preparation induces the necessary receptiveness in the 
students. 

The question as to whether the moment has come to agitate 

1 Mittheil. z. Gesch. d. Med., etc., Leipz., L. Voss, 1909, viii, 448. 



the subject cannot be answered in a general way. I believe it 
has come for certain schools, and others vill follow when the 
fundamental principles are once established and a start is 
made. In our time the desirability of a broader culture for 
the physician fortunately needs no special pleading. That 
this is powerfully promoted by historical knowledge and 
method is also recognized by many. But as to how this latter 
is best furthered and utilized to the greatest advantage for 
the pupil and teacher and for medical art and science in 
general is a question which I believe has not often received 
the consideration it deserves. 

To start with first principles, it must be admitted that we 
often overlook the obvious fact that every medical man, con- 
sciously or unconsciously, bases his conceptions and their ap- 
plication on those of his predecessors, and that whenever we 
acknowledge this indebtedness we are to a certain extent using 
the historical method, for it is fundamentally unimportant 
whether our predecessors lived five or five hundred years ago. 
This axiom, in the present case, finds its practical expression 
mainly in bibliographic search, which every medical man has 
to take up sooner or later if he wishes to add his share to the 
sum of knowledge which determines progress. Here again 
Billings has given pertinent advice when he said (London, 
1881) that since there is no lack of men who have the taste 
and time to search the records of the past, the man who has 
opportunities of making experiments or observation for him- 
self wastes his time to a certain extent if he tries to do biblio- 
graphical work so long as he can get it done for him. " .Yet," 
he adds, " he should know how to make the search, if only to 
enable him to direct others," advocating also instruction in 
bibliographic methods. In our days, and especially through 
the labors of Billings and Fletcher, this task has been greatly 
facilitated, but none the less few physicians know how to use 
systematically the aids provided by wise forethought and an 
incredible industry. Here practical instruction of the student 
would bear good fruit and demand but little time. He could 
learn how to select proper references and to give them with 
accuracy, and, what is still more important, learn to eliminate 
the useless ones. As Oliver Wendell Holmes said, " there is 
a dead medical literature, and there is a live one. The dead 
is not all ancient; the live is not all modern." To distinguish 
the one from the other is the task of the teacher. It takes 
long and intimate acquaintance with the matter to develop the 
necessary judgment, but much useful guidance can undoubt- 
edly be conveyed to a student. 

While thus an acquaintance with the literature and an ac- 
quisition of bibliographic technique is of primordial impor- 
tance to any educated physician and can be promoted usefully 
by appropriate instruction, it forms but a part of that true 
erudition which is attainable only by a deeper knowledge of 
the historical evolution of our art and science. A certain 
kind of erudition, it must be admitted, may superinduce a 
one-sided philologic and antiquarian standpoint, or, as Billings 
put it, lead the student off " from his direct research into the 
many attractive by-paths of quaint and curious speculation." 



Jamaky. 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



This danger must always be kept in mind and be guarded 
against, but it is n* valid argument against eruditioo as an 
objective of medical education. "While erudition certainly 
• nothing, it loads to creation," said Verneuil. 

II story primarily demands farts which have to be Bought for. 
Search for them must be undertaken, however, without exclus- 
ive reference to the results. There is no reason why medico- 
historical research should not be regarded in the same light 
as is any other form of research. When this is once fully re- 
cognized the needed workers as well as the means ought to be 
procurable. Both have been found abroad; they surely can 
be found here. 

The lukewarm interest shown heretofore in historical medi- 
cine as a feature in the scheme of medical education ought not 
to discourage further efforts. If a distinct place were assigned 
to it in the medical curriculum it could, by its achievements, by 
the influence it would exert on students and teachers of all de- 
partments, form one of the most useful and inspiring feature- 
in the whole scheme of medical education. Some such influence 
led. We are cultivating too much the purely 
medicine ; we are depending too exclusively 
on physics and chemistry to explain life in its various manifes- 
tations. Sir Oliver Lodge only lately' has sounded a note of 
warning which we also may heed. " Biology." he said, '" is an 
independent science, and it is served, not dominated, by chem- 
istry and physics." We physicians, who are applying the 
of biology, must remember that physical science can- 
not explain everything; that it furnishes only "proximate 
explanations. *' The "philosophic scepticism" voiced by 
William James. Bergson, and other-. en- and has 

led to "a mistrust of purely intellectual p la rec- 

ognition of the limited scope i Such a mistrust 

again finds expression in antagonism to scientific medicine in 
the serious attention paid by a large public to certain methods 
of healing not within our BCope. Legislation alone cannot 
counteract these tendencies, and one who has his linger on the 
pulse of the times will realize that these things connoi be dis- 
using fad- r fashions, or the like, hut that there 
are causes bcneatli them for which, to a certain extent, we 
are ourselves responsible. Anything that will, so to speak. 
humanize our art and science, will not only make us happier, 
but more satisfied with and proud of our profession and its 
aims, more inspiring to our students, better friends and 
■ to our patients. With history as helpmate we apply 
"not the experience of one man only or one generation, but 
the accumulated experience of all mankind in al! i 
John Hersehel's phrase. 

Review op the Lttkeatuhb. 

It Is obviously impossible to give anything but a most sum- 
mary review. To the student who wishes to inform himself in 
detail about the general historical literature, the following works 
are indispensable: Choulant <L. ), Biblioth. medic.-hist., Lips., 
1ML', with the additions by Rosenbaum (Halle, IML'i; Pauly, 
i A. i . Bibliographic des sciences medicales, Paris, 1S74 ; Pagei (J.), 



1 President's address, British Assoc, Birmingham, Sept. 11, 1913. 



Hist.-med. Bibliographie, 1S75-1S96, Berlin, 1898; furthermore the 
library catalogues of the Biblioth£que Nationale de Paris, cata- 
logue des sciences medicales, 3 vols. Paris. Didot, 1857-89, All 
these works except that of Choulant have the common defect 
of not providing an alphabetical index of authors and subjects, 
which makes a search most difficult. This difficulty has been 
most happily obviated in the Index Catalogue of the Library 
of the Surgeon General's Office by the introduction, by John S. 
Billings, of alphabetically arranged subject key-words as well as 
the author's names. For the modern literature information is 
supplied by the Index Medicus and the Mitteilungen eur Qe- 
schichte der Medizin, etc., Leipzig, the latter giving excellent 
reviews of the literature since 1902. This has also been done 
by the " Janus.'' Amsterdam and Leyden, on a smaller scale, since 
1896. 

The most marked expression of the growing interest in the 
historical side of medicine is to be seen in the increasing number 
of articles and books dealing with it. There Is an abundance of 
pleasantly written papers, not particularly profound and often 
inaccurate. They can only be of real use when the authors are 
careful enough to state their sources. The excellent custom of 
prefacing their work with a historical review has been more 
and more adopted by authors on general and special Bubjects. 
In this country biography has probably furnished the theme 
for the greater part of the literature produced. It is the field 
most happily cultivated by Osier (The Alabama Student, Linacre. 
etc.), and from it has sprung Kelly's imposing "Cyclopedia of 
American Medical Biography." Billings, Fletcher. Green, Bolton, 
Weir Mitchell. Garrison, Cushing. Thayer, Roswell Park, Shattuck, 
Fitz, Locy and others have given us admirable i ssays on many 
interesting phases in the evolution of medical thought and prac- 
tice. Of textbooks worthy of the name only one so far meriting 
this name has appeared here, the excellent translation by H. K. 
Handerson (1S89) of Baas' " Grundriss " (1876). Judging from 
the advance sheets of the modestly named " Introduction to the 
History of Medicine " kindly put at my disposal by the author. 
Dr. Fielding H. Garrison, we shall soon be in possession of a 
home product, which, as regards accuracy, lucidity and mode of 
presentation, will rival the best of other lands. Here for the first 
time modern medicine is fully dealt with, occupying moi 
half the volume. Those stupendous creations of Billings, the 
Surgeon-General's Library, its Catalogue and the Index Medicus, 
which the whole medical world envies us, give an unparalleled 
basis and incentive to solid historical work, not yet sufficiently 
appreciated here. 

In Europe the serious and systematic study of the history of 
medicine began in the eighteenth century. During the preceding 
centuries, especially since the invention of printing, what may be 
called historical work consisted in commentaries on the works 
of those ancient authors which had appeared In multiple • 
In several of these biographical notes about famous physicians 
were given, which practice was also followed in certain 
collections of woodcut and engraved portraits. 

Among these some deserve an interest even now, notably 
those of Bolssard and Theodore de Bry, Frankfurt. 1597-8; ol 
Sambuco. Antwerp. l.'.TI and 1603; the Icones Reusneri. 
burg, 15s7, and several later ones. 

With the end of the seventeenth century, considerable collec- 
tions of antiquarian interest, books, pictures, gems, coins and 
other curiosities, had accumulated In the homes of some i 
men. Several of these later on laid the foundations of tl 
museums and libraries of which we are still the 
The Impetus to sift and study this material and to put It before 
a greater public issued from two widely separated ,i 

and London. Dr. Daniel Le Clerc < 1662-1728), son of a physician, 
a fine Greek scholar, devoted himself very early to the study of 
the ancients. His " Bistolre de la Medicine" appeared aa early 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 275 



as 1696 and saw many later editions (the best being that of the 
Hague, 1729), which are profitably consulted to this day. His 
work, however, covered only the period of ancient medicine up 
to and including Galen. The learned Dr. John Freind (1675- 
1728) issued in 1725 his "History of Physick, from the time of 
Galen to the Beginning of the Sixteenth Century," thereby con- 
tinuing the work begun by Le Clerc. Freind's book contained 
important contributions to the subject of Arabic medicine. For 
the understanding of the periods treated by him later research 
of the original texts has considerably modified our conceptions. 
In spite of its deficiencies Freind's book has undoubtedly acted 
as a stimulus for similar undertakings, especially among Eng- 
lish speaking physicians. Several special monographs as well as 
essays and books on general medical subjects betray this influ- 
ence. "Mead's Medicina Sacra" (1749) and J. Coakley Lettsom's 
" History of the Origin of Medicine" (1749), followed by the bio- 
graphical collections of John Alkin (1780) and Hutchinson 
(1799), are probably the most notable English contributions of 
that period. Directly inspired by LeClerc and Freind was J. H. 
Schultze's scholarly " Historia Medicinae " (1728), not nearly as 
connected and readable a work as its two prototypes, but con- 
taining a wealth of antiquarian and especially numismatic infor- 
mation. 

The most marked and lasting influence in favor of the histori- 
cal method in medicine was probably exerted by Boerhaave (1668- 
1738) and systematically applied by his greatest pupil, Albrecht 
von Haller (1708-77) in his edition of Boerhaave's " Methodus 
Studii Medici" (1751), in his own " Bibliothecae " (anat. 1774-77, 
chirurg. 1775, med. pract. 1776) and in the "Artis Medics Prin- 
cipes" (1769-1772). 

Probably no one before and few after him have so successfully 
utilized in practical work the teachings of history as this founder 
of modern experimental physiology. To Haller the discoveries 
and errors of his predecessors and contemporaries served as guid- 
ance and control in his own labors, and he did not shrink from 
the gigantic task of collecting, classifying and annotating all 
the available literature. Although he has not written a systematic 
work on the history of medicine, the lesson of his works and 
teaching, as well as his bibliographic collections, have done sig- 
nal service in introducing to succeeding generations the advan- 
tages of historical thought and method, not the least of his many 
achievements. For over a hundred years medical historians and 
bibliographers have benefited by the work of this great man. 

Of the historical treatises of the end of the eighteenth century 
and the beginning of the nineteenth, a few may here be men- 
tioned. Chomel wrote in 1762 an excellent little book on the 
medical history of France, thereby popularizing local historio- 
graphy, in which branch some tentative efforts had been made 
before him. In the seventies Antoine Portal began his great his- 
tory of anatomy; and Moehsen, the physician of Frederic the 
Great, published a medical history of Brandenburg and several 
other important contributions on various historical subjects (med- 
ical numismatics and iconography). Here we should also mention 
the historical dictionary by Eloy (Mons 1778, the first edition 
of 1755 was wholly inadequate), which brought together a great 
mass of biographical information. It formed the stock and basis 
of several later French works. 3 Other excellent treatises were 
furnished in Germany by Gruner (1774), Blumenbach (1786) 
and Ackermann (1797), but It was the well-known work by Kurt 
Sprengel (1776-1S33) * which inaugurated the epoch of applied re- 



' The "Biographie Mgdicale," edited by Panckoucke, 7 vols., 
1S20-25; the " Dictionnaire Historique," by Dezeimeris et al., 
4 vols., 1828-39; and another by Bayle and Thillaye, 2 vols., 1855. 

* " Versuch einer pragmatischen Geschichte der Arzneykunde," 
first issued in 1792 and rapidly followed by other editions and 
additions which were translated into several languages. 



search in medical history. The interest of the previous epochs 
had been centered chiefly in classical Green-, Roman and Renais- 
sance medicine; now, with fresh discoveries of general historians, 
archaeologists and others at hand, new sources for a deeper and 
wider knowledge were opened and medical students availed them- 
selves of these new opportunities. Sprengel attacked the subject 
from diverse philosophic points of view or ranged it in distinct 
epochs and schools, or in relation to the various branches of the 
healing art. Certain diseases, as, for instance, syphilis, leprosy, 
the plague and other epidemics, were separately studied. 

The principal exponents of this phase of literary work may be 
indicated in the annexed list, 5 which, however, makes no claim 
to completeness and can only serve to mark the cornerstones on 
which the present generation continues to build. 

The abbreviated titles in parenthesis indicate only the gen- 
eral trend of a given work with the date of publication. For 
living writers only the earliest work appears here. For further 
details see Index Catalogue, Library S. G. 0. and especially the 
admirable list arranged by Dr. Fielding H. Garrison in 2 series. 
Vol. XVII, 1912, pp. 89-178, under the title: " Texts Illustrating 
the History of Medicine." 

Research. 
During the period immediately behind us, the first decade of 
the twentieth century, historical medicine, like history, 
archaeology and medical science in general, has made more 
rapid progress for various reasons. On the one hand, scientifi- 
cally trained adepts have increased in number, and on the 
other, highly improved and specialized methods and instru- 
ments of research have been applied. A feature of this 
advance is that a great number of ancient texts have been 
brought to light and made available for study by photographic 
reproduction, transcription and translation. By this means we 
are increasing and amending continually our knowledge of, for 
instance, ancient Greek medicine through Arabic and Syriac 
manuscripts, into which it has passed in a less altered version 
than in those from which, after many manipulations during 



"Hecker (Medicine, 1S22; Epidemics, 1S65) ; Broeckx (Belgian 
Medicine, 1837; Choulant (Bibliography, 1828-1840; Anatomy, 
1852); Henle (Pathology, 1840); von Siebold (Obstetrics, 1839-45) ; 
Wu'stenfeld (Arabs, 1S40); Haeser (Medicine, 1845); Malgaigne 
(Surgery, 1840); Morejon (Spanish Bibliography, 1842-52); Ros- 
enbaum (Syphilis, 1839; Dermatology, 1844); Puccinotti (Italian 
Medicine, 1850-66); de Renzi (Salerno, 1859); Flourens (Physi- 
ology, 1S54) ; E. H. F. Meyer (Botany, 1854-57) ; Wunderlich (Med- 
icine, 1859) ; Virchow (Leprosy, I860) ; J. Banga (Dutch Medicine, 
1868); Daremberg (Medical Philosophy, 1S70) ; Littre (Bio- 
graphy, 1S72); Ingerslev (Scandinavian Biography, 1S71-73) ; 
Rohlfs (German Medicine, 1875-85; Surgery, 1883); Baas (Medi- 
cine, 1876); Julius Peterson (Medical Therapeutics, 1877); Hyrtl 
(Arabic and Hebrew terms, 1879; old German Anatomical Ex- 
pressions, 1884); A. Hirsch (Geography and Epidemics, 1S81-S6; 
Biography, 1S84-8S) ; Puschmann (Education, 1SS4; English 
Translation, 1891); Predohl (Tuberculosis, 1888); Charcot & 
Richer (Art, 18S7-S9); Proksch (Venereal Bibliography, 1899); 
Roth (Vesalius, 1892); Creighton (Epidemics, 1894); Sudhoff 
(Paracelsus, 1S94-99) ; Pagel (Medicine, 1896) ; Neuburger (Physi- 
ology, 1897); Berendes (Pharmacy, 1898); Hirschberg (Ophthal- 
mology, 1S99); von Toply (Anatomy, 1898); Fasbender (Obstet- 
rics, 1906); Politzer (Otology, 1907-13). 

6 Galen's anatomy from the Arabic by Max Simon, 1906, and quite 
recently the book on Syriac medicine by E. A. Wallis Budge, 
London, 1913. 



Janiahy. 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



the Middle Ages, it aine down to us in the lir>t instance. 
Verv much widened have become our conceptions of the an- 
cient medicine of the Mesopotamia]!, Indian, Chines 

in civilizations, as a result of the extensive document- 
ary materia] excavated and made available. America has 
entered this iield of research lately in the edition of the Hearst 
Papyrus, but there still remain in this country many unex- 
plored treasures which would add to our knowledge of these 
Much progress has been made in the exploration of 
mediaeval medicine, and evidence is accumulating which shows 
that the darkness of that age was not so profound as is com- 
monly supposed, and that it can still throw much light. 

The medical historian of our day is, however, not satisfied 
only to decipher the written word of past ages. He attempts, 
and in many cases very successfully, to obtain direct evi- 
dence of the diseases and medical practices of former times. 
The study of living primitive peoples, which is industriously 
pursued, gives many hints in this direction. But much inter- 
esting information can be obtained from all that excavations 
have brought to light: bones, mummified bodies, implements. 
imple of this is the story read out of the 
trephined skulls found in various widely separated districts. 
American students, Robert Fletcher (1882) to name one, have 
assisted materially in unravelling the meaning of these finds. 
Very interesting and valuable are also the results of most 
original investigations carried on in Egypt and Nubia by 
English scientists, especially Drs. Q. Elliot Smith and M. A. 
Runner. Mummies are being searched for traces of disease 
->'. 1910, facial paralysis, hand deformities, 1912), 
not only with the naked eye. but also microscopically. The 
i'ound on some bodies have told us most accurately how 
eople dealt with bone fractures and with what result. 
With the accumulation of greater material, the mooted ques- 
"f tuberculosis, syphilis or arthritis in the 
product tain alterations found in prehistoric bones 

as studied by Virelmw. Paul Raymond and others, is approach- 
solution. None of these findings are so far abundant 
enough to allow far-reaching conclusions, hut they open al- 
l wide outlook and a field of research, which will yield 
valuable information in time to come.' 

alization thai artists, humble craftsmen as well as 
great n ■ from earliest times, depicted with knife, 

r brush, subjects or scenes of medical interest, has 
naturally led to a Bearch fur such artistic represent 

objects had furnished information even to 

older oh-, rvi re. Paintings of all kinds, including illumina- 

manuscripts, hav< now become the object of minute 



'Very valuable Assyrian documents seem to be available In 
Philadelphia, and the Central Asiatic treasures of the Field 
Columbian Museum also await further scrutiny from a medico- 
historical point of view. 

* It Is significant that a special periodical devoted to the his- 
toric biology of pathogenetic agents has begun to appear In Ger- 
many: Zur historlschen Blologie der Krankheltserreger. Edited 
!>y K. Sudhoff and G. Sticker (Giessen); 5 parts have appeared 
since 1909. 



scrutiny from the medical poini of view. Virchow (1861) 
may be called the father of this arch by his analysis 

of the painting of St. Elizabeth and the lepers by the Elder 
Holbein. Charcot's mon work in this direction was 

inspired when he saw, in the church of San" Ambrogio at 
Genua. Rubens' masterpiece, " Ignatius de Loyola healing the 
sick."' He was struck by the wonderfully lifelike n 
tation of the possessed woman, which vividly recalled what he 
had daily observed in his clinic at the SalpStriere. Paul 

. then his interne, tells of this and of the beginning of 
their joint researches on the demoniacs, the Bick and d< 
in art. These were collected and published in the " Nouvelle 
iconographie d< a Salpetriere " (since 1888), and brought out 
by Richer in connected form in that beautiful work " [/art et 
la medecine" (1900). Similar wor taken up by 

many, and from various points of view. Landouzy, Crawfurd, 
Peters. Miillerheim. Wickersheimer and others have added 
most effectively to our knowledge by the study of | 
representation. The efforts of Hollander, who has given 08 
three monumental contributions on this subject (classical art, 
caricature, plastic art and medicine), merit separate mention. 
As a related movement may be considered the establishment 
of a special department on art at The Johns Hopkins Medical 
School. Here the main aim is a directly practical one, the 
teaching of pictorial representation of medical or surgical 
objects for publication. It seems very likely that, as this work 
develops, a historical consideration of the subject will become 
desirable and help to broaden the scope of this interesting 
departure. 

It is regrettable that the results of these researches a 
scattered in many different publications, which arc in some 
cases rather difficult of access. The " Mitteilungei 
footnote 1), the official periodical of the German S 

is to review all this work, and succeeds admirably, but 
naturally the German publications receive the prii 
tion. With the establishment of more intim 

u med ical bJ utiles, means 

will undoubtedly be found by which international co-operation 
can be assured. A rection wa 

by the creation of a tion for the history of medicine 

at the r ational Medical < ongrese in I 

in tiring 
efforts of its president, Dr. Norman Moore, with I 
tion of such men as Sir Wil 

Sudhoff, Sticker, Bo la chard, 

Wickersheimer, I 1 
Walsh and otl 

The mosi important r. 
Bearch 

nann found 
Medial " 

edited by Karl Sudhoff. 
1901 and i mts lutifully ill' 



•Another painting of this same subject, also by Rubens, and 
of still greater foi 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 275 



articles, which are distinguished by accuracy and profound 
scholarship. These two publications, containing minute 
analyses of the sources by experts, bring out the new facts or 
corrections of older conceptions. They are of the greatest value 
to one who wishes to enter more deeply into the subject. The 
interested student and practitioner will have occasion to con- 
sult them only on rare occasions. In this connection it may 
be said in general of the literature above enumerated for the 
purpose of showing the evolution of medical historiography, 
that it contains very few works which merit study by one in 
search of historical information for the purpose of writing an 
article. The teacher ought to familiarize himself with it, but 
the student need only know where he may find further enlight- 
enment on a given subject not, or only insufficiently, provided 
in the more recent works at hand. The writing of historical 
papers from information found in other historical works is 
devoid of any real value, except in the case of avowed compila- 
tions or historical prefaces, and then only when an indication 
of the sources is given. The field is open to any educated 
person who has a sufficient interest in the personality, the sub- 
ject, or the epoch he wishes to discuss. The life and work of 
some physician, the genesis and evolution of a thought or 
method, and many other themes, offer plentiful material which 
can be studied with profit directly from the sources. The early 
history of American medicine is still a practically unexplored 
territory and there are surely in many communities valuable 
data which might shed interesting light on the activities of 
those men who work under the strain and stress of primitive 
conditions. Many an object lesson of practical bearing might 
be so obtained. 

There are a few modern treatises or text books which can 
give to the student a comprehensive view over the immense 
field of the history of medicine as based on recent research. 
The voluminous " Handbuch der Geschichte der Medizin," 
founded by Puschmann, was edited by Neuburger and Pagel 
(3 vols., Fischer, Jena) in 1902 to 1903. It is intended to 
cover, in a series of articles by different writers, all the periods, 
including contemporaneous history. Primitive, ancient and 

i liaeval medicine, various special branches and some diseases, 

are separately treated with an index of subjects for the whole 
work. This ambitious program has not found an absolutely 
satisfactory fulfilment. The necessary connection between 
the different articles is wanting and the articles themselves are 
of very unequal value. The brilliant introduction which Neu- 
burger wrote for the second volume, and which surveys in mas- 
terly style the whole historical evolution, does not compensate 
for the inherent defects of the whole, although some of the 
articles have distinct merit. Apparently aware of this short- 
coming Neuburger began to publish in 1906 his "Geschichte 
der Medizin " ( P. Enke, Stuttgart). The first volume con- 
tains primitive and Oriental medicine and that of classical 
antiquity. This part has been translated into English by Play- 
fair and prefaced by Sir William Osier (London, 1910). Of 
the second volume which is to terminate Hie work, the first pari 
has appeared (1908-1911) and brings the subject down to the 



end of the mediaeval epoch. Here we nave a master-piece of 
historical synthesis. Nowhere is one bothered by a tedious 
insistence on irrelevant details, although the author's inti- 
mate acquaintance with the results of analytical research is 
revealed everywhere. Never does he lose the thread which 
joins the thoughts and accomplishments of succeeding periods, 
and never does he isolate the history of medicine from that of 
human culture in general, which would be, to use Billings' 
phrase (Lowell lecture, 1887), "like cutting a narrow strip 
from the center of a piece of tapestry and speculating upon 
the origin and purpose of the cut threads and fragments of 
pattern that may be found in it." A fascinating, inspiring 
work which no one interested in the evolution of medical 
thought and deed can afford to ignore ! 

It is to be hoped that the second part of this volume will 
soon appear and that the English translation will speedily 
follow. Its possession, together with that of Garrison's " In- 
troduction " (1913), will enable the English-speaking student 
and physician to dispense with any other works. For com- 
pleteness' sake I must mention a French work, which has ap- 
peared lately from the pen of Dr. L. Meunier (Paris, Bailliere, 
1911). It is a readable treatise which attempts to cover the 
whole field in condensed form (640 pages sm. 8°). Unfor- 
tunately the illness and untimely death of the author have 
prevented his correcting the many errors in form and sub- 
stance which have crept into the text, thus making unequivocal 
recommendation of the book impossible. 

Exhibitions and Museums. 

Special museums for the illustration of historical medicine 
are of very recent date. The basis was usually formed by a 
library to which were added curious objects, brought together 
by one or more collectors. No special plan was followed, only 
the whims or the good fortune of the individual amateur found 
expression. The modern museum has a more definite pur- 
pose; it attempts to illustrate the evolution of ideas and en- 
deavors in given fields, and maintains the sequence by the sub- 
stitution of facsimile reproductions where originals are not 
available. Modern technique has greatly facilitated this aim 
at completeness. With the realization of the eminent value 
of objective demonstration in teaching, the technique of 
museum organization in general has received, of late, very 
serious attention. The collective objects are not only placed 
in logically arranged groups, but also in a way to make them 
readily accessible for demonstration. Museums of historical 
medicine, if organized and utilized in this way, will surely 
become a necessary adjunct to every teaching establishment. 
Tins feature is as yet in an embryonic state. Still, we can 
observe some splendid efforts in this direction. Before I 
enter upon a rapid survey of the achievements in recent years, 
I wish to call attention to an American undertaking which has 
a suggestive bearing upon our subject. I mean the educational 
museum of the Teachers' College, Columbia University, of 
New York, organized by Prof. D. E. Smith. Here illustra- 
tions for lectures on the history of'mathematics and of geogra- 



January, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



phv are collected and s' pplied to lecturers where needed. The 
results have been so encouraging that an extension of the 
to other scientific branches is planned. 
In this country there does not yet exist a historical medical 
. properly speaking, although there are several promis- 
■ ,.; gs. First of all is to be mentioned the Army 
Museum in Washington, also in part a creation of 
Billings. It contains mnch of historic importance, as does also 
the tine Warren collection at the Harvard .Medical School. 
ally historical is the magnificent collection of 
medical classics in the library of the Surgeon-General's Office. 10 
With this collection are exhibited portraits and some objects 
of medical interest, so that the nucleus of a historical museum 
may be said ; I ■ '.. Walter D. McCaw deservi 

credit for having thereby materially enlarged and made use- 
ful and inspiring this great national library. The incentive 
to this came to some extent from Baltimore, where the 

rit has been cultivated for many years by such physi- 
cians as Welch, Osier, Cushing, Thayer and others, and has. at 

found expression in demonstrations and exo 
appropi ts. Among these, the historical tuberculosis 

exhibition at Baltimore will remain memorable. As a similar 
effort may be mentioned the exhibition, arranged by the John 
Crerar Library in Chicago, in 1907-S, of rare medical works 
of the Senn collection. The George Washington University 
of St. Louis, which has recently acquired the library of the 
medical historian Pagel, will probably soon be prepared for 
similar work. In the National Museum at Washington there 
is an interesting collection of objects illustrating folk-medi- 
cine, which was prepared by Admiral James M. Flint, Surgeon 
I . 8. Navy (retired). 

Holland is the country which has taken the lead in the 
inent of medical historical exhibitions and mus 

in Leersum and others were, and still are, 
the principal inspirers. At the fiftieth anniversary of the 
Nether M 9 historical exhibition \ 

ranged at Arnhem in 1899, the extent and scope of which was 
much enlarged in a later one held at Leyden in 1907. The 
Arnhem exposition led t.. the organization of a per; 
one in the States (S " m in Amsterdam by Dt. 

('. E. Daniels, who with great knowledge of the subject and 
an indefatigable energy, ha- brought together and most 
fully arranged the objects illustrating Holland's gloriou 
in the evolution of our art and science. 

I medical n 
rurally led to corresponding efforts in tins 
direct].' 1 and continual inspiration ha 

nated principally from Karl Sudhoff, who in 1898 organized 
the historical exhibition of medicine and natural scii 

lorf, and has been active, directly or indi- 

rectly, in many other similar undertakings. With Hollander 
and Pagel he made his influence apparent in tie B 
hition (190G) of "The History ••: Medicine in Art 



"For detailed description see Jour. Am. Med. Assoc., 1911, hi. 
1785-1 : 



Crafts," held in the Kai-erin Friedrieh-llaus. where a similar 
permanent museum will probably he established. At the Ger- 
manic Museum in Nuremberg, Boon after, several rooms were 
set aside for a medico-historical museum, which is being added 

■ dually. The Historical Museum for Natural Sciences, 
opened in Munich (1906), has inspired a similar plan for 
medicine in the saute city, hut 1 do not know how far this has 
materialized. A great feature of the Hygiene Exposition at 
Dresden (1911) was the historical department, mad.' ; 
through the efforts and munii i i . K. A. Ligi 
organized by Sudhoff and Neustatter. Although limited to 
the history of hygiene, it formed a mo>t complete objective 

-i ration of the evolution of medicine from earliest times 
to our day. Since the closing of the exhibition, the gathering 
of historical material has been pursued by the directors of this 
department, and will probably soon assume a permanent form. 
The very impi i tion of th< 

of Medicine at the University of I.. 11 consider in 

connection with the subject of teaching. 

In England, where CO I of national 

hobby, treasures have accumulated from an earl 
icine has profited by the labors of Sloane, Mead. Freind and 
Hunter in this direction. The British Museum, the collec- 
tions of the Royal College of Physicians, and the Hunterian 

Museum at the Royal College of Surgi s in London, are 

storehouses of priceless treasures of interest to us. But the 
and specifically directed effort has found its 
happy denouement in the opening on June 24th of this year 
(1913) of tli- li Medical Museum in London. The 

bulk of the objects here brought together were collected by Mr. 
Henry S. Wellcome with great wisdom and a generous disre- 
gard of expenditure. His purpose was, as he expn 
himself, "'not simply to brim: together a lot of curios for 
i. .nt." but to make it •"useful to •' I to all 

■ Qgaged in research." because be had found " that the 
study of the roots and foundations of things great!;, 
research and facilitates discovery and invention." He intends 

to make the museum a permanent To Mr. ('. J. S. 

Thompson and J>r. Louis W. Sambon has been assigned the 
formidable task of findii a fying and arrang- 

ingtl xhibits. They have dit I with signal - 

and tb. - which have not found ampli 

tration. Many valuable i . oed in these 

exhibits, a fact to which Sir Preder 

ingcercmom- alluded in tb 

"One cannot help noticing in this n 

and science of surgery is concerned, in what narrow lini 

made: and knovi 
can for. in the 

future will ■ 

London offered this summer anothi r I 
of interest to physii ians, at the British Museum. Here, in the 
Library. V ! in chroi ler an 

admiral 1 ill us- 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 27c 



trations, which no other single institution would be able to 
duplicate. 

In France, historical museums exist only, as far as I know, 
in "Rouen and Lyons. In the latter city one has been organized 
as an adjunct to the University through the efforts of Prof. 
Lacassagne. In Paris, such a museum has been planned for 
some time by the medical faculty, and the dean, Prof. Lan- 
douzy, is making every effort to complete the collections, so 
that in the near future the plan will become a reality. An 
interesting historical museum on vaccination has been estab- 
lished just outside Tours by Dr. Edmond Chaumier. 

The Teaching of Historical Medicine. 

Courses of lectures, given by academic lecturers or pro- 
fessors to students, are a novel feature in some of the Euro- 
pean universities. The holder of the chair in some cases re- 
ceives a salary, but usually the positions are honorary ones and 
the lectures are delivered gratuitously. Nowhere, I believe, 
are these courses obligatory nor are examinations held on the 
history of medicine. In Great Britain there are, so far as 
I know, only two lectureships, one in London, founded on the 
advice of Dr. Norman Moore by Dr. Friz-Patrick's widow at 
the Royal College of Physicians. The lecturers have been 
J. F. Payne, Norman Moore and Sir Clifford Allbutt; the 
other at the University of Edinburgh, where J. C. Comrie 
has lectured. In Germany courses are given at Leipzig (Sud- 
hoff), Jena (Meyer-Steineg), Freiburg, i. B. (Diepgen), 
Berlin (Pagel's successor not yet appointed), Wiirzburg 
(Helfreich). In Austro-Hungary there are also several chairs : 
in Vienna (Neuburger and Senfelder), Graz (Schrutz), 
Budapest (von Gyory). In Paris a professor for the his- 
tory of medicine was appointed for some time among the 
members of the faculty, the present appointee being Prof. 
Letulle. At Geneva, a successor to the late incumbent, Dr. 
Naegeli-Akerblom, has not yet been chosen, and at Basel, Prof. 
Roth and Prof. His (now in Berlin) and others have lectured 
on the history of medicine. At Copenhagen, Dr. Maar has 
just been appointed to the chair of Prof. Julius Petersen, 
and at Rome the lectures are given by Prof. Pensuti. 

From this enumeration it becomes apparent that the custom 
of establishing such lectureships, although frequent, is by no 
means universal, and that so far the appointments depend 
mainly upon local opportunities, not upon a general demand. 
It lies in the nature of the subject, which has no apparent 
relation to practical aims, that such a demand will probably 
never become generally manifest and I must confess that the 
introduction of such lectures into the already overcharged 
curriculum does not seem to me to offer adequate advantages. 
On the other hand, there can be no doubt that just as the 
individual physician will gain by acquiring a knowledge of 
the historical evolution of his art and science, so will the medi- 
cal school, and the question as to the best policy to be followed 
ought to have the serious .attention of those in charge. 

Personally, I believe that it will be done best by the encour- 
agement of systematic historical research. Some few physi- 



cians will be found who have the tiirib and the inclination to 
devote themselves exclusively to historical work. If they 
possess or aquire the necessary knowledge in general history, 
classic, modern languages and bibliography, and are given 
proper facilities, they will soon increase the number of those 
who already take a manifest interest in the history of med- 
icine. This is the available ground -to be cultivated and if it 
is worth doing at all it is worth doing well. History is con- 
stantly teaching the statesman, the lawyer, the geographer, and 
the artist ; why not also the physician, who practices the most 
human art, the development of which has been promoted by 
various influences, often outside the scope of what we term 
exact science? 

Such reflections, I hope, will lead medical schools sooner or 
later to take up the matter seriously and to introduce into the 
range of their .activities the cultivation of historical research 
in some form or other. As an example of how this may be 
done successfully I think I may best describe, in conclusion, 
the method pursued and the results obtained at the Univer- 
sity of Leipzig. 

Endowment of Historical Research. 

I have referred already to some publications of the " Pusch- 
mann Foundation." Theodor Puschmann was professor of 
history of medicine at Vienna. He and his wife both had 
independent fortunes, which they bequeathed in a joint testa- 
ment " to the University of Leipzig for the promotion of 
scientific work in the field of the history of medicine." Pusch- 
mann died in 1899 and left his own property to his wife, with- 
drawing, however, his share in the above mentioned bequest. 
Frau Puschmann apparently expressed a desire to withdraw, 
but reconsidered the matter in 1900, which vacillation led, 
after her death in 1901, to a contest of the will. It was de- 
cided, however, in favor of the University of Leipzig after 
prolonged legal procedure. The sum of about 500,000 marks 
which thus came to the University, was put into the hands 
of nine trustees, under the presidency of the rector. Four 
members of this board are professors of the medical faculty, 
including the dean and the newly elected professor for his- 
torical medicine, whose salary was provided for in the articles 
of the foundation. The chair was offered to Prof. Karl Sud- 
hoff, then at Diisseldorf, who accepted after the fulfilment of 
his condition that a research institute should be established. 
Aside from the superlative capacities of this first incumbent, 
it is undoubtedly due to the establishment of this institute 
that great results were obtained, and the authorities showed 
wise forethought in granting the creation of an entirely novel 
and untried scheme. Duriug the eight years of its existence 
an enormous amount of constructive work has been done. It 
was not until 1906 that adequate premises became available 
for working rooms and collections. The latter had to be 
brought together piece by piece, no light task in itself, when 
one considers the degree of completeness that has been reached 
at present. All this labor of preparation did little to retard the 
principal work. Already in 1907 the " Studien " and " Sud- 



Janvai;y. 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



hoffs Archiv " began to appear. They at once became the 
rally ing-point of those devoted to serious scientific research, 
true to Sudhorf's principle that "one single fact, COi 
or newly obtained through the study of the sources, is worth 
more to true science than a dozen or more of the most bril- 
liant apercus." Of course, criticism and attack were not want- 
ing, but such epithets as " paper science."' " antiquarian amuse- 
ments," " useless encumbrance." and the like, thrown at the 
new venture, soon grew scarce, for it became more and more 
evident that the results of this earnest and sustained effort, 
generously put at the disposal of a wide circle, tended to form 
a bond between diverse efforts, and to promote general respect 
for medical art and science as a whole. 

A detailed description of this institute may be welcome to 
those desirous of establishing something similar. In its pres- 
ent quarters it occupies a wing of the building of the Zoolog- 
ical Institute and Museum. Besides five well lighted, spa- 
cious rooms, it has a laboratory for photographic work. All 
the materials for study, such as books, photographs, engrav- 
ings, models, etc., are classified and distributed on shelves, in 
drawers, or in showcases, distinctly labelled. Thus a student 
can find, easily accessible, all the available material for the 
study of a given subject, without having to begin with tedious 
bibliographic studies. In making the collection, Prof. Sud- 
hoff has not endeavored to bring together original manuscripts, 
incunabula, first editions, and other objects of great material 
value, which would have required very large funds. For the 
purposes in view photographic reproductions or models were 

t to serve fully as well. Nonetheless, origin i 
readily obtainable from other libraries and some choice e 

:ig to university and city libraries are permanently 
the institute. In this way material is accumu- 
lated here from all parts of the world and from every phase 
of civilization. 

In order to give an Idea of the extent and method of arrange 
ment of this collection I shall give the Inscriptions of the various 
cases In their sequence. The numbers in parentheses indicate 
approximately the relative space, In shelves or drawers assigned. 

In the first (so-called seminary) room is found the reference 
library (encyclopedias, dictionaries, biographic and bibliographic 
works, etc.), general and special historical and philosophical 
works (48). The room contains also files of medico-historical 
journals, the catalogue, and lockers for workers. 

• oond room Is given over to the collection of works on 
medicine from the prehistoric to the Renaissance period. The 
works are usually so placed that the original texts (or their repro- 
duction) and the commentaries thereon stand separately. The 
divisions are as follows: Prehistoric and Oriental Medicine: Pre- 
historic and anthropology (3), Popular medicine and folk 1 1 
Chinese and Japanese (1 I, Hebrew (2), Babylonian and Assyrian 
(4), East Indian (2), Egyptian (4), Greek Medicine: General 
history, geography and philosophy (8), Hlppocratic (o>. Natural 
(2), Galen (3), Alexandrian (1), Aristotle (1), Mystic 
(3), other Greeks (1), l'ioscorldes (1), Greek texts in folios (1). 
Roman to Salernitan Mpdicine: Roman (5), Byzantine (5), Ara- 
I, Monastic medicine (2), Salerno (1). Middle Ages: Me- 
dieval northern, Anglo-Saxon (3), German (3), Roman (1), 
Mystic (1), Scholastic (1), Surgery (2), Folio texts (1). Renais- 
sance: Medical education, universities (5), Leonardo da Vinci. 
folios and codices (1). This room contains also an additional 



collection of works on hospitals, epidemics and files of journals. 

The third room Includes mostly the collections on special sub- 
jects from the sixteenth century to modern times, ami tin' museum 
exhibits in the following order: Endemics (1), epidemics (5), 
pathology (2), physiology (2), anatomy (2), Leonardo da Vinci 
and Vesalius folios (2): hygiene, medical Jurisprudence, clinical 
and pharmacologic material (14): sixteenth, seventeenth and 
eighteenth century and corresponding text folios (14); nine- 
teenth, twentieth century, local medical history, otology and 
dentistry, ophthalmology, surgery, Paracelsus and Fabrlclus Hil- 
danus folios (14); local medical history, psychiatry, pediatry, 
gynecology and obstetrics (7). 

The museum exhibit embraces a collection of portraits, carica- 
tures, etc., of physicians (alphabetically arranged on 18 sliding 
shelves). The four showcases contain under glass various orig- 
inals and models (some on loan) of instruments, ex-votos, ortho- 
pedic and surgical appliances, etc. Below these are placed in 
about 120 drawers various photographic and other reproductions 
arranged in suitable groups. Given the great diversity of sub- 
jects so illustrated, the advantage to the teacher and student of 
having them appropriately classified is obvious. 

A list of the various headings under which this remarkable 
collection appears, may be welcome. I give it in alpli, 
order of the translation: Adam and Eve; alchemy, allegorical, 
America, prehistoric, anatomy from MSS.; aqueducts and hygiene 
(Roman); Arabic, care of sick, hospitals, veterinary medicine, 
pharmacy; Asia Minor; Asklepios and family: astrology; Baby- 
lonian gods and demons, cuneiform texts, medical and magical 
utensils; bandaging ( M. A.) ; baths in open air, sea bathing, public 
baths, single baths, foot and hand ablutions: Bathsheba and Su- 
sannah; birth of Mary, of St. John, etc.; the blind; blood-letting; 
burial; care of wounded, clothing, utensils (ancient Greece) ; care 
of children, nursery (antiquity and M. A); China and Japan; 
Christ's body; cholera; clothing and bedding; circumcision, cos- 
metics, Cosmos and Damian, life, cures, types, Cyprus and Crete; 
Dances of Death: death, suicide; death of Mary, the Sai 
urrection; deformities; demon exorcism: dietetics; dissections; 
dwarfs: Egyptian texts, gods, physicians, magical. 
utensils; Etruscan gods and donaria; eyeglasses: folklore: preg- 
nancy and obstetrics; Greek MSS. and texts, healing divinities, 
physicians; healing springs and mineral baths: hermaphrodites; 
holy healers of the sick (M.A.); Incunabula; India: instruments: 
Israel; the lame and cripples; Leda; leechdom and " Lasstafeln "; 
leprosy, lice, etc. <M. A.i; lying in room; magicians and 
medieval charlatans and quacks, clysters, barbers, natural sci- 
ences, lustrum 08, universities: modern MSS .; op ra- 
tions ( M. A.i: ParacelBUS, MSS., localities, friends; 

jihallic worship; Phoenicians; physicians' co 
plagues: prehistoric; poet physicians; resurrection (M, A.i; 
Roman bealin Saints (M. A.i: Btlgmata of CI I 

( M. A.); Buffering of mankind (M. A.i; superstition (ancient); 
syphilis, temples and donaria, Creek; thermal; tooth extraction; 
urinoscopy; Venus antique et modems; Vesalius and pre-Vesaltan 
anatomy; veterinary. 

These rooms, which are daily accessible to workers on 
subjects and to students, adjoin two other rooms containing the 
offices of the director and I 

collection of the German Society for the i I i--t<>ry of Medli 
Natural Sciences. 

I 
is no gun rani' useful work. 

ance and inspiration. But such an 
facilitates ti 
stand it 
always lidactic 



Ill 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 275 



teaching the history of medicine. Billings, in his memorable 
address at the International Medical Congress of London in 
1881, had some such scheme in mind when he said that 
instructions in the history and literature of medicine might 
be of great value, " not only as a means of general culture, as 
teaching students how to think, but, from a purely practical 
point of view, in teaching them how to use the implements of 
their profession to the best advantage — for books are properly 
compared to tools, of which the index is the handle. Such 
instruction should be given in a library, just as chemistry 
should be taught in the laboratory. The way to learn history 
and bibliography is to make them — the best work of the in- 
structor is to show his students how to make them." 



Resume. 

Historical study and research, if forming an integral part 
in the scheme of medical education, will exert a most bene- 
ficial influence on student, teacher and medicine in general. 
Didactic lectures alone are insufficient and time-consuming. 
Whatever direct teaching is given students would be based 
best on objective demonstration and practical work in biblio- 
graphical and historical methods rather than on systematic 
historical lectures. Such instruction will best be given in 
separate premises easily accessible to all departments, where 
the objects for demonstration should be collected and classified 
and where special research can be carried on. 



JOHN HUNTER: HIS LIFE AND LABORS. 1 

M. D., Baltimore, Md. 



By C. W. G. Eohrer 

For several years 1 have been pleasantly engaged in col- 
lecting the works of John Hunter, the founder of scientific 
surgery. I now have them complete; and for this reason 
I venture to bring before you a brief review of the life and 
labors of one with whose career you already are reasonably 
familiar. 

Birth and Parentage. 

John Hunter was born at Long Calderwood, Scotland, on 
the 13th of February. 1728. Long Calderwood is a small 
estate still belonging to his descendants, improved by a good 
stone house two stories high, situated about eight miles from 
Glasgow, in the parish of East Kilbride, county of Lanark. 
Here, in the second story room above the kitchen, John 
Hunter was born. There is some doubt concerning the exact 
date of his birth, but the one given above accords with that 
of the parish register. 2 

Strange to relate, Everard Home, in his " Life of Hun- 
ter," prefixed to the first edition of the " Treatise on Blood, 
Inflammation, and Gunshot Wounds," gives the 14th of July 
as the correct date. This is manifestly wrong. The Htk 



1 Paper read at the meeting of the Johns Hopkins Hospital 
Historical Club, January 13, 1913. 

2 The following letter from the registrar for the parish of East 
Kilbride to Dr. James Watson, the president of the Faculty of 
Physicians and Surgeons of Glasgow, together with the accom- 
panying register, are added as authority for any future biogra- 
pher of John Hunter, and will doubtless be read with interest: — 

East Kilbride, 29 March, 1859. 
Sir: — I HAVE searched the records of Births and Baptisms 
for this parish and have found the name of John Hunter, and 
send you the Extract. You will observe that the Christian name 
of his mother is blank, and the place of birth a-wanting, neither 
being in the Register. On making further search, I found the 
name of a sister " Isobel," two years older than John the same 
omission occurs with the name of the mother; but the place of 
birth given is Calderfield and I am of opinion that the farm 
now known as Long Calderwood would at one time be divided 
into two farms named respectively Calderfield and Long Calder- 
wood a circumstance very common in this Parish and I am led to 



of February is the date on which the anniversary of his birth 
is celebrated by the Eoyal College of Surgeons of England, 
and which he himself observed as his birthday ; but " prob- 
ably ", as Stephen Paget writes, " he was born during the 
night of the 13th-14th and in the room over the kitchen." 

He was the son of John Hunter and Agnes Hunter, his 
wife, whose maiden name was Paul. They were married on 
December 30, 1707. His father, who appears to have been 
a small farmer living on his own estate, was descended from 
a very old Scotch family, probably of Norman origin, the 
Hunters of Hunterston 3 in Ayrshire, whose history goes back 



this conclusion by the name of the farm adjoining that in question 
being likewise Long Calderwood, and no place known to me here 
having the designation of Calderfield. 

I am, Sir, Yours, &c, 

Matthew Dalglish, Registrar. 
Dr. James Watson, 

153, St. Vincent Street, Glasgow. 

Copy of Register Enclosed. 

"John, a lawful son procreate between John Hunter and 

Paul, born February 13th and baptized March 30th, 1728." 

Extracted by me from the Register-Book of Births and Baptisms 
for the parish of East Kilbride, in the county of Lanark, this 
28th day of March, 1859. 

Matthew Dalglish. Registrar. 

In confirmation of the correctness of the registrar's notion, W. 
Hunter Baillie, the grandnephew of John Hunter, wrote as fol- 
lows to John F. South, vice-president of the Royal College of 
Surgeons, under date of April 9, 1859: 

" In looking at an old map I have of Long Calderwood farm 
and mansion, which belong to me, I find that a portion of this 
small property was called Calderfield, and that the larger portion 
was named Long Calderwood. Upon this latter stands the house 
which I have always heard was the birthplace of William and 
John Hunter. It was externally in good repair when I saw it a 
few years since, and is still serviceable for farming purposes, 
such as lodging for farm servants, &c. The house used for habita- 
tion by the farmer is on another part of the property." 

3 The old manor-house of Hunterston, with its tower of great 
antiquity, is still standing: once a strong-hold, now a farm-house. 



■dart, 1014."| 



JOHNS HOPKINS HOSPITAL BULLETIN. 



11 



I to the thirteenth century. He was a man of refinement and 
I of some education, with a high moral and religious - 
I He was nearh seventy years old at the time of John's 
I birth, who was the youngest of ten children, five dying in 
I infancy. He died in 173S' at the age of seventy-eight The 
I mother was the daughter of a respectable citizen of Glasgow. 
I According to M. Baillie, she was " a woman of great worth 
and of considerable talents."' John was thus left, at the age 
of ten, to her sole car.' and, although a woman of strong 
mind, she was particularly indulgent to him. She died on 
ber 3d, 1751, aged sixty-six years. 
Jan* of the brothers who attained to manhood, 

was born in 1" L5. He was brought up to the law, but in 17 12 
he went to London to visit his brother William, who was at 
that time a teacher of anatomy, and was so captivated by his 
brother's pursuits that he relinquished the law to Income a 
practitioner of medicine. Intense application to anatomy 
impaired his health and made it necessary for him to return 
to Long Calderwood, where lie died of a pulmonary hemor- 
d 1743, in the twenty-ninth year of his age. He was 
a young man of pleasing address, and brilliant promise. Wil- 
liam said of him, that if he had lived to practice physic in 
London, nothing could have prevented bis rising to the top of 
his profession. 

William, born on the 23rd of May. 1718, early rose to 
unrivalled distinction as a teacher of anatomy in London, 
attained a professional reputation which could not 
(■■■. d< d. and a celebrity second only to that of his brother 
John. He was cot only famous as a physician and physiol- 
ogist, hut also as the founder, so-called, of scientific mid- 
wifery. It was under the fostering care of this elder brother 
ihn was initiated into those pursuits in which he soon 

al of his instructor. He died in London. 
; March, 1783, universally mourned and lamented. 
The younger daughter, Dorothea, married Rev. James Bad- 
lie, the minister at Hamilton, near Kilbride, from whom de- 
I the illustrious Hr. Matthew Baillie. and the no less 
distinguished Hie, an authoress of high repute and 

one of Sir Walter Scotfs closest friend-. 

DOD \M> Vol Til. 
Very little is known of the boyhood and youth of John 
Hunter. His biographers are unanimous in Btating that be 
was wilful and disobedient, and much given to idleness. A.1 

the game time he was g ] ;it outdoor games, and observani of 

nature. While be i ared little for hooks his mind was not wholly 
inactive, as the following Btatemeni concerning himself will 
show: "When 1 was a hoy. I wanted to know all about the 

A report of the house, written in iM',7. says that it has not 
changed since 17^s. except that it was then thatched ami is now 
slated, and two rooms downstairs have been thrown into one. 
From Hunter of Hunterston was descended Francis Hunter, John 
Hunter's paternal grandfather. 

is the date given by Ottley. According to Dr. S. Foart 
Simmons, the correct date is October 30, i;n. This would make 
Hunter thirteen years old at the time of his father's death. 



rl " ,llU •""' > -I why the [< .,! color in the 

autumn ; I watched the ants, be idpoles, and caddis- 

3tered people wit .,;„„,, „),,,, . 

knew or cared anything about." 

above, after all. is perhaps the besl education he .-.mid 
have had for sharpening his - erve, and bringing 

his reasoning powers to hear upon problems of the highest 
inter, st. in the pursuit of which he was late,- | 
acknowledged leader. A- si,- J . :ll ,i ,,,- |,j m . .. ]| ( . 

was impelled to obtain knowledge by intellectual self-exertion. 
and like an athl.te restless in I of hi- strength, bo 

he could not rest: he could not hut search, and watch, and 

m nature; he must compel her to answer, and I 
set ii- limit to In- search. Within the range of thi 
world of life he must seek by every method of inquiry, 
kind ami degree of know |. 

Al l! '' 'i. learning that his brother-in-law, a 

cabinet-maker at Glasgow, man :, r whom he 

loved, was laboring under pecuniary embarrassment, he paid 
him a visit, and for a time assisted him in his but 
"ii apprentice but as a volunteer, working probably at small 

iplj I'm- his board and clothing. It was tl 
cumstance which induced some of his envious contemp 
I" assert that in early life he had been a wheelwright or a 
carpenter: 1 a statement for which then i- not the slightest 
foundation in truth. For three years he generously aided his 
brother-in-law, hut tiring of an occupation which was in no 
wise congenial to him, he was seized with a desire to visit his 
William, who had I n living for some time in Lon- 
don, and had up a large and lucrative 
practice, and was growing rapidly in reputation. Be 
him. asking leave to come and he his assistant in his anatom- 

ar< In- ; or, if thai - lould not be accepted, ex- 

l a wish to enlist in the army. In answer he n 
a very kind invitation from his brother, and immediai 
off for London, where be arrived in September, 1748, about a 
fortnight before the commencement of the autumnal c 
lectures. An arrangement was promptly made by which .John 
became an assistant to his brother. Herein was arousi 
latent fin- of his remarkable genius, which nevi 
burn from that auspicious moment until the day of his widely- 
lamented death. Ill- reception in London is described b\ 
3i mm 1 D. I Iross, in the follow ing words : 

The ii rdlal, and ar- 

rangements v. 

I in William |j !i only 

recently opened, bad already acquired marked celeb 
account of their educational advantages it was there thai young 
Hunt) i 



•Reference is bere madi a p. 10, 

of his "Life of Hunter," which 

" A w 'it II tin 1 

event of William Hunter ubllc lecturer in u 

■ of his future occupatlo 
him to iwn the 

chisel, the rule, and the mallet: ami take up the ].- 
pipe, and the pre 



12 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 275 



the incubus which had so long oppressed his soul. A new life 
broke in upon him; his ambition was aroused; industry, steady 
and unremitting, took the place ot idleness, and the undecided, 
wavering, erring youth, stimulated by the new atmosphere in 
which he was now daily immersed, assumed the attitude and the 
assured character of the philosopher and the student of nature. 
Who or what brought about these wonderful changes in the life 
and conduct of this young man, so sudden, so unexpected? It is 
not difficult to answer the question. It was simply William Hun- 
ter, and the influence of his example. John saw the wonderful 
things which his brother was doing in building up a great ana- 
tomical museum, and it is, therefore, not surprising that his tastes 
should soon have taken a similar direction." 

Early Education. 

Hunter's preliminary education had been almost wholly 
neglected, a lack which was never made good, and which, in 
his maturer years, he never ceased to regret. Before his 
father's death he had been sent to a Latin school at Kilbride, 
where he made no progress in his studies, and from which 
he was removed. Later he went to -the grammar-school of 
Glasgow, but he had little or no taste for books and preferred 
sports to study. 

He tried to remedy his ignorance of the fundamental 
branches in 1753' by entering St. Mary's Hall, Oxford, as a 
gentleman commoner. The motives which led him to take 
this step are not satisfactorily explained by any of his 
biographers, but it seems probable that he was urged to do so 
by his brother and friends. His brother was very anxious 
that he should abandon surgery and study medicine, which 
was regarded, and, perhaps not without reason in the then 
existing state of the science, as a higher branch of the healing 
art. With this end in view it was deemed very desirable that 
John should have a sound knowledge of Greek and Latin, as 
no physician was considered properly educated without it. 

The effort, however, proved abortive. Hunter was now 
twenty-five years of age, and he had no disposition to shut 
himself up in a college, or to give up the idea, formed soon 
after he settled in London, of becoming a great surgeon. 
He looked upon such studies as a waste of time; and in 
referring to the subject some years afterwards, in a conversa- 
tion with Sir Anthony Carlisle he thus feelingly expressed 
himself: "They wanted," he said, "to make an old woman 
of me, or that I should stuff Latin and Greek at the Uni- 
versity; but," added he, significantly pressing his thumbnail 
on the table " these schemes I cracked like so many vermin 
as they came before me." 8 

One cannot but regret that Hunter did not carry out the 
wishes of his friends. A little " stuffing " of Latin and Greek 
would have been of vast benefit to him, in preventing those 
errors of style and literary composition which so greatly dis- 
figure and obscure his writings. 



" " John Hunter and his Pupils," p. 13. 

7 In the buttery book at St. Mary's Hall the date of Hunter's 
admission is given as June 5, 1755. 

" Ottley's " Life of John Hunter " Palmer's Edition, vol. I, page 
14, London, 1837. 



Medical Training. 

Hunter received much of his inspiration and medical train- 
ing from three celebrated teachers — his brother, William 
Hunter, William Cheselden, and Percivall Pott. Symonds,' 
his brother's assistant in the dissecting room, also gave him 
much instruction. 

Having been duly installed as assistant he set resolutely 
to work. He took, as it were, a new lease on life. Languor 
and indecision gave way to steady, unremitting toil, sustained 
by a definite purpose. It is stated of him that "he did not 
work in Anatomy, as is usually done, for a few hours in the 
day, but was employed in it from the rising to the setting of 
the sun." 

The first task assigned to him was the dissection of the 
muscles of an arm, which was so well and so rapidly done 
that lie was next set to preparing an arm in which all the 
arteries were injected, and these, as well as the muscles, were 
to be exposed and preserved. This labor was also performed 
in so satisfactory a manner as to elicit the highest commen- 
dation from his brother, who predicted his future greatness 
as an anatomist, and told him "he should not want for em- 
ployment." His proficiency as a practical anatomist was so 
very rapid that, before the end of twelve months, he was 
intrusted with the preparation of his brother's subjects for 
his anatomical lectures. 

The summer of 1749 was spent by Hunter at Chelsea Hos- 
pital, under the instruction of the celebrated Cheselden. 
Under this worthy master he learned the first rudiments of 
surgerv, an exceptional opportunity which came to him at the 
request of his brother. 

In the succeeding winter he was so far advanced as to 
become demonstrator of anatomy, assisting and directing the 
pupils in the dissecting-rooms, while his brother confined his 
attention almost exclusively to the regular lectures in the 
class-room. 

The assiduous discharge of these most laborious duties 
gave Hunter full employment during the winter of 1749-50. 
During the summer he resumed his attendance at the hos- 
pital at Chelsea. In 1751 he entered St. Bartholomew's Hos- 
pital as surgeon's pupil to Percivall Pott, another great lumi- 
nary in British surgery. In 1754 he became surgeon's pupil 
at St. George's Hospital. In the winter of 1755, seven years 
after his arrival in London and after he had acted as assist- 
ant for five years, he was admitted to a partnership in his 
brother William's private school of anatomy." Besides a 
certain portion of the course of lectures allotted to him, lie 
gave lectures when his brother was called away to attend his 
patients. 

Professional Car em;. 

Hunter's professional career may be said to have begun 
in May, 1756, when he was appointed house-surgeon to St. 

9 Sometimes spelt "Simmons," and also " Symons." 
10 1 have purposely refrained from making even brief allusion 
to Hunter's differences with his brother William, as these unfor- 
tunate occurrences will be fully narrated in a subsequent paper 
on William Hunter. 



January, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



13 



George's Hospital, which position he retained, however, only 
for the short space of five months. The reason of his resig- 
nation is not recorded, but it was probably because he longed 
to return to the more congenial work of the dissecting room." 
He worked for ten years on human anatomy, oaring which 
period, as Everard Homo informs us, " he made himself mas- 
tor of what wns already known, as well as made some addition 
to that knowledge." Some of his discoveries called forth the 
highest commendations of Baron Haller, then considered the 
first physiologist in Europe, and still command admiration. 
At thai time he also began his studies in < iparative anat- 
omy, a new and untrodden field of scientific inquiry in which 
- soon to become a distinguished authority. Unfortu- 
nately, owing to his incessant labors, his health was beginning 
to suffer. In the spring of 1759 he was attacked with inflam- 
mation of the lungs, from which he made a tardy recovery, 
Lse leaving in its wake certain sympi estive of 

pulmonary tuberculosis. 13 He was strongly advised to go 
abroad; and in October, 1760, through the agency of his 
friends, he was made a staff-surgeon in the army. In the 
following spring he went with the army to Belleisle, off the 
western coast of France. He served as senior surgeon on 
v . both in Belleisle and in Portugal, till the year 1763, 
when peace having been proclaimed, he returned to Ed 
completely restored to health, and set i in Golden Square, 
London, to start practice as a surgeon. He soon found that 
his half-pay as a military surgeon, and the emoluments de- 
rived from private practice, were inadequate for his support. 
Therefore, in order to increase his income, he taught pi 
anatomy and operative surgery for several winters. I 
took private pupils, each of whom was apprenticed to him for 
ire, at a fee of five hundred guineas (about $2,650.00), 
which included board and lodging. Among his private pupils 
whom he continued to receive until within a short time of bis 
Edward Jenner, John Abernethy, Henry Cline, 
Philip 3 Cooper, Everard Heme, and 

• 

At this time Hunter resumed, with unabated zeal, his re- 
searches in comparative anatomy and physiology. Finding 
that bis experiments could not be conducted properly in the 
midst of a large city, in 1764 be purchased two acres of 
ground about two mile- from London, beyond Brompton, and 
built upon it a small bouse to suit himself, w 
's Court. 

In 1768 a vacancy on the surgical staff occurred 
- Hospital, and Hunter became a candidate fi 
position. Aided by his brother William, he v 
to the hospital, where he Berved until his death, twenty-live 
years later. 

Soon after his appointment - Hospital he 

11 In 1757, at the age of 29 years. Hunter was made Prosector 
and Demonstrator in Dr. William Hunter's Theatre of Anatomy. 
In Great Windmill Street (Professor Owen). 

"There was a tuberculous taint in the Hunter family, James, 
an older brother of John, dying of "a spitting of blood," in the 
twenty ninth year of his age, as stated in a preceding paragraph. 



though the corporation embrao -dent men. B 

bad so lit! i 

ings or took any active part in its deliberal 

In the winter of | rmined to become a pub- 

lic lecturer on thi nd principli ry, his 

- for which were u£ 
his cour.-e. lie stated that be bad so frequent] 

deliv- 
ered as t lie found 

or two 
• lectures gratuitously t 
'< Hospital, and in 1775 publi i in his 

house in Jenny n S 

. Contributions to Mi on w. s, 

Hunter made many notable contributions to medicin 
surgery. Several of his early ; published, u 

in Dr. William Hunter's "Medical I 
are: \n account of bis injecting thi 
the descent of that body, with s on the her: 

genita, and ; nts in proof of I I being 

absorbents. 

Anion in human anatomy, and his contri- 

butions to that - the follow ■ 

He traced the ramification of the olfactory nerves upon the 
mucous membrane of the nose, and discover* d of some 

of the branches of the fifth pair of nerves— the trifacial. 

He traced, in the gravid uterus, the- arteries of the ul 
their termination in the plai 

He was the first to demonstrate the function of the lymphatic 
vessels as absorbents in the human economy. 

In the course of his inquiries in comparai 

ued from animal 
other i 1 
have a distinct bearing upon human inc.! 

He ascertained thi tnlmal and • 

stances undei 
juice. 

Hi 

, r, which I 
retains its shape during Its growth. 

He explained the i Hon by wide'. . 

of bone is bi i the Living. 

In 1776 Kunti i 
ently drowned, tn 

■ M 

formldal 

,. the bi 
light in Sndii 

■ r each ' 
isfaction 

his ansv tory and Intelllgibl 



1 1 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. a 



The prevention of rabies or hydrophobia early engrossed 
Hunter's attention, and lie was one of the first surgeons who 
taught that deep excision of the wounded structures is the 
most successful method of operation. 

He also made experiments upon the transplantation of 
l' <lii in ilir human subject, and upon skin grafting." 

The most remarkable operation associated with Hunter's 
name is the one in which he tied the femoral artery in the 
"aponeurotic space in the middle third of the thigh," in what 
lias since been termed, and rightly, "Hunters canal," for the 
cure of a popliteal aneurism. This one feat of surgical dar- 
ing, novel alike for its resourcefulness and originality, is in 
itself sufficient to give him undying fame. It was performed 
in December, 1785, at St. George's Hospital. The particulars 
of this case are given in the London Medical Journal, and in 
the Transactions of a Society for Improving Medical and 
Chirurgical Knowledge. The patient, a coachman, forty-five 
years of age, in six weeks walked away from the hospital 
cured. 

In his "Lectures on the Principles of Surgery" (Palmer's 
edition, vol. I. p. 551,), he comments upon this operation, as 
follows : 

In December, 17S5, I performed the operation at St. George's 
Hospital, in a case of popliteal aneurism, in a manner different 
from that ordinarily practiced, and with success. ****** I would 
only observe, that in future I would advise only tying the artery 
in one part, and not to endeavor to unite the wound by the first 
intention. In that case four ligatures were applied upon the 
artery. 

The three important principles on which the Hunterian 
operation is founded are : 

1st. That the impulse of the blood into the aneurism being 
restrained by a ligature placed on the artery above the tumor, 
the further progress of the disease will be checked, without the 
necessity for a ligature being also placed on the artery below the 
tumor. 

2d. That the powers of absorption would suffice for the removal 
of the coagula in the sac, and the necessity for opening it be 
thus done away with. 

3d. That the anastomosing vessels of the limb, in their natural 
state, would be capable of immediately taking on such increased 
action as would suffice for carrying on the circulation to theparts 
below the point at ivhich the main artery was tin/. 

1 1 is a singular fact that Hunter foreshadowed the princi- 
ples which now guide the surgeon in the treatment of club- 
foot and similar deformities. In 1767 he ruptured his tendo 
Achillis, a circumstance which led him to institute a series 
of experiments upon the reunion of divided tendons in the 
dog. 

Books and Publications. 

Hunter's merits as an author are truly great. Notwith- 
standing bis want of scholarship, and the labor with which he 
composed, he was a prolific writer. Like his celebrated 

""May we not claim for him." says Sir YA'm. Fergusson, with 
reference to these experiments, " that he anticipated by a hundred 
years the scientific data on which the present system of human 
grafting is conducted?" {Hunt. Orat., 1871, p. 17.) 



teacher and older brother, William, he early formed the habit 
of committing his views to writing, even when he did not 
intend to give them immediate publicity. Owing to an unfor- 
tunate circumstance (the burning of the Hunter MSS., by 
Sir Everard Home, in July, 1823), much that he wrote never 
met the public gaze. Many of his early contributions, especi- 
ally those on comparative anatomy and physiology, found 
their way into the ' Transactions of the Eoyal Society and 
other similar publications, where they elicited much attention. 

Hunter's first systematic work was his "Treatise on the 
Natural History and Diseases of the Human Teeth," the 
first part of which was issued in 1771, and the second seven 
years after (17TS). 10 The work was well received, and 
greatly enhanced his reputation as an acute observer and 
investigator. His attention seems to have been originally 
directed to the subject by the deplorable state of dentistry, 
which was almost solely confined to the barber or ignorant 
mechanic, whose chief occupation consisted in extracting and 
plugging teeth. 

On pp. 121 and 122, of Part I, in his remarks entitled " Of 
the Diseases of the Teeth," he says : 

The Teeth are subject to diseases as well as other parts of the 
body. Whatever the disorder is that affects them, it is generally 



13 On the occasion of the publication of Part II, a new title-page 
was added to Part I, and the two (being bound together) were 
sold as the second edition. 

The full title of Part I, which consists of 12S quarto pages, is: 

The 

NATURAL HISTORY 

of the 

HUMAN TEETH: 

Explaining their 

Structure, Use, Formation, 

Growth, and Diseases. 

Illustrated with Copper-plates. 

By John Hunter, F. R. S. 

Surgeon Extraordinary to the King, and Fellow of the 

Royal Society. 



London, 
Printed for J. Johnson, No. 72, St. Paul's Church-yard. 

MDCCLXXVIII. 

The full title of Part II, also containing 128 quarto pages, is: 

A 

PRACTICAL TREATISE 

on the 

Diseases 

of the 

TEETH; 

Intended as a 

Supplement 

to the 

Natural History of those Parts. 

By John Hunter, 

Surgeon Extraordinary to the KING, and Fellow of the Royal 

Society. 

London. 

Printed for J. Johnson, No. 72, St. Paul's Church-Yard, 

MDCCLXXVIII. 



Jahoahy, 191 1.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



attended with pain; and from this indeed we commonly first 
know that they are affected. 

Pain in the Teeth proceeds, I believe, in a great measure, from 
the air coming into contact with the nerve in the cavity of the 
Tooth: for we seldom see people affected with the Tooth-ach, but 
when the cavity is exposed to the air. 

It is not easy to say by what means the cavity comes to be 
■ I 

The most common disease to which the Teeth are subject, 
begins with a small, dark coloured speck, generally on the side 
of the Tooth where it is not exposed to pressure; from what cause 
this arises is hitherto unknown. The substance of the Tooth thus 
discoloured, gradually decays, and an opening is made into the 
cavity. 

Part IT consists of ton chapters, treating <>f a variety of 
topics. For example, Chap. I. See. IV. is devoted t" 
sideration of gum boils; Sec. VTT. • the Antrum 

Mariner. . Sec. I, of Chap. Ill, is allotted to a discussion oi 
the scurvy in the gums; while in Chap. IX. the transplanting 
of teeth is discussed pro and con. In Chap. X, pp. I . ■ 
127, he relates the following ease where a disorder of the 
urethra was produced by dentition : 

A boy, about two years of age, was taken with a pain and 
difficulty in making water; and voided matter from the urethra. 
I suspected that by some means or other this child might possibly 
be affected by the venereal poison; and the suspicion naturally tell 
on the nurse. 

These complaints sometimes abated, and would go off alto- 
gether: and then return again. It was observed a; last, 'hat they 
returned only upon his cutting a new Tooth: this happened so 
often, regularly and constantly, that there was no reason to doubt 
but that it was owing to that cause. 

The text of Hunter's book on the Teeth shed by 

sixteen plates. It also has a copious index. Th< 
through three editions, the last having been issued h 
ten years after Hunter's death. 

The "Treatise on the Venereal Du 

followed by a second edition in 1788. A third 



" The first edition was a handsome quarto volume of 398 pages, 
illustrated with seven full-page plates from drawings made by 
William Bell, and provided with a most comprehensive index. 
Its simple, but all-expressive title is: 
A 
TREATISE 
on 
THE VENEREAL DISK U3E. 
By John Hunter. 
London, 
Sold at No. 13, Castle-Street, Leicester-Square. 
MDCCLXXXVI. 
The dedicatory page of this pioneer and famous publication Is 
interesting. It bears the following inscription: 
To 
SIR OEOROE BAKER, Bart. 
Physician to Her Maji 
President of the College of Physicians. 
and 
Fellow of the Royal Society, 
THIS WORK 
Is i n s I 
As a Mark of Est 

By His Friend, and 
Leicester-Square, Humble Servant. 

March 30, 1786. John Hunter. 



was issued by Everard II in 1810. Eaving been long 

and impatiently expected, it at once attract 
tion. Hunter had spi nl manj bis material; 

- to produi |y upon 

his personal observations. Be had seen much of I 
during army, and aft< rwards in civil 

practice, and he felt that he 
it- own inn a 

was for upwards of a third of a century the host auth 
the Bubjecl in any language, and bis description of the indu- 
rated i i graphic and distinct that it will always 
be called by his name. It runs in 

This, like most other Inflammations whicb termln 

first with an Itching in the part; if II 
thai is inflamed, generally a small pimj 

without much hardi eeming Inflammation, and with 

very little tumefaction, the plaits not being bo readily tumefied 
from inflammation as many parts are, especially thi 
are the chancres attended with so much pain or 
as those on the prepuce; but if upon the franum. and more 
especially the prepuce, an Inflammation moi ile than 

the former soon follows, or ai 1 he Inflamma- 

tion are more extensive and visible. Those parts i„ 
of very loose cellular membrane, afford a ready passage for the 
extravasated juins: continued sympathy also J take* 

place in them. The Itching is gradually changed to pain: the 
surface of thi 
wards ulcerates: in others a small pimple, ( ,r 

on the glans, which forms an nicer, A thickening of tie- part 
comes on. which at first, and while nf the true venereal Kind. 
is very circumscribed, not diffusing Itself gradually anil Imper- 
ceptibly into the surrounding parts, bul terminating 
abruptly. Its base is hard, and the edges a little prominent 

When it begins on the franum, or near it. that pari is very com- 
monly wholly destroyed, or a I o ugh it. 
which proves rather Inconvenient in the cure, and 

had better, in such cases, he divided at first. 

In 1 i 

quarto volume, pi 
this work Hunter had :ti infinity of ti" 

trouble : and before publ irl of it 

■ 

I Ir. Ford ce, Dl ". Marshal 

the first and second edil I and public 

1 : 



third quarto edition was publish 

death, by Everard Home. This was print) 
from the first Instead of from I 

much pains to correct A fourth edition, In 

with notes by l>r. .' 

, rint from tl 
elaborated by Adan 
■ 

nils pay, limit, r - ; 

■• i would ad 
book in the order He « 111 ' 

Introduction •■■ 
him. 1 
and ot!.. 

without adding sufficiently »■• It 

cannot ' In hi* mem- 



16 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 275 



Of the " Treatise on the Venereal Disease," Jesse Foot has 
this to say (Life of Hunter, pp. 272 and 273) : 

The sale of it was rapid at first from curiosity being arti- 
ficially raised, as the papers of the day had announced that it 
was to throw all former productions at an humble distance. 

Hunter's " Observations on Certain Parts of the Animal 
(Economy" was first published in 1786. It is dedicated to 
Sir Joseph Banks, president of the Royal Society." A second 
edition appeared in 1792; and in 1837, a third, edited by 
Richard Owen. The first two editions are quarto; and, like 
the corresponding ones of the "Treatise on the Venereal 
Disease," were printed and sold at Hunter's own residence. 
The third edition, the one by Owen, is an octavo volume of 
506 pages. 

The "Treatise on the Blood, Inflammation, and Gun-shot 
Wounds," a work of vast labor and the most patient research, 
and upon which Hunter's fame as a surgeon and a medical 
philosopher largely rests, was published in 1794, under the 
supervision of Dr. Matthew Baillie and Everard Home, only 
about one-third of the proofs having been revised by the 
author at the time of his death. A life, by Everard Home, 
was prefixed to the volume, but this, for some reason, was 
omitted in the succeeding editions of 1812, 1818, and 1828. 10 



ory, and the remarks being chiefly practical, must be referred 
to as often as intricate cases occur. If therefore these chapters 
are read in their order, the student must not be angry with his 
Author or himself, if he cannot keep up his attention to every 
minutia. Whenever he has an intricate case, in his own prac- 
tice, he will not accuse Mr. Hunter of prolixity." 

A fifth edition, quarto, consisting of 429 pages, with notes by 
Sir Everard Home, Bart., was published in 1S09 and 1810, it 
being the second edition by this editor, in which, however, few 
deviations from the first are observable. A supposititious title- 
page, purporting to be the third edition, seems to have been 
added in 1810, in order to increase the sale. The copy which I 
possess, of this edition, came from the library of Joseph Henry 
Green, who was president of the Royal College of Surgeons of 
England, in 1859, when Hunter's remains were transferred from 
the vault of St. Martin's-in-the-Fields to Westminster Abbey. 
It has for a frontispiece a print of Sharp's engraving of Rey- 
nolds' celebrated portrait of Hunter. 

M TO SIR JOSEPH BANKS, Bart., 
President of the Royal Society, &c. &c. &e. 
DEAR SIR, 

As the following Observations were made 
in the course of those pursuits in which you have so warmly 
interested yourself, and promoted with the most friendly 
assistance, I should be wanting in gratitude, were I not to 
address them to you, as a public testimony of the friendship 
and esteem with which I am, 

Dear Sir, 
Your obliged and 
Very humble Servant, 
JOHN HUNTER. 
Leicester Square, 
Nov. 9, 1786. 

"The original edition of this splendid work was issued in a 
quarto volume of 575 pages, with eight plates. Prefixed to it 
is an account of Hunter's life and writings, consisting of 67 



Abernethy, in his " Lectures on Local Diseases," pays the 
following splendid tribute to this work: 

I know of no book, to which I can refer a surgical student for 
a satisfactory account of those febrile and nervous affections 



pages. An engraving of his head forms the frontispiece. 
full title of the volume is: 

A 
Treatise 

on 

The Blood, 

INFLAMMATION, 

and 

Gun-Shot Wounds, 

By the Late 

John Hunter. 



The 



To Which is Prefixed, 

A Short Account of the Author's Life, 

By His Brother-in-Law, 

Everard Home. 



London : 

Printed by John Richardson, 

For George Nicol, Bookseller to His Majesty, Pall-Mali. 



1794. 

It is dedicated to his Majesty, the King, in the following lauda- 
tory terms : 

TO THE KING. 
MAY IT PLEASE YOUR MAJESTY, 
In the year 1761, I had the honour of being 
appointed by your Majesty a surgeon on the 
staff in the expedition against Bellisle. 

In the year 1790, your Majesty honoured me 
with one of the most important appointments in 
the medical department of the army, in fulfilling 
the duties of which every exertion shall be called 
forth to render me deserving of the trust reposed 
in me, and not unworthy of your Majesty's pa- 
tronage. 

The first of these appointments gave me ex- 
tensive opportunities of attending to gun-shot 
wounds, of seeing the errors and defects in that 
branch of military surgery, and of studying to re- 
move them. It drew my attention to inflamma- 
tion in general, and enabled me to make obser- 
vations which have formed the basis of the present 
Treatise. That offlce which I now hold has af- 
forded me the means of extending my pursuits. 
and of laying this work before the public. 

As the object of this book is the improvement of 
surgery in general, and particularly of that branch 
of it which is peculiarly directed to the service of 
the army, I am led by my situation, my duty, 
and my feelings, to address it, with all humility, 
to your Majesty. 

That your Majesty may long live to enjoy the 
love and esteem of a happy people, is the fervent 
wish of 

YOUR MAJESTY'S 
MOST FAITHFUL SUBJECT, 
AND MOST DUTIFUL SERVANT, 
Leicester Square, JOHN HUNTER. 

May 20. 1793. 






Jakuary, 19] 1. 1 



JOHNS HOPKINS Il.-SLMTAI. IH'LI.KTIN. 



17 



which local disease produces, except that of Mr. John Hunter's 
TREATISE ON THE BLOOD, INFLAMMATION. &c. 

That Hunter was pre-eminently fitted to write such a 
treatise, the following quotation from the advertisement to 
the English edition will abundantly show : 

Mr. Hunter, in the year 1760, went as senior surgeon on the 
staff to Bellisle and Portugal, and continued abroad in active 
employment during the war, and there acquired a complete 
knowledge of gun-shot xcounds, which can alone be procured by 
actual experience. In the year 1790 he was appointed inspector- 
general of hospitals, and surgeon-general of the army. Three 
years after this appointment, having long maturely weighed the 
important subject of gun-shot wounds, with the effects thereby 
procured (having now had three and thirty years ample experi- 
ence) he brought forward his immortal treatise on the blood, 
inflammation, and gun-shot wounds. The expectation of the pub- 
lic was great, nor was it disappointed; for this work was found 
to answer the exalted reputation of the author. It was not a col- 
lection of the sentiments of others, but his own observations. It 
was wholly original. 

It i- interesting for Americans to note that a number of 
the experiments contained in Hunter's " Treatise on the Blood " 
were performed by one of his American pupils. Dr. Philip 
_ Physick of Philadelphia, later known as icr of 

American Surgery. *' In this treatise, on p. 94, Bunter Bays: 
"■ Many of these experiments were repeated, by my desire, by 
Dr. Physick. now of Philadelphia, when he acted as house- 
surgeon at St. George's Hospital, whose accuracy I could 
ad un"ti." Hunter was so pleased with Physick that he 
offered him a share in his business, which, fori 
• :\. he declined. 
A complete edition of Hunter's works was issued in London 
in 1837, in four octavo volumes, illustrated by a volume of 
plates in quarto, under the supervision of James F. Palmer. 10 
v. ry Ottli'v, Thomas Bell, George B. Babing- 
ton. and Richard Owen. Palmer himself superintended the 
publication of the "Lectures on the Principles of Surgery," 
ami on the "Treatise on the Blood, Inflammation, and G 

Wounds'*; to Bell, an eminent dentist, was assigned the 
trad of the "Teeth "; Babington, a physician of wi 
i took charge of the " Treatise on the Venereal Disea 

■ In vol. I, of Palmer's edition of Hunter's complete works, 
appears nttl.ys admirable "Life of Hunter," by far the best 
which wo possess. It comprises 198 pages. The remainder of 
this volume contains Hunter's "Lectures on the Principles of 
Surgery." Vol. II contains the two treatises on the "Teeth," and 
the "Treatise on the Venereal Disease." Vol. ill is a reprint of 
the " Treatise on Inflammation," comprising 638 pages, and an 
elaborate general index to the three volumes, consisting of the 
remaining 38 pages. Nine pages descriptive of the plates then 
follow, the plates themselves appearing in a separate volume, 
quarto in size. Vol. IV is a reprint of the "Animal CEconomy." 

In 1m',i the scientific works of Hunter were published, in two 
octavo volumes, under the and observations on 

Natural History, Anatomy, Physiology, Psychology, and Geology." 
These were edited by Professor Richard Owen. Vol. I contains 
observations on natural history, physiology, palaeontology, phy- 
tology. and a treatise on animals. Vol II contains the observations 
on comparative anatomy. 



and Owen edited the pap "I Anatomy and 

Physiology." incl •' those published in the 

Philosophical I ns. Ottley furnished a 1 

Hunter for the first volume, which contains by far tin 
able and lucid account of him and of his writta 
ever been written. The " □ the Principles of Sur- 

gery" were mainly printed from a copy, taken in short hand, 
I ianiel Rumsey, a pupil .if Hunter. 
In 1842, "A Descriptive and Ilh; .f the 

Calculi and other Animal ('• u the 

a of the Royal College of Surgeons in L 
published. The greater part of this collection, amount 
about six hundred specimens, w I inter. 

Degiu:i s \m> Ho 

Hunter received numerous testini" teem and ap- 

• on from learned societies at home and abl 
as friendly recognition from his own Bovereign. In 1767 he 
was made a Fellow of the Royal Society of Lon.i 
Surgeon Extraordinary to George III; in 1783, a mer 
the Royal Society of Medicine and of the !. mj of 

Surgery in Paris; in 1786, Deput] of the 

army ; and in 1789, four years before his di 
eral and Inspector. The Copley medal of t 

tion in its gift, was conferred upon him 
in 1787, in recognition of the value of bis 
nal investigator. The American 1" S ty, the 

Royal Collegi 

of Edinburgh, ai 
Belles-Lettres of < . 
members. 

Private Lin:. 

Hunti life. Hi 

trious of men, sp< tiding, 

ally all that he made. His brother-in-law, - 

as that for '■' 

pounds 

amount 

a thousand pounds 

ads. 

In 1768 H 
Square 

William. I 

llistor 

and twi 

Unbelt B 



18 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. :75 



stated that he used the proceeds of the above publication to 
defray the expenses of his wedding. Their married life is said 
to have been a happy one. Four children were born unto 
them, only two of whom grew to maturity. 

In 1783, Hunter's lease of the house on Jermyn Street came 
to an end. His collection had grown s.o rapidly that he sought 
for more commodious accommodations, and purchased a large 
house on the east side of Leicester Square, with the ground 
behind it, and a house on Castle Street (it was No. 13), now 
part of Charing Cross Road. He continued to reside in Lei- 
cester Square until he died, with the exception of the sum- 
mers, which were still spent at Earl's Court. Between the two 
houses he erected a building for his museum, on which he 
expended above three thousand pounds. It was ready for 
occupancy in April, 1785. Everard Home, William Bell, and 
a new assistant, Andre, helped to move the preparations and 
arrange them in the new building, which was opened to visi- 
tors in 1787. 

With the exception of an attack of pneumonia in 1759, 
Hunter enjoyed excellent health during the first forty years 
of his life. In 1769 he had a severe attack of gout, and 
another in 1773, accompanied by a spasmodic affection of dif- 
ferent parts of his body, eventually involving his heart. From 
this time his cardiac disturbance was apt to recur after 
exertion, fatigue, or mental irritation. 11 In December, 1789, 
four years before his death, he was suddenly seized with a 
total loss of memory, lasting for fully half an hour. In the 
autumn of 1790, and in the spring and autumn of 1791, 
his attacks of angina became more and more severe; in the 
beginning of October, 1792, he had one so violent as to almost 
cause his death." 

In person Hunter was about the middle stature, measuring 
five feet two inches in height, uncommonly strong and active, 
very compactly made, but free from corpulency, and capable 
of great bodily exertion. His shoulders were high, and his 
neck short. His eyes and complexion were light, his brows 
heavy, his cheeks rather high, and, as one of his biographers 
(Jesse Foot) expresses it, his mouth was somewhat under- 
hung. In a word, his features were rather large, and strongly 
marked. His hair, in his youth, was inclined to red, but as he 
advanced in life it became gray, and at length partially white. 
His countenance was animated, open, and in the latter part of 
his life deeply impressed with thoughtfulness. When an en- 
graving of him was shown to Lavater, he said, " That man 
thinks for himself." He required little sleep, often working, 
with hardly any intermission, for nearly twenty hours out 
of the twenty-four. He was unassuming in his manners, but 
rather cold and reserved at times; in his dress he was plain 
and simple, and not always neat. 



*■ He was accustomed to say that " his life was in the hands 
of any rascal who chose to annoy and tease him." 

x In addition to the above he had a severe attack of illness in 
the spring of 1777, and another in 17S5. lasting about fifty days. 



Closing Years. 

Hunter's final hour came at last — death, sudden and unex- 
pected, overtook him at St. George's Hospital. A special 
meeting of the governors and of the surgical staff of that 
institution had been called, to discuss business of importance 
connected with the admission of pupils and the mode of 
instructing them. A remark which Hunter made during the 
discussion was flatly contradicted by one of his colleagues. 
This disturbed Hunter immeasurably; and, as a consequence, 
he was seized with a most excruciating attack of angina. He 
immediately ceased speaking and hurried into an adjoining 
room, to fight out his pain by himself. His nephew, Dr. Mat- 
thew Baillie, followed him from the board-room; he went a 
few steps, gave a deep groan and fell into the arms of Dr. 
Robertson, one of the physicians of the hospital who chanced 
to be present, and expired. 

Hunter's brother-in-law and assistant, Everard Home, who 
was in the hospital at the time, was also summoned. Various 
attempts were made for upwards of an hour to restore anima- 
tion, under the hope that the attack might prove to be a 
fainting fit, such as he had before experienced, but in vain. 
His body was placed in a sedan chair and conveyed to Lei- 
cester-Square, followed by his now vacant carriage. 23 

This most distressing event put an end to the business of 
the meeting. The only notice to be found on the books of 
that day's proceedings is the following minute: 

" Resolved, — That Mr. Hunter's letter to this Board relating to 
two of the surgeons' pupils, which was received this day, be 
preserved for future consideration." 

An occurrence so sad and so unusual called forth a wide- 
spread sympathy, and created a profound sensation wherever 
Hunter's name and fame were known and appreciated. In 
the language of Professor Gross, (" John Hunter and His 
Pupils," pp. 26 and 27) : 

Like Caesar, Hunter was murdered by his friends, not in the 
senate chamber, but in the consultation room of a hospital which 
had so long been the recipient of his services, of which he was 
the chief ornament, and which should have overlooked his infirm- 
ities, some of them inherent in his nature and others the result 
of long-continued overwork of mind and body. 



211 Mrs. Hunter survived her husband twenty-seven years, dying 
January 7, 1821, aged seventy-nine. According to Ottley, " she 
was an agreeable, clever, and handsome woman, a little of the 
bas bleu, and rather fond of gay society, a taste which occasion- 
ally interfered with her husband's more philosophical pursuits." 
She wrote the Shepherd's Song, " My Mother Bids Me Bind My 
Hair," immortalized by the setting which Haydn gave it; she 
also wrote the words for Haydn's " Creation." In her latter 
years she published a small volume of poems, which possess con- 
siderable merit as a light effort. She was universally beloved 
and esteemed, retaining her wit and beauty to the end of her 
da'ys. The Hunterian orator of 1821 paid to her memory this 
heavy compliment — that "she had sustained an honourable 
widowhood, estimable for talents of her own, and venerable as 
the relict of her illustrious husband." 



January, 1914.] 



JOHNS IIOl'KINs HOSPITAL BULLETIN. 



Even Jesse Pool was moved to eulogistic expression when 
he wrote the following (" Life of John Hunter," p. . 

On being told of this event, on the same day, I recollected 
seeing the bay stallions returning, through Piccadilly, hom\ 
without their master; and this circumstance introduced to my 
reflection the sympathy which Virgil has attributed to the war- 
horse of young Pallas in his funeral procession 

Post brllator Equus. positis insignibus i:thon 
It lti< hrumans. 

Hunter's death occurred on Wednesday, October 16, 

in the sixty-fifth year of his age. On the following T 
(October 22) his body was interred" in one of the public 
vaults of the church of St. Martin's-in-the-Fields, the ol 
being attended only by the family and a few intimate medical 
friend-. 

rformed by Everard Home and Dr. Mat- 
thew Baillie, amply confirmed the diagnosis of his friend 
and pupil, Pr. .Tenner. It revealed the existent 
Hon of the mitral valves of the heart and dilatation 
aorta, with thickening of its valves and degeneration of its 
The coronary arteries were converted into lorn:, rigid 
The heart itself was uncommonly small.'' 
That Hunter wished an autopsy to be performed upon him. 

the subjoined foot-nol i p. 132, of Ottley's " Life," would 

indicate : 

It has been supposed by some that Hunter had the same antip- 
athy to the scalpel of the anatomist as was felt by his brother; 
but this was by no means the case; on the contrary, he always 
spoke of it as a matter of course, and used, in the strongest lan- 
guage, to express his condemnation of those who should 
to examine his body and preserve his heart. It is to be regretted 
that no relic of this sort has been preserved." 



death. ( Ittley, on the following 



mmenting upon Hunter*: 
adds : 

Thus, in his sixty-fifth year, died John Hunter, celebrated alike 
as a surgeon and as a naturalist: in neither of which capacities 
has he hail many equals, — in his combined character, none. 



"The burial took place at quarter past four in the afternoon, 
as the following entry in the sexton's old register-book at St 
Martin's Church would indicate. The statement, however, that 
Hunter died of apoplexy, is inaccurate. 

Oct. 22. John Hunter, Esq., Leicester Square. No, 3 
vault. 61. 10j. Od— no candles, ' , past 4. Apoplexy." 

"For a detailed account of the post mortem appearai: 
thoughtful reader Is invited to turn to pp. lxii. to Ixv. of the 
Life by Home, prefixed to the " Treatise on Inflammation ": or to 
an artirie entitled "Angina Pectoris and AH 

Qairdner, II D.. in vol. IV, of Reynolds' "Sj 
icine," p. 5<'.0 < / t< </. 

"I am inelined to believe that the aneurlsmal dilatation of 
Hunter's aorta, and the other pathological conditions note 
which caused his death, were largely due to an attack of 
which he had had in early manhood as the result of his li 
ing himself on the glans and prepuce, in May, lT'.T. with 
from what was probably a concealed urethral chancre, m 
it for gonorrhceal discharge. Then, too, he was subji 
other perturbing influences productive of arteriosclerosis — worry, 
overwork, financial embarrassment, loss of sleep, and ■ 
temper. 



ith by 
ther-in-law, Everard Home, J< -- I 

Dr. Joseph Ada- , r 

Hunter's " Treatise on [nflammatioi . mirted in the 

labors, and privati , 

ish Burgeon, " the . j n the 

world." as manj talked oi him 
and eventful ear. 
In the t 

: tunter," an oi tavo \rolui 
was not well received I 

aemies paid Foot four hundrt 
writing it. The work is 

as a scientific man. and abounds, s 

flagrant mist ind wilful n "If 

the author had sel out," be continues, " with a 

to gain an ignominious immortality, 

I It spite the numerous - which havi 

upon Jesse I' b*s book, I find 1 in it. 

Hi- desci iption of 11 unto r"s ibits of h rk, 

hand from »lm knew him personal!). 

which we have (p. 285) : 

I believe John Hunter to have 
of men. The waj in which his tin. 
obtained the public appo 
very early in the morning, and 

room, — w hi i 
concerning, what he won! 
After breakfa 
house. At elevi a hi 
patients. — attending at the ho 
called for it. in opening 
dinner,- -and rarely drank more, than 
times not that. In 

. and writing down ol : mndo 

through the day. or preparing, for thi 
I om retired to rc.-t till twi 

In 1817 a men' 
of the 

" 

portra I 



■ Hi 

1 
furnish 



20 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 275 



In 1833, Parkinson's " Hunterian Reminiscences " were 
published.* 

In 1837 appeared the excellent memoir by Drewry Ottley, 
prepared for Palmer's edition of Hunter's complete works. 
This is by far the most able, full and impartial memoir that 
we have of him. The portrait of Hunter is identical with 
that in the second (1818) edition of Adams' "Memoirs." 

A good memoir of Hunter is to be found in Vol. XXII. 
of the Naturalist's Library, edited by Sir William Jardine 
and published in 1854. In 1SS1, there was published a small 
octavo volume by Professor Samuel D. Gross, of Philadelphia, 
entitled "John Hunter and His Pupils." In his opening 
paragraph he says : 

All intelligent readers of biography are more or less familiar 
with the labors and writings of John Hunter, his marvellous 
genius, and his vast contributions to science. In the medical 
profession his name is, and always will be, a household word 
throughout the civilized world; it is spoken with respect and 
reverence in every college amphitheatre, and is deeply engraved 
upon the mind of every student of surgery. Nevertheless there 
are, it may safely be asserted, many points of interest in his life, 
and many traits of character, which have escaped our memory, 
or which have never been so thoroughly impressed upon our 
attention as to enable us to appreciate them at their full value. 



28 The following is a copy of the title-page of this comely vol- 
ume, now excessively rare and extremely difficult to obtain: 

HUNTERIAN REMINISCENCES; 

Being the Substance of a 

COURSE OF LECTURES 

on the 

PRINCIPLES AND PRACTICE OF SURGERY, 

Delivered by the Late 

MR. JOHN HUNTER, 

IN THE YEAR 1785: 

TAKEN IN SHORT-HAND, AND AFTERWARDS FAIRLY 

TRANSCRIBED, BY 

THE LATE MR. JAMES PARKINSON. 

Author of "Organic Remains of a Former World," &c. 



Edited By His Son, 

J. W. K. PARKINSON, 

Fellow of the Royal College of Surgeons, In London, 

By whom are appended 

ILLUSTRATIVE NOTES. 



LONDON: 
SHERWOOD, GILBERT, AND PIPER, PATERNOSTER ROW. 



The dedication is interesting, and calfs to mind many historical 
associations. It reads, as follows: 

TO 

MR. WILLIAM CLIFT. 

Formerly the Zealous and Diligent Assistant of the Late 

MR. JOHN HUNTER, 

Now the Able Conservator and Intelligent Illustrator 

of the 

HUNTERIAN MUSEUM, 

THIS WORK IS INSCRIBED, 

by 

THE EDITOR. 



In 1893, George Mather, a celebrated British physician, 
wrote an engaging volume entitled " Two Great Scotsmen — 
William and John Hunter," in which is contained a most 
fascinating record of John Hunter's life and labors. In the 
"Masters of Medicine" series, there is an admirable little 
book entitled "John Hunter, Man of Science and Surgeon," 
1897, by Stephen Paget. Notices, more or less elaborate, of 
Hunter have also appeared in the various orations which have 
been delivered, since 1814, in commemoration of him by the 
president and fellows of the Royal College of Surgeons of 
England. The brief eulogy by the president, Sir William Mac 
Connac, at the centenary festival of the Royal College of 
Surgeons held in London on Thursday, July 26, 1900, is the 
most beautiful tribute to Hunter that I know. He says: 

Of John Hunter (172S-1793) no detailed mention is required 
here. His memory and his methods continue a living influence 
amongst us. He made our Surgery a science, and has given to us 
in our Museum an imperishable memorial of his industry. In it 
are illustrated those marvellous powers of observation which had 
never before been equalled, and will never in all probability be 
surpassed. So long as Surgery continues, Hunter's influence must 
be felt. It is witnessed in the creation of so many distinguished 
disciples imbued with his principles and able to expound his 
doctrines. He embodies and represents the glory of our Science, 
our College, and our Country. 

Memorials to Hunter. 

The casual observer will find much to remind him that 
John Hunter lived among men. Of the various portraits that 
are extant of him, that by Sir Joshua Reynolds, painted in 
1787, is by far the best. It represents him as sitting in a 
chair in deep thought, with a pen in one hand and the other 
supporting his chin. Three of the folio volumes of MSS., 
burned thirty-six years later by Sir Everard Home, are placed 
at his side. Other things around him, in addition to the 
manuscripts, are the jars containing preparations, and the 
dangling feet of the Irish giant's skeleton, the latter said to 
have cost Hunter the extravagant sum of £500. From this 
portrait by Reynolds an admirable engraving was made by 
Sharp. 

As a frontispiece to Hunter's " Essays and Observations " 
there is a good likeness of him, after a medallion taken in 
1791. Another favorite likeness is a pencil drawing taken 
by Sir Nathaniel Holland in 1793, the year of Hunter's death. 
After Hunter's death a bust of him was made by Flaxman, 
in the execution of which he was assisted by a cast taken dur- 
ing life. 

The Hunterian museum, purchased by the British Gov- 
ernment and placed in custody of the Royal College of 
Surgeons of England, is another mighty reminder of Hunter 
and his indefatigable industry. Hunter's executors, Sir Ever- 
ard Home and Dr. Matthew Baillie, on June 13, 1799, sold 
the museum to the Government for £15,000. It cost £70,000. 
The trustees held it for six years, but Mrs. Hunter's financial 
needs were pressing, and for this reason they urged the sale. 
The original (-11- tion w&s estimated by Prof. Charles Stew- 
art and Timothy Holmes to consist of 13.GS2 specimens, the 



January, 193 L] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






number ever gotten together by one man, distributed 

ondi r the following heads: 

I. PiiysiouhUial Hituumi \i. OB Nokmal STBUI i 

1. Physiological preparations in spirit 3,745 

2. Osteological preparations 

::. I >ry preparations, 617 

4. Zoological preparations ^.,968 

5. Fossils: — 

a. Vertebrate 1,215 

b. Invertebrate 2,202 

c. Plants 292 

II. Pathological Dkpabtmeht, oh Abnormal Struct tees. 

1. Preparations in spirit 1.0S4 

2. Dry preparations (including bones) 625 

3. Calculi and concretions 536 

4. Monsters and malformations 218 

III. Microscopic preparations 215 

Catalogues of the Hunterian Museum, comprising ten 
quarto volum pared many years a:_ r o (1833-1856) 

by Professor Richard Owen and Mr., later Sir James, Page 

the latter having charge of the pathological specimens. The 
first curator, or. as he is styled in England, conservator, of 
the museum was William Clift, Ilunter's last assistant. 
In the year 1813 Dr. Matthew Baillie and Sir Everard 
executors of John Hunter, " being desirous of show- 
ing a lasting murk <>( respect to the memory of the late Mr. 
John Hunter," gave to the Royal College of Surgeons of Eng- 
land the sum of £1084 As. id., for the endowment of an 
annual oration, to be called the Hunterian oration, and to be 
delivered in the theatre of the college on Hunter's birthday. 
The first Hunterian oration was delivered on February 14, 
- r Everard Home being the orator. In 1853 it was 
I that the oration should in future l«' ■!■ 
nially instead of annually. The next IIui tion will 

be delivered by S Q ee," president of the Col- 



*The following reference thereto appeared on p. 146, of T. P.'s 
Weekly, of date January 31, 1913. 

" The Hunterian Festival, which is held biennially, takes place 
on February 14 at the Royal College of Surgeons. The oration 
will be delivered by the president. Sir Rickman J. Godlee, in the 
afternoon, and the customary banquet will be held in the library 
of the college in the evening." 

"At the same time I received the subjoined letter: 

Royal College of Surgeons of England, 
Lincoln's Inn Fields, 
London, W. C. 
2d day of December, 1912. 

Dear Sir: — I am desired by the president. Sir Rickman Godlee, 
to send you the enclosed particulars with reference to tl 
terian oration. 

Each oration Is called simply the Hunterian oration, and no 
other title Is ever adopted. 

I>r. Frank Buckland presented to the college a photograph of 
John Hunter's coffin, taken when it was removed from St. Mar- 
tlns-in-the-Fields, and this is in the library ol I 
There are, however, no duplicates, nor have we any phot. 



lege, on Frids him I 

am indebted for 

1814. Sir Everard Home, 

1815. Sir William Blizard, Knt 

1S16. Henry Clitic. „ ul ij. 

1817. William Norris. 

1818. Sir David Dn L861. Willi. i 

1819. John Abernethy. 

1820. Sir Anthony Carlisle, Knt 

1821. Thomas Chevalier. 1867. John Hilton 

1822. Sir Everard H ml Qualn. 

1823. Sir William Blizard, Km. 1871. Sir William Fcrgusson, 

i line. 
1825. William Norris. Henx] Hani 

Sir Anthony Carlisle, Knt is::.. Fre.ien^k U 

lM'T. Honoratus Leigh Thomas. 1S77. Sir .1 

1828. Sir William Blizard. Knt. 1879. tieorpe Mun 

1829. John Painter Vincent 1881. Lnther Holden. 

1830. George James Guthrie. 1SS3. Sir Thomas Spencer 

1831. Anthony White. Wells, 

1832. Samuel Cooper. 1885. John Marshall. 

1833. John Howsliip. lsvT. William Seovell Savory. 

1834. William Lawi 1889. Henrj P 

1837. Sir Benjamin Collins 1891. Jonathan Hutchinson. 

Brodie. Hart. ant. 

1838. Benjamin Tim John Whitakcr Hulke. 

1839. Edward Stanley. 1897. Christopher Heath. 

1840. Joseph Henry Green. Sir William MacCormac. 

1841. Thomas Callaway. Bart. 
George Gishorne Bablng- 1901. Nottld 

ton. namara. 

limes Moncrieff Arnott. 1903. Sir lleni 
Ml John Flint South. Knt 

1846. William La* \ 1905. John T 

1847. Joseph Henry I 'ham Ilutlln. 

\ Morris. 

1849 Cassar Henry Hawkins. 1911. Edmund Ov 

1850. Fi I'M.:. Sir R 

1852. James Luke. 

In 185! n Hunter n ! from 

St. Martin's-in-tlc 
bey, largely thn 
nent naturalist." I "it. he 



of the tomb in Westminsti 
to send you I 

The pi 
lets which >• '' to him. 

faithfully, 

Dr. C. W. r, Rom "> r V- 

"Th. 
1859, ot of John Hui 

in-the-F 
in Mr I 
of his "Curiosities of Natural 

" In the month of J 

Of the 

sheet of I 

"'ST. MARTIN 
CATACO 

any ot I 
under tl 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 275 



searched the vaults of St. Martin's, before finding Hunter's 
coffin. It was well preserved, bearing upon it, besides the 
brass name plate, Hunter's arms — a hand with an arrow in 
it, and the three horns of the hunter. The happy culmination 
of this extraordinary labor of Mr. Buckland, this " chivalrous 
devotion to the relics of a great man," can best be described 
in his own words. 32 

After a time all the coffins were removed away from the vault 
but five; two lay side by side upon the floor, and three one over 
the other in a corner of the vault; and I could see the names on 
all these coffins except two: my chance was now therefore limited 
to these two coffins. 

The total number of coffins in No. 3 vault was over two hun- 
dred. The total number of coffins removed was three thousand 
two hundred and sixty. This will give some idea of the task that 
I had undertaken and had now nearly finished. If one of these 
coffins therefore was not John Hunter's, all our labours would 
have been in vain. The workmen stood at the head and foot of 
the uppermost coffin of the three, and slowly moved it away that 
I might see the name upon that immediately below it. As it 
moved slowly off, I discerned first the letter J, then the O, and at 
last the whole word John. My anxiety was now at its height, and 
quickly running to one end, Mr. Burstall at the other, we moved 
the coffin away. At last I got it completely off, and to my intense 
delight read upon the brass plate the following inscription; — 
JOHN HUNTER, 
Esq., 
DIED 16TH OCTR., 
1793, 
Aged 64 Years. 

The Hunters' arms, viz., a hand with an arrow on it, also the 
three horns of the hunter, were upon the plate. 

Lest there should be any subsequent doubt upon the identity of 
this coffin, a photograph was taken of it by Mr. Soame, which I 
have presented to the Royal College of Surgeons. 

On March 28, re-interment was made in Westminster Abbey 
with impressive ceremonies. 33 On the following day, March 



remove the same before the 1st day of February 1859; after which 
date, all coffins remaining in the said vaults or catacombs will be 
reinterred in the same place, and finally built and closed up in 
accordance with the said Order in Council, and cannot afterwards 
be inspected on any pretence whatever. 
" ' BENJAMIN LATCHFORD, ~> Churchwardens of the said 

CHARLES H. PETTER, j Parish. 

" ' All communications to be made in writing, addressed to us at 
the Vestry House. Adelaide Place, W. C 

" Why, surely John Hunter is buried in this church, was the 
thought that immediately struck my mind: his remains ought cer- 
tainly to be looked after; but who is to do it? I will try to rescue 
his remains. If I fail there will be no harm done." 

33 " Curiosities of Natural History," Fourth Series, pp. 225 and 
226. 

M I take pleasure in giving the following brief account of the 
funeral rites at the re-interment of the remains of Hunter, 
because such information is not readily accessible to the reader: 

Very great interest had been excited among the profession 
when the intention of the Council of the College to undertake 
the pious duty of the removal to the Abbey had been made public, 
and a very numerous assemblage collected there early in the 
afternoon of the 2Sth of March; and it having been intimated that 
the choral service would be suited to the solemnity, which would 
take place immediately afterwards, the choir was crowded with 



29, 1859, an address was delivered by Joseph Henry Green, 
president of the Eoyal College of Surgeons of England, urg- 

medical men, of whom many had come from the country to testify 
their respect for John Hunter's memory. 

The Musical Service consisted of — 

Single Chant to Psalms Turle. 

"Magnificat" and "Nunc dimittis " Farrant. 

ANTHEM. 
" When the ear heard him." 1 Handel 

" His body is buried in peace." J 

Soon after four o'clock the procession, headed by the vergers, 
passed from the Jerusalem Chamber into the Abbey, arranged in 
the following order: — 

The Dean of Westminster. W. Hunter Baillie, Esq. 

Frank T. Buckland, Esq. Richard Owen, Esq. 

The President of the Royal Col- Earl of Ducie. 

lege of Physicians. 

The President of the Royal College of Surgeons of England. 

The Vice-Presidents and 

The Council of the Royal College of Surgeons. 

The Censors of the Royal College of Physicians. 

The Master of the Society of Apothecaries of London. 

The Director-General of the The President of the Linnaean 

Navy Medical Department. Society. 

And other Members of the Medical Profession. 

The procession having reached Abbot Islip's Chapel, and the 
coffin, uncovered and placed on a bier, having been raised on 
shoulders, proceeded round St. Edward's Chapel into the nave, 
the Dead March in " Samson " being played by Mr. Turle, and 
continued till the grave was reached, in which the 

REMAINS OF JOHN HUNTER 

were lowered whilst the pealing organ poured forth Handel's grand 
and sublime chorus, well suited to this memorable occasion — 

HIS BODY IS BURIED IN PEACE, BUT HIS NAME LIVETH 
EVERMORE.* 

*A very handsome ornamental brass tablet now covers the tomb, 
upon which is the following inscription, written by John Flint 
South, the well-known author of Memorials of the Craft of 
Surgery: — 

" Lord, how manifold are Thy Works." 

Beneath 

are deposited the remains of 

JOHN HUNTER. 

Born at Long Calderwood, Lanarkshire, N. B., 

on the 13th of February, 1728. 

Died in London on the 16th of October, 1793. 

His Remains were removed from the Church 

of St. Martin's-in-the-Fields to this Abbey 

on the 2Sth of March, 1859. 



The Royal College of Surgeons of England have placed this 
Tablet over the grave of Hunter, to record their admiration of 
his genius, as a gifted interpreter of Divine Power and Wisdom 
at work in the Laws of Organic Life, and their grateful venera- 
tion for his services to mankind as the founder of Scientific Sur- 
gery. 



" In wisdom hast Thou made them all." — Ps.civ. 24. 



Janiary. 1014.] 



JOHNS HOPKINS HosiMTAL BULLETIN. 



in<r the erection of a statue to Hunter. Mainly through the 
efforts of John Flint South, one of the vice-presidents of the 
college, the sum of '-'l 178 17s. Id. was promptly raised for that 
object The work was intrusted to Mr. Weekes, the eminent 
Bculptor, who produced an admirable likeness which was com- 
pleted in 1SG4, and now graces the tirst room on the lower 
floor of the museum of the college. 

On -May •„".'. isst;, a statue of John Hunter was unveiled in 
the University museum, at Oxford, England, on which oc- 
. a-ion Sir James Paget was one of the speakers. A bust of 
Hunter, along with that of Newton, of Hogarth, and of Rey- 
nolds, occupies one of the four corners of Leicester Square, 
London; and there is a window to his memory in the church 
of St. .Mary Abbott's, Kensington. 

Another constant reminder of John Hunter and his on- 
wearied labors is the Hunterian laboratory connected with the 
medical school of this university — the leading institution of 
its kind on the Western Hemisphere. Founded in 1906, it 
stands to-day a pioneer in the diffusion of such knowledge as 
Hunter endeavored to convey. Truly, " its line has gone out 
to the ends of the earth;" and it not only reflects lasting 
credit upon those who nurtured it and gave it birth, but also 
bears with dignity an appellation which can justly be applied 
to it: namely, "the greatest of all memorials to John Hun- 
ter." 

Simmaky of Life W'okk." 

John Hunter not only laid the foundations of scientific 
surgery, but his name is also indelibly associated with the rise 
and progress of histology, physiology, and comparativi 
omv. 

In the language of Professor Gross: 

He was not only a great surgeon, a wise physician, and a great 
anatomist and physiologist, human and comparative, but, above 
all, he was a philosopher whose mental grasp embraced the whole 
range ot nature's works, from the humble structure to the most 
complex and the most lofty. He was emphatically the Newton 
of the medical profession, and what Pope said of that great phil- 
osopher may, by paraphrase, be said with equal force and truth 
of Hunter: 

"Nature and Nature's laws lay hid in night; 
God said ' Let Hunter be,' and all was light." 

Hunter is peerless In the history of British surgery; and after 
the lapse of nearly a century the profession turns to his memory 
with Increased reverence for his transcendent genius, his match- 
less ability, and his unequalled services. To say thai ' 
simply the founder of scientific surgery would fall far short 
great deserts: to do him full Justice we must add thai 
the father also of scientific zoology and of comparativi- phj 



' Briti>li Burgeon, anatomist anil physiologist. First to dis- 
cover the system of vessels known as lymphatics, although the 
function of these vessels was suggested by his brother. William 
Hunter. His studies of tendons laid the foundation for tl 
tion for the cure of club feet. His experiments to di 
blood-supply for the growing antler of a deer led to thi 
of the "collateral circulation of the blood" — one of the most 
important discoveries In surgery. This led directly to his 
tion of the " Hunterian " operation for aneurism, an opera! 
in use. and which has made the name of Hunter immortal in the 
annals of surgery (Henry Smith Willi 



It i- nit i, sting to record that Ja . Jr., M. 1>.. 

of pious memory, in a letfc thi r, is loud in his 

of Hunter and his work, 

London, Septeml 

Would you w.tc her.-, my dear Cat] with DM the 

study of John Hunter's works, and to kindle with me in my 
admiration of his genius; the ■ of which I 




an HtpoBitra the Rrmama cf 

SortPBJTm^fjt. 

Bcrnet i.oimattrroniH.LnMtalnniiH 
oattt i.t°of PfoiaaTj). ir?* 

Mrtmlionluic 

lets Rnnainanm Trne: ; . 

of s'QartmU mitiiPif iHstt I" 
nttii I'^ti Qani 

i.'itnlnl 
ttaorplscra this oiblri turn ttu p i 
rmntrr.lc moritttiF aimir-- 

suLm. 

SJfik 



tiirmxit 



M 




m 
1 

r 
i 



. 






24 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 275 



For more than forty years Hunter toiled as never man 
toiled; and yet, so it is stated, his doctrines were not well 
received by his contemporaries. Some were incited by prej- 
udice, some by envy and jealousy, whilst still others were im- 
pelled by a spirit of indifference. Is it any wonder, then, that 
he should have become discouraged at times ? " The few good 
things I have been able to do," he was heard to say, "have 
been accomplished with the greatest difficulty, and encoun- 
tered the greatest opposition." 

His labors increased with his years and with his honors; 
and when the end came, sudden though it was, it found him 
assiduously engaged in those pursuits which had been the joy 
and the delight of his life. He pursued studies in every de- 
partment of natural history and surgery, and added luster to 
them all. His " mind was like a bee-hive " — full of industry, 
method, and the laying-up of stores for future use; and what- 
ever he touched he adorned. Hunter had a high opinion of 
putting one's thoughts into writing. " It resembles," he said, 
" a tradesman taking stock, without which he never knows 
what he possesses or in what he is deficient." The infinite 
variety and wide range of his mental qualifications, is shown 
in a chronological list of his works and papers, to be found 
in Ottley's "Life of Hunter" (pp. 189-192). 

So far as a bank account was concerned, John Hunter died 
a poor man ; yet who is there among you who would call him 
poor ? His name comes down to us as one of the great figures 
of the eighteenth century — a century famous for a wonder- 
fully rich harvest of discovery in anatomy and physiology, in 
medicine and surgery. The mystery, however, is solved when 
we remember' that he rose regularly at four o'clock in the 
morning, and seldom retired before twelve o'clock at night. 
The compliment which Cecil paid to Sir Walter Ealeigh was 
equally deserved by Hunter : " I know he can labor terribly." 
His mind was incessantly in his work. 31 



30 The following is a summary with the ages and the dates, of 
the chief events of his life (after Professor Owen, "The Scientific 
Works of John Hunter," vol. ii, pp. 492, 493. Sir James Paget, 
in the Hunterian oration for 1877, pp. 37 and 38, also gives a 
fine calendar of the chief events of Hunter's life) : 



Event. 

Birth, 13th or 14th of February, at Long Calderwood, 
Kilbride, near Glasgow. 

Migration to London to his brother, Dr. Wm. Hunter. 

Entered as " Gentleman Commoner " at St. Mary's, 
Oxford. 

House-surgeon at St. George's Hospital, London. 

Prosector and Demonstrator in Dr. Wm. Hunter's 
Theatre of Anatomy, in Great Windmill Street. 

As Surgeon in the Army, accompanied the Expedition 
to Belleisle. 

Returned from Portugal to London. 

Communicated his first Paper, printed in the Trans- 
actions of the Royal Society, entitled " Anatomical 
Description of an Amphibious Bipes." 

Elected Fellow of the Royal Society of London. 

Became " Member of the Corporation of Surgeons." 



4ge 


Year 




1728 


20 


174S 


25 


1753 


28 


1756 


29 


1757 


33 


1761 


35 


1763 


38 


1766 


39 


1767 


40 


1768 



Surgery of to-day is immensely indebted to Hunter." His 
constant saying was : " We are but beginning to learn our 
profession." Dead though he has been for an hundred and 
twenty years, yet the principles which he taught and the foun- 
dations which he laid have become the woof and warp of the 
surgical fabric of the present day. The ever-widening circle 
of his influence still abides. 

To quote again from Professor Gross: 

The lesson of the life of such a man, in every respect so grand 
and colossal, so powerful and majestic in intellect, and so indis- 
solubly associated with the scientific history of his age and coun- 
try, is full of instruction, not only to the members of our own 
profession, but to men in every avenue and pursuit in life. His 
example of industry and of steady, persistent effort in the cause 
of human progress reflects the highest credit upon his character, 
and is worthy of the imitation of every student ambitious of 
distinction and usefulness. Nowhere, either in ancient or modern 
times, can there be found a nobler pattern for the formation of a 
truly scientific career. Commencing life as an erratic, hesitating 
youth, undecided what to do, or whither to turn, without any 
promise or definite aim, a source of constant annoyance to his 



Age. Year. Event. 

41 1769 Elected Surgeon to St. George's Hospital: had his first 

attack of the gout. 

42 1770 Jenner became Hunter's House-pupil. 

43 1771 Married Miss Home. Published his " Treatise on the 

Natural History and Diseases of the Human Teeth." 

44 1772 Communicated his Paper " On the Torpedo " to the 

Royal Society. Mr. (afterwards Sir Everard) Home, 
his wife's brother, became his pupil. 

45 1773 His first attack of " Angina pectoris." 

46 1774 Gave his first Course of Lectures " On the Principles 

of Surgery." 
48 1776 Appointed Surgeon Extraordinary to His Majesty. Mr. 

Wm. Bell became Hunter's assistant. 
55 1783 Purchased the lease of the house No. 29 Leicester 

Square, and the ground extending to and including 

a house in Castle Street, and began to build his 

Museum on the intervening space. 

57 1785 Museum completed, and arrangement of the Prepara- 

tions begun. 

58 1786 Published his " Observations on the Animal Economy," 

and his work "On the Venereal Disease." Made 
Dep. Surgeon-General to the Army. 

59 1787 Preparations arranged in the Museum, which was 

opened to Visitors. 
61 1789 Mr. Wm. Bell left Hunter for an appointment in 
Sumatra, where he died in 1792. 

64 1792 The printing of the work " On the Blood and Inflam- 

mation," was commenced. Mr. Wm. Clift was arti- 
cled as an " apprentice " to John Hunter. 

65 1793 Died suddenly, October 16th, at St. George's Hospital: 

was buried in St. Martin's Church. 
1859 Was re-interred, March 28th, in Westminster Abbey. 

37 In " Leisure Hour," No. 385, May 12, 1865, Frank Buckland 
wrote: 

Without slighting the labours of other great surgeons and 
anatomists, it may be confidently affirmed that there is not a man, 
woman, or child among us who, when struck by the sting of 
disease, and receiving relief from the art of medicine, does not 
directly or indirectly receive relief to his suffering from the 
discoveries of John Hunter. 



THE JOHNS HOPKINS HOSPITAL BULLETIN. JANUARY, 1914. 




.Iiiiin Hunter. Engraving m Reynolds' Portrait. 





LONCCALDERWOOD- 

LO.NO I ILDBRWOOD, II" BfRTRPLACI "I 1 1 1 "■ I B 






THE JOHNS HOPKINS HOSPITAL BULLETIN. JANUARY, 191- 




.Ii.m \ llr\ i h:. Al i if; .Iosi, S( n PTOR. 




Johh Hunter. Afteb \ Mkdallio> I iki % i n 1701. 





Johs Hunteb. I'imh Drawing by Holland. 



I. ,1|- I! 



Jamary. 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






family and of disappointment to his friends, he became eventually 
one of the most illustrious men In all Europe, leaving behind him 
imperishable monuments of patient research, of vast genius, and 
of wonderful philosophical acumen, destined to grow brighter and 
more stately as the ages roll on, and as men become more and 
more appreciative of man's work and of man's intellectual powers. 

Hunter, to use Dante's phras I his star; and in 

finding the good that he wished for humanity, found, along 
with it. name and fame. 

His death though precipitate, and in a measure une\; 
was doubtless as he would have wished it to be. He was 
thereby mercifully delivered from those " cold gradations of 
— that time in life when old age creeps on apace, and 
the hands tremble and the eyes grow dim. 

Thus ended a career of almost unexampled industry and 

usefulness; a life abounding in zeal and good deeds, which 

made the world wiser and better. So we shall leave him — 

beloved during life, honored at death, secure in his fame; senti- 

most beautifully expressed in the following 



' In 1804, eleven years after Hunter's death. 



ten by Mrs. II into r, ' and n final! 
tion upon her husband's s 

Here rests in awful silence, cold and still, 

One whom no common sparks of genius lit 
Whose reach of thought ' l fill. 

Whose deep research thi tore of Trnt] 
Hunter! If years of toll and watchful 

If the vast labours of a powerful mind 
To soothe the ills humanity a 

Deserve the grateful plaudits of mankind, — 
Then be each human weakness buried ! 

Knvy would raise to dim a name so bright: 
Those specks which in the orb of day n; ■ 

Take nothing from his warm and welcome light 

Acknowledj ereby gratefully ma 

of this Henry Bart for much valuable 

■ire and kindly encoura) beerfully gi 

its secretary. Dr. Thomas B. Futcher; bo I 1 
pie, of the Hunteriiin laboratory; I 

I - nd; and 

last, but by no means least, to my photographer, Mr. Harry 
I'.. Weaver, of this city, who has been untiring in In- 
to prepare a series of accurate an.! 



NOTES AM) NEWS. 



Dr. A. D. Atkinson is Physician in Chief to St. Agnes Hospital, 
Baltimore. 

Dr. John Auer is Associate Member, Department of Physiology 
and Pharmacology, Rockefeller Institute, New York City. 

Dr. J. R. B. Branch is Attending Gynecologist to the Macon Hos- 
pital, and Anaesthetist to the Williams Private Sanitarium, Macon, 
Qa. 

Dr. Walter V. Brem is Professor of Pathology and Bad. 
in the Los Angeles Department of the College of Medicine of the 
University of California. 

Dr. J. S. Brotherhood is Associate Physician, the Sanitarium, 
Clifton Springs, N. Y. 

Iir. .1. I. Butler is President and Manager of the Rodgers Hos- 
pital, Tucson, Arizona. 

Dr. John W. Churchman is Assistant Professor of Surgery, Yale 
Medical School, and Assisting Yisiting Surgeon, New Haven Hos- 
pital. 

Dr. A. L. Fisher is Assistant in Orthopedic Surgery, Stanford 
University, San Francisco, Cal. 

Dr. Emil Goetsch is Assistant in Surgery. Harvard Medical 
School, and Resident Surgeon, Peter Bent Brigham I 
ton, Mass. 

Dr. Kr Went Surgeon, I 

Brigham Hospital, Boston, Mass. 

Dr. F. Webb Griffith is Surgeon to the Mission, Uiltmore and 
Meriwether Hospitals. Asbevllle, v C. 

Dr. Louis P. Hamburger, in addition to his appoint! at in the 
Johns Hopkins Hospital Dispensary, Is Attending P 
the 1'nion Protestant Infirmary, Hebrew Hospital. H( pita] for 
Women of Maryland. Church Home and Infirmary and Children's 
Hospital School. 

IT. c W. Hennlngton is Surgeon to the Rochester SI ■■ 
pital, and Surgeon to Outpatient Department of the lo 
General Hospital. 



Dr. Arthur I). Hirschfelder is Professor of Than 
Director of the Department of Pharmacology, University of Mln 
nesota Medical School. 

Dr. J. Gardner Hopkins is Associate In Bacteriology, Columbia 
University. Address: 350 Washington Avenue. Brooklyn, N V 

Dr. Henry T. Hutchim is Assistant In i H irvsrd 

Medical School, surgeon to the Outpatient Department, 'i 
Hospital for Women. Brookline, 
Rufus s. Frost General HospH i alting 

Gynecologist to the Memorial Hospital, PawtUCket, K I. V 
;:?! Marlborough SC 

Dr Han- i. ton Uni- 

versity Medical School, and Resident Patholoi 
University Hospital, si I 

I>r. David R, I.yrnan Is Clinic;,! Lecturer on Till 

Yale Medical School. 

Dr. F. W. Lynch 

1st and 

Obstetrician, I ■'"• m 

Iir I 

■ 
of Pent 
ternity 
Phipps Instil 

]>r. I'r 

Brlghan 
Dr. 1 

stltllte ■ 

Hr II W PI 

Surg, r . 



26 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 275 



Dr. R. E. Powell is Demonstrator in Anatomy at McGill Uni- 
versity, and Clinical Assistant in Surgery and Genito-Urinary Sur- 
gery, the Montreal General Hospital, Canada. 

Dr. J. C. Pratt is Assistant in Surgery, the University of Cali- 
fornia. Address: 291 Geary Street, San Francisco, Calif. 

Dr. Alexander Randall is Assistant Instructor in Surgery, Uni- 
versity of Pennsylvania, and Assistant Surgeon in the Genito- 
urinary Dispensary, University of Pennsylvania. 

Dr. S. W. Schaefer is Resident Physician, the Glockour Sani- 
tarium and Hospital, Colorado Springs, Colo. 

Dr. Benjamin R. Schenck is Associate Professor of Gynecology, 
Detroit College of Medicine, Gynecologist to the Harper Hospital, 
and Consulting Obstetrician to The Woman's Hospital, Detroit, 
Mich. 

Dr. W. G. Sexton is Medical Superintendent of the Hebrew Hos- 
pital, Baltimore, Md. 

Dr. William Sharpe is Adjunct Professor of Surgery, the New 
York Polyclinic Hospital; Assistant Surgeon, the New York Neu- 
rological Institute, and Attending Neurologist, Hospital for Rup- 
tured and Crippled. Address: 20 West 50th Street, New York City. 

Dr. F. J. Sladen is Director, the Department of Medicine, Detroit 
General Hospital, Detroit, Mich. 

Dr. J. M. Slemons is Professor of Obstetrics and Gynecology, the 
University of California, and Director of the Woman's Clinic, the 
University of California Hospital. Address: 3404 Clay Street, San 
Francisco, Calif. 

Dr. Joseph T. Smith, Jr., is Instructor in Gynecology, Western 
Reserve University Medical Department; Assistant Surgeon, Dis- 
pensary of Lakeside Hospital, and Western Reserve University 
Gynecological Department. 

Dr. A. de T. Valk is Visiting Physician to the Twin City Hos- 
pital, Winston-Salem, N. C, and Lecturer in Anatomy and Physi- 
ology to the nurses of that institution. 



Dr. A. Raymond Stevens is Instructor in Genito-Urinary Sur- 
gery, New York University; Assistant Attending Genito-Urinary 
Surgeon to Bellevue Hospital, and Chief of the Genito-Urinary 
Clinic, Presbyterian Hospital Dispensary. Address: 40 E. 41st 
Street, New York City. 

Dr. Solomon Strouse is Associate Attending Physician, the 
Michael Reese Hospital; Directing Physician, Chieago-Winfield 
Tuberculosis Sanitarium; Attending Dispensary Physician, Mu- 
nicipal Tuberculosis Sanitarium, and Instructor in Medicine, the 
University of Illinois. Address: 104 S. Michigan Ave., Chicago, 
111. 

Dr. J. H. J. Upham is Professor of Medicine and Clinical Medi- 
cine in Sterling, Ohio, Medical College; Attending Physician to St. 
Francis Hospital, Consulting Physician to Mt. Carmel Hospital, 
and President of the Ohio State Medical Association. Address: 
Columbus, O. 

Dr. Douglas Vanderhoof is Associate Professor of Clinical Medi- 
cine, Medical College of Virginia. 

Dr. H. I. Wiel is Assistant in Medicine, Mt. Zion Hospital, San 
Francisco, Calif. 

Dr. Otis B. Wight is Assistant Professor of Gynecology, Medical 
Department, University of Oregon. 

Dr. Helen Watson Winternitz is Lecturer on Anatomy, Johns 
Hopkins Hospital Training School for Nurses. 

Dr. Eleanor B. Wolf is House Physician, New York Infirmary for 
Women and Children. 

Dr. J. M. Wolfsohn is Instructor in Neurology, Leland Stanford 
Jr. University; Neurologist to the San Francisco Hospital, and 
Neurologist to the Children's Hospital, San Francisco, Calif. 

Dr. P. G. Woolley is Professor of Pathology and Head of the De- 
partment of Pathology and Bacteriology, Medical Department, 
University of Cincinnati, and Director of the Laboratories of the 
Cincinnati Hospital. 



NOTES ON NEW BOOKS. 



Practical Physiological Chemistry. By Sydney W. Cole, M. A. 
7/6. Third Edition. (Cambridge [Eng.]: W. Heffer & Sons, 
Ltd., 1913.) 

This work is intended as an exercise book, largely to aid students 
to pass examinations in medical chemistry, and it is so arranged 
as to be useful for students who are not thoroughly grounded in 
chemistry. Its third appearance would seem to indicate that it has 
met with a certain success in England, and it may be used by some 
schools in this country. The author discusses the proteins, car- 
bohydrates and fats, then passes to the chemistry of some foods, 
the composition of the digestive juices, and the action of certain 
enzymes. After these introductory chapters he takes up the blood, 
bile, and urine, and has a final chapter on the detection of sub- 
stances of physiological interest. 

The Psychoneuroses and Their Treatment by Psychotherapy. By 
Professor J. Dejerine and Dr. E. Gauckler. Translated by 
Smith Ely Jelliffe, M. D. $4.00 (Philadelphia and London: 
J. B. Lippincott Company, 1913.) 

At a moment when so much attention is paid to mental disorders, 
it is all important to have all the aid to be obtained from every 
source, and it is especially valuable to secure the opinions of 
foreigners whose work along these lines has been more thorough 
and exhaustive than ours up to the present. So few of our 
physicians read French easily that they may consider themselves 
very fortunate to have secured this admirable translation of an 
important work. Dejerine's practice and writings have been of 
the utmost interest to all psychiatrists, for he has worked out his 



own therapy with originality and has been a leader in the modern 
treatment of psychoneuroses. His book is divided into three parts; 
the first analytical, or " the study of all the symptoms which are 
observed in the course of the psychoneuroses " ; the second 
synthetic, or the explanation of " the general mechanism of the 
foundation of the psychoneuroses, as well as their variations and 
nature "; the third therapeutic, which needs no definition. This is 
a book well worth study by the general practitioner. 

Irritability. By Max Verworn, M. D. (New Haven: Yale Uni- 
versity Press. London: Henry Frowde, 1913.) 

Dr. Verworn, Professor at the University of Bern, was invited to 
deliver the Silliman Lectures at Yale University in 1911, and this 
volume is the result. The author's reputation as a brilliant 
physiologist has been long established, and his work is, therefore, 
of very great interest as presenting for the first time in English a 
comprehensive treatise of irritability or the " effect of stimuli on 
living substance." To the advanced student of physiology it will 
be a great aid, and stimulus to new investigations along fresh lines 
for Dr. Verworn is most suggestive and his book is full of meat. 

An Elementary Study of the Brain. By Ebex W. Fiske, M. D. 
Illustrated. $1.25. (New York: The Macmillan Company, 
1913. 1 

For certain college and possibly high-school courses this is an 
excellent work, from which students will get a very clear idea of 
the structure of the brain. It is based on the dissection of the 
brain of the sheep, and should prove useful just as books detailing 



January, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






the anatomy of the cat, frog, and lobster are used for demonstration 
courses in biology or zoology. With this book an energetic, bright 
student, working alone, could acquire much information during a 
summer holiday, and thus prepare himself for more advant i 
in the anatomy of the human brain. 

Les Epanch' mrnts du I'erirarde. Tar DOCTBCB GERMAIN BLECH- 
maw. ( Paris: J. Ii. Iiaillii're et File, 1913. ) 

As is common with French theses, the author dedicates his work 
to many of his professors and others, amongst whom it is pleasant 
to note the name of Thomas Morgan Kotch: and in the text he 
refers frequently to Rotch's early experimental work on peri- 
carditis. The thesis is a careful study of this disease; the author 
that the subxyphold puncture is the best means of 
diagnosticating a pericardial effusion, and that, along with surgical 
measures that may he necessary there is room for a new active 
medical treatment which is being developed. This treatment, as 
the author states, will justify Wright's so frequently repeated re- 
mark that " the physician of the future will be an immunisator." 
A valuable bibliograph\ accompanies the work, which is of 
interest to the Internist. 

Sterility in the Male and Female and its Treatment. By Max 
Hi Bins, M. D. $2.00. (New. York: Iiebman Company. WIS.) 

Dr. lluhners findings are based upon experimental work of a 
nature unpleasant to undertake, and he deserves credit for his in- 
vestigations, which, presented with greater modesty, would make a 
better impression. One-half this fair-sized volume of 250 pages 
gives the author's views, as based largely on his own work, the 
other half is merely a record of his case histories. The whole 
might have been condensed with profit into less than one-half and 
the results offered in a more concise and practical manner. That 
the author has added something to our knowledge of this trouble is 
unquestionable, and so the book has its value, but its value hardly 
calls for book form. As a journal article it would have had many 
readers and found its true place. 

Massage: Its Principles and Technic. By M w Bohm, M. D., Edited, 
with an Introduction, by Chables I' Painteb, M. I). Illus- 
trated. $17.". [Philadelphia and London: W. Ii. Saunders 

■any. /.''/■'. i 

The illustrations of this book, with the simple accompanying text, 
make it an exceptionally useful one for both students and 
The general princlpb 

of the volume makes it acceptable. It does not pretend to cover 
very special forms of massage, as of the eye, the larynx. 
generative organs, etc. but is limited to the massage of tl 
arm. back, abdomen, etc., such as is usually required of nui 
irs. 

Sex: Its Origin and Determination. By Thomas E. Rexd, M. i> 
my. i 

The author has prepared an interesting w<.i 
theory that the origin and determination of sex. the ci 
disease, parturition, etc., are the result of the metal 
and katabolic) cycle in man. but the proof b>- brlr 
inconclusive. Mow far the human system and it > man;, fui 
both normal ami abnormal are dependent on dail] 
monthly cycles. Is a much mooted question. I >r Ret 

■ much material to demonstrate the effect of th( 
but a good deal of the evidence is hypothetical, and Me- origin of 
sex still remains a problem to be worked out by experimei 
than by theorizing on Bucfa an uncertain factor ai thi 
tidal influence on the earliest forms of life. 



•7 "I St. Marys Hospital ( Mayo Clinic) 
for 1912. [Uusti {Philadelphia ■> 

W. 1! 

This is a fresh volume of verj ti am the 

Mayo Clinic. They | journals, but. 

gathered together in this handsome form, they furnish 
cellent index of the broad BCOpe and high quality of the work done 
by the Mayo brothi rs and their staff. 

Summaries "f Laws Relating to (he Commit* a o/ Ihe 

Insane m tin- United States. Prepared by Johh i: 

Published by The National Committee for Men) 
forts, 1913. I 

The National Committee, In publishing this volumi 

excellent piece of work. The compilation of tl" portul 

for the physicians, lawyers, and 

when our Btate legislatures are preparii or modify old 

laws in regard to the Insane. As our views in earing for tl 

are undergoing radical changes, it is likely tl 

will be much changed within a • ■. this 

volume will be of very great help to those intrusted with tl 

aration of new laws. 

ISurdett's Hospitals am! CharitU 

Philanthropy and the Hospital Uinual, containing 
haustl pltal work tor the year. By Bm ' 

i i r, K C B„ K C V. O. I Lot 
Limited. 18 and ."■> Southampton ■•<:>• rt. strand, H 

This standard annual Is now in the 24th year of publication. It 

seems surprising that, dealit of many 

thousand institutions, it should find it i 
fully at such an early date in the current year. Tie • 
his plea for the establishment of an Instltutloi 
pital, to correspond with 

e comparable for an Identical period ot 

It is gratifying to read i furnlan 

necessary information 1 y It 
instruction or advice in the line of hospital I 
of construction. 

The I- Englishmen In 

pitals. i " KI|IK 

Edward's Fund," tl"' " !•• ' 
Sunday." and 
,,.■« . ompulsoi j in urai ■ foi worl mi n 1 

furnish valuable hint 

the world and nera] applii 

pital Annual 

voluntary hospitals connect* d « i'h medl 
of the value of tl 

m could come in I 



88 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 275 



books dealing with this field. As in the first edition, the numerous 
illustrations greatly assist one in obtaining a proper comprehension 
of the subject matter. 

George Crocker Special Research Fund. Vol. IV. Studies in 
Cancer and Allied Subjects. {New York: Columbia University 
Press, 1913.) 

The eight papers in this handsomely printed, and finely illus- 
trated volume all deal with the anatomy and development of the 
salivary glands in the mammalia. Carmalt, Huntington, and 
Schulte are the three contributors, the work of the two latter 
amplifying observations already begun and reported upon by 
Carmalt, who died in 1905, after having made interesting investiga- 
tions of the problem noted. The salivary glands were studied in 
the hope of throwing light "on the phylogenetic aspect of the 
epithelial neoplasms of this area." The volume is an important 
addition to our knowledge of these glands. 

Acute Poliomyelitis (Heine-Medin's Disease). By Dr. Ivan Wick- 
man. Translated by Db. F. Wm. J. A. M. Maloney. $3.00. 
{New York: The Journal of Nervous and Mental Disease Pub- 
lishing Company, WIS.) 

This is an important contribution to the literature of the disease 
which, within the last few years, has been so profoundly studied 
with such brilliant results in America. To students at Harvard 
belongs the honor of having found the transmitting agent in the 
fly, and to Drs. Plexner and Noguchi of the Rockefeller Institute 
the glory of having isolated the causative organism. The mono- 
graph by Dr. Wickman gives an excellent picture of the disease, and 
it is fortunate that the editors of the Nervous and Mental Disease 
Monograph Series selected it for translation. 

Pathological Inebriety: Its Causation and Treatment. By J. W. 
Natley Cooper. $1.50. (New York: Paul B. Hoeber, 1913.) 

Physicians who undertake the scientific care of inebriates will 
find this small brochure of value. Dr. Cooper has had a large ex- 
perience with this class of patients, and what he says in regard to 
their treatment is well worth careful reading and consideration. 
Chronic or periodic drinkers are extremely diflacult to treat so 
as to effect a radical cure and prevent their returning to their old 
habits, and, therefore, any serious work of this nature is useful. 

Vaccine and Serum Therapy. By Edwin Henry Schoreb, M. D. 
Second Revised Edition. $3.00. (St. Louis: C. V. Mosby 
Company, 1913.) 

In the last four years, since this book first appeared in 1909, 
vaccines and serum therapy have been much studied and we have 
a better comprehension of their value than at that time. Dr. 
Schorer has incorporated the newer findings in his second edition 
and otherwise added to his work, which can be recommended to 
the profession as a thorough and clear presentation of the subject. 

A Reference Handbook of The Medical Sciences. Third Edition. 
Edited by Thomas Lathrop Stedman, M. D. Vol. II. BAD- 
CHL. (New York: William Wood d Co., 1913.) 

The three longest articles in this volume, as might almost be 
guessed, are on the brain, 165 pages; the blood, 125; and the breast, 
55. These are well prepared, and, in view of their importance in 
medicine, not too long. Cancer is dealt with in 15 pages, which 
seems short. But this merely draws attention to one of the obvious 
difficulties in the preparation of such a handbook. Different contrib- 
utors cannot be expected to treat their subjects in similar manner, 
for one will write profusely, the other briefly and compactly. The 
original handbook was highly appreciated by the profession in its 



day, and there is no doubt that Dr. Stedman's will prove even more 
complete and valuable when finished. The two volumes just issued 
promise excellently for the success of the entire eight. Anyone 
who undertakes such a work deserves the hearty thanks of all its 
readers, and it is certain that the profession-at-large will warmly 
endorse this new edition. 

Indigestion, Constipation and Liver Disorder. By G. Sherman 
Bigg, F. R. C. S. (Edinburgh). $1.50. (Hoeber: New York, 
1913.) 

This is a book of slight value and an unpleasant impression is 
aroused in looking through it to find that remedies are quoted 
with the makers' names or initials, e. g., P. D. & Co.; B. W. & Co.; 
Fairchild; Mellin; Messrs Kirby of Newman St.; Van Horn and 
Sautell, etc.; as though the author were writing to advertise the 
products of various firms. 

Blood-Pressure, from the Clinical Standpoint. By Francis Ash- 
ley Faught, M. D. Illustrated. $3.00. (Philadelphia and 
London: W. B. Saunders Company, 1913.) 

The author speaks of this book as a " little work," but it covers 
270 fair sized pages. As there is no other comprehensive book on 
blood-pressure in English this one will serve the student well; 
in it he will find most of the needed information to guide him 
along his way. Printed on thick paper it is heavier than necessary 
for which the publishers are to blame. 

Blood Pressure in General Practice. By Percival Nicholson, 
M. D. $1.50. (Philadelphia and London: J. B. Lippincott 
Company, 1913.) 

" This treatise therefore starts with the assumption that the 
writer is dealing with a new subject, and an effort has been made 
to present the material given in as simple a manner as possible." 
The manner has been carried out too simply, with the result that 
the book in places is not clear, and as an entity has small value. 

Diagnostic Methods: Chemical, Bacteriological, and Microscopical. 
By Ralph W. Webster, M. D. Third Edition, Revised and En- 
larged. Illustrated. (Philadelphia: P. Blakision's son it Co., 
1913.) 

Three editions within four years speaks well for the popularity 
of this work, and it deserves this mark of success. The author 
keeps his book up-to-date, and has covered the ground thoroughly, 
so that the work is a serviceable one for students and general 
practitioners. 

Manual of Operative Surgery. By John Fairbairn Binnie, C. M. 
(Aberdeen), etc. Sixth Edition, Revised and Enlarged. Il- 
lustrated. $7. (Philadelphia: P. Blakiston's Son & Co., 
1913.) 

This surgery w T ell merits its popularity and to each edition the 
author adds something to bring the work up-to-date and thus 
make it really serviceable for the advanced surgeon. Rare and 
difficult operations are described in detail, because any man, who 
rightly calls himself a surgeon, should know how to perform the 
simpler operations when he commences practice. It is an ex- 
cellent book, clearly written by a man of wide experience and 
sound judgment. 

A Manual of Venereal Diseases. By Sir Alfred Keogh, K. C. B., 
and others. Second Edition. Revised and largely Rewritten. 
$3.75. (London: Henry Frowde and Hodder d Stoughton, 
1913.) 

This work is essentially a treatise on syphilis, as out of 280 
pages, 230 are devoted to this disease. Discussion of gonorrhoea, 
soft-chancre and balanitis takes up the remaining pages. Im- 



.Iam \uv. 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



portaut as syphilis is, yet treated only as a venerea] disease, the 
disproportion of space allotted to it and gonorrhoea seems a mis- 
take, since the latter trouble, from several points of view, is as far 
reaching in its disastrous results as the former. It is, leaving 
this point out of consideration, a useful book for the general prac- 
titioner, and we are glad to note its second appearance. 

Malaria. By Grauam C. Hbnson, M. D. Illustrated. $2.50. (St. 
Louis: C. V. Mosby Company, 1913.) 

Dr. Bass in a brief introduction warmly indorses this work, and 
his endorsement is merited. Dr. Henson has written an excellent 
manual on the etiology, pathology, diagnosis, prophylaxis, and 
treatment of tins disease, and physicians throughout the South 
will find it most useful. It is a good practical handbook, covering 
all the essential features of malaria, which, unfortunately, is not 
yet generally recognized as one of our worst diseases, and in parts 
of the country most prevalent. It is to be hoped that Dr. Henson's 
treatise will help to awaken the public to the urgent need of 
action in eradicating malaria wherever it exists, and this is gen- 
erally not a difficult or very costly task. 

A Manual of Surgery. By Francis T. Stewart, M. D. Third Edi- 
tion. Illustrated. $4. (.Philadelphia: P. Blakiston's Son <& 
Co.. 1913.) 

This is one of the many surgical manuals, which are on the 
market, and which have found favor with the profession. Stu- 
dents of surgery will be glad to have the revised edition of Dr. 
Stewart's work which contains important additions and is a prac- 



tical book. As it covers a great dial of ground, t! 
not go into minute detail as to operations, but I 
are clearly present 

Vicious Circles in Disease. By : Scut, m. D 

tab.). Illustrated. Second ami Enlarged Edition 
(Philadelphia.' r. BlaMtton'i 

This work can i»' read with benefit I 
for unless his experience la large hi frequently tail I 

the existence and number ol 

associated witti almost all organs and systems. The ma] 

the book is more like that of a gift-hook, than a >■ I 

work — pagfs gilded on their edges, and unusual t\ ; 

the reader to question the value of the worl 

and to put it aside as unimportant it is unfortunate that it 

should appear in this Bomewhat fantastic dress, tor it merits 

attention. 

Progrcssire Medicine. Edited by Hobaki ajiobi Ham, m D., etc 

Assisted by Lr.io.nTos F. Aim'ikmw, M 1>, etc. Vol 111. 

September, 1913. (Philadelphia and New York: 

ger.) 

Ewart of London, Gottheil of New York, with Davis and Bplller 
of Philadelphia respectlvel: a and 

its viscera, dermatology and syphilis, ohstcti 

the nervous system. The reviews are satisfactory and aid the busy 
doctor to keep himself abreast of the best thought ami i 
both here and abroad. 



BOOKS RECEIVED. 



Book on the Physician Himself and Things that Concern His Repu- 
tation and Success. By D. W. Cathell, M. D. The twelfth and 
final edition, enriched and strengthened by the author and his 
son, William T. Cathell, A.M., M.D. 1913. Svo. 407 pages. 
F. A. Davis Company, Philadelphia. 

Pathological Inebriety: Its Causation and Treatment. By .1. W. 
Astley Cooper. With Introduction by Sir David Ferrier. M.D., 
F. R. S. 1913. 12°. 151 pages. Paul H. Hoeber, New York. 

The Karcotic Drug Diseases and Allied Ailments. Pathology, 
Pathogenesis, and Treatment. By Geo. E. Pettey, M. D. Illus- 
trated. 1918. 8°. 516 pages. P. A. Davis Company, Phila- 
delphia. 

Qolden Rules "/ Iiiai/nosis and Treatment of Diseases. Aphorisms. 
Observations, and Precepts on the Method of El&mlnatli 
Diagnosis of Diseases, with Practical Rules for P 
Remedial Procedure. By Henry A. Cables, B. S., Mi i 
Second edition, revised and rewritten. 1913. 12°. 318 pages. 
C. V. Mosby Company, St. Louis. 

8urgery of the Eye. By Ervin Torok, M. D., and Gerald H. Grout. 
M. I). With 509 original Illustrations, 101 in colors, and 2 
colored plates. 1913. 8°. 507 pages. Lea & Febiger, Phila- 
delphia and New York. 

Clinical Pathology. By P. N. Panton, M. A., M. B., B.C., Cantab. 
With 13 plates (11 colored) and 45 illustrations In ti 
1913. 8vo. 446 pages. P. Blakiston's Son & Co.. Philadelphia. 

The Difficulties and Emergencies of Obstetric Practice. By Comyns 
Berkeley. M. A., M. D.. B.C., Cantab., F. R, C. P., Lond., 11 R. 
C. S., Eng., and Victor Bonney, MS. M.D., B. Sc. Lond., 
F. R. C. S., Eng., M. R. C. P., Lond. With 287 illustrations. 
1913. 8". 787 pages. P. Blakiston's Son & Co . Phils 



Text-Book of General Pathology. Edited by m a 
J. Ritchie. 1913 B". 
York: Edward Arnold, London. 

Vaccine and Scrum Therapy. Including also a Study of Inf- 
Theories of Immunity, Specltie 
By Edwin Henry Schorer, B B., M. I 1 . I >r. P. B 
vised edition 1913. v . 
St. Louis. 

I 

Wick- 
man. Authorized Engl! on by Dr. J. \\m. J 
Maloney, r. i; 8. Ed. Illustrated. 19 
Journal of Nervous and M< I 
New York. 

the Philadl 

Publication 

Published 

General Index. Tran 

si pagei Publ 
Medii 

ohapti 

Mental i 

•idon. 

Summaries of 

pages. 

The \ 



30 



JOHNS HOPKINS HOSPITAL BULLETIN. 



I No. •?;.-) 



Diseases of the Ear. By Philip D. Kerrison, M. D. 331 illustra- 
tions in text and 2 full pages in color. [1913.] 8°. 588 pages. 
J. B. Lippincott Company, Philadelphia and London. 

Ophthalmoscopic Diagnosis. Based on Typical Pictures of the 
Fundus of the Eye, with Special Reference to the Needs of 
General Practitioners and Students. By Dr. C. Adam. Trans- 
lated by Matthias Lanckton Foster, M. D. With 86 colored 
pictures on 48 plates and 18 illustrations in the text. [1913.] 
4°. 229 pages. Rebman Company, New York. 

A Course in Normal Histology- A Guide for Practical Instruction 
in Histology and Microscopic Anatomy. By Rudolph Krause. 
Translation from the German by Philipp J. R. Schmahl, M. D. 
With 30 illustrations in text and 208 colored pictures, ar- 
ranged on 98 plates after the original drawings by the author. 
[1913.] 4°. Part I, 86 pages. Part II, 406 pages. Rebman 
Company, New York. 

Therapeutics of the Gastro-Intestinal Tract. By Dr. Carl Wegele. 
Adapted and Edited, with Additions on the Diagnosis of the 
Diseases of the Esophagus [etc.]. By Maurice H. Gross, M. D., 
and I. W. Held, M. D. With 52 illustrations in the text and 2 
figures in colors on one plate. 1913. 8°. 329 pages. Rebman 
Company, New York. 

Sterility in the Male and Female and Its Treatment. By Max 
Hiihner, M. D. 1913. 8°. 262 pages. Rebman Company, New 
York. 

Sex: Its Origin and Determination. A Study of the Metabolic 
Cycle and Its Influence in the Origin and Determination of 
Sex, the Course of Acute Disease, Parturition, etc. By Thomas 
E. Reed, M. D. 1913. 8°. 313 pages. Rebman Company, 
New York. 

Laboratory Methods. With Special Reference to the Needs of the 
General Practitioner. By B. G. R. Williams, M. D., assisted by 

E. G. C. Williams, M. D. With an introduction by Victor C. 
Vaughan, M. D„ LL. D. Second edition. Illustrated with 
forty-three engravings. 1913. 8°. 210 pages. C. V. Mosby 
Company, St. Louis. 

Blood Pressure in General Practice. By Percival Nicholson, M. D. 
With seven illustrations. 1913. 12°. 157 pages. J. B. Lippin- 
cott Company, Philadelphia and London. 

Les Epanchements du Pcricarde Etude Clinique et Therapeutique. 
La Ponction Epigastrique de Marfan. Par le Dorteur Germain 
Blechmann. 1913. 8°. 349 pages. J. B. Bailliere et Fils, 
Paris. 

Progressive Medicine. A Quarterly Digest of Advances, Dis- 
coveries and Improvements in the Medical and Surgical 
Sciences. Edited by Hobart Amory Hare, M. D., assisted by 
Leighton F. Appleman, M. D. Vol. II, June, and Vol. Ill, 
Sept., 1913. 8°. 449 pages. Lea & Febiger, Philadelphia and 
New York. 

International Clinics. A Quarterly of Illustrated Clinical Lectures 
and Especially Prepared Original Articles. By Leading Mem- 
bers of the Medical Profession Throughout the World. Edited 
by Henry W. Cattell, A. M., M. D. Volume II. Twenty-third 
Series, 1913. 8°. 312 pages. J. B. Lippincott Company, Phila- 
delphia and London. 

Reports from the Laboratory of the Royal College of Physicians. 
Edinburgh. Edited by George Lovell Gulland, M. D., and 
James Ritchie, M. D. Vol. XII [1912]. 1913. 8°. Oliver and 
Boyd, Edinburgh. 

A Text-Book of Midwifery. By R. W. Johnstone, M. A., M. D., 

F. R, C. S., M. R. C. P. E. Contains 264 illustrations. 1913. 
12°. 485 pages. The Macmillan Company, New York. 



Diseases and Injuries of the Eye. By William George Sym, M. D., 
F. R. C. S. E. With twenty-five full-page illustrations, sixteen 
of them in color and eighty-eight figures in the text. Also a 
type test-card at end of volume. 1913. 12°. 493 pages. The 
Macmillan Company, New York. 

A Text-Book of Biology. By William Martin Smallwood, Ph. D. 
(Harvard). Illustrated with 243 engravings and 13 plates, in 
colors and monochrome. 1913. 8°. 285 pages. Lea & Febiger, 
Philadelphia and New York. 

The Modern Treatment of Nervous and Mental Diseases. By 
American and British authors. Edited by William A. White, 
M. D., and Smith Ely Jelliffe, A. M., M. D., Ph. D. Volume II. 
Illustrated. 1913. 8°. 816 pages. Lea & Febiger, Philadelphia 
and New York. 

The Psychoneuroses and their Treatment by Psychotherapy. By 
Professor J. Dejerine and Dr. E. Gauckler. Authorized trans- 
lation by Smith Ely Jelliffe, M. D., Ph. D. [1913.] 8°. 395 
pages. J. B. Lippincott Company, Philadelphia and London. 

Diseases of the Stomach. Including Dietetic and Medicinal Treat- 
ment. By George Roe Lockwood, M. D. Illustrated with 126 
engravings and 15 plates. 1913. 8°. 624 pages. Lea & 
Febiger, Philadelphia and New York. 

Irritability. A Physiological Analysis of the General Effect of 
Stimuli in Living Substance. By Max Verworn, M. D., Ph. D. 
With diagrams and illustrations. 1913. 8°. 264 pages. Yale 
University Press, New Haven; Henry Frowde, London. 

Burdett's Hospitals and Charities, 1913. Being the Year Book of 
Philanthropy and the Hospital Annual. By Sir Henry Burdett, 
K. C. B., K. C. V. O. Twenty-fourth year. 1913. 12°. 1047 
pages. The Scientific Press, Limited, London. 

General Malaria Committee. Proceedings of the Third Meeting 
held at Madras, November 18, 19 and 20, 1912. Fol. 2S9 pages. 
1913. Government Central Branch Press, Simla. 

A Reference Handbook of the Medical Sciences. Embracing the 
Entire Range of Scientific and Practical Medicine and Allied 
Sciences. By various writers. First and second editions 
edited by Albert H. Buck, M. D. Third edition completely 
revised and rewritten. Edited by Thomas Lathrop Stedman, 
A. M., M. D. Complete in eight volumes. Volume II illustrated 
by numerous chromolithographs and seven hundred and fifty- 
four fine half-tone and wood engravings. 1913. 4°. 832 pages. 
William Wood & Co., New York. 

Ergebnisse der Chirurgie und Orthopadie. Herausgegeben von 
Erwin Payr, Hermann Kiittner. Sechster Band. Redigiert von 
H. Kiittner. Mit 147 Textabbildungen. 1913. 8°. 716 pages. 
Julius Springer, Berlin. 

Diseases of the Eye. A Handbook of Ophthalmic Practice. By G. 
E. de Schweinitz, A. M., M. D. With 360 illustrations and seven 
chromo-lithographic plates. Seventh edition, thoroughly re- 
vised. 1913. 8°. 979 pages. W. B. Saunders Company, Phila- 
delphia and London. 

Gonorrhea in Women. Its Pathology, Symptomatology, Diagnosis, 
and Treatment; Together with a Review of the Rare Varieties 
of the Disease which Occur in Men, Women and Children. By 
Charles C. Norris, M. D. With an Introduction by John G. 
Clark, M. D. Illustrated by Dorothy Peters. 1913. 4°. 521 
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Vol. XXV.-No. 276.1 



BALTIMORE, FEBRUARY. 19 14. 



[Price, 25 Cents 



CONTENTS. 

Obstruction: formation and Absorption of Toxin. Earh History of the ( are and treatmont ,,f Cripptw 

By David M. Davis. M. D 33 By Douoias C. McMcbtbd 

Natural Immunity of Animal.* Against I'., son of Intestinal 

.traction. ' ''''' 'pearing During ti. ,,„ „, 

David M. Dams. M. ]).. and Harold S. Morgan "'" "" " " v ''> PreBen< ■""' ' ' v ' " 

l-ital or Medical School Staff 

Kiela Stin-. n. illlustraW.) 

By William Snow Miller 41 First Announcement in Ri ebration ol 

A Brief Historical Sketch of Some of the Early Studies of the ''"' 2 '? th A ""' v '-'- | "y "' I fobm Hopkins 

Finer Structure of Plant and Animal Tissues. (Illustrated.) Hospital 

Bj Richard M. Peabce, M. D 51 a - 



INTESTINAL OBSTRUCTION: FORMATION AND ABSORPTION 

OF TOXIN. 

B] David M. Davis, M. D., 
Assistant in Pathi 
ihr Bunterian Laboratory of Experimental Pnth<, 



The historical Bide of the investigation of intestinal obstruc- 
tion has been gone over so frequently and well by thi 
writers that only a very brief outline will be given hi 

• principal theories have been propounded to explain 
ttb wlii.h occurs when the gut is obstructed : 1. thai of 
■ x: 2, that of infection; ■">. that of into? 
The first of these has received little attention of late. The 
second has had strong >n , «[ •< >rt from such invi 

ersii li (12) and lately Murphy ai 
ceni (49). Their case is, however, at best doubtful, and an 
overwhelming amount of evidence has been brou 
by Albeck I l i. Kukula I 11 i. Clairmont and H 
' : 

tnd Bernheim i 6' 
i - - at work in ' 

without ■ "ii of the peritoneum or 

with the principal ones an I 

sidcred that the - i 
■ re due i" a ceri iral anemia • ■ 

. and il< hydra! ion of the blood . 
FJ and Benedii I who felt that 

., 

: the harm. Whipple, Stone and B< 
immun iii sublethal dosi - of I 

lodenal loops, ma 
alive « ith closed duodenal loops o i 



unknown with unimniunized animals, 
ibt that a toxin found in thi 
it part, al 
occurring in uncomplicated ileus. 
The |i"ini about whi< ; 

Vmussal | i |, Humh (11), All 

Nikola] f th<' 

(41), ' 



34 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 271 



Closed Loots. 

In dealing with the intestinal contents in ileus, it has been 
found of advantage to make two obstructions, thus confining 
the material between them, and making the entrance of food, 
or the withdrawal of any of the contents, as, for instance, by 
vomiting, impossible. The material which is found in these 
loops is the resultant of a number of processes going on simul- 
taneously, and no one of them must be forgotten when the 
whole is considered. These processes are: 

Secretion of digestive fluids; 

Breaking up of food by digestive Eerments; 

Putrefaction of contents by bacteria: 

Absorption of substances by the mucosa ; 

Excretion of waste products by the mucosa. 
The last-named factor is one concerning which our knowledge 
is unsatisfactory, in spite of the large amount of careful work- 
done upon it. The pioneers in the field were Bischoff and 
Voit (10), who were followed by Muller (48), Rieder (59), 
v. Moraczewsky (47), Hermann (31), Ehrenthal and Blitz- 
stein (25), Fr. Voit (6G), Berenstein (!)). Klecki (38-39), 
Corlette (20), and many others. It was found that starving 
animals still continued to form a certain amount of dark, 
pasty feces for an indefinite period, and soon the aid of the 
closed intestinal loop, first made by Halsted (26), was also 
invoked toward the elucidation of the problem. It showed 
that a very considerable amount of material was the result of 
the mucosal activity, but what proportion was necessary di- 
gestive secretion, and what proportion waste matter, still re- 
mains unknown. At any rate, there are many arguments in 
favor of the idea that the intestinal mucosa regularly has an 
important excretory function. The possibility immediately 
arises (if this excrementitious matter providing some or all of 
the toxic substances. 

As has been stated above, the products of putrefaction were 
first seized upon as the most likely to be toxic. Efforts to 
isolate toxic split products, for example, those of Kukula, 
Barger and Nesbitt (6, ;. II, 50), have been unsatisfactory. 
The possibility of decomposed food as a source was ruled out 
by the use of the closed loop, from which food is excluded. 
When the mucosa was destroyed in a closed loop by Whipple 
(68), the clinical course was not at all characteristic; the 
animal died of septicaemia, and the loop contents were not 
toxic. This indicates that the mucosa is necessary for the 
development of the ordinary toxin. The efforts to fix the 
Maine on bacteria being on the whole unsuccessful, it occurred 
to the writer to try to tesi the toxicity of the intestinal secre- 
tion, while si ill uninfluenced by microorganisms. 

I (rained Duodenal Loop. 
The first steps towards this end were taken in the observa- 
tion of intestinal loops, which, instead of being closed, were 
drained to the outside. The ends of the loop were fastened 
to the skin, and rubber tubes put in them. It was difficult to 
keep the tubes in place, but even after they had come out, the 
loop was easily washed by inserting a catheter. Whipple (69) 
has performed this experiment frequently on dogs, and often 
they die with typical symptoms of ileus in spite of the drain- 



age. The writer prepared one cat in this manner. It re- 
mained strong and healthy during the time (10 days) when 
daily lavage was done. The washings showed a slight yellow- 
ish brown coloration, and contained flakes of mucus. Cor- 
lette (20) shows that this coloration is due to a pigment 
secreted by the mucosa, and not to blood pigment. The total 
amount, mixed, of course, with wash water, for the ten days 
was about 1200 cc. It was preserved with chloroform and 
toluol. This was evaporated at 60° C. to a volume of 115 cc, 
filtered, and injected into the veins of a dog weighing 8 lbs. 
The dog died in 44 hours, with the symptoms and autopsy 
findings described as typical for closed loop fluid by Whipple. 

Fistula Experiments. 

It was desired, however, to devise an experiment which 
would do away altogether with obstruction, and allow the 
mucosa to secrete as nearly as possible under normal condi- 
tions. To this end dogs were prepared by tying off the bile 
duct, dissecting the pancreas away from the duodenum or 
removing it altogether, and opening a fistula 30-35 cm. below 
the pylorus. Three dogs were operated upon thus, the details 
being given in the appended protocols. The intestinal secre- 
tion failed to flow out freely, so that lavage was again neces- 
sary. The whole procedure was completed, however, in a 
short time — much less than that required for the death of 
animals from closed duodenal loops — and at the end there was 
no perceptible lesion of the mucosa except a slight hypenvmia 
from handling, opposite the head of the pancreas. The fluid 
obtained in this manner when given intravenously to dogs 
had, in all eases, effects identical with those caused by closed 
loop fluid. 

Discussion. 

In this series of experiments, the material dealt with was 
washed out of the intestine within a few minutes at most after 
its secretion and preserved at once with chloroform and toluol. 
This effectually removes the possibility of bacterial action in 
the formation of a toxic substance. Nothing is present except 
that which has been produced by the intestine itself. It may 
indeed be argued that the intestine is in a pathological con- 
dition from the operation. This possibility cannot be denied, 
yet the handling of the gut was not greater than that suffered 
by it in great numbers of operations performed daily on men 
and animals, in which no noteworthy toxic symptoms are seen. 
At any rate it seems clear that the intestinal mucosa is capable, 
under certain conditions at least, of producing unaided some 
very toxic substance or substances. 

Absorption from the Intestine. 
The next question that arose. was of the manner in which 
these or other toxic substances gained entrance to the bloodJ 
stream. It is evident from the work of almost every investi- 
gator that in animals and men a fatal toxaemia may exist with- 
out demonstrable lesions of the mucosa. Must it be assumed 
that the normal mucosa can absorb the toxin? Upon consult- 
ing the numerous researches (8, 17, 19, 30, 32, 35, 52, 59 
etc.) made by physiologists on the absorption taking place in 
the small intestine, one sees that a conception of the normal 
mucosa is a very difficult one. It acts in many ways as a semi- 



Febim af;y. 1914. J 



JOHNS EOPKINS BOSPITAL BULLETIN. 



permeable membrane, obeying the laws of osmosis and dif- 
fusion, yet very slight influeni - it, and cause 
-orb substances in a way very different from the normal. 
For instance, the sugar in a 2 per cent solution of d 
will be absorbed at a dilferent rate when the carbohydrate 
d in a 5 per cent solution of Xat'l from that at 
-orbed when place. 1 in , : | solution oi 
. the one-sided permeability of the mm 
has been regarded as a criterion of it- normal stal 
Cohnheim (17, 18, 19) has shown that the mucosa mi 
some damage yet -till retain this one-sided permeability. If 
mechanical factors can cause the mu 
would expect every operation on the bowel to be follow 
toxemia. In obstructions and closed loops, however, there are 
other factors: tlr^r. an accumulation of toxic products in the 
often distended intestine, with a possible concentration due 
to absorption of water from the mass. It is known | 
that water under all conditions from the intestine 
much more rapidly than organic solid-, presumably consisting 
of very large molecules. Secondly, the substances i 
trated or dilute in this mass might, since the epithelium is so 
sensitive, act as mucosal poisons, breaking down a normal 
ini]>ermeability of the intestine to such toxic substances. To 
test these points, two series of experiments were carried out, 
one, absorption experiments with toxin, the other, absorption 
experiments with phenolsulphonephthalein. The experiments, 
with toxin will he described first. 

M'TIOX of Toxix. 
Fresh duodenal loops were made in dogs, and in! 

• the time of operation fluid- of known 
toxicity from other closed loops, which had been allow, 
on •'!-! days. One exception to this rule was in experii 
where fresh, nnpreserved loop contents of unknown b 
pom a dog just dead, were used. It 1 that if 

the normal mucosa was capable of absorbing this 

would influence the mucosa, chem- 
ically or othe . that the animals 

rhev did i!. ' 
r, the clinical com tly the 

ptoms an. I 

ited in any way 
i tly the supplied toxin n d 

during the tir-t 2 1 hour-. 

Abso Phbnolph I II \i 

If the toxi. symptom; depend upon the 
injured mucosa .ill. Mm; 

■ i. Hartwell and 

nolsulphonephthal. 
.il lumen, might 

.ii (65) that 
I within an hour by the kidneys of healtl 
ntity appi aring in the urine ivill givi 
proportional amo 
It must be understood thai the absorption 

me like phenolsulphonephthalein 
testinal mucosa will not necessarily l>e paralM a; all 



". - 

loops with a tine i 
of phtl 

ithdrawn h. 

ITS after the 
out with warm water each tin 
detenu 

were Utilize: 

made in which tie 

into the normal The follow i- 

i HART \. 

I'ii 







. 
















— 


— 






>-,] 


Into closed low 
ileum lcx»i>. 

do 


1 










'.- 










' 






" 























36 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 276 



Difficulty was encountered in introducing the dye into the 
loops on the days following the operation. The few observa- 
tions made seem to indicate that absorption of phthalein is 

unusually low in these late loops. This is in accord with the 
experiments of physiologists made with many other sub- 
stances. If gives no support to the contention that injury to 
tin- mucosa increases its absorptive powers. The table points 
rather consistently toward a more rapid absorption in the 
upper part of the small intestine than in the lower part. Aside 
from this, the results are subject to a very serious error, in 
that absorption varies with the concentration, and it is im- 
possible to control the concentration of the dye in the intestine. 
Even in the loops, the quantity of fluid present is very in- 
constant. This fact also undoubtedly accounts for the low 
absorption when the phthalein is given by mouth. 

Discussion. 

What conclusion, then, is to be drawn from these several 
considerations? If we grant that toxic substances are present 
in the normal intestine, we can go far on that hypothesis. 
It has been seen that the normal duodenal mucosa is ap- 
parently impermeable to the toxin; in addition the chyle is 
swept very rapidly through the small intestine, as has been 
shown by Cannon (15) for the cat. Its speed is greatest in 
the duodenum and upper jejunum, giving time for little 
absorption, and while it slows down in the ileum, it should be 
past the ileocecal valve in 4-5 hours. Once in the colon, the 
organism is safe, for the colon itself is comparatively im- 
permeable to the toxin, and so remains. Closed loops of colon 
full of feces can exist almost indefinitely in man or animals, 
as the writer has found by experiment, and as many others 
testify (15, 20, 25, 26, etc.). The only danger is from dis- 
tention, perforation and peritonitis. Kukula (41) describes 
a eat with a simple obstruction at the sigmoid, which lived in 
good health for several weeks. Even the lower ileum of dogs 
is much less active than the gut higher up, since dogs with 
closed ileum loops may live very long periods, e. g., 550 days 
(20). In case of an ileus, continuous secretiou with absorp- 
tion of water would serve to concentrate the poison in the loop 
or above the obstruction. With copious vomiting, lavage, and 
infusions, the toxin would be removed and life might be pro- 
longed (28). 

At this point, however, serious objections to the theories of 
absorption by normal mucosa intervene. It has been seen that 
concentrated toxic substance when placed in contact with 
normal mucosa, is not absorbed. 

Whipple (72) has shown that dogs may die with all the 
symptoms of obstruction, when a closed loop has been made 
and drained to the outside. There is no accumulation of 
fluid in such loops, and the mucosa appears normal. 

The only inference which can be drawn from these facts is 
that, in obstruction and closed loops, a subtle change takes 
place in the mucosa — nothing is seen with the microscope, yet 
tin' cells in some manner discharge or allow to be discharged, 
the fatal toxin into the blood. It has been impossible up to 
tin- present to demonstrate any increased permeability of the 
mucosa to the toxic substance. 



Conclusions. 

This paper has shown that the duodenal and upper jejunal 
mucosa, unaided by bacterial action, and in conditions not far 
removed from normal, can produce a highly toxic substance) 
and that although phenolsulphonephthalein is readily absorbed 
by the normal mucosa of the small intestine, this toxic sub- 
stance is not. 

In closed loops one deals with a mucosa which displays 
nothing more than a slight hypersemia, sometimes not even 
that. Injuries from handling are negligible, and absence of 
normal secretions from above. is readily excluded as a cause 
of the mischief. Loop contents themselves in concentrated 
form will not stimulate absorption of toxin from the lumen in 
a freshly made loop. It seems clear, then, that some condition 
existing in closed loops causes slight but important functional 
changes in the mucosa, resulting in fatal toxaemia. But 
further investigation of the details of this change must be 
made. 

I am indebted to Messrs. Harold S. Morgan and Eoy E. 
Fallas for their assistance in a number of the experiments. 

Protocols. 
drained duodenal loop. 

Experiment 1. 

Cat, D-39. — Maltese, female, middle sized. Operation Jan. 16, 
1913, 3.30-6.00 p. m. Isolated duodenal loop, upper end brought to 
surface and sutured in a stab wound in right flank, lower end 
brought to surface and sutured in median laparotomy incision. 
Intestinal ends inverted, lateral duodenojejunostomy. Rubber 
drainage tubes inserted in each end of loop. 

Jan. 17, 1913. Lies quietly in cage, but is strong and active 
when handled. Washed out with 200 cc. of warm water; washings 
slightly discolored, yellowish brown, very little solid material, few 
flakes mucus. Preserved with chloroform and toluol. 

Jan. IS, 1913. Larger amount mucus and granular material 
to-day. 

Jan. 24. Is being irrigated daily. Strong and bright, no toxic 
symptoms have been noted though loop ends are infected. 

Jan. 26. To-day animal's appearance is entirely changed; sick 
and weak. Killed with ether. At autopsy, fresh peritonitis and 
failure of one of the intestinal blind ends, possibly due to a large 
piece of pig's aorta which cat has eaten, and which blocks up the 
duodenojejunostomy. Mucosa appears normal except for absence 
of bile pigmentation. Microscopic section of loop shows villi 
pressed together; epithelial cells appear healthy and active; many 
goblets. In the interstitial tissue which is not especially cellular 
are some places where there are small numbers of polymorpho- 
nuclears. No congestion or desquamation. Peritonitis, quite 
superficial. 

About 1200 cc. of light brown, slightly turbid fluid had been coK 
lected in the 9 days. It was evaporated under reduced pressure 
at 60° C. to 115 cc, and filtered, giving a clear, slightly opalescent 
fluid with a slight, pleasant odor resembling that of beef broth. 
A more pungent odor resembling that of pentamethylendiamiffl 
which had- been present when washings were made, was driven off 
by the evaporation. 

The fluid was given intravenously to a dog, D-65, male, weight I 
lbs., at 3.00 p. m., March 6, 1913. Kymograph record of B. P. 
respiration made. Pall, then rise of B. P.; temp, at end of injec- 
tion, 35.8° C. Condition seems good. 1V 2 hours later, animal 
lying on side, breathing rapidly, comatose. Pulse rapid, weak. 



ABY. 1!>1 I. | 



JOHNS HOPKINS HOSPITAL BULLETIN. 



..! yet bloody S p. ni., animal di 
At autopsy, splanchnic ar. 

tonitls. On opening bowel, exl 
is seen, beginning at pylorus, and Involving entire small - 
colon, l 1 itli fluid contents, layer of mui 

thelium. Blood dark, thick, docs not clot readily. Mil 

tion of duodenum shows tremendous congestion i 
quamation of epithelium. No cellular infiltration or other signs 
nf Infection. This corn sponds in every way with the picture 

■ d by Wl ipple in his 
fluid. 

FISTULA. 

Dog, D-66. — Large, black, male, weight 20 lbs. Operation March 
S, 1913, 2-3.30 p. in. Intestine about 20-33 cm. belo« pylorus 
sutured to an opening in the skin, left rectus : tula not 

Second operation, April :;. 1913, 10-12 a m. Bile duct 
doubly ligated, cut between ligatures. Pancreatic ducts tied and 
cut. Head of pancreas dissected away from duodenum. Fistula 
opened, tube inserted. Collection begun at U noon. On 
of vomiting, little ci ibe, and the gut is trrigai 

warm water. Total collection. 000 cc. turbid tluid, with Bi 
mucus, foil 6 hours. 

Autopsy shows mucosa of duodenum slightly pink. In 
good condition opposite head of pancreas, except for hyperemia. 
Fistula 55 cm. below pylorus. The fluid collected was a) once 
mixed with chloroform and toluol and to it was added th< mucosa 
taken from the intestine al autopsj 

a hole evaporated to 55 cc, and injected into jugul 
of dog, D-96, male, weight ll 1 , lbs. April 11, 1913 
was also given 2 per cent solution of peptone and 1 5000 

gm. hirudin for another purpose, transient fall of B. P onl3 
Kymograph record of B. I', and respiration mad 
washings caused no fall of B. P., slight acceleration of respiration. 

37-9 C R< covi i- quickly, , 
p. m. i 5 hrs.) animal is quiet, weak, drowsy. Lies on side, profuse 
tern-fecal mucoid bloodstained iluid diarrhoea. Respin tion rapid 
and labored Temper ture 40 S moribund. 

April 12, 1913. At 9 .. m dog is weak, but rather bri. 
ring. Diarrhoea is li ss, discharf 
fecal character. Appetite fair Respiration still a littli 
■rated. 

April 13, 1913. Do? red This animal h 

•ymptoms, but evidently the dose was Just sublethal. 

• 71.- White, male, weight 27 lb 

h low pylorus ■ ... d to ud 

I 1. recti! 

April 1 1, 1913 ' oi dltli 

April 15, 191.1 l • . 
1 

. from intc I 
through gradually h 

reaembl. 

way. At auti p 

much watei 
Is not added ti 

1 

at 10 a. m., kymograph r 



April 

Of which tin 

of diarrhoea must, ii 

to paralysis of the I 

■ Ion. 

;■ in. Kile duet ti. d and 

ileum sutur.d to abdominal wall i-i 
ditlon go,,d at end. Maj 

A little water is given by BtOm 

small dose of chlon 

fistula, 

ube tied Into pyli • 
solution is irrigated through to 

form. Dog n man 
Autopsy Is performed Mui 

amount 

i 

Infiltration. 

■ 

qutckl] 






■ 



38 



JOHNS HOPKINS HOSPITAL BULLETIN, 



[No. 276 



sutures of fine silk. 6S cc. of fluid, D-40-43, put into loop. Gastro- 
enterostomy. Condition good at end. Temperature 35.3° C. 

February 12, 1913. Dog much better, brighter, but vomits large 
amounts when he tries to eat. 

February 13, 1913. Better, good appetite, still vomits occasion- 
ally. Remains in fair condition with some loss of weight, until 
February IS, when another operation is performed. 

Autopsy: February 19, it is found that there is a slight leak at 
the lower end of the loop. 60 cc. of the fluid, D-40-43, which was 
from duodenal loops in cats, had previously killed a dog weighing 
10% lbs. The dose then was a lethal one, but the value of the 
experiment is lost, through development of a leak in the loop. 

Experiment 6. 

Dog, D-137 — Black, female, weight 14 lbs. Operation July 23, 
1913, 2.30-3.00 p. m. Closed duodenal loop, ends crushed and tied 
with double heavy silk, closed over with running mattress suture . 
of fine silk. 52 cc. of fluid 0, Dogs S6, 87, 91, 93, inserted into the 
loop through a needle. No gastroenterostomy. Condition good 
at end. 4.30 p. m. Has recovered from ether, but is very quiet. 
Vomits. 

July 24, 1913. Walks about, wags tail, appetite poor. 

July 26, 1913. Becomes very sick in afternoon, etherized 3 days 
after operation. Autopsy: General peritonitis from perforation 
of the loop, which has been distended. It cannot be said that this 
animal, who lived 72 hours, died any sooner than others into the 
loops of which nothing had been put. There was some hyperemia 
of the mucosa of the unobstructed part of the gut below the loop. 

Experiment 7. 

Dog, D-138. — Male. Operation July 30, 1913. Closed duodenal 
loop, ends crushed and ligated with heavy silk, closed in with fine 
silk. No enteroanastomosis. Condition good at end. 

Lived about 50 hours, dying at noon, Aug. 1, 1913. No diar- 
rhoea. Autopsy, no peritonitis. Loop is almost empty, but does 
not leak. Contains 10-13 cc. soft, putty-like greenish-gray material. 
Mucosa appears quite normal. No injection of any part of small 
intestine. The contents of the loop of D-138 were put at once into 
a fresh duodenal loop made at 3.30 p. m., Aug. 1, 1913, in dog, 
D-139, weight 11% lbs. The ends of loop of D-139 were also 
crushed, tied with heavy silk, and closed in with fine silk. No 
enteroanastomosis. The contents had been diluted with salt 
solution to a volume of 100 cc. Condition good at end. 

Aug. 2, 1913, 24 hours after operation, runs about, pulse good 
quality, condition almost as good as before operation. No evidence 
of toxaemia. 

The mucosa from the loop of D-13S was ground up with about 
75 cc. salt solution, and put at once into a fresh duodenal loop 
made at 4.40 p. m., Aug. 1, 1913, in dog, D-140, weight 20% lbs. The 
ends of the loop of D-140 were also crushed, tied with heavy silk, 
and closed in with fine silk. No enteroanastomosis. Condition 
good at end. 

Aug. 2, 1913, 24 hours after operation, runs about, pulse good 
quality. No evidence of toxaemia. 

Whipple (personal communication) has performed similar ex- 
periments as 5, 6 and 7 with the same result. 

With the exception of D-114, where chloretone was given, all 
operative procedures described in this paper were carried out 
under full ether anaesthesia. 

LITERATURE. 

1. v. Albeck: Arch. f. klin. Chir., 1902, LXV, 569. 

2. Albu: Ueber die Autointoxicationen des Intestinaltractus, 
Berlin, 1895. 

3. Idem: Berl. klin. Wchnschr., 1913, L, 1909. 



4. Amussat: Relation de la maladie de Broussais, Paris, 1839. 

5. v. Baracz: Arch. f. klin. Chir., 1899, LVIII, 120. 

6. Barger: J. Physiol., 1909, XXXVIII, 343. 

7. Barger and Dale: J. Physiol., 1909, XXXVIII, 77. 

8. Beddard: Chapter on "Absorption from Small Intestine," 
Hill's Recent Advances in Bio-Chemistry and Physiology, London, 
1904. 

9. Berenstein: Pfliiger's Arch., 1893, LIII, 52. 

10. Bischoff and C. Voit: Die Gesetze der Ernahrung des Fleish- 
fressers, 1860. 

11. Bouchard: Leeons sur les autointoxicat : ons, Paris, 1887. 

12. Borszecky and v. Genersich: Beitr. z. klin. Chir., 1902, 
XXXVI, 44 S. 

13. Braun and Boruttau: Deutsche Ztschr. f. Chir., 190S, XCVI, 
544. 

14. Bunting and Jones: J. Exp. Med., 1913, XVII, 192; 1913, 
XVIII, 25. 

15. Cannon: Mechanical Factors of Digestion, 1911. 

16. Clairmont and Ranzi: Arch. f. klin. Chir., 1904, LXXIII, 696. 

17. Cohnheim: Ztschr. f. Biol., 1S97, XXXVI, 129. 

18. Idem: Ztschr. f. Biol., 1899, XXXVII, 443. 

19. Idem: Ztschr. f. Biol., 1899, XXXVIII, 418. 

20. Corlette: J. Physiol., 1899-1900, XXV, 344. 

21. Cushing and Livingood: Johns Hopkins Hosp. Rep., 1900, 
IX, 543. Experimental and Surgical Notes Upon the Bacteriology 
of the Upper Portion of the Alimentary Canal, etc. 

22. Draper-Maury: Johns Hopkins Hosp. Bull., 1909, XX, 838. 

23. Idem: Am. J. M. Sc., 1909, CXXXVII, 725. 

24. Idem: J. Am. M. Ass., 1911, LVII, 1338. 

25. Ehrenthal and Blitzstein: Pfliiger's Arch., 1891, XLVIII. 74. 

26. Halstead: Am. J. M. Sc, N. S., 1887, XCIV, 442. 

27. Hamburger: Osmotische Druck v. Ionenlehre, Wiesbaden, 
1902, I, 1 et. seq. 

28. Hartwell and Hoguet: Am. J. M. Sc, 1912, CXLIII, 357. 

29. Idem: J. Am. M. Ass., 1912, LIX, 82. 

30. Heidenhain: Pfliiger's Arch., 1894, LVI, 579. 

31. Herman: do., 1S90, XLVI, 93. 

32. Hober: do., 1S9S, LXX, 624. 

33. Idem: do., 1899, LXXIV, 246. 

34. Idem: do., 1901, LXXXVI, 199. 

35. Idem: do., 1903, XCIV, 337. 

36. Humbert: Etude sur la septicaemie intestinale, Paris. 1S73. 

37. Kader: Deutsche Ztschr. f. Chir., 1S91-2, XXXIII. r,:. 

38. Klecki: Rozpr. Akad. Uniej. wydz. nuitemat.-przyr.. Krakow, 
1895, 2. s., VII, 63. 

39. Idem: Wiener klin. Wchnschr.. 1S94, VII, 437. 

40. Kocher: Mitth. a. d- Grenzgeb. d Med. u. Chir., 1S9S, IV 

41. Kukula: Arch. i. klin. Chir., 1901, LXIII, 773. 

42. MacCallum, A. B.: J. Physiol., 1S94, XVI, 268. 

43. Idem: Am J Physiol., 1904, X, 101, 259. 

44. McClure: J. Am. M. Ass., 1907, XLIX, 1003. 

45. McLean and Andries: J. Am. M. Ass., 1912, LIX, 1615. 

46. Matthews: J. Am. M. Ass., 1910, LV, 293. 

47. v. Moraczewsky: Ztschr. f Physiol. Chem., 1898, XXV, 12 
4S. Muller: Ztschr. f. Biol., 1SS4. XX, 327. 

49. Murphy and Vincent: Bost. M. and S. J., 1911, CLXV. >;s4. 

50. Nesbitt: J. Exp. Med., 1S99, IV, 1. 

51. Nicolaysen: Studier over aetiologienog pathologien at 
Ileus, 1S95, Kristiania. 

52. Reid: J. Physiol., 1890, XI, 312. 

53. Idem: do., 1S96. XIX, 240 

54. Idem: do., 1S96, XX, 29S. 

55. Idem: do., 1897. XXI, 40S. 

56. Idem: do., 1901, XXVI, 437. 

57. Idem: do., 1902. XXVIII, 241. 

58. Idem: Phil. Tr. Roy. Soc, 1900, CXCII, 211. 






Fkbrfart. 1014.] 



INS HOPKINS HOSPITAL BULLETIN. 






tiider Xts.hr. f. Uiol.. lv\4. XX, 

Roger and Gamier: Compt. rend. Sec. de bii 
'(. 677 

61 I mod., 190<>. XXVI 

62. Idem: Compt. rend. Soc. de biol.. 19iu">, I.Vill. 27. 

6 t. Idem: do., 1908, l.XVI. 426, 610, 

64 Idi i : !'. . d. med., 1910, XX. . 



''' v ' i Hull 



NATURAL IMMUNITY OF ANIMALS AGAINST POISON OF 
rNTESTINAL OBSTRUCTION. 

(avid M. Davis, M. D., 
and 

I I \ ■ 5 AX. 



rature of inb stinal obstruction, it will bi 
• many investigators have used main different kinds 
i of animals in their experiments, from hedgehogs I 

n from many standpoint 
■ tly contradictory character u - drawn 

will be very bewildering to the render. It is hoped that the 
■ t paper may explain some of these contradict 
In the experiments leading up to their paper on ii ■ 

Stone and Bernlieim noted that in the 
- when they injected the toxic material, ■ 
duodenal loops in dogs, into the 
' lie animals appc an d to hi n 
• writer then began to investigate this phenomenon. 
ist step taken was an effort to produce a b 
inner in which it had In 
making a closed duodi n ith an 

nit the intestinal current past tl 

thread, 

-tomy made. '1'hree animals 
' his. and the resii I rely unsati -I 

if an\ produced, the animals 

ntil the ligatun s cut 1 
lity. In two 1 I between t 1 

and thin walled, 
atures cut through, it had 
other ligature matei ials and 

I li-lS i in. long wil • 

iv. The u 
'I variably from 1 . 

In looking through Table I it wi 

pane) in the n suits. P 

_ i. while this 



No. I '. 

taining a small q 
of the 

in Table 1 1 1. I 
clear : 

■ 
to a la 

Table 1 1 



40 



JOHNS HOPKINS HOSPITAL BULLETIN. 



N T o. 371 



TABLE I.— CLOSED INTESTINAL LOOPS IN CATS. 



Anastomosis 



2 Lisrated, Bilk.. 



do 

Ligated, cord. 
Ligatcd. silk.. 
do 



< iastro-enterosl \ 

do 

do 

do 

do 



Ligatcd, cord. 



Wooden clamps. 

do 

do 

Ligated, cord. . . 



Upper end. ligated, cord 
Lower end sectioned 
inverted. 

do 



Ligatures leak freely 
do 



Normal . 

do . 



Upper end ligatcd tape do 

Lower end inverted. 
Sectioned; inverted. .. .Obi i que duodeno- 
jejunostomy. 

do .'..'.do ' 



.do. 



Lateral duodeno- 
jejunostomy. 



Oblique duodeno- 
jejunostomy. 

Lateral duodeno- 
jejunostomy. 



7!t .N. None. 

8!> Ligatcd. silk None. 



Distended, does not leak on light pres- 50 cc. thin, white 
sure; mucosa hyperem ic, hymoses. llnid, granular. 

Distended, hut ligaturee leak; mucosa Thick, light yellow.. 
looks normal. 

Distended, but ligatures leak; mucosa Dirty, mucoid, bile- 
normal, tinged. 

mucosa Gray, muddy 



Leaks at lower end only 

norma]. 

Xot distended, mucosa normal, leaks Small amount, dark, 
into peritoneum. | clay-like. 

Leaks into peritoneum ; mucosa slight- Thin. gray, muddy. . 
ly injected. 

do.. Small amount, like 



Ligatures leak; mucosa normal; en- 
la r^cd and thin walled. 

Upper ligature leaks into peritoneum ; 
loop distended, mucosa reddened. 



pea soup. 
Normal 



Etherized while in good condi- 

t ion. 

General peritonitis; necrosis 
about ligatures. 
I)o 

Xo peritonitis; etherized while 
in fair condition. 

No peritonitis; intestines con- 
tracted, partial obstruction? 
Pneumonia. 

Ulcer with perforation and local 
peritonitis, just below gas- 
troenterostomy. 

Necrosis under clamps; general 
peritonitis. 
Do 

Do 

Cause of death unknown. 



Thick, like pea soup, General peritonitis; necri 
but red in color. about ligature. 



At end of 10 days, laparotomy shows Larue amount light No peritonitis at 2d operation. 
loop enlarged, thin walled, but liga- brown material. At autopsy, beginning peri- 
ture leaks. Etetied. At autopsy, loop like bean soup. tonitis due to eversion of cut 

distended; no leak; mucosa red- j end from pressure, 

dened. 
Slight leak to peritoneum upper end; .">."> cc. like pea soup. Beginning peritonitis; slight 

distended, mucosa reddened. I necrosis under ligature. 

Distended, hut leaks into peritoneum; Dark, almost black Peritonitis; necrosis under lig- 
mucosa injected. | fluid. ature. 

Distended, but leaks into peritoneum : do Do 

mucosa reddened. 
Perforation; mucosa green, friable ; Dirty, black, syrupy. Peritonitis following perfora- 

hemorrhages, ulcers. tion. 

Distended, dark, no leak; mucosa in- 40 cc. greenish black. Died under ether; fluid was lo 

jected, ecchymoses. fluid. be withdrawn from loop. 

No leak, distended, black; mucosa 50 cc. black, fluid. . . Peritonitis; anastomosis leaks. 

dark red, in places greenish. 
Loop excised, 2nd day; mucosa 7 cc. dark brow n. No peritonitis at second opera! 
slightly reddened. pasty. tion; death from peritonitis 

due to failure of closed end of 
duodenum. 

Distended: mucosa reddened Green, like pea soup. Beginning peritonitis over loop 

only; enteritis. 
D i s t e n d c d ; mucosa hyperemic, in Green, like pea soup. Beginning peritonitis over loop 
places greenish. 75 cc-50 cc. only: 75 cc. withdrawn on 2d 

day. leaving loop very hyper- 
emir. 
Distended, no leak; mucosa injected. . oil cc. like pea soup. Peritonitis from a leak in duo- 

deno- jojun ostomy. 
Not distended. 35 cm. long; mucosa 2 cc, dark red. Do 



si ightly injected. 
Loop leaks; mucosa slightly injected. . 

Gangrenous, perforation; mucosa 

da i k, g reenish friable. 
Distended, no leak; mucosa in jected. 

dark. 
Distended, dark ; mucosa injected, no 

ulceration. 



mushy. 

4H r>n cc. like pea Peritonitis from leak at upper 

SOUp. end of loop. 

50 cc. like pea soup. Peritonitis from perforation, 

convexity of loop. 
■10 cc. like pea soup. Peritonitis from leak at duode- 
num, closed end. 
35 cc. like pea soup, slight beginning peritonitis 
over loop only. 

Not distended: mucosa not injected 1 <c black, thick, Dry fibrinous peritonitis; ori- 
or hemorrhagic. | semifluid. gin? 



-\ Distended, no leak; mucosa dark, fri- 
able, no ulceration. 

3 \ol distended, dark; mucosa dark. 
not injected or hemorrhagic. 



3 Notes lost. 

G-12Loop 

hrs. 



Large amount, like Peritonitis over liver only. 

pea soup. 
Small amount, dark Slight beginning peritonitis 

red. thick, like over loop only. 

salve. 



mucosa appears normal . Small amount, semi- No peritonitis 
llnid. dark brown. unknown. 



cause of death 



TABLE II. l\ OX OF LOm» II. I ID is 



D4. 

DJ. 

D8. :'• !"• 



H D18.21.23. 
|g D31. 



:;.; D15. 12. 20. 



Duodenal loop, at 

Normal mucosa, cat 

Duodenal loop, rat, contents and mu- 

I luodenal loop, cat, mu- 

cosa, sepai i 
Buman jejunal obstructions 

,!.. 



Duodenal loops, cat, n 

intents. . 



Duodenal loops, cat, contents 



D26. 
D5C. 



Normal ru 

Ileum I" nts and mucosa . 



Mt'llt-. 



Il.fi 

40 









■ 

(Small.) 

■ 

ilc III.' 
A little d 









is intravenous, exi i pt as - 

TABLE Hi. INJEC i |.,\ OF CA1 LOOP II. 1 ID IN I" I 



22 D15. 17. 20. 

26 ! i 



2!' D18. 21.23. 

1. 



Sfl D18. 21. 2 

42 1 12 

47 D31. 2.H 
A:> D18.21.2 





Duodenal loop, cat, 115 



Duodenal loop, cat, 
and m 

Duodenal 

Duodenal loop, cat, content ■ 



.do. 






Duodenal loops, cat, contents 1"" 

Normal mucosa, cat 



Duodenal loop, cat, contents and n 
....do 



120 



Norma 

Ileum loop, '-.it. contents and mi 

U aahings from drained lo ll" 1 



: nullum 



■ 

lati 

I 
and i' 



■ 



i ABLE V. Nil ii:\i.ix\H"N 01 LOOP i I. rin WITH CA1 






ixlenal loops, rut. ■ •'" N 
tents and n • 

: • mil loop, ..it. .nil i -i 

■ 

1 1,-nal 

Dii.hI.m.iI 

I 

mu. oi 
• rols. 












■ 






None. 









42 



JOHNS HOPKINS HOSPITAL BULLETIN. 



No. 271 



-ni ; .tools and some vomiting, were elicited. Cat, No. 31, died 
with severe diarrhoea, but it developed rather late, and micro- 
scopic examination showed an cedematous colon mucosa, 
heavily infiltrated with polymorphonuclear leucocytes, and 
alive with bacteria. The process extended, in a milder degree, 
some distance into the ileum. 

Table III gives the results when toxic material was injected 
intravenously into dogs. 

It also shows that the fluids obtained from different 
animals of the same species, operated upon, as nearly as 
possible, in the same manner, may differ greatly in toxicity. 
The fluids used with dogs, Nos. 29, 38 and 47, were resisted in 
ordinary doses, but when combined and a large dose given, 
they proved fatal to dog, No. 49. Dogs, Nos. 37, 55 and 68, 
however, succumbed to moderate doses. Dogs, Xos. 37 and 68, 
\vi re injected at the same time as cats. Xos. 36 and 69. The 
results are placed side by side in Table IV. 

TABLE IV.— IMMUNITY OF CATS TO POISOX OF 
CLOSED LOOPS. 



No. 


Fluid from cat 
duodenal loops 


1 
< 


Weight 


Dose per 
gm. in cc. 


Species 


Result 






cc. 


gm. 








36 


D15. 17. 20. 


45 


2560 


0.0180 


Cat 


Recovery, no symp- 
toms. 


37 


D15. 17. L'll. :,0 


6660 


0.0075 


Dog 


Death in 4 hours; 
typical lesions. 


69 


D35. 44. 48. 50 


204S 


0.0240 


Cat 


A little diarrhcea; 




54. 03. 










recovery. 


68 


D35. 44. 48. 
54. 63. 


50 


43C0 


0.0114 


Dog 


Death in 7-8 hours; 
typical lesions. 



Intravenous injections in each experiment. 

In each experiment (Table IV) the cat received more than 
twice as much poison, per gram of body weight, as the dog, 
and in each case, it recovered easily, Avhile the dog succumbed. 
It would have been desirable to push the dose to the lethal 
line for cats, but the supply of material was insufficient. 

The results in the above tables were taken to show that 
dogs reacted to the toxic substance produced in closed loops 
of eats in the same manner in which they react to that from 
closed dog loops. This reaction is described by Whipple, Stone 
and Bernheim, 1 and is in brief as follows: At the time of 
injection, the blood pressure shows a transient fall, and res- 
piration is accelerated. The animal recovers from ether and, 
if not too strongly poisoned, walks about and seems fairly 
normal. Diarrhcea may begin at any time; soon, usually in 
about If hours, the animal grows quiet, a slow but steady fall 
of blood pressure and temperature commence, diarrhoea in- 
creases, becoming mucoid, then fluid and bloody, copious 
vomiting occurs, coma intervenes and death takes place in 
4-8 hours, with convulsive muscular twitchings and paralysis 
of respiration. There may be slight variations, as, for in- 
stance, if the dose is overwhelming, the animal may succumb 
in 2-4 hours without vomiting or diarrhcea, whin the bowel 



and stomach will lie found tightly distended with bloody fluid 
which has not had time to find an exit. 

The autopsy findings, which are designated in the tables as 
" typical lesions " are quite constant. The appearance is that 
of great splanchnic congestion. The veins are full, the 
intestine and stomach distended and dark colored, the peri- 
staltic movements active. On incising the stomach, it is full 
of fluid and mucus, which may be blood-stained. The gastric 
mucosa may show slight hyperemia, but never a very marked 
grade. Beginning, however, at or slightly below the pylorus, 
the intestinal mucosa shows the most extreme hyperemia and 
swelling, and is covered over with a thick, buttery layer of 
yellow mucus. The lumen is filled with a thin, blood-stained 
fluid. The normal bile-stained color of intestinal contents is 
entirely lacking. This turgidity of the mucosa is most pro- 
nounced in the duodenum. It is always uniform, never patchy. 
In mild cases, it may extend downward only to the upper 
jejunum, while in severe cases it involves duodenum, jejunum, 
ileum and colon in an almost uniform congestion. If diar- 
rhoea has existed for any length of time, everything resembling 
normal contents or feces will have been expelled, and nothing 
remain in the gut except the watery, blood-stained, choleraic 
fluid with flakes of mucus described above. The heart usually 
stops in diastole, though it may beat for some time after 
respiration ceases. The blood is very dark and thick from its 
dehydration, and clots with great slowness. This last phe- 
nomenon is due, according to Whipple, to the presence of an 
excess of antithrombin. Microscopically the mucosa shows 
tremendous swelling, distention of the blood vessels and ex- 
travasation of blood. There is an enormous amount of epi- 
thelial desquamation, but no polymorphonuclear infiltration or 
other sign of infection. 

All these details were observed in the dogs poisoned with cat 
material, and therefore it would appear that the toxic sub- 
stance present is probably similar to that found in the closed 
loop of dogs. Dogs seem to have a tendency to react in this 
manner, witness the similar, but not identical, pictures in 
"anaphylactic enteritis" and poisoning with typhoid and 
colon bacillus toxins. 2 s 4 

In Table IY, animal, No. 42, is shown as being fatally 
poisoned by an extract of normal cat small gut mucosa. Since 
the material had stood some time, however, and since a later 
experiment with fresher material (No. 53) failed to support 
the finding, it is not thought to be of great importance. Why 
the first-mentioned extract should have been or have become 
toxic is not at present evident, though the conjecture of a 
possible secretion of toxic substance by normal or apparently 
normal mucosa at once presents itself. 

In Table III, again, animal, No. 65, was killed in a few 
hours, with symptoms and autopsy picture the same as in those 
poisoned with closed loop material, by a fluid which was ob- 
tained by daily washing out a cat duodenal loop which had 

I ii brought to the surface at each end. This cat, D. 39, 

remained in excellent condition during the time the loop was 
irrigated daily. The secretion was in the form of almost clear, 
slightly yellowish fluid, containing flakes of mucus. It was 






mv Utt . 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






imnie.liat. 1 ■ - i .ed with chloroform and toluol, at id 

0. to suitable volume for injection. Here 
material was removed as it formed from tl 
ment of gut, ami the eat did not show the e ' ibsorp- 

tion. The mucosa of this drained loop at the end of I 
perimiiit was macroseopically normal. 

The reader will have noted that the toxicity of the various 
cat loop fluids has been judged in this papei solely by their 
action'- animals. Efforts were n 

smaller animal whi< h would he suitable for this 
purpose. It was felt that any modi' of injection except the 
intravenous was unsatisfactoi o the difficulty in 

Sterilizing the fluids, ami the somewhat irritant nature of 
some of thi exti 

Guinea-pigs, rats ami mire were abandoned. Other oh- 
bave found guinea-pi 
materials as to render them useless.' A loi injec- 

tions was made in 35 rabbits with the result thai th 
seem unsuitable for the purpose. Their hold on lit'. 
insecure, ami they readily succumb to infection, intercurrent 
or even preexistent disease. A rabbil th coccidiosis 

will die from a much smaller dose than will he sustained by its 
ted brother. Ohl sed in 

i. the animal may die in , onvulsions in a few minutes, 
while if it does not, it often lives 24-48 hours, when the possi- 
bility of ill When death do. - 

in a few hours, no typical symptoms have been noted, and the 
autopsy findings are indefinite. All this i> in contrast •■ 
which readily resist the infection from injections id' non-toxic 
fluid, hut which die with remarkably constant symptoms, and 
which present a typical picture' at autopsy. 

Drained loops like that described own as Vella 

lave long been used by physiologists in investigating 
the intestinal secretions. U ha- been noted bj —in. of them 
that if a Becond dog receives an injection of the 
Bach a loop, he himself is better able to withstand th 

a similar loop of his own intestine. W bippl 
and Bernheim di mi 
this -ori in dogs " hi n not. d ■•■• il 

.! they Bupport a lethal aously, 

and al-o live mm h longer than otherwise . 

■ u made. The researches ":' I 
that the immunity in these animal- resides principally in the 
pleen ami ink 3tii al mm at all in the 

it appeared that in tl 
tnjoying a natural immunity, it became of u 

lie, wherein that immunity lay. With this L I 
known toxic fluids, principal! 

from no! i h l at whole 

md with cat -.rum. allowed t" -land for 
the incubator, and then filtered ami 
(small dogs i . 

Table V shows that little - 
ports. Two of tii. 
In th. 

■ 



: ion with tie 
although this animal die 
not just 
of neutralization o 

The death 
the tin 

neutralizatioi 
terial chance. In I 

■ail. Withii 
entirely normal, ami making the 
break down the di 

tralized by autolysi 

autolysates of immune .. 

I M'.l.i \ I 1 M M 1 NIZATION OF i: \ 









1 1 2 5 

5 |s ,-, | 000 

.". 2 I 



100 
110 

111 



5 17 
i 17 



■ 






0217 



Well. 

Well. 

1 1) : 

Well. 
Well. 

■ 






44 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 270 



supposedly toxic intestinal material into animals of various 
species. In going through the literature, one finds that all 
experimenters have had difficulty in poisoning cats with in- 
testinal toxins. Usually where they have succeeded, it has 
been by intraperitoneal injection, with lethal result in 14-18 
hours, in which case the possibility of infection must enter. 
Von Albeck is an exception. He was able to induce the death 
of kittens by the introduction, intravenously as well as intro- 
peritoneally, of 5-20 cc. of the contents of strangulated in- 
testinal loops, suitably diluted with water. Some of them 
died in as short a time as 4^- hours. He, however, states that 
many kittens and cats proved extremely resistant.' 

Another source of confusion lies in the ease, with which 
animals of any species may be killed by introducing this sort 
of fluid too rapidly into its veins; for example animal, Xo. 24, 
in Table II. It is, however, especially important in the ease 
of rabbits, and mars the value of the work of Eoger and his 
associates. In their results, all except immediate deaths are 
ignored, and it is only by perusing their tables carefully that 
one learns that some of the animals succumbed at the end of 
5-2 1 hours, often with diarrhoea. 8 

Conclusions. 

1. Cats will survive two to six days after the production 
of closed duodenal loops, often dying of peritonitis. 

2. The contents of these loops after heating and filtration, 
will kill dogs, when injected intravenously, with the same 
symptoms and anatomical picture seen wdien dog loop contents 
are used. 



3. Cats are resistant to this toxic material, withstanding 
with ease doses of over twice as much per gram of body weight, 
as is necessary to kill dogs. 

4. Efforts to neutralize the toxin of duodenal loop contents 
by incubation with eat organ extracts, cat blood, and cat 
serum, have been unsuccessful. 

5. Rabbits and guinea pigs are much less suitable for test- 
ing the toxicity of intestinal fluids than dogs, owing to their 
great susceptibility to hurtful influences of all sorts. 

6. Cats are also less suitable for the same purpose than dogs 
owing to their high natural immunity against closed loop 
toxin. 

The last two considerations must receive careful attention 
in drawing conclusions from any set of experiments dealing 
with the poisons of intestinal obstruction. 

We are indebted to Mr. Roy E. Fallas for his assistance in a 
number of the experiments. 

REFERENCES. 

1. Whipple, Stone and Bernheiru: Johns Hopkins Hosp. Bull., 
1912, XXIII, 159; also J. Exp. Med., 1913, XVII, 286, 307. 

2. Arinia: Centralbl. f. Bakt. 1912, LXIII, 424. 

3. Schittenhelm and Weichardt: Miinchen. med. Wchnschr., 
1910, LVIII, 769. 

4. Schittenhelm, Weichardt and Grisshammer: Ztschr. f. Exp, 
Path. u. Ther., 1912, XI, 412. 

5. McLean and Andries: J. Am. M. Ass., 1912, LIX, 1615. 

6. Whipple, Stone and Bernheim: Forthcoming publication. 

7. v. Albeck: Arch. f. klin. Chir. 1902, LXV, 569. 

8. Roger and Gamier: Compt. rend. Soc. de biol., 1905, LVII, 
388, 674, 677; 1906, LVIII, 27; 1908, LXIV, 426, 610, 883. 



NIELS STENSEN.* 

By William Snow Millek, M. D., 
(Anatomical Laboratory, University of Wisconsin, Madison, ~\Yis.) 



Pulchra sunt quae videntur, pulchriora quae sciuntur, longe pul- 
eherrima quae ignorantur. — Stensen. 

Situated below 7 and in front of the ear is the largest of the 
salivary glands. Extending from its anterior border, at its 
most prominent part, is a duct which opens into the mouth 
cavity by a small orifice opposite the second upper molar. 
This is the ductus parotideus, commonly known as the duct 
of Steno, or Stensen's duct. 

As one wanders through the University of Copenhagen one 
will see hanging on the wall, surrounded by many of the old 
anatomists, a picture of a Catholic bishop. His curiosity 
is aroused by seeing a churchman placed in such strange 
company. The picture is that of Niels Stensen. 

In the fall of the year 1881, the president of the Interna- 
tional Congress of Geologists, then meeting at Bologna, sent 
a delegate to Florence to lav a wreath on the grave of a man 
who is considered one of the great men in the history of 
geology. The grave is that of Xiels Stensen. 



* Read at the January, 1913, meeting of the University of Wis- 
consin Medical History Seminar. 



How comes it that the man, who lies in that quiet tomb of 
the Medici in the Basilica of St. Lawrence at Florence, has his 
name connected with so varied a life as is indicated by the 
above statements? 

I shall not attempt to answer in full the above question, 
for it would take more time than I have at my disposal. I 
shall confine myself largely to the anatomical side of the 1 
question referring to the rest sufficiently for a full under- 
standing of the character and motives of our anatomical- 
geological-bishop. 

Steen Pedersen, Stensen's father, was a goldsmith in Copen- 
hagen; his mother was Anna Xilsdatter and was probably the 
second wife of Pedersen. On the 10/20 of January, 1638, 
there was born to the couple a son. who. as was the custom at 
that time, took the Christian name of his father. Besides 
a brother. 3'? year- old, by the name of John, Stensen had a 
sister, Anna, who married a certain Jacob Kitzerov and lived 
at Copenhagen. Stensen's father died before he was six years 
old and, as his mother soon married again, he lived with his 
grandparents. In regard to this period of his life Stensen's 






IKY. 1014.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



Wttemhrances were m>t very pleasant, for from his third 
until his sixtli year he was sickly, and, li\iiiL. r as he did with 
idparents, he had too much of "old folks" and too 
little of the companionship of children of his own age. The 
conversation to which he had t.> listen was larg 
Hgious nature and, as Foster says, he " heard much, too much 
perhaps, I rines of Luther." 

qow but little of the early education of Stensen. 
del states that his grandparents provided him with a private 
tuto- in order to tit him for the university. However his 
early education was acquired it musl have : rough, 

for in later life he spoke and wrote Latin. German, Dutch, 
French, Italian and English. Hi also had a fiindainrnt.il 
II. iivu and Greek. II.- was especially fond 
of mathematics, and had not circumstat I him 

otherwise, would probably have made them his life study. 

The University of Copenhagen was founded by Pope Sixtus 
1Y in 1 175, and the tir-t instruction was given in Juni 
At this time the university was under th of the 

Catholic church ami so continued until mation, 

when, after various vicissitudes, it was discontinued in 1">:'.-".. 

: i hristian 1 1 1 restored tin- uni 
a- a Lutheran institution. 

In 1656, at th.' age "i 18, Stensen entered the uni' 
or, a- they -aid at that time deponirte. The word deponiren 
ha- quite another significance than " matriculation "' : it refers 
t" the highly grotesque ami no! always agreeable ceremony 
which took the place of the simple matriculation of the 
day. 

Within a specified time the young .-indent, after depositing 
rtificate, and it had been found satisfactory, had 

to present himself t" tl Idesi ho was always one 

d' the oldest students) to he prepared for the academ 
-..ration, (in the appointed festive day the candidate 
ed, with other candidates, at the Studienhof in a 
arnival costume. The more grotesque it was the more 
pleasing it wai to the student body. The pedell then came 
on the scene clothed in like manner and provided with whip, 
pinchers, plane and like instruments. Hi 

victim.- with shout.- and blows into a r whi 

examination was held; hut n alter how well I 

qswi n d it always ended with i 
the\ w. re -ulije. led to all kind- ol 

- and were pushed about unl 
completi • leir clothing. \\ 

then dashed ovi r thi ir In ads in order t. 
smudge from then- faces. When this wa« 
Students \uie deponirt. The "freshmen" t 1 

the dean of the univi rsity in propi One 

of them besought him, in the Latin languaj 
into academ ii i tizenship in order that tl ■ 

and purer life than they had 
lean commended thi ir zeal and i ■ p 

! ing should 
from which th.- had l 



should 

in the future which shoul 

as the 

they 1 . 

animal conditio,, t. 

which human nal 
which impro 
At : 

young studi 

had called them to 
their tongui - 

DOW .-true of th.ir own a. . ord, DOl 

or whip. 

ft w 
students to i 
should be 1 - 

i d in him a student w 
statement w hen i - 
this day are exceedingly proud, and with _ 
famil. in, who not ..nl\ taughl a; I 

throughout the enl nth century, but, I 

students, broughl to their university 
over all Europe. 

CTnder the direction of Bartholin, S 
of anatomy and at the 
studies. He pursued with Bpecial indusl 
matics but also Hebrew, in which hi 

ly read his Bible in thai 
The years during n hi. 
stormy. In 1658 the Swedes invaded Denmark and I* 
( openhagen. The student- rallied I 

and foi 

ing. I'p" 11 ' 

'. ; he hi Id 

under his . h 

r life than 

■ 



46 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo.27« 






studies at reign university, and their preceptor gave 

them a certificate and often letters of introduction to some 
special friend or colleague. Thomas Bartholin gave Stensen 
such a certificate and a letter of recommendation to Professor 
Gerhard Blasius of Amsterdam. 

At the beginning of the seventeenth century the medical 
schools of Holland enjoyed a great reputation because of the 
advantages which they possessed in the teaching of anatomy 
and because of the men who taught anatomy: at Amsterdam 
was Blasius or in Dutch, Blaes; at Leyden were van Home 
and Sylvius. Stensen pursued his studies at both of these 
places. Stensen first went to Amsterdam and became an 
inmate of the house of Blasius. Scarcely had he taken his 
scalpel in his hand when he made a discovery which will per- 
petuate his name — the discovery of the duct of Steno. No 
sooner had he made the discovery than he was involved in a 
controversy with Blasius. At that time discoveries in anatomy 
led to very acrimonious strife and, in the case of Wirsung, 
to murder. We have a very complete account of the con- 
troversy and it may be of interest to follow it, for it sheds 
light on the methods of the day. 

Stensen himself, in a very modest way, gives an account of 
the discovery, in a letter which he wrote from Leyden, April 
22. 1661, to his old preceptor Bartholin at Copenhagen. I 
will ijiiote part of the letter: 

Since you request of me in your letter to publish a representa- 
tion of the external salivary canal, I am induced to explain 
to you briefly the envy which this otherwise unimportant discov- 
ery has caused me, as also the lessons which I have learned from 
it, not in order to seek glory in little things but to refute the 
hated accusation that I am anxious to adorn myself with borrowed 
plumage. 

It is not a year since I was hospitably received by Blasius. He 
permitted me at my request, to dissect with my own hand what- 
ever I should purchase, and fortune so favored me that in dissect- 
ing in my first study, the head of a sheep, which I had purchased 
on the 7th of April, I discovered a canal, which, so far as I know, 
no anatomist has as yet described. As I was just about to separate 
the well known tissues and then to dissect the brain, it occurred 
to me that I ought to first examine the vessels which surround 
the cavity of the mouth. While I was examining for this purpose 
the veins and arteries, I noticed that the point of my knife no 
longer wedged in between the tissues, moved more freely in a 
large cavity, and I soon heard as I pushed forward the iron the 
sound it produced by striking the teeth. Astonished at this dis- 
covery I called the master of the house to get his opinion. He first 
ascribed the sound to the thrust of the knife, then he had recourse 
to explaining it as a "freak of nature"; finally, he consulted 
Wharton, but since this also did not help us, and since the ves- 
sels, which had not been very carefully handled, did not permit 
of further examination, I determined to again make the same 
examination but with greater care. I succeeded, though not as 
well as the first time, on the head of a dog. 

In the same m S1 n mimunicated his di 

to his friend Jacob Henry Paulli, who in 1662 was made 
professor of anatomy at Copenhagen, and later to Sylvius, 
belter known as Du Boe or Dubois, at Leyden. Syl\ ins found 
the duct in man. In a letter to Eysonius of Groningen, the 
younger brother of Blasius ascribes the discovery to Stensen. 
Blasius, the elder, did not agree with him. lie was greatlj 



enraged that Stensen should claim the discovery which he 
declared he himself had made. Instead of bringing proof 
that the discovery was his, he called Stensen " liar," " blas- 
phemer " and " malevolent fellow inflated with envy." Good 
proof that Stensen's assertions were true. Further on in his 
letter to Bartholin, Stensen says: 

Had not the celebrated Mr. van Home given my name to the 
canal in so conspicuous a place, before such a circle of learned 
men, I should gladly have renounced my rights. But to proceed 
to other things: I shall mention one fact which I consider the 
most conclusive proof. Blasius shows plainly in his treatise " De 
medicina generale " that he has never sought for the duct; for 
he does not give to it either the proper point of beginning or 
ending, and assigns to the parotid gland so unworthy a function. 
that of furnishing warmth for the ear, that were I not right 
certain to have shown him the duct, I should be tempted to assert 
that he had never seen it. 

Bartholin replied to this letter on the 10th of the following 
May, and says among other things : 

The fatherland congratulates itself upon such a citizen, I upon 
such a pupil, through whose efforts anatomy makes daily progress 
and our lymphatic vessels are traced out more and more. You 
divide honors with Wharton, since you have added to his internal 
duct an external one, and have thereby discovered the source of 
the saliva concerning which many have hitherto dreamed much, 
but which no one has (permit the expression) pointed out with 
the finger. Continue, my Steno, to follow the path to immortal 
glory which true anatomy holds out to you. 

Bartholin regretted the controversy that had arisen with 
Blasius. Probably his own controversy over the discovery of 
the lymphatics, which occurred about this time, made him 
somewhat cautious. 

The annoying experiences to which Stensen was subjected 
at Amsterdam made his stay there disagreeable; besides he 
had outgrown Blasius. He therefore went to Leyden where 
Sylvius and van Home taught. The ill will of Blasius fol- 
lowed him. Ole Borch, a fellow student of Stensen's at Ley- 
den, wrote to Bartholin on the 20th of March, 1661, that he 
had heard that Blasius claimed the discovery of Stensen as 
his own. 

But Stensen will answer him, not on account of the glory which 
is attached to the discovery, but because Stensen will not wish 
it to appear as though he had misled Sylvius and van Home, who 
have publicly called the duct " Steno's duct." 

About this time Blasius published his " De medicina 
generale." above spoken of, in which he expressly claimed 
the discovery of the duct. This claim Stensen proceeded to 
refute. On the 6th and 9th of July. L661, Stensen conducted 
a brilliant public debate, over which van Home presided, 
which did great honor to a young man only 23 years old. 
The debate increased the bitterness of Blasius and he com- 
plained in a letter written on the 16th of July to Bartholin, 
that Stensen takes to himself, regardless of propriety and in 
violation of the truth, a discovery the glory of which belongs 
to him — Blasius. Bartholin, although he did not openly 
-. answered lihisius on the 1st of September and 
called his attention to hi- ridiculous behavior. "Your con- 



Fbbbcmry, 



JOHNS BOPKINS EOSPITAL BULLETIN. 






will tell you who is right in this matti 
eludes his letter, " and control you 
In the mean time Stensen proceeded to investigate the 
glands of tin r he had returned from a short jour- 

e reported the results to Bartholin, on the 12th of 
September. Bartholin r ss of hi* 

pupil, and wrote him on the '< ib< r, " X iur fame 

grows from day to day. Your pen and sharp eyes know n" 
Bartholin was right. Stensen worked incessantly and 
made discover] afl 
the results of his work <>n the gland 

of the i • tin- early pari of 1662, this was followed 

ollection of bis observations, 
tly elated by the his student, Bartholin 

ed to heartily recommend him to the Bang. "You 
may count upon the favor of the King, as well ae I 
of the learn olin wrote S the lltli of 

February. 

Daring the latter part of 1662 and in L663, Stensen seems 
to have burn busy with his invi - jpeciall) 

that of the heart, and defending hin 

Blasius. On March 5, 1663, he wrote Bartholin that the 
controversy had again broken out; yet in thi mean time 
Blasius had not learned where the ided. 

In the early part of 1664 Stensen went on a - 
Where he went no one has been able to discover] but on bis 
return he w> • ■ ! agen. It is quite probable thai the 

death of his step-father whicl al this time 

him home; possibly the | appointmenl 

of anatomy was another reason. During his stay in I 

ie published his "Di 
tionum specimen," which he dedicated to King Friedricb 111. 
His com eption oi 
ion. 

The heart has I :onsldered the Beat of natural warmth, 

,!' the bouI and I lie soul Itself, Boo 
greeted I the s\m. others as the kin--: but If you i «am- 
lne It more closely, one flnda It to be aothlng more tha uscle. 

- Hie writing in 161 " This simplt 

overthrew a system to which medicine cliu 

: v "; the • elebrab d pi Mailer, writ 

L774, did not hesita 
book which contaim ■ 

reputation which I 
support of Bartholin, 

• 

and Sti I!- n has 

II irst went to Holland at 
Pari> where he remained until 
: 1665. I ■ 

I I ■ 
him he gained enti u 
about Thevenot An add 



S 

1 i K ' n ir won- 

:. but aftei ) 'King at 

all; all 
the one grey, the ■ I 

tinned 

ither. If W( a i, whnt 

manner the nerves are united with the wine 

:'■(] a |M'|l|t 

admired by a er unions public. 

■■: anatomine 
In the fall of 166' S 
France where he foun 

I for liim t 
With lial\ so near be could not this land whi 

so interesting 

tells n- that in the early part 
Rome. From t ; ■ 
Florem 

Italian langl 

- 
the Medici 
Italy. The Grand 

Grand Duke, but I 

■ 
appointi 

which 



JOHNS HOPKINS HOSPITAL BULLETIN. 



I sro.ari 



This brings us to an exceedingly interesting period in the 
life of Stensen; his conversion from Lutheranism to Catholi- 
cism. I wish 1 had more time in which to discuss this change 
in his life and work. I do not believe with Foster that it 
was a sudden change, but rather one that was reached after 
mature deliberation. Science lost a most brilliant worker, 
but the Church gained an earnest, lovable devotee who spared 
no effort to promote her interests. 

When 21 years old Stensen left the university of his father- 
land a faithful Lutheran. With impetuosity and vigor the 
young man gav< himself up completely to the scientific cur- 
rent which met him in Holland; in scientific relations truly 
it was not to his disadvantage. Not so fortunate was the new 
atmosphere for his orthodox belief. Many of his friends were 
atheists, others, as Spinoza, pantheists; the greater number 
belonged to the motley crowd of Calvanists. Stensen soon 
became aware of the danger which threatened him from 
fellowship with such men. The study of the heart and 
other portions of the body had, so Stensen wrote a friend in 
Hannover in 1680, brought him back on the right track, since 
he had become convinced that so wonderful a structure could 
nut arise by accident or fate hut must be the work of a master 
workman whose wisdom was unending. As such he found 
(hiil. the Creator of all things. His scientific studies carried 
him still further. The discovery of numerous errors which 
men of science advanced as established truths, shook power- 
fully his belief in his " infallibility " in religious things. 
Still more, and certainly forever, was his faith in the teach- 
ings of the Reformation shaken. Thus, step by step, he no 
longer held to the tenets of his father, no longer to his former 
dogmatism. This showed itself especially when he met with 
Catholics. Generally he abstained from discussing religion 
with them. If he could not prevent it. he defended himself 
bravely, as he said, so long as he held Luther's translation of 
the Bible ami Catechism as the true, undoubted word of 
God. Still he could not conceal from himself that the life of 
smile of his Catholic friends made a deep impression mi him, 
a life which he neither found in philosophy nor had oppor- 
tunity to observe in his friends of other faiths. 

Stensen was not far from Catholicism. The only change 
that he perceived in himself was. that he saw less in his earlier 
religious belief to maintain, ami more and more laid aside the 
resentment which he felt against other faiths. During his 
journey to Paris in 1664 lie met a Jesuit father in Koln who 
told him many things about Catholicism ami asked him ques- 
tions in regard to his own belief that he found hard to 
answer. Here again bis active mind was directed into new 
lines of thought. Certain it is that his intercourse with 
Bossuet in Paris removed many of his prejudices against 
Catholicism. 

You will recall that in 1666 Stensen went from Paris mi a 
jounioN ; this brought him to Rome ami later to Livorno just 
at the time of the Corpus Christi procession, which made a 
great impression on him. From Livorno lie went to Florence 
and became connected n Hospital of Santa Maria 



Nuova; a Lutheran connected with a Catholic institution, re- 
versing the position which he later occupied: a Catholic con- 
nected with a Lutheran institution. 

One day Stensen came into the pharmacy connected with 
the Cloister attached to the hospital. There be met Sister 
Maria Flavia del N T eno who had charge of the pharmacy. 
She belonged to a prominent family in Tuscany ami had been 
in the Cloister since 1631. Quite naturally, she regretted that 
the Qoted anatomist and physician was a Lutheran. The 
devout nun took this seriously to heart and she sought by 
prayers and friendly words to win him for the Catholic 
church. Stensen listened to the unaffected words of the 
Sister willingly for they came from a heart that, as he soon 
noted, was concerned for his best welfare. 

In Florence. Stensen met still another woman who was to 
be influential in forming his decision. As body physician to 
the Grand Duke, and a famous anatomist, be easily gained 
entrance into the associations and scientific circles of the city. 
Among these, the most noted, was one that assembled at the 
house of the ambassador from Lucca, Arnolsini. His wife, 
Signora Lavinia. was everywhere known as a generous and 
devout woman. She soon discovered the lofty sentiments of 
the young Protestant savant and joined-with Sister Flavia in 
prayers and penance that they might win from God his con- 
version. 

As Signora Lavinia saw with what industry her friend 
studied the Catholic teachings, she urged him to talk with 
her father-confessor, the Jesuit Savignani. The nun gave him 
the same advice. Stensen followed it and consulted him; he 
soon gave him bis complete confidence and opened to him his 
innermost thoughts. They frequently met and held long con- 
versations together. By means of these interviews the last 
doubts were soon removed. Stensen's mind was convinced, 
but as yet the last " I will " would not come from bis lips. 
When at last it did come, it formed the sudden conversion 
spoken of by many authors. On the Feast of the Immacu- 
late Conception, November ?, 1667, Stensen consummated his 
renunciation before the Nuntius. In Florence great joy pre- 
vailed over lii- i onversion. 

In December. 1667, Stensen's friend. Viviani. wrote to 
Magalotti, who was at that time in Flanders, that on the 
very day that Stensen finally appeared before the Xuntius. 
after he had declared his conversion, he received a letter from 
the Danish King offering him the professorship at Copenr 
hagen with a yearly compensation of -400 scudi with the pros- 
pect of increased compensation. Stensen did not start at once 
on bis journey for Denmark, hut wrote the King asking if he 
were willing that he should change his belief; but no word 
came from Denmark-. We know that during the following 
years Stensen wandered through Austria, France ami Hol- 
land where he remained waiting for an answer to his letter 
to the King, who was at this time very ill and who died the 
2d of February, L670. 

While Stensen was waiting in Holland there arose in Den- 
mark, a man who exercised a great influence on the later 






February, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN, 






• of the kingdom. This man 
feld. I rich III lie had been advanced i'« honorable 

n and Christian V made him his Prime M 

nd in him a friend and supporter. In hi-, in- 
augural add - i. thanked him for his appointment 
in the university. Griffenfeld for a long time Btr 

in of religious belief; finally, on the 26th of September, 
1671, a royal ee permitted the Catholics to build a church. 
(>n th,- 13th of February, lii;-.'. Christian V sent an order 
ae to Denmark and stated thai he was to 
have a yearly pension of 100 Reii bsthaler and that his 
would begin as soon as he began his homeward journey. 
• ads were afraid that he would go back entirely 
to his scientific work. Magalotti wrote to Falconier 
dom of thought has robbed us 8 was not 

the case. 

le 3d of July. lii;-.'. Stensen retui ohagen 

and took up his residence with his sister. From her I ■ 
S si Flavia at Florence " I am living with m 
I have perfect freedom: no one says aughi againsi a 
many hold the belief that every on,- i- saved in his own 
religion, if only he lives rightly." 
With the return of Stensen to Copenhagen there reap 

i'aulli and of Bartholin. In his inaugural 
addre-- - wed himself to he a man of deep i 

convictions as well as a true scientist. 1 "ill i 
u r e: 

What one sees is beautiful; more beautiful what one knows; Inn 
by far the most beautiful things are beyond our knowledge 
the true purpose of anatomy to direct the observer through the 
astonishing structure of the body to the dign iul, and 

finally to lead him through the wonders of both to the kn- 
and love of the Creator. For who can contemplate tie- wonderful 
structure of the human organism without asking who 
author? 

I • Cniversity of < n was not, 

for any great \< ngth oi timi . II' 

at Berlufs- 
liolm. Johannes Brunsmann. 1 1 
Lutheran uni 

■ 
tention. Just what the 

church. 

well at th 
- 
jition which 

which was rii h in 

■ 

al museum. Am ' . ' 



- ich well ki 

5 

S 

■ 
body the kn ivhich he did not enrich." 

He discovered the duct 

lingual gland and of the bui 
nd and its 
disputed subject. Il«- had n 
about capillary circulation, • 

truth and served as a useful basis for further inquiry." 
He i- N' rv clear in differentiatii i 

though lie did not properly interpn I :" mus- 

cular contraction, he did point out th.it ti 

ot depend upon an in, n 
His recognition of th,- i 

dation by II 
our knoi olatory apparatus. 

I havi 
intluei 
also made i 

: foundatioi 

In 1 

I 

■ 



' 



50 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| ffo.gfl 



enunciate definite natural laws governing the formation of a 
stratigraphical succession in the earth's crust. 

Stensen also realized that a series of strata originally hori- 
zontal might become relatively displaced by subsequent earth 
movements. He cited examples of local crust-inthrow, show- 
ing how individual strata might remain horizontal, while 
others might be tilted or even thrown into a quite perpendicu- 
lar position, others again might be bent into the form of 
arches. The occurrence of crust-inthrows, together with the 
effects of surface denudation, might give shape to mountains 
and valleys, plateaus and low lying plains. Mountains, he 
said, might also originate from the upward action of the 
volcanic forces on the crust. In cases of active volcanic 
eruption, ashy and fragmental rock material were ejected, 
intermixed with sulphurous vapors and mineral pitch. 

Thus Stensen's work already contained the kernel of much 
that has been under constant discussion during the two cen- 
turies which have passed since his death. If one reads the 
most recent text-books of geology, it will be evident that 
science has not yet securely ascertained the share that is to be 
assigned to subsidence, to upheaval, to erosion and to volcanic 
action in the history of the earth's surface conformation in 
different regions. 

Stensen's work "De- soli do intra solidum naturaliter con- 
tento," was first published in Florence in 1669, and was 
intended merely as the prodrome of a larger work: but no 
later work appeared. A second edition was printed at Leyden 
in 1679, and a third edition was published in Berlin in 1901 
two and a quarter centuries after the first edition appeared. 
The original edition of Stensen's little book is a bibliographi- 
cal rarity. 

We will now go back to the year 1674. When Stensen left 
Copenhagen in July of that year, he journeyed leisurely to 
Florence where he took charge of the education of the son of 
the Grand Duke Cosimo III. By some it is asserted that this 
was the occasion of his resignation. Facts do not, however, 
substantiate this statement. 

The conversion of Stensen to Catholicism in no way inter- 
fered with his studies. After his conversion he occupied the 
chair of anatomy at Copenhagen and wrote his epoch-making 
work on geology, to which I have just referred. That the 
acceptance of Catholicism did not at that time necessarily 
kill science in the man is shown in the case of Winslow, 
Stensen's grand-nephew, who also, after leaving Denmark, 
became a Catholic and was one of the great anatomist; of 
Paris. 

Although Stensen, while at Copenhagen, had full liberty 
he did not in his lectures permit religion to supersede an- 
atomy. Still he had a far stronger desire to communicate 
the fruits of his religion to Iris compatriots than to transmit 
to them the knowledge of anatomy : the moral appealed to 
him more than the physical. 

In 1675 Stensen became a priest. Just when and where he 
took holy orders I have been unable to ascertain. On Sun- 
day the 25th of September, L677, Pope Innocent XI con- 



secrated him Bishop of Titiopolis. A short time after this, 
Jean Frederick, Prince of Braunschweig, who had already 
abjured Lutheranism called him to his court. Innocent XI 
consented and bestowed upon him the title of " Apostolic 
Vicar for the Northern Missions." It was for this reason 
that Stensen visited the different cities of Germany: Minister, 
Hannover and Mecklenburg being the principal scenes of his 
missions. 

When Frederick died suddenly, his brother, Bishop of 
Osnabruck, succeeded him; and, as he was a Lutheran and a 
very zealous partisan of his religion, he enjoined upon Sten- 
sen to leave his country. Stensen went to Minister; frOBB 
Minister he went to Hamburg, and, after a short and un- 
satisfactory stay, to Swerin where he led a quiet and peaceful 
life and died November 25, 1686, at the age of 48. 

The death of Stensen made a sensation among the savants 
of the world. Men of letters had watched him. His rare 
knowledge of anatomy and his unexpected conversion to 
Catholicism made an epoch in the history of science. The 
Grand Duke of Tuscany hearing of his death desired to have 
his body. He sent immediately .an order to transport it to 
Florence where he had it entombed with the Grand Dukes in 
St. Lawrence. 

Stensen's zeal for the church and his religion, his lovable 
character and kind sympathy made him unusually successful 
in his work. The text chosen for his funeral discourse by 
Engelbert Schmall, who for five years was Stensen's chaplain, 
" Follow me, I will make you fishers of men," plainly shewed 
the estimate placed on the life work and the character of the 
subject of this sketch. 

NOTES. 

The main facts of this sketch are derived from Plenkers. See 
Bibliography. 

The following variations in the spelling of Stensen's name are 
met with in the literature: Steno; Stenon; Stenone; Stenonis; 
Stenonius. In the " Epistolarum " of Bartholin and in the " Acta " 
the last two forms are used. The signature of the letters in the 
Epistolarum is " Stenonis ". I have followed Plenkers and used 
Stensen because it is the modern Danish usage and also because 
Stensen signifies " son of Sten ". 

An illustration of the " Domus Anatomica," and of its amphi- 
theater, in which Stensen gave his lectures may be found in 
Bartholin's " Cista Medica Hafniensis"; Hafniae, 1662; also in 
Chievitz, " Anatomiens Historia"; Copenhagen, 1904. Chievitz 
gives a number of illustrations of persons and places mentioned in 
this paper. 

Stensen did not take his medical degree at Copenhagen. Whert 
and when he did take it no one knows. Plenkers thinks he 
received it in 1665 at some University in southern France. Barth- 
olin does not address him in his Epistolarum as " Doctor " until 
1667. 

I have not been able to consult Stensen's original publications. 
Abstracts and reprints may be found in Vesling's " Syntagma anas 
tomicum"; Amstelodami, 1666; and in Mangetus " Bibliotheca 
anatomica," Geneva, 1685. The notes sent by Stensen to Bartholin 
and the correspondence of Bartholin with Stensen, Ole Borcli ami 
Blasius I have read; they are found in the two publication 
under Bartholin in the Bibliography. The complete text of Sten- 
sen's inaugural address is given in Acta Hafniensis, Vol. II. 



THE JOHNS HOPKINS HOSPITAL BULLETIN, FEBRUARY, 1914. 




Ik i i rom > Bti ti -.11 




V". •_• Tbomai Bartholin. From i < 




' 



1014.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



BIBLIOGRAPHY. 

Bartholin. Thomas: Acta medica et pMlosophica Hafnimsla. 
I wis., 16711679; Hafnia?, Eplstolarum medicinalium. 

Cent. MY. Hafnia 

Blonde], 1. es Saints pour chaque jour do Can nee. 

Paris, 1722 

Daremberg, Ch.: Historie des Sciem • 

Foster, M.: History of Physiology. Cambridge, 1901. 



'■ 

WlM 

huinain. Pw 

I K A. HI 



A BRIEF HISTORICAL SKETCH OF SOME OF THE l.AIM.Y STUDIES OF 
THE FINER STRUCTURE OF PLANT AND ANIMAL I I — I ES/ 

Bj l.'u 11 u:i> If. :. 1»., 



The theory which is based on the al all animal 

and that all 
cells are derived from preexistii 

I most i in - 
generalizations in biology — ranking with Darwin's th< 
evolution — is usually linked with the nai 
Schwann and Vircliow. representing the period from ' 

1 he work of the three individuals mentioned i 
is true, always stand as important determining 

[] the development of the cell theory, hut m 
interest to workers in the biologica ed the 

studies of these three gnat investigators and many in;; 
studies of cell structure followed their ann< and led 

eventually to the exact 1 i mitosis whii 

ate with Flemming' on in 1882. ork ami 

■ we hear lit! 
many valnabli 

and Virchow, have been obecun 
of the • 

value, but it is the earlier work that hat 
primitr 
Schwann tie' 

of animal ti-- 

to the i .-lilt up lln 

definite, ev< n mathi 

than 1 " 

Sooke, S 

S 



for lanti rations, lllu 

vario\is i. 

Medical Club of All. any. N J 

sity of Pennsylvania, the Section on tl 

the Collope of l 

sophical Society. 



rlier than hie ' I S 

that lie made an in.: 
st met u : 

bryo.' I 

in which tii"St im: i 
struchi 

- ■• \ 

: ]'■', l . hi \* ' 









i 



52 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[ Xo. 2ft 



am the first who have given a Map of the Country," and 
again, " In sum. your Majesty will find, that we are come 
ashore into a Xew World, whereof we see no end." 

Malpighi's letter of transmissal to the Royal Society, shows 
the importance which he, likewise, ascribed to his investiga- 
tions/ (irnv's numerous plates as also those of Malpighi pre- 
sent figures illustrating the finer details of plant structure. 
They show, in brief, that plant tissue consists in part of little 
cell-like cavities and in part of long tube-like vessels. This 
conception of vegetable tissue is one of small vesicles or blad- 
ders clustered together and intermixed with ligneous fiber. 
Grew, for example, compared cellular tissue to the froth of 
beer or of beaten eggs. Malpighi showed that the cells could 
be separated one from another, and gave to these bodies the 
name " utriculus." It is not to be supposed, however, that 
they had the conception of cells which we have to-day. Their 




conception of a cell was that of a cavity and not of a minute 
protoplasmic mass. As the Latin "cell" was in its earliest 
application " a small detached room in a building, particularly 
a small monastic house " s — and was also used to describe a 
small sleeping apartment, and later a room in a prison, and 
likewise the small compartments composing a compound struc- 
ture, as a honeycomb, so it was applied by early microscopists 
to the spaces which they saw in vegetable or animal tissues. 
lt> lir-t use in this latter sense appears to be by Hooke, 6 who, 
iii 1665, observed and described the vesicular nature of cork 
and similar vegetable substances and applied to the cavities the 
term " cells." (See Figs, land'.'i. In the same sense the word 



* Anatome Plantarum: see Opera Omnia, Ks;. 

5 Encyclopedia Britannica. 

6 Hooke, Robert: "Of the Scheruatisrue and Texture of Cork, 
and of the Cells and Pores of some other such frothy bodies " begin- 
ning on page 112 of his " Micrographia, or some Physiological De- 
scription of minute bodies by Magnifying Glasses," London, 1665. 



"cellula" is \\rr<\ by Swammerdani ' in describing the nests 
with many compartments of various insects.. 

During this period certain other cells were at least seen and 
pictured, if not wholly understood or seriously studied. Thus 
Swammerdam saw the red blood corpuscles and recognized 
them as such: Malpighi likewise saw them in the mesentery 
but interpreted them as fat droplets; Leeuwenhoek accurately 
described and pictured them and at the same time supple- 
mented Malpighi's discovery of the capillaries — the necessary 
link to the completion of Harvey's theory of the circulation 
of the blood. A protozoan, a form of vorticella in all probabil- 
ity, was seen by Leeuwenhoek (1675), who also saw and pic- 
tured several forms of bacteria. Leeuwenhoek (or his pupil, 
Ludwig Hamm), also saw spermatozoa (1677). The concep- 
tion which these early observers had of the structure of cells 
was not that which we have to-day. Leeuwenhoek, for exam- 
ple, went beyond the limits of simple observation and 
ascribed to his " spermatic animalcula " a system of muscles, 
tendons and articulations by which they moved their tails, 




and he suggests that the animalcula of stagnant water (pro- 
tozoa) have organs similar to those of the higher animals. 

One cannot avoid being impressed by the industry and de- 
tailed observation of these early microscopists, and though 
often it appears that they sought merely the curious and odd, 
one examines with amazement the wide scope of their work. 
Boerhaeve's edition of Swammerdam with its parallel columns 
in Latin and Dutch, and voluminous plates on many forms of 
Me. offers glimpses of fundamental observations on the 
i tion of striated and cardiac muscle and on phenomena 
of respiration in mammals. One of the must striking plates 
is that dealing with certain phases of the life history of the 
mosquito, a species re of the larva 

and its breathing apparatus worthy of any modern work, ami 
which could be used as an explanation of the efficacy of the 
modern oil treatment of breeding pools. Likewise Lceuwen- 
hoek's observations cover a great ran-' . ;i- til'' animalcula <•'■ 
various fluids, the distribution of the blood capillaries, 

: Johannes Swammerdam: " Biblia Natura? sive Historia Insec- 
torium ": arranged and published by Boerhaeve, 173S-5S, after the 
author's death, but representing work done between 1665 and 1680. 






IBT, 1914.] 



JOHNS HOPKINS BOSPITAL BULLETIN. 



■tincture u feathers and of insects, and though hie micro- 
r. magnified only 10 to 1(!0 times, he 
pictured Hooke, though he made many fun- 

damental i iservations. was interested also in the casual and 
curious, a- the microscopic appearance of an ink drop, the 
point of a needle, or the edge of a razor. 

Grew devoted his efforts almosi entirelj to v< getable tissues 
but Malpighi in addition to the study of plants made most 
important contributions to the liner structure of animal tis- 
sue-, as of the capillaries, the surface of the tongue and the 
structure of the skin, spleen and lung. 

A word must in said about the mil this period.' 

There has been much discussion of the earliest use o 
for purposes of magnification, and of the firs! use of the com- 
pound microscope. The invention of the latter i> usually 
credited to Zacharias Jansen, in 1590; simple lenses appear, 
r. to have been used since the time of Seneca, who died 
65 A. 1>. At the time of the earlier discoveries in hi 
which arc here discussed, both simple and compound micro- 
■■■ ere in rogue, the former as made and used by Leeuw- 
enhoek, and the latter bj Hoc 




silver perforated \* ith 

i] which t" pi 

ind adjust it t" the eye of the beholdi 

:: i. II - ... of I 

i tin /' 
said by many authors I l 

a doubli 

■ 

t ier. II • - 

of the • 



* The 

raphia lUustrat i. London, 

Jabez: The M 
tion. London, 



magnif , ,\ ,| u> 

• 10. 

ipe, which In 
of In- •• M 
instrument with ocular, ■ 
in a hiIk' much lil 

being the now familial 
filled with brine placed in hat.lv in fronl i 

convex just above il b i ith ita 

simple upright with an ad 

Hooke also made globular li i 
threads of glass until thi m; the 

end where the thread was broken on 
and polished. For these he clainn 
than for " any of the mi 

In 1698, Bonanni invented a compoum 
used in a horizontal position, « 
the former was obtained by a rack and pinion mo 
tire frame, the latter by a screw in I 




I 






.-I I 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 276 



placed at one end of a brass tube about one inch long, and one 
inch in diameter; the light from, this lens is concentrated on 
the speculum (1) which again further condenses the rays on 
the object on the disk (C), which object, when so illuminated, 
can be readily adjusted by the little knob (D) so as to be 
in the focus of magnifying lens (A). Lieberkuhn worked 
chiefly with minute injected specimens and these, when placed 
on the object holder, were covered with a varnish. As was 
the case with Leeuwenhoek, the microscope went with the 
preparation to be studied, and according to Quekett, the Mu- 
seum of the Royal College of Surgeons contained in 1848 
twelve such exhibits which, after a century, wore unchanged 
except for slight cracks in the varnish over the mounted spec- 
imens. 

These various advances in the making of microscopes had 



i*Vy. 




J^tj.i*. 



**?- 



a direct bearing on the development of the cell theory in 
that they encouraged the study of the finer structure of plant 
ami animal tissues. The conception of the essential structure 
of these tissues was. however, no more exact than in the time 
of Grew and Malpighi. Nevertheless, noteworthy discoveries, 
though not always understood, were made. Thus many forms 
of protozoa were studied and described, and finally Trembly 10 
(1744-174?) studied the life history and observed the longi- 
tudinal division of a fresh water protozoon (see Fig. 5). In 
I7"i0, Hill published a detailed account of the microscopic 
structure of timber. Each of these publications revived at the 
time the pursuit of microscopic studies, as did also the inven- 
tion by Adams," somewhat later, of a machine fur cutting 



10 Trembly, Abraham: Observations upon several newly discov- 
ered species of fresh water polypi. Philos. Trans. Royal Society, 
1756, XI, Part III, 801, 807. (Read Nov. 22, 1744, and May 21 and 
June 18, 1747.) 

11 Adams, G.: Essays on the Microscope, London, 1798. 



transverse sections of wood so that they might. readily be ex- 
amined by the microscope. That there was also at this time a 
popular interest in the use of the microscope is shown by the 
titles under which Baker's " books appeared. 

It was not, however, until 180G that a fundamental dis- 
covery, capable of advancing the knowledge of tissue structure 
beyond the conceptions of Grew, Malpighi and Hooke. was 
made. Adams in HI'S, in discussing the structure of plants, 
makes the statement concerning cellular tissue that " the 
nature of this substance, its form and structure are at present 
little known." and quotes chiefly Grew and Malpighi, but men- 
tions also Duhamel, Hill, Bonnet and DeSaussure. A £rreat 
advance was, however, made when Treviranus, 13 as a result of 
the study of the growing parts of young plants, discovered 
that tlie tubes and vessels of Malpighi arose from cells by be- 
coming elongated and attached end to end, the intervening 
walls eventually breaking down. Although this discovery is 
credited to Treviranus there seems to be some question as to 
whether he thoroughly understood that the vessels were modi- 
fications of cells, for we find von Mohl " in 1852 stating that 
early errors " were followed even by Treviranus " and " I was 
the first to detect their origin from rows of closed cells." von 
Mohl made many important contributions to the subject of 
plant structure. He began his work in 1828 with an investiga- 
tion " On the Pores of Cellular Tissue," was appointed Pro- 
fessor of Botany at Tiibingen in 1832 and made many contri- 
butions to the study of vegetable cells," and as we shall see 
his work was an important factor in setting aside some of 
Schleiden's erroneous conclusions. This work by the early 
botanists gave to the cell some importance, but no law was 
established until the time of Schleiden and of Schwann, and 
though many interesting observations were made, the signifi- 
cance of these was not always appreciated. This is especially 
true of the first description of the nucleus presented by Robert 
Brown 16 in 1831, as an incidental result of his study of the 
organs and mode of fecundation in orchids. Brown's account 
is purely descriptive, with no attempt at explanation or theory, 
but in view of the important position which the nucleus now 
occupies in cytological problems, some of his sentences are 
worthy of quotation. "In each cell of the epidermis of a 
great part of this family (Orchideae) especially of those with 
membranous leaves, a single circular areola, generally some- 
what more opake than the membrane of the cell is observ- 
able " ; and again, " This areola, or nucleus of the cell as 



12 B;iker, Henry: The Microscope Made Easy; Loudon, 1754; 
ibid., Employment for the Microscope, London, 17C4. 

M Treviranus, C. L.: Von inwendigeu Bau der Gewachse, 1S06. 
This work I have been unable to examine In the original, as it is 
not catalogued in the most important libraries of this country. 

14 English Translation. Principles of the Anatomy and Physiol- 
ogy of the Vegetable Cells, London, 1S52. 

13 See Vermischte Schriften botanischen Inhalts von Hugo von 
Mohl, 1845; and English translation of " de Palmarum Struetiira " 
in Reports and Papers on Botany (Ray Society), London, 1S49. 

10 Brown, R.: On the Organs and the Mode of Fecundation in 
Orchideae and Asclepiadae, Transactions of the Linmvan Society, 
1833, XVI, 085 (read at meetings of Nov. 1 and :>. 1831 1. 



1914.] 



JOHNS Hopkins BOSPITAL BULLETIN 



- it might be termed, is 
mini .... in many cases in the parenchyma 01 

This is the firs! !< - ription of the nucleus and I 
servation of its occurrence in all cells. It had undo 
Brown in the fame communii 
Meyen, Purkinje, Brongniart and 
in which arc depicted the e*pidermis and the - 
and which offer a few indical 
■ : to the nucleus, or areola, but. as B 
say. -.1 little importance was usually 
that it is seldom mentioned in the text, [i 

i; a name. 
These advances, beginning with Tn ided to 

-i in the improvement of the m 

liromatic compound mi< i 
about 1S00, and although it was not unti 

result of the experimental work of Joseph Jack- 
no Lister (the father of Lord Lister), that exai I know] 
mbination of lenses and the use of a trans 
cement (Canada balsam) for the fixation i 
tuned, -till, the improvements were such as to aid tl 
in hist 

A- Schleiden's work appeared in 1838 and Schwa 
ad especially as Schwann acknov. 

his work from a o with 

Bchli i 1 

theory may be considered at oi 
connection it is worth while also to recall thai 

■•■ Yin-how. who later ha< 
ppment of : : y, were pu] 

ible cells, and - liwann, had ■ 

ilarity " in - 
Certain embryonic an n 

3 ileideh," however, who 

of his work on I gamia, thai a 

table tissues are com] 

icleus ) and that in the undiff 

and that it is 

table tissue n mindi d Si > n ; - m 
in the- em iryonii 

of the a 

ind Val< ntim 
to the similarity ol 

ISTS 
• id. ii. .Mat'.: las Jakob 

"Schwann. Theodor: Mlcroscoplscb 
astimmung in d< r Strtiktur and 
und I'tlanz. n, 

E 



S 

- 

■ 
■ 






56 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 276 



After Schwann, the next important studies were those con- 
cerning the division of the cell and the importance of the nu- 
cleus in this process. Although both Schleiden and Schwann 
had shown that the new cells developed about the' nuclei of the 
" cytoblastema," the importance of the nucleus in cell forma- 
tion was not immediately appreciated. That cells divide was 
cautiously surmised by Schwann, was more boldly stated by 
Henle (1841), who, however, found no example of it in ani- 
mal cells, and was supported by Eeiehert (1840) in his study 
of segmentation of the egg. (See Figs. 6 and 7 for views 
concerning cell division in 1855 and 1859.) 

The first recognition of the fact that the nucleus shares in 
cell division is usually credited to Martin Barry (1840), who 
was supported shortly by John Goodsir (1845) and Remak 
(1852). 

In 1858, however, the cell doctrine was definitely and finally 
established by Tire-how.- 1 who postulated that all biological 
doctrines, whether dealing with normal or pathological proc- 
esses, must be based on the fact that all cells are derived 
from preexisting cells and that the primary origin of all cells 
is the ovum, thus substituting for Harvey's aphorism omne 




vivum ex oro his own omnis cellula e celluJa. Yirchow stated 
this as follows : "' Where a cell arises, there a cell must have 
previously existed (omnis cellula e cellula), just as au animal 
can spring only from an animal, a plant only from a plant. 
In this manner, athough there are still a few spots in the 
body, where absolute demonstration has not yet been afforded, 
the principle is nevertheless established, that in the whole 
series of living things, whether they be entire plant or animal 
organisms, or essential constituents of the same, an eternal 
law of continuous development prevails." 

While tins announcement had the special effect of giving 
to pathology a " cellular theory " to replace the older humoral 
theory, its broader effect was to stimulate the study of the 
normal cell. 

It was evident that the cell must be more thoroughly stud- 
ied and it is from the period (1860) shortly after this an- 
nouncement of Yirchow, that we date the consistent and 
and thorough study of that form of cell division now known 
as mitosis or karyokinesis. We may leave this — the problem 



of the nucleus — a moment, however, to say a few words about 
the cell protoplasm. 

About the time of Schleiden and Schwann's work the pro- 
tozoa, largely as the result of the work of Dujardin ~ (1841), 
were recognized to be simple, slightly differentiated struc- 
tures, quite unlike the complex organisms described by 
Leeuwenhoek and his followers, and to be composed of a fun- 
damental living substance to which Dujardin gave the name 
sarcode. 

It was also about this time (1838) that Ehrenberg made 
his celebrated classification of protozoa, which was so accurate 
in the description of species that 45 years later Biitschli was 
able to recognize more than 100 as identical with the well- 
studied species of his own time. 

Likewise at this time (1839) the suggestion was made for 
the first time, by Meyen, that protozoa might be single cells, 
the entire infusorian body being analogous to a single plant 
cell. This theory was applied directly by Barry, in 1845.^ 
who also compared the nucleus of protozoa to the cell nucleus 




of higher animal forms. Finally Siebold, in 1848, asserted 
the unicellular nature of all protozoa.* 

Keilliker, in 1841. showed that spermatozoa are not parasitic 
animalcules, but not till 1865 was it known that they are com- 
plete cells with nucleus and protoplasm. 

In accord with Dujardin's conception of sarcode as the basic 
substance of protozoa, von Mohl, in 1846. substituted for 
Sehleiden's "plant slime" the term "protoplasm,"" which 
had also been used previously by Purkinje, for the formative 
substance of young animal embryos. Later (1852) Remak ap- 
plied the term to the substance of any animal cell. Studies 
of the streaming of protoplasm within the cell, of ameboid 



"Virchow, R.: Die Cellularpathologie in ihrer Begriindung auf 
physiologische und pathologische Gewebelehre, Berlin, 185S; also 
English Translation by Frank Chance, London, 1S60. 



--' See Dujardin, F. : Histoire Naturelle des Zoophytes-Infusories, 
Paris, 1841. 

-' For the state ot microscopic study at this time see Dujardin, 
F.: Nouveau Manuel Complet de l'Observation du Microscope, 
Paris, 1S43. 

-'Calkins. G. N.: The Protozoa. New York. 1301. 

■'■ For an excellent historical summary of the development of 
the knowledge of cell structure which is here quoted, see article 
on " Cytology," by G. C. Chubb, in the eleventh edition of the 
Encyclopedia Britannica. 






JOHNS llol'KINS IlnsnTAl. BULLETIN. 



Motion, and also the recognition pf cells without membrane, 

I he v iew, now liehl. that net the cell wall hut tin- nucleus 

ami protoplasm are the essential parts ••!' the cell. This 

of view was due particularly 1" Max Schultze, who 

Bhowed by In- careful comparative studies thai one and the 

ed in both tin' unicellular 
ami the higher forms of plants and animals alike, and while 
in some j vegetable, this substance *> 

rule enclosed within a membrane, in many higher animals 
and unicellular forms a membrane «:i- frequently absent. 
This constituted, in contradistinction to the "cell theorj " of 
Schleiden and Schwann, his " protoplasmic theory " which di>- 
fined a cell a- "a small mass of protoplasm endowed with the 
attributes of life" (1861). In the same year Briicke put 
forth his views of the cell a- an "elementarj organism" 
with the assumption that the protoplasm had a complex 

structure. in\ isible onlj bei an I' imperfect methods of obser- 

vation. 

At til'- same time rapid progress was mid,- i i- 
the knowledge of the nucleus ami its part in cell division. 
Schleiden's " cytoblastema " theory (1838) which postulated 
tin' origin of vegi table cells from the fluid of the mol 
by a process analogous to crj stallization, the nucleolus appear- 

• i. then tin- i I Snally the ■ i 

which was extended by Schwann (1839) t" include animal 
cells — did not long remain uni I l'.\ 1846, Is 

suit of the work of von Mohl and Naegeli," botanists 

ted the general law that cells arise only by the division 

of preexisting cells. The application of the law to animal tis- 

me slowly, hut as the result of the work lar^ 
Kolliker, Beichert and Remak, it . as we have 

seen, for Virchow to make, in 1858, 
tion concerning the genetic continuity of i 



" See English translation df Naegell'a paper In Raj Societj 'a i>ul>- 
llcation, Reports ami Papers on Botany, London, 1849. 

Tor a general review of the cell theory In 1863, Bee Huxley, T II 
The Cell Theory. British and Foreign Medlco-Chlrurgical Review, 



■ 

with thi 

with the publication of v\ 
iid includin 
Flemming to a 

Thus, 

ILLUSTRATIONS 

Fig. 1.— Page from Robert Hooi 
Brat description o( I 

the use of the word " ■ • 11 li 

Fio. 2. — Kol irl II 
cork. 

- perforations In twi 
holder ami mi H Ing. 

Fio. i Lleberkuhn's M 
tion of structure and method ol 

Fio. •". First rw ordi 'I ■ 
a protozoon (Vorticella). Trembly, Kit it 

Fio. 6. — Cell division according to Remak eci di\t 

sion of blood cells in the embryo chick. 

Tiikoii from Hogg, i li< Mli i 

formed cell. 2, Subdii Ision of the nui leua 3, The tin 

. itioii, and at I, BUbdiV Idi 
of the I'll Increase in ti 
ite t. Two 

. and run inn I form 

■ Mm.' multllocular. i". II 
membrane ai 
which at 13, have coalesced to form tl 



Philadelphia 



EARLY BISTORT or THE < 'AIM-: \M> TREATMENT OF CRIPPLES. 



■ 



The cripple msidered, at least 

fields, as the prototype of the handicap^ 

We may. then ly of the 

of the attitude of -■■ iety toward the deformed to throw •■ 
nderable light on thi ■_ row I 
sibility for thi unfortunate meml 

thus torn hes intii 

From the earliest times the tot of the crippli 
hard one. The fir-t mention of physical 
with it Btigma in other well. With pr 

the cripple was very commoi I 
to peii-h of di 

'Albert Hermann Post. Orundi 
denz. Oldenburg and Lelp ig, 1894. Vol. 2, p 



■ 

■ 

I 



5S 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 276 



could also be sacrificed al the death of kings and great men. 
Deformed infants were abandoned or killed by various tribes 
living on the islands of the Pacific; Australia," Hawaii,' and 
others, 8 as they were by some negro-peoples as well." In the 
kingdom of Assinie, on the Gold Coast, children with six 
fingers on either or both hands were buried alive. 10 Among 
the Indo-Germanic peoples exposure of deformed infants u 
was a custom of frequent occurrence. In the early law of 
Northern Germany the right to kill monsters and deformed 
persons is often mentioned." 

Isolated cases of the practice of the exposure of infants 
occur in Japan" as in other countries, but it has never ap- 
proached recognition as a general custom. From the myth 
of the god lliruko (leech-child) it may be inferred that the 
abandonment of deformed infants was not uncommon in the 
earliest times. The Nihongi tells us that the god had com- 
pleted his third year and was still unable to walk. His parents, 
therefore, placed him in the rock-camphor-boat of heaven 
and set him adrift. 

Data concerning the exposure of infants in Persia " are 
scanty. According to the A vesta, 13 all deformities were re- 
garded as the work of the Evil One. It is not impossible, 
therefore, that deformed children were exposed with more or 
less frequency. 

Among the Pima Indians, a Xorth American tribe,, with 
the consent of the parents, deformed infants were taken by 
the midwife, who watched them until they died of exposure 
and want of nourishment." So strong was the feeling of the 
Pimas against the abnormal that they tried in recent years 
to kill a grown man who had six toes. 

In this connection James Mooney, of the Bureau of Ameri- 
can Ethnology, in a communication to me, notes as follows: 

Among the Kiowa I knew personally a twelve-year-old girl, of 
receding forehead and halfwitted, who had been buried alive 
immediately after birth and rescued and brought to the Catholic 
mission by a captive woman who knew what was about to be 
done. The missionary priest, from his experience waiting on their 
sick in camp, believed that they had killed other defective infants 



'Albert Hermann Post. Bausteine filr eine allgemeine Rechts- 

wissenschaft auf vergleichend-ethnologischer Basis. Oldenburg, 
1SS0-1SS1. Vol. 2, p. 119. Also Joseph Kohler, in Zeitschrift filr 
riil. Rechtswissenschaft, vii, 355. Also Waitz-Gerland, Anthro- 
pologic, Vol. G, p. 779. 

7 Waitz-Gerland, Anthropologic, Vol. 6, p. 139-140. 

* Albert Hermann Post. Bausteine filr cine allgemeine Rechts- 
wissenschaft auf vergleichend-ethnologischer Basis. Oldenburg, 
1880-18S1. Vol. 2. p. 119. 

"Albert Hermann Post. Afrikanische Jurisprudenz, Oldenburg, 
1887, Vol. 1. p. 2S5. 

'"Globus. 1891, No. 11, p. 17G, after Reichenbach, Ktude sur le 
Royaume d'Assinie. Bull. Soc. Gcogr. 1S90, p. 316. 

11 Grim, Rechtsaltert, p. 456. 

"Maurer. Wasserweihe des germ. Heidentums. 1880, p. 14 ff. 

"James Hastings, Encyclopaedia of Religion and Ethics. Edin- 
burgh, 1908. Vol. 1, p. 7. Article by W. G. Aston. 

"Ibid., Vol. 1, p. 7, article by Louis H. Gray. 

" Vendidad, ii, 29. 

"Frank Russell, The Pima Indians. i6th Annual Report. 
Bureau of American Ethnology. Washington, 1908, p 



at birth. I know also of instances of abandonment of the helpless 
aged in the same tribe. 

Travelers have asserted the existence of the practice of killing 
defective infants, in various tribes, and I am inclined to think 
that it was quite general. Some tribes, especially in Oregon, kill 
one of a pair of twins. The reason in both cases seems to have 
been partly economic, to be rid of a future burden, and partly 
from a superstitious fear of the abnormal. 

With the dawn of our present civilization the condition of 
the cripple did not improve to as great an extent as we should 
ordinarily expect. Oriental peoples turned forth their crip- 
ples to wander in the wilderness. The inhabitants of Ancient 
India cast them into the Ganges; the Spartans" hurled them 
from a precipice into an abyss, Apothetos. The Jews in the 
earliest time- banished their cripples so that they had, per- 
force, to beg by the roadsides. The general attitude was to 
regard physical deformity as a blight sent by God or as a 
punishment for sin. 

The Hebrew Scriptures reflect the attitude that the de- 
formed person must be spiritually and mentally unfit as well, 
in Leviticus" we encounter a passage illustrative of this: 

And the Lord spake unto Moses, saying: speak unto Aaron, say- 
ing, whosoever he be of thy seed in their generations that hath 
any blemish, let him not approach to offer the bread of his God. 

For whatsoever man he be that hath a blemish, he shall not 
approach; a blind man or a lame, or he that hath a fiat nose or 
anything superfluous. 

Or a man that is brokenfooted, or brokenhanded, 

Or a crooktbackt. or a dwarf, or that hath a blemish in his eye, 
or be scurvy, or scabbed, or hath his stones broken; 

No man that hath a blemish of the seed of Aaron the priest 
shall come nigh to offer the offerings of the Lord made by fire; 
he hath a blemish; he shall not come nigh to offer the bread of his 
God. 

Later on in the same passage it is stated that the reason 
for this is that the sanctuaries be not profaned. 

There are references to the cripple in the Old Testament 
in the form of similes showing that physical deformity was 
familiar to the people." The first reference to a deformity 
caused by accident occurs in the Second Book of Samuel. 

And Jonathan, Saul's son, had a son that was lame of his 
feet. He was five years old when the tidings came of Saul and 
Jonathan out of Jezreel, and his nurse took him up, and fled; and 
it came to pass, as she made haste to flee, that he fell and became 
lame. And his name was Mephibosheth.™ 

This accident was probably the forerunner of many subse- 
quent accidents to children in charge of nurses. 

Kindly references to the cripple in early times are scarce. 
In Job's recital :l of his circumstances when God was with 
him, recounting his various benevolences, he says, " I was 
eyes to the blind and feet was 1 to the lame." 

In referring to inheritance, the Dadistan-i-Dinik," one of 






"Douglas C. McMurtrie. The Primary Education of Crippled 
Children, New York, 1910, p. 5. 
" Leviticus, xxi, 16-21. 
" See Proverbs, xwi, 7. 

" // Samuel, iv. 4. 

2i Job. xxix, 15. 

-- Chapter Ixii, paragraph 3 



February. 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






oks of the I ' i 

one of the sons, or even the wifi lio i- blind 

crippled m both feet, or maimed in l*>th his hands, is 
twite a> much as that of sound." 

The Greeks, worshipping as they did the ; 
bodily form, regarded a cripple as the incarnati 
thing unlovely," i"t only physically, but also mentally ami 
morally. Homer describes Thersiti 
ugly attribute ami equally deformed in body ami mind.' S 
was the arnij In fore 

Troy for indulging in vituperative laj did not 

abstain from directing it even against Agamemnon himself. 
It i- related that he ultimately perished at the hand of Achil- 
les, while he was ridiculing the sorrow of that hero for the 
slain IVnthesilia. 

The advent of Christianity struck a new note in the attitude 
toward the crippled and deformed. Even in Isaiah's pro] 
of the coming Messianii kingdom, •■■•■lis that " then shall 
the lame man leap a< a hart."' ( hrist, referring to His min- 
i-try/ says: "the blind receive their sight, and the lame 

walk " It i- also related" that "the blind and the 

lame came to Him in the temple and He healed them." 
cures of cripples are also attributed to li;*' A 
"A certain man lame from his mother's womb" was healed 
by Peter." It is related that " immediately hi- fi 
bones received Btrength." During the ministry of Philip" 
■•many taken with palsies and that were lame, were healed." 

During the inL-sion of the Apostle Paul in Lycaonia, he 
healed" a cripple described a- follows: " ^nd thi 
eertain man at Lystra, impotent in his feet, being ;i 
from his mother's womb, who never had walked." It 
eating to note that this is the iir>t use in the Scriptun 
generic term, cripple. The Greek word v in the 

original. 

The influen f the < hristian attil 

upon the lot of the cripple. 1 recall one illust 
tion." 

Also cripples and the sick v 

ives" In Iran as In Armenia and they led a wret 
istence. In Armenia it was one of the great s. an 
anity that it ameliorated the fate of these unfort-: 

But the new influence was not profoum 



" Sacred Books of the East, edited bj P Max Mflller 
1882. Pahlavi Tests, translated by B. W. v 

"Douglas 0. McMurtrie, Tin Prima 
Children, New York. 1910, I 

"Homer, mad, ii, 212 ff. 

* Isaiah, xxxv, c.. 

. 5. Also ref( rred to In I 
ii, 14. 

"Acts of II ii. 2. 

"Acts of the Apostle*, vlii, 7. 

" Acts of t) 

"Ft. Spiegel, Erai 
3. p. 682. 

u i. e.. abandoned. 

"See also Fatistits of /?i/:<ni/i 
-. iii. 20. 



the am 

birth. In ninny ii 
il City. Ti 

pillar in the eleventh 

enough in thi 

eaten b 

and tl ■ 
their di 
enough 

- 
ting thc-ir mutilated n 

off their arm- 
humpbacked. If I 
of th>- 

wret< i "You havi 

the whip; 

alms and could ha 

that tl 

indulgi 

; 



GO 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| No. -.'76 



Blaise de Vigenere in the notes to his Images et Tableaux 
de platte peinture de PhUostrate Lemnien remarks that when 
in Rome in 1566 he was invited to a dinner by Cardinal 
Vitelli, where the table was served " by at least thirty-four 
dwarfs, almost all hideous and badly formed." 

With the opening of the Middle Apes the chief occupation 
of the crippled came to be that of court fool or jester. These 
personages almost universally found a place in the retinues 
of princes, and often in the households of noblemen. 30 

These court fools can be divided under two classifications. 
In the first would come those creatures who by reason of 
deformity in body or mind were calculated to excite laughter 
and ridicule. In the second would be placed those chosen for 
a certain superficial quickness of wit and power of repartee. 
It is the first class with which we are especially concerned 
in our study of the attitude of the community toward the 
crippled and deformed; and they were to be found, unfortu- 
nately, in large numbers. The attire *° of these jesters was 
distinctive, though varying slightly during different periods. 

To judge from the prints and illuminations which are the 
sources of our knowledge on this matter, it seems to have changed 
considerably from time to time. The head was shaved, the coat 
was motley, and the breeches tight, with generally one leg differ- 
ent in color from the other. The head was covered with a garment 
resembling a monk's cowl, which fell over the breast and 
shoulders, and often bore asses' ears, and was crested with a 
cockscomb, while bells hung from various parts of the attire. 
The fool's bauble was a short staff bearing a ridiculous head, to 
which sometimes was attached an inflated bladder, by means of 
which sham castigations were affected. 

The impressing of cripples into service as court fools con- 
tinued and the institution was firmly entrenched for many 
years, despite many tendencies operating to improve the situ- 
ation. Even a number of decrees passed by the Reichstag 
during the sixteenth century failed to obviate the practice. 
Not until the time of the Enlightenment was the final stage 
reached and the custom abolished. 

Even after this time the court fool was still in vogue at 
the Russian court, Peter the Great having so many jesters 
of this type that it was necessary to divide them into classes. 

When the Spaniards under Fernando Cortez accomplished 
the eoncjuest of Mexico, court fools and deformed human 
creatures of all kinds were found at the Court of Montezuma. 

It will be observed that the most significant fact developed 
by the history of the court fool is that during the period cov- 
ered the victims of human deformity were regarded with ridi- 
cule ami contempt, hi the existence of such an attitude on 
the part of the general public, a sympathetic or merciful 
consideration can hardly be conceived. 

During the latter part of the Middle Apes cripples came 
to be regarded superstitiously, this attitude being respo 



30 K. F. Flbgel, Geschichte der Hofnarren, Leipzig, 1789. Nick, 
Die Hof- unci Volksnarren. Stuttgart, 1861, 2 vols. Ebeling, Die 
Kahlenberger, OescAichte der Eofnarren, Berlin, 1890. 

40 Walter Hepworth, Encyclopwdia Brittanica, Eleventh Edition, 
Cambridge, England, 1910, Vol. 10, pp. 614-615. 



for a miserable existence for those deviating in any way from 
the normal." 

Ignorant people and scholars alike were influenced by such 
prejudice, and it is easily seen how cripples and deformed 
people were regarded as devilish monsters. Several circum- 
stances gave rise to the general superstition. One of the 
most instrumental was the frequent confession on the rack by 
unmarried pregnant women that they had been seduced by 
the devil. This led indirectly to the belief that humpbacked 
and deformed children might have been of diabolical pater- 
nity. 

Others regarded the deformed as victims of the wrath of 
God, and put them to death. King Francis I had burned to 
death at Avignon a woman who had given birth to a mal- 
formed child. Often, on the birth of a cripple or of a child 
with superfluous members, the attack of a hostile army was 
feared. There is a similar legend of Babylonian origin. 

'Martin Luther shared the belief, current at his time, in 
the theory of changelings. At the birth of an undesirable 
child it was believed that some diabolical mother had stolen 
away the right child and substituted her own offspring instead. 
Thus the child was known as a changeling. Cripples, rachi- 
tics and cretins were regarded as changelings. The idea was 
that if such children were maltreated sufficiently their mothers 
would come again to pet them and leave the rightful children 
in their stead. It is easy to conceive the attitude which such 
a concept would engender. Luther 4 " also regarded malformed 
children as mere masses of flesh and considered that killing 
them was a work well pleasing to God. 

Another phase of superstition affected the cripple — the be- 
lief that offspring could be harmed by " somebody " or " cast- 
ing the evil eye " upon the pregnant mother. Parents were in- 
clined to bring the deformity of their child into causal rela- 
tion to a terrifying pre-natal experience on the part of tin 
mother. In 1673 it is related that a citizen's wife was so 
frightened at the sight of a one-eyed, lame beggar that when 
she soon after bore a son, the infant lacked a hand and had a 
crooked leg. Many other similar instances can be found in 
literature. 

One cripple, Thomas Schweicker (died 1602) of Schwabisch- 
Hall, came to be highly regarded* 3 on account of his learning 
and culture. 

The first glimmer of hope for the welfare of the cripple 
began to appear in the eighteenth century, though the progress 
in this direction was very slow. The first measures did not 
in a strict sense mark the beginnings of care for cripples, but 
they operated to the ultimate advantages of those who. by 

41 T. D. Herholdt, Betrachtungcn iiber den medizinischen Aber- 
glauben und iiber Missgeburten im Allgemeinen. Appendix to 
BescHreibung sechs menschlicher Missgeburtcn, Copenhagen, 
1S30, pp. S3-102. 

<: Martin Luther. Table-Talk. (Table-talk of the devil ana his 

work — Changelings from the devil — History of a changeling at 

Dessau— Another history of a changeling.) Theo. Kirchoff. 

driss einer Geschichte der deutschen Irrenpflege, Berlin. 

1S90, p. 65-76. 

Martin Ulbrich. Th. Si i a, L909 



\RY. I'M 1.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






of their infirmity were east upon the pity ol 
hUow-ir sion in man. 

however, was utilitarian in char, i I was that all 

cripples might be co : a< they should not annoy the 

community by their deformed a 

■ >f the many monasteries which had not 
since the tinn re thrown op 

verted into orphan asylums, mad-hi 
In the est t of the various institutions the ■ 

ilv considered. 
Those handicapped by deformity \ for at 

ital for wretched and pauper inval shed at 

iin" in 1722 by Couni Luitgard of Baden. This was 
later transformed i harles Frederic of Baden into 

an orphan asylum, but ma 

old cripples. Kirmsse* quotes parts of the official ordinance 
on this matter as follows: 

Cripples, by Margravi Charles Frederic ol Baden. The princely 

ordinance of May 11. 1758, sa>s cm this: 

we now assume the place of a father to those who are 
orphaned in our territory or who arc otherwise afflicted with grave 
misfortune, we cannot but desire special experience of our most 
gracious care to those who, in addition to such afflictions, an at 
the same time stripped of temporal wealth, and who are, there- 
fore, stricken with double affliction." 

"And the third class is composed of those who lii' 
' defects that they arc an especial abomination and 
to other men when. ir sicht. There are 

utterly misformed crippli 

IV. v. 
"As many <■]' these Inm I ployed in any work 

shall be obliged to perform it. yet wit to distinction 

of age, sex, and their physical Infirmities. Here it Is ■ 
to see in the tir.-t plan — unless their I 

ill.. Bought out fori ■ maj i>- performed 

In '! eir rooms 

X Punish 

other Inmati punish- 

it a few strip.- will be allowed, although they may be 
chastened either with withdrawal of food or of drink oi 
but in every case after careful consideration ol tlnir circum- 
stances." 

, •■! ['in -i< iss. 

" In thi rphan asylum i an utterly 

1 of the entire country, including thi 
in con^- lod laid upoi 

horror I . but all the more a trui 

And. althougl . . ordit g to I our bumai 

standlo 5 I 

I 
case, therefon 

should 



S 
I 

d which ha 

■ 

- 
( 7/ iru r 

ble. 

tution for tie' deformi d, at Orbe, S 
■ did valual 

<>n tl" 

in an institution an.! 
founded in tl 
example, tl>" 
Berlin, an.! 

n.l in 

Germany. 

■ 
al Berlin 

ipled • hildn 
- 
ity, of which he 

bis institut 

An i: . • ■ ■ 

oar monarchy; all the e 
and sickness In questli 

■ 



It, 10 ff. 

• ttir K •.</■>/. • 
iv. in ff. 



. 



62 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 271 



that the elements are usually disparate is responsible for failure 
in many cases. 

Since a large number of the sick who visit the institution are 
still young, special attention must be devoted to their education. 
That the invalids may not be impeded in their intellectual develop- 
ment by residence — which is often of long duration — at the insti- 
tution, my endeavors were naturally directed toward providing for 
them training adapted to their ages and individual capacities — 
especially in view of the fact that the intellect is usually very 
acute and active in sufferers of this type. For still another 
reason I have been led to devote special attention to the subject 
of education. In ordinary life a certain obstinacy of character 
is usually attributed to those who suffer from bodily deformity — 
unfortunately not always without cause. A very natural cause 
is the mockery to which these unfortunates are often exposed by 
their frivolous playmates. They are shunned because their in- 
firmity does not permit them to engage in many games of child- 
hood and youth; they are restricted to their own company, and, 
imprisoned in their isolation, become not infrequently malicious. 
These faults, however, can be more easily removed during youth 
by continuous moral and intellectual training in an institution; 
more especially since the similarity of infirmity makes for much 
in common and demands mutual cooperation. The training is 
entrusted to a special teacher, who watches in a parental spirit 
over their morals and instructs them in varied school subjects. 
Naturally it must be my chief care that such an important 
position as that of teacher should always be filled by persons of 
intelligence and integrity. 

Not desire of gain; but only the warmest interest in the matter 
itself, and a deep-seated longing to advance so far as possible the 
common weal, could lead me to establish an institution for the 
deformed in which even those of the most slender means can find 
the fountain of their healing and so look foward to as happy a 
future as possible. 

The number of those seeking assistance, however, soon de- 
manded a large institution. This at the same time placed me in 
a position further to extend my observations. Nevertheless, there 
were many difficulties to be contended with in connection with 
such an institution; the exactions demanded of the man who 
becomes its head are so considerable that long preliminary work 
and the greatest exertions were required before the institution 
could enter upon full activity. Considering the end in view, the 
earthly reward to be hoped for is extremely scanty in return for 
the manifold and ceaseless efforts expended; the sweetest recom- 
pense here is the consciousness of having laid a small gift on 
the altar of humanity, and of having opened to the poor no less 
than to the rich the fountain from which they may hope to draw, 
without expensive outlay, the healing of their infirmities. 

BlSmer had a workroom for making apparatus, bandages 
and artificial limbs. It is not known how Ion- his institution 

lasted. 



A similar institute was founded in Stockholm, Sweden, in 
1.821 by Dr. Ackermann. 52 There was much difficulty en- 
countered in overcoming public suspicion and distrust. Dr. 
Giinther maintained an institution in Hamburg "" during the 
years 1832-1837. While visiting Hamburg, Dr. Zinc of Vienna 
became acquainted with this establishment and upon his return 
to Vienna founded a similar one/ 4 May 1, 1838. This latter 
much resembled the institute of Blomer at Berlin. 

In the meantime, however, there had been founded in 
Munich in 1832 the first comprehensive institution for the 
care and education of cripples. The Konigliche Ba\ 
Zentralanstalt fiir Erziehung unci Bildung kriippelhafter Kin- 
der was brought into being by an eminent philanthropist, 
Johan Kepomuk, and the principles then exemplified have, in 
general, been followed by most of the modern institutions 
which have since been established. A description of subse- 
quent work, however, is outside the scope of the present article. 
In Denmark," England, 56 Italy." as well as in Germany" 8 and 
the tinted States.' 1 extensive systems of care have been built 
up, and in almost every civilized country of the world 
is made some provision for the welfare of the cripple. 

The community has now realized to a very considerable ex- 
lent its responsibility toward the cripple and the early vicissi- 
tudes to which the deformed were subjected are indeed a 
matter of history. 



" 2 C. J. Eekstrbm. Ars-Berattelse om Svenska Lakiire-Sallska- 
petts Arteten, Stockholm, 1829. 

a H. Gleiss. Lebenserinerrungen von Elise Averdieek, Ham- 
burg, 1908, pp. 4S-50. 

M Erster Bericht, 1853; Jahresbericht .... fiir 1853, Vienna, 
1S54; Correspondenz-Blatt der dcutschen Gesellschaft fiir Psychia- 
trie. 1S54, p. 16; Die angeJ>orencr Verrenkungen, Vienna, 1S45. 

" Douglas C. McMurtrie. The Copenhagen Institution for 
Cripples, Boston Medical and Surgical Journal, Boston, 1911, clxv, 
794-79S. 

56 Douglas C. McMurtrie. Crippled Children in the English 
Public Schools, New York Medical Journal, New York, 1913, xcvii, 
1SS-199. 

ST Douglas C. McMurtrie. The Care of the Crippled and Rachitic 
in Italy, Medical Record, New York, 1911, lxxx, 1218-1222. 

58 Konrad Biesalski, I'm fang und Art des jugendliehen Kriippel- 
turns in Dcutschland. Hamburg and Leipzig, 1910. Also the 
files of the Zeitschrift fiir Kriippclfiirsorge. 

'"Douglas C. McMurtrie. The Care of Crippled Children in 
the United States. Ameriian Journal of Orthopedic Surgerii, 
Philadelphia, 1912, ix, 527-556. 



TITLES OF PAPERS APPEARING DURING THE YEAR, ELSEWHERE 
THAN IN THE BULLETIN, BY PRESENT AND FORMER MEM- 
BERS OF THE HOSPITAL OR MEDICAL SCHOOL STAFF. 



Abel, J. J., Rowntree, L. G., and Turner, B. B. 

i >n the removal of diffusible substances from the circulating 

living animals by dialysis. — /. Pharm, .( Bxpct L9] 

Allen, M. D. 

Asraris luml.i-ioiicl, s as a t - . i u i ] . 1 i ■ al ii u 
if. Ass., 1913, l\. 1953. 

Al i v.. .1.. and MELTZEB, S. J. 

1 afferente Splanchnikus i D i r. ZentraW. f. Phusi 

xwi. I lie 

■ ~-.hr iin.i lahmende Wirknne ron Mi 
i (lurch Ather, Zentralbl. f. Physiol., lm 



in. imter- 



Auek, J., and Robinson, G. C. 

I listurbaiie.-s of the heart-heat in the dog msed b\ serum anaphy- 
laxis.— J. Exper. M., 1913, xviii. 551 

An electrocardiographic study of the anaphylactic rabbit. — J. Exper. 
.1/.. 1913, xviii. 450. 

Anaphylakiis ' mum l.eim lluml. — Zrnlralbl. 1. Physiol., 

1913, xxvii. 383. 

Acer, J., and Van Slyke, D. D. 

a contribution to the relation between proteid clearage pr duns and 
■n h'\is ' / < ... 1/.. l'.n:;. xviii. liii 

■:■'■"' . : 1 1 K t .■ mid Ana pli vlaxie. — ZentraJbl. f Physiol. 1913, 



\ky. 10H.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






Baetjer, F. H., and Fkikiii \« 
The vali 



■Tad., 191 



Bai 1 mi >:. W. A 

rpermeablllty In nephritis. Irch 

Baetjer, W. A., and Rowntree, L. G. 

■■..I phar 



-i 1 1 









l\l. 1 138. 






B vi:ki ::. L. 1*. 
im the eultli 

, xjtxvll. 731. 
ommoner forma of renal disci *e « Itb spei 
knowledge "f them most useful at present to the general practitioner. 

r, 12. 
The clinical s >upplj Ing th 

and their relations lad. If. 

, 1913, III, 043: also i 

hygiene. Texas If. •' . 1913 \\i\. 1 15. 
\ ind Insomnia 

icini- ai ■ the Baltlmo II. Iferf. 

1 Iff/., 1913. v. 97. 
- of ill-- mental hygiene movement and I 
work of the National Committee for Mei ' 

112 [ 1913], III 168. 
DihTerentlatloi 

1913. 

Barkm:. I. I'. M-. i:m\ C. M., and BUBBOW, T. 
Neurasthenic and psj cbastl • nlc 

Beall, F. C. 

lure of the kidii" 

Berry. J. M. 

The classiflc itlon of aril 



Ved. Bee . 1913, bn 



irltls 54. 

Black fan. K. D.. and Dandy, W. E. 

An experimental and clinical study of Internal byd 
: III. 2218. 

IN, K D., Nil B il 30 . S. T.. and WHITE, T. W. 
ly of Hi" Wasserman reaction In one hundred Inl I 
■ Mid . 1918, vi, 182. 

Block, E. B. 

The treatment "f chorea with rheumatism ph 
Oa . 1913, in. 150. 

• r 
Traumatic shock and the Ptnplo 
Iti prevention and treatn < l 

Studies in hi I pressure during, and after operations with 

iniltion, prevention an 
i. 721. 
Ulaimosls and line patholog 

..f th. 

1918, \liv. 115 

: 
Ti'ir 

Bi.i mer, G. 

ns 
The ni 

I : 

T. R . and G\ 
Boyd, m. U, and Sila W P 

I1T 
H, .1. It. I! 

W. V. 



• 






Bbothi bhood, J. S 



■ 






T. II. 

>Nlll. 

. ('. H., and Jo51 S, A P. 

■ 

Bmrrnto, C. H., and Yati b, I L 

Cultural results In 1 



I'M I K. J. U. 

-.DJlIn 





















1 . M. 
' 
Cm in iim u. J. W. 

will. 1^7. 

Cm in ii man, J, \\'., and Hi v./, I.. V. 
Clarke, T. W 

1913 

i'i n 1 \. E, K 

. E. K„ and M u i . P. P. 

A n 

' 
The i 
1913, i 

Addi 

Cl BHINQ, II 
Addn - 

tvv.. |l II 

the 












Dandy, W. E . and K D 

Dandy, \v i 












I 






' 



' 












64 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| Xo. -r.r, 



Flexner, S. 

I!m' results of the serum treatment in thirteen hundred cases of 
epidemic, meningitis. — J. I'.riier. 1/.. 1013, x\ i i. 553. 
Accidents following the suhdur.nl injection of the antimeningitis serum. 
—J. Am. M. Asa.. 1913, lx. 1937. 

The local specific therapv "f infections. I. The biologic basis. — T. Am. 
If. Ass.. 1913, Ixi. 447. 

II. Treatment of certain in- 



The local specific therapv of infections. II. Treatment of 

fections. — J. Am.M. Ass. t 1913, lxi, 1872; also Bull. Med. d Chir. 

pide 



Poo. Maryland, 1913-14, 

Results of the serum treatment of i 
Intermit. Cong. Hiig. d Demog. [1913], i 



Flexneb, S., and Clark, P. F. 

Paralysis in a dog simulating poliomyelitis. — .7. Exper. M., 1913 

.*i77. 

Flexnee, S., Clark, P. F., and Fraser, F. R. 

Epidemic poli yelitis. Fourteenth note: Passive human carri 

the virus of poliomyelitis. — „ 



of 



U. Ass., 1913, i\. 201. 

poliomyelitis epidemica. — Berl. 



Flexner, S., and Nogtjchi, H. 

Kultivierung d( s Mikroilrga nismus 

l.lin Wchnschr., 1913, 1, 1693. 

Fxporinioiits on the cultivation of the microorganism causing epidemic 

poliomyelitis.— ./. i'j'/.cr. .1/., 1!H:;, xviii, 401. 

i'xperiinents on the cultivation of the virus of poliomyelitis 

note.- •'. Am. M. Ass., 1913, lx. 362. 



Fifteenth 



Flint, J. M. 

Acute traumatic subdeltoid bursiti 
—.7. Am. If. Ass., 1913, lx. 1T21. 

Ford, W. W. 

Plant poisons ami their antibodie 
/. Ait., 1913, Iviii, Kef-. 129; 193. 

Ford, W. W., and Bronson, E 



and simple treatment. 



-Centralol. /. Bakteriol. [etc.}, 



amanita-toxin.- 



Pharmacol. .(- Exper. Therap., 1913, 



intra-abdominal 



-Lanct t-Clinie, 



Ford, W. W., and Rockwood, E. M. 

Mode of union between the' atuanita-ha.'inolysin and its autibapmulysin. 
— J. Pharmacol, .t Exper. Therap., I'M:'., iv. 235. 

Ford, W. W., and Sherrick, J. L. 

Further observations on fungi, particularly Clitocybe sudorifica Peck, 
Pholiota autumnalis I'cck, and lnocybe decipiens Bresadola. — J. Phar- 
macol, it /.'/'per. Therap., 1013, iv, 321. 

FUTCHEB, T. B. 

Eugenics in iis relationship to the welfare of the public. — jVei< Orl. 
If. <6 S. J., 1913, lxvi. 1. 

Gatch, W. D. 

The intrathoracic and 

1013, ex, 594. 

Gatch, W. D., Gann, D., and Mann, F. C. 

The danger and prevention of severe cardiac strain during anesthesia. 
— J. Am. M. Ass., 1913, lx. 1J73. 

Geraghtt, J. T. 

\ studv of the accuracy of the phenolsulphonephthaleiu test for 
renal function. -J. Am. M. Ass., 1913, lx, 191. 

Geraghty, J. T., and Plaggemeyer, H. W. 
The practical importance of infantile kid 
.l<ii. M. Ass., 1913, lxi, 2224. 

Geraghty, J. T., and Rowntree, L. G. 

Tlic value and limitations of functional renal tests. — .7. Am. M. Ins., 
1913, lxi, 939. 

Geraghty, J. T., Rowntree, L. G., and Cary, F. S. 

The value and limitation of diastase, urea and phthalein in estimating 
renal functi a in association with ureteral catheterization. — Ann. 
Burg., 1913, Iviii, 800. 

Geraghty, J. T., Rowntree, L. G., and Fitz, R. 
The effects of experimental chronic passive conj 
tion. — Arch. Int. Mel.. 1913, xi. 121. 

GlFFIN, H. Z. 

The diagnosis of diseas 
— JournaULanct t. 1913, 
Clinical noles on patie 
entamebas.- J. A m. u 
Clinical observations ci 
[m. .1 If. Be.. 1913, i 



in renal diagnosis. — .7. 



stion 



renal fune 



associated wilh enlargement of the spleen. 
:iii, 97. 

fr the middle northwest Infected with 

., 1913, Ixi. 675. 

■ruing twenty-seven cases of splenect 



Gilchrist, T. C. 

Vaccine therapy as applied to cutaneous 
inrl. Syph., 1913, xxxi. 077. 

GlLMAN, P. K. 

Axillary teratoma. — Philippine J Be., 1913., 
Appendicitis. — Philippine ■/. Be, 1913, viii. 

Goeham, L. W. 

The school child as 
1913. xxxiv, 6 19. 

Grey, E. G., and Hirsciifelder, A. D. 
A clinical investigation of the carbonic 
Int. Med., 1913, \i. 551. 



rrii'f of whooping 



Grey, E. G., and Emerson, L. E. 

A striking' acquirement of visualizing power and lie development of 
dreams following a cerebral tumor extirpation. — J. Am. M. Ass., 191% 
lxi, 2141. 

Guthrie, C. G., and Boggs, T. R. 

a brief sut arj oi Bence-.Iones proteinuria. — Internat. Clin., 1913, 

23 s„ i. 86. 

Guthbie, C. G., Moss, ,V. L., and Gflien, J. 

Diphtheria bacillus carriers.— Tr. AT Internat. Cong. llyg. d ; 
1912-13, iv, 156. 

GRIFFITH, F. W. 

The etiology and treatment of cystitis in women. — Southern M. J.. 
1913, vi, 458. 

Halsted, W. S. 

I. The excision of both lobes of the thyroid gland for cure of I 
disease. II. The preliminary ligation of the thyroid arteries and of 
the inferior in preference to the superior artery. — Ann. Surg., 1013. 
Iviii. 178; Tr. Am. moo. Vss., 1913, xxxi, 312; 319. 
Partial occlusion of the thoracic and abdominal aortas by bands of 
fresh aorta and of fascia lata. — Ann. Xing., 1013, Iviii, 1S3 ; alsa 
Tr. Am. Surg. Ass.. 1913, xxxi. 218. 

Developments in the skingrnf ting operation for cancer of the breast. 
—J. Am. I/. Ass., 1913, lx, 416. 

Ligature and suture material. The employment of fine silk in pref- 
erence to catgut and the advantages of transfixion of tissues and 
vessels in control of hemorrhage; also, an account of the introduction 
of gloves, gutta-percha tissue and silver foil. — .7. Am. J/. Ass., 1013, 
lx, 1110. 

Factors which may be concerned in causing hypertrophy of the 
thyroid gland, and the effect of excision of this organ upon other of 
the ductless glands. — To appear in: Tr. Ass. Am. Ptnfsi.itnis. I'.n::. 

Hastings, T. W. 

Reciprocal relations of the clinic and the laboratory in medicine. — J. 
Am. M. Ass.. 1913, Ixi. 651. 

Complement-fixation tests for streptococcus, gonoeoccus and other 
bacteria in infective di forming arthritis and arthritis deformans. 
— J. Am. M. Ass.. 1913, lx, 1208. 

Hastings, T. W. and Boehm, E. 

A study of cultures from sputum and blood in lob; 
Exper. 1/ . 1913, xvii, 239. 

HlNMAN, F. 

An experimental study of the antiseptic 
internal use of hexamethylenamin. — J. At 



pneumonia. - 



alue it 
M. As 



the urine of the 
, 1913, lxi, 1601. 



Hirsciifelder, A. D. 

Diuretics in cardiac disease. — J. Am. M. Ass.. 1913, lxi, 340. 

Simple methods in the diagtn sis of cardiac disease. — To appear in : 

Proc. XVII Intermit. Cong. M. Limit., 1913. 

Hirsciifelder, A. D., and Grey, E. G. 

A clinical investigation of the carbonic acid in the alveolar air. — Arch. 
lut Med., 1913, xi. 551. 

Hirsciifelder, A. D., and Winternitz, M. C. 

Studies upon experimental pneumonia in rabbits. 
— J. Exper. M., 1913, xvii, 657. 

Hocil, A. 

The problem of toxic-infectious psvehoses.- 
xiii, 86. 

Hoch, A. and Amsden, G. S. 

A guide to the descriptive study of the personality. With special 

refer, nee to the i a k i 1 1 g of anamneses of cases with psychoses. — Rev. 



Parts I to III. 



.V. lor/.- State J. .If., 1013, 



rot. <! PsyChi 

Hopkins, J. G. 



it.. 1913, xi. 57 



bacterial vaccines.- 



.7. Physiol., ioi::. xxvii. 



Howard, C. P. 

Differential diagnosis of diseases of the upper abdominal quadrants, 
— Tour. Iowa State M. Soc., 1913, ii. 864. 

Howell, W. H. 

Rapid method of preparing thrombin 
264. 

HOWLAND, J. 

The scientific basis for the artificial feeding of infants. — Am. J. Die. 

Child; 1013. v, 390. 

The Harriet Lane Home for Invalid Children. — Julius Hopkins Ainu 

Mail.. 1913, i. 115. 

Direct calorimetry of infants, with a comparison of the result 
obtained by this and other methods. — Tr. AT Intermit. Com/. Hug. 
Demog., 1912 [1913], ii, 438. 

Howland, J., and Dana, R. T. 

A formula for the determination of 
—Am. ./. ins. Child., 1913, vi. ::::. 

Hurd, H. M. 

Three-quarters of a century of institutional care of t lie insane in the 

I nited States.— Am. ■/. /titan., 1913, Ixix. 469. 

Early days of the Johns Hopkins Hospital and Medical School. — Julius 

Hopkins Alumni Wag., 1913, i, 105. 

The present status of voluntary admissions to institutions for the 

insane in the United states. — Am. J. Insan., 1913, ixix. 7st;. 

Hospitals and the reform of medical touching. \iml. Hasp., 1918, 

i. 182. 

The hospital as a factor in modern society. — Mod. Hosp., 1013. i, 33. 






JOHNS BOPKINS HOSPITAL BULLETIN 



■ 



Kelly, II. A. 

Incontlm i 

T:ilk ..ii radium. deliver. .1 

II. 1' I 

nal ami uret< r ..f the 

Ki 1 1 v. II. \ . and Lewis, K. M. 

- 

- 
tract. 
Kline, B. S., and Winthsmi/. M. C. 

s 

mini I- 

i II. M., Jr. 
Heel of moderately high I 
191. 

rhlrd ..I. w 
V..rk. 

Knox, .1. II. M., .Tk., and Thom \-. II. M. 

ndent Infants In 
I . p, V. X. 

On il . ■ nf maiiimnn' 

. 1013. Ivlll 
.liiUcultv of pr 

J. Ob*t.. 191 

imputation of 

Lyman, D. R. 

■nix in the M 
r. So. . 1913. 
LTS( if. P. \V. 

j.r.— -ur. during pregnam 
172. 

iii-v and labor. I m. I . "'.«( . 1013, 

IXTllI. IU7. 

Mv.i'iii hi, W. G. 

die IVberern 

Veil. i/. i ),,, . 1913. x\v. '.HI 
Ittitude "f undertakers Inward i 1 

Path. 8or.. 1913, xlll. 104 

M v, Cm ii m. \V. i; . and VOOEL, K. M. 

Kuril.. 

Mi Oak, T 

177. 
Mm ii r. M I. 

III. ! 

M m ii r. I>. I . and \'..i ..i i ■ 

McPlimHAV W. F. 
On tn< 

R. II. 

M.U'ii:, K. II . and Nobi i. E. 

Mm i. P. P. 

Ix. ) 
Mam. ! 

' IV. 


















. i: 

Nu i. I 

N'lMiN. P. I. 



3tB W. 


















66 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 276 



Randall, A. , „ ... , M , 

The etiology of unilateral renal hematuria.—./. Am. M. Ass., ivia, 

A' study o£ Hi,, benign polvps of the male urethra.— Surg., Gynec. d 
Obst., 1913, xvii, 548. 

Refd J V 

The financial obligation of the specialist to the physician.— Indian- 
apolis it: J., 1913, xvi. 94. 

Remsen, CM. „ . . . , . . __ 

n surgical complications in the abdomen during typhoid fever. 

The°hernUl' sac in its 'relation to concealed intestinal injuries.— Ann. 

Acute 1 perforatiTe cholecystitis complicated by general peritonitis. 
—Surg., Ounce. d Obit., 1913, xvi, 3S6. 

Rices X F. 

Report of four cases of tubal pregnancy. — Journal-Lancet. 1913, xxxm, 

Fistula in ano— its rational and successful treatment.— St. Paul M. J., 
1913, xv, 461. 

Iodine' in sterilization of the skin.— Surg., Gynec. .f Obst., 1913, xvii, 
324. 

Resistance to a tumor-producing agent as distinct from resistance to 

the implanted tumor cells. — J. Expcr. it., 1913, xviii, 41o. 

False transitions between normal and cancerous epithelium.- 

U . 1913, xvii. 404. 

The growth i if tissue in acid media. — ./. Expe 



Exper. 
1913, xviii, 183. 



Rous, P., and }Iurphy, J. B. 

Variations in a chicken sarcoma caused by a filterable agent.— J. 

Beobachtungen an ein'en Hiihnersarkom und seiner filtrierbaren Ursacbe. 
i.r, n . H onnschr., 1913, 1, 637. 

Rous, P., and Lange, L. B. 

The characters of a third transplantable chicken tumor due to a 
filterable can-. A sarcoma of intracanalicular pattern. — J. Exper. 
M.. 1913, xviii, 651. 

Rowntree, L. G., Abel, J. J., and Turner, B. B. 

On the removal of diffusible substances from the circulating blood 

of living animals by dialysis.—/. Pharm. d Exper. Therap., 1913, 

\. 275. 
Rowntree, L. G., and Baetjer, W. A. 

Radium in internal medicine: its physiologic and pharmacologic effects. 

— ./. Am. M. Ass., 1913. lxi. 1438. 

Rowntree, L. G., and Dandy, W. E. 

Peritoneale und pleurale Resorption in ihren Beziehungen zu der 
ijtg, rungshehandUing.— Beitr. :. klin. Chic. 1913, Lxxxvii, 539. 

Rownteee, L. G., and Fitz, R. 

Studies of renal function in renal, cardiorenal and cardiac diseases. 
—Arch. Int. Med., 1913, xi. 258. 

Rownteee, L. G., and Geraghty, J. T. 

The value and limitations of functional renal tests.—./. Am. M. Ass., 

1913, lxi. 939 
Rowntree, L. G., Geraghty, J. T., and Cary, F. S. 

The value and limitation of diastase, una and phthalein in estimating 
renal function in association with ureteral catheterization. — Ann. Surg., 
1913, lviii. sou. 
Rowntree, L. G., Fitz, R., and Geraghty, J. T. 

The effects of experimental chronic passive congestion on renal func- 
tion.- . I ,i li. Int. Med., 1913, xi. 121. 

Rowntree, L. G., and Marshall, E. K., Jr. 

i action of radium emanation on lipase. /, Biological Chan., 1913. 
xvi. II7I". 

Sampson, J. A. 

Results of the radical abdominal operation fm' cane r of the uterine 
cervix. Surg., Gynec. a Obsi . 1913, xvi, 304. 

The influence of myomata on the blood supply of the uterus, with 
special reference to abnormal uterine bleeding.- Surg., Gynec. d Obst., 
1913, xvi, 144. 

SCHENCK, B. R. 

Thrombosis and embolism following "petition and child birth. — Surg., 
a Obst., 1913, xvii. 603. 

Sellards, a. W., and Walker, E. L. 

Experimental entameebic dysentery. — Philippine ./. gc, 1913, viii. 253. 

Shallenbeeger, W. F., and Boyd, M. L. 

Di onstration before the Georgia Surgeons' Club. — Atlanta Jour.- 
Bei ord M., 1913, ix. 417. 

Sharpe, W., and Farrell, B. P. 

A new operative treatment for spastl 
.;, Lm. I/. Us., 1913, lxi, 1982. 



paralysis. Preliminary report. 



Slemons, J. M. 

Is albuminuria likely to recur in successive pregnancies? —Am. •'. 

Obst., 1913, ixvii, 849. 

Chorion and Decidua. — Re) A. Wm. Wood & 

Sons. New York. 

The prospective mother. — N. Y.. 1913, D. Appleton & Co. 



-Boston 31. and S. J., 1913, clxix. 



Smith, J. T., Jr. 

The prognostic value of the Ieucocvte count in pelvic suppurative 
conditions.— Surg., Gynec. d Obst., 1913. xvi. 403. 
Complement leviation by corpus lutean antigens. — Am. J. Obst., l\)li, 
lxvii. 1107 

Smith, W. H. 

Muni, ipal hospitals -their importance and their management. — tancet- 

CMn* . 1913, ex. 128 : 454. 

The real hospital problem. — .l/o<7. Hasp., 1913. l, 34. 

The per -capita cost. — Mod. Eosp., 1913, i. 184, 

Steiner, W. R. 

Digitalis : its action and its uses.- 

S28. 

Stevens, A. R. 

On the value of cauterization by the high frequency current in certain 
cases of prostatic obstruction. — V. York M. J. [etc.], 1913, xcviii, 170. 

Stone, H. B. 

Immediate and late results of the Whitehead operation for hemorrhoids. 
— Ann. Surg., 1913, lviii. 647. 

Stone, H. B., and Young, H. H. 

A new operation for the cure of recto-urethral fistula. — To appear in: 
7'r. Am. Iss. Genito-Vrinary Surg., 1913. viii. 

Stone, H. B., Whipple, G. H., and Bernheim, B. M. 
Intestinal I ibstruction. 

I. A study of a toxic substance produced in closed duodenal loops. 
II. A study of a toxic substance produced by the mucosa of closed 
duodenal loops. — J. Exper. M., 1913, xvii, 286 ; 307. 

STROUSE, S. 

The simplification of some diets. — in'scotisin M. J., 1913, xi, 239. 
Brill's disease, mild tvphus fever, in the Michael Reese Hospital. 
— Illinois 31. J., 1913, xxiii, 37. 

Strocse, S., and Jobling, J. W. 

Studies on ferment action. VIII. The toxicity of some proteoses. 
— J. Expcr. M., 1913, xviii. 591. 

Studies on ferment action. IX. A note on the relation between lysis 
and proteolysis of pneumococci. — J. Exper. M., 1913, xviii, 597. 

Thayer, W. S. 

Some questions concerning medical education 

ix, 1. 

On some Junctions of the free dispensary .- 

clxviii. Is:,. 

Dr. Fitz as a teacher. — Bost. M. d 8. J., 1913, clxix, 897. 

Towles, C, and Voegtlin, C. 

Treatment of experimental beriberi with extracts of spinal cord. 
— J. Pharmacol, d Exper. Therap., 1913, v, 67. 

Voegtlin, C, and Mactit, D. I. 

The action of nitrites and drugs of the digitalis group on the isolated 
coronary artery. — ./. Pharmacol, d Exper. Therap., 1913, v. 77. 
Isolation of a new vasoconstrictor substance from the blood and the 

adrenal cortex. Presen f the substance in the blood and its action 

on the cardiovascular apparatus. — •/. Am. M. Ass., 1913, lxi, 2136. 

Voegtlin, C, and Towles, C. 

Treatment of experimental beriberi with extracts of spinal cord. — J. 
Pharmacol. A Exper. Therap., 1913, v, 67. 



Ohio Stale if. ./., 1913, 
tost. M. d S. J., 1913, 



Warfield, L. M. 

The auscultatory blood pressure phenomenon. - 
14. xii. 71. 

Watts, S. H. 

Some observations on acute pancreatitis. — South. M. ./.. 1913, 
The treatment of facial paralysis by nerve transplantati 
to, ninion J. M. d S., 1913, xvi. 259. 

Whipple, G. H. 

II. Hemorrhagic disease. Antitbrombin 
— Arch. Int. Med., 1913, xii, 637. 



11 is, misin M. J., 1913- 



ud prothrombin factors. 



Whipple, G. H., and Goodpasture, E. W. 

Acute hemorrhagic pancreatitis. — Surg., Gynec. d Obst., 1913, xvii. 
041. 

Whipple, G. H., and Hooper, C. W. 

Icterus. A rapid change of hemoglobin to bile pigment iu the circu- 
lation outside the liver. — .1 . Exper. 31., 1913, xvii. 612. 
Hematogenous and obstructive icterus. Experimental studies by means 
of the Eck fistula.. — J. Exper. J/., 1913. xvii. 593. 

Whipple, G. H., Stone, H. B., and Bernheim, B. II. 
Intestinal Obstruction. 

I. A study of a toxic substance produced in closed duodenal loops. 
II. A study of the toxic substance by the mucosa of closed duodenal 
loops. — J. Expcr. if., 1913, xvii, 286; 307. 



Wiel, H. I. 

Evolution in the 
1913, xi. 272. 



Wight, O. B. 

Ovarian cyst with twisted pedicle 



, the heart ; a survey. — Calif. Stati 



\'oi thwest Med., 1913. v, 140. 
Winternitz, M. C., and Hirschfelder, A. D. 



Studies upon expeii uta! pneumonia 

U L913, xvii, 657 



rabbits. Tarts I to III. 



LET, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



WuTttirrrz, M. C, and Ki.ixe, B. S. 

Similes u|». ii i-x|»-riiiii'iiiiil pii.ii nla In rnliliiis. \ The role of the 

expert mill 1. 11,11111. miii. Tin' relation ,.f tin- mi 

lo tin- mortality.— J. Brper. if 1913 . 

upon ■ \|„ rim. mini pn ii, oiiii in rahl.il-, - In immn 

1/ . 1913. xvlll, 61. 

\Y,'i l SOHJT, J. M. 

new lumbar-puncture w if. (**., 1913, |\. 1204. 

The cutaneous reaction in syphilis. Second report. ' In 
1013, 

The cutaneous reaction ,.f syphilis .in. tin reaction). (Third c m 
monlcatlon). Calif. Stale J. If.. 1913, \i. 365. 

Jfoou > v. I' G 

Inflammation. f.arirrt-CHnir. 1913. clx. 36 

Public liealili for undergraduates in medical ■ ifofi If 

-/ . 1018, ll 

Medical education and the Ohio-Miami I 
CHnli . 1013. clx. 581, 

Undergraduate research work in medical schoo - r..i:: n 

- wxvli. 1 16. 

Hospital social service, l.aneet -Clinii . 101 
Small-pox and raccinatlon In Slam. I, \l Internal ■ 
Demog 1012 I 1013], It. 225. 
Insolation, Leprosj i ague, 

/inifi. , '.. Therapeutic) 0/ Internal Uedlcin 

SATES, .1 I., .mil Hi \iin... C. H. 

Cultural result! In Hodgkln Irch, Int. Med., 1913 

•Mi.lv ,,f HOdgklD'S iliseas.'. ./. {,., \l |.. 1913 |\i 

1808. 

Y..i 110, H. H. 

.\ Dew procedure (punch operation) for small prostatli 
tractnre ,.f the prostatic orifice. J. Iwi U 253 

The role ..f the prostate and Bemlnal resides In gen 

J. 1st. u, 1st 1918, III, B22 
The present status ,,f the diagnosis nl of vesical I 

J lm. if. Im . 1913 Ixl 
The diagnosis and treatmenl ,.f early malignant disease of the prostate. 
ppear In Proi rr// Intei Cont ' » 1918. 

Y..i \... II H . and Stoni . H. B. 

A new operation for the cure of rectourethral fistula. To appear In: 
<;. ml; I Hnary Surg., 1913, Till. 



FIRST ANNOUNCEMENT IN REGARD TO THE PROJECTED 
CELEBRATION OF THE 25TH ANNIVERSARY OP THE 
OPENING OP THE JOHNS HOPKINS HOSPITAL. 

Bai nMOKE, October 18, 1913. 

At an informal gathering of tormer officers and members of the 

i Ileal Fohna Hopkins Hospital upon October 10, 1913, 

11 was unanimously agreed thai the 26th anniversary of tl 
lng of the hospital should be commemorated by approprli I 
clses of a special character at the hospital during the Hi 
of October, 1914. II "f the 

Johns Hopkins Hospital and the Johns Hopkins fjniverslt) 
ami members of the hospital Btaff and all teachers and former 
students of tin' medical department ol the ould be 

cordially invited to participate in a general reunion 
commemoration exerclsi - are planned to ■ 
of three or four days at a time when it ma; 
that tli. the Herter Foundation will b 

Dr. William Osier has promised to be present in addltloi 
win be commemorative addressee and a -■ lentlflc programme with 
■inlcs, demonstrations and i o pltal rounds conducted b) ; 
and former mi i It Is antlclpi 

Buchanan Brady Urological Institute i appro 

mortal tabli I 
late I ir John Hewetson, 
on the walls of the general dining room II 

.it a similar tablet in mi mor) ol .ill di 
the house staff be prepared and placed I 
'- era, class reunions and receptioi i during I 

All details ol tl lebral I I n fullj 

the work of preparation will be p 

committees The co-operation and pr< 

of th« hospital <ir : 

or graduates of the mi rdlally lnvlti 



presenting full deu 

"Hi be sent from ,„„, ,„ ,..,_ eomm . 

wbota Interested .. timet] r plana 

Wll I iwi II Wi i, ii, 

\\ 1 1 , 

William 8 H u - 

II. .W V 

I Biting 
celebraUon of this anniversary from all 

'•'"' ™ maj i to Dr Hi arj M ilur : 

Building. Baltimore, Maryland, or to l>r Rupert 
of the Committee, 
Maryl 



NOTES ON M.w BOOKS. 

ti N-.N. m ii. 
etc /•,!»/ /t //,, 

i- an Interesting bi i from rartoui 

English medical Journals, Bhowlng I 
strain In producing various reflex neuroses Although ti 
-tress has been laid posslblj on the i D 
a great varli tj ol ■ • ur rlcal and other t i 

' • re i- foubt I 

factor at times In Illness ol varl 

and this little I k is of ValUI 

drawing his attention to I 

i ur. nervous Bymptoms whli 

ordinary treatment. 

■ 
By K It Sin r. M. D., .t. Third Bdltloi 
larged. Illustrated 

Son .i Co . /.''/.: i 

lng different 

iter! .1 without material!) 
■ ket manual, whli 
iMily In i 

or it la 
by a thorough!) well-lnfoi 

■ 

■ . that Still 

study ■ I 

It 

■ 



68 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[ No. 27€ 



The author's experience has been very large, and the cases he re- 
ports are of unusual interest. The general practitioner will do 
well to buy and study this book — he cannot know too much about 
syphilis, most know far too little — and he will find the perusal of 
Nonne most profitable. 

Tuberculin Treatment. By Olive Riviere, M. D., etc., and Egbert 
Morland, M. B., etc. Second Edition. $2. (London: Henry 
Froicde and Hodder d- Stoughton, 1913.) 

This is a second edition, indicating a well-deserved popularity 
of the work. Corrections and additions have been made through- 



out, the chief alterations being under the headings, " The Tuber- 
culin and their Preparation," " Tuberculin in Mixed Infection," 
and " Ambulant Treatment of Phthisis." These three headings 
are a decided improvement on the first edition — all three being 
clear, concise and to the point. 

The book should be of interest and assistance not only to physi- 
cians who are making a specialty of tuberculosis but also to those 
in general practice to whom many tubercular patients are referred 
on leaving a sanatorium or dispensary supervision. 

The authors are to be complimented on their work which ought 
to meet with popular approval. 



STAFF OF THE JOHNS HOPKINS HOSPITAL, FEBRUARY 1, 1914. 



Superintendent: 

WINFORD H. SMITH, M. D. 

Assistant Superintendents: 

RUPERT NORTON, M. D., KARL H. VAN NORMAN, M. D., 

RALPH B. SEEM, M. D. 

Physician-in-Chief : 

LEWELLYS F. BARKER, M. D. 

Associate Physician: 

WILLIAM S. THAYER, M. D. 

Surgeon-in-Chief : 

WILLIAM S. HALSTED, M. D. 

Associate Surgeon: 

JOHN M. T. FINNEY, M. D. 

Gynecologist-in-Chief: 
HOWARD A. KELLY, M. D. 
Obstetrician-in-Chief: 
J. WHITRIDGE WILLIAMS, M. D. 
Psychiatrist-in-Ciiief: 
ADOLF MEYER, M. D. 

Pathologist: 

WILLIAM H. WELCH. 

Pediatric ian-in-Chief: 

JOHN HOWLAND, M. D. 

Dermatologists : 

T. CASPAR GILCHRIST, M. R. C. S., J. WILLIAMS LORD, M. D. 

Ophthalmic Surgeon : 

SAMUEL THEOBALD, M. D. 

Assistant Ophthalmic Surgeon: 

ROBERT L. RANDOLPH, M. D. 

Neurologist: 

HENRY M. THOMAS, M. D. 

Associates in Surgery: 

JOSEPH C. BLOODGOOD, M. D., HUGH H. YOUNG, M. D., 

RICHARD H. FOLLIS, M. D. 

Associate in Orthopedic Surgery: 

WILLIAM S. BAER, M. D. 

Externe in Surgery: 

SAMUEL J. CROWE, M. D. 

Associate in Actinograpiiy: 

FREDERICK H. BAETJER, M. D. 

Assistant Actinographer: 

CHARLES A. WATERS, M. D. 

Associates in Medicine: 

THOMAS B. FUTCHER, M. D., LOUIS HAMMAN, M. D. 

Associates in Gynecology: 

WILLIAM W. RUSSELL, M. D., GUY L. HUNNER, M. D., 

THOMAS S. CULLEN, M. D., CURTIS F. BURNAM, M. D. 

Associate in Psychiatry: 

C. MACFIE CAMPBELL, M. D. 



Assistant in Obstetrics: 

KARL M. WILSON, M. D. 

Assistant in Pediatrics: 

EDWARDS A. PARK, M. D. 

Resident Physician: 

PAUL W. CLOUGH, M. D. 

Assistant Resident Physicians: 



CHAS. R. AUSTRIAN, M. D., 
THOMAS P. SPRUNT, M. D., 
ALAN M. CHESNEY, M. D., 
WILLIAM L. MOSS, M. D., 
CLYDE G. GUTHRIE, M. D., 



ANDREW L. SELLARDS, M. D., 
ARTHUR L. BLOOMFIELD, M. D., 
EVELETH W. BRIDGMAN, M. D., 
GEORGE MINOT, M. D., 
CARL VON NOORDEN, JR., M. D. 

Resident Surgeon: 
GEORGE J. HEUER, M. D. 
Assistant Resident Surgeons: 
ROY D. McCLURE, M. D., HARRY R. SLACK, M. D., 

WALTER E. DANDY, M. D., CARROLL W. WALDRON, M. D., 

FRANK HINMAN, M. D., LEWIS C. SPENCER, M. D., 

JOSEPH E. KERNEY, M. D„ CHARLES H. WATT, M. D., 

FELIX LANDOIS, M. D. 
Resident Gynecologist: 
LEON H. WATKINS, M. D. 
Assistant Resident Gynecologists: 
J. CRAIG NEEL, M. D., VEADER N. LEONARD, M. D., 

WILLIAM M. DUMM, M. D. 

Resident Obstetrician: 

HENRY A. STEPHENSON, M. D. 

Assistant Resident Obstetricians: 

WILLIAM L. MILLEA, M. D., WILLA M. FRICKE, M. D. 

Resident Pediatrician: 

KENNETH D. BLACKFAN, M. D. 

Resident Psychiatrist: 

DAVID K. HENDERSON, M. D. 

Assistant Resident Psychiatrists: 

EDWARD J. KE.MPF, M. D., RALPH P. TRUITT, M. D., 

HENRI FLOURNOY, M. D. 

Resident Pathologist: 
GEORGE H. WHIPPLE, M. D. 
Assistant Resident Pathologists: 
ERNEST W. GOODPASTURE, M. D., MONT R. REED, K 

Resident House Officers: 



WILBUR G. CARLISLE, M. D., 
HENRY W. CAVE, M. D., 
HOWARD L. CECIL, M. D., 
HELEN D. CLARKE, M. D., 
ERNEST C. FISHBAUGH, M. D., 
ROSCOE W. HALL. M. 1 >., 
JAMES R. GARBER, M. D., 
EDWARD JELKS, M. D., 
TEDROW S. KEYSER, M. D., 



ROBERT L. LEVY, M. D., 
LOUIS D. MINSK, M. D., 
GROVER F. POWERS, M. D., 
LAWRENCE T. POST, M. D., 
HENRY N. SHAW, M. D., 
F. JANNEY SMITH, M. D., 
MARTILLUS H. TODD, M. D., 
JOSEPH R. TURNER, M. D., 
WALTER R. HOLMES, M. D. 



The Johns Hopkins Hospital Bulletins ore issued monthly. They are printed by the LORD BALTIMORE PRESS Baltimore. Subscriptions J2.00 
year (foreign poslage. 50 cent.), may be addressed to the publishers, THE JOHNS HOPKINS PRESS. BALTIMORE; single eop.es icMl be sent 
mail tor twenty-fire cents each. 



Single copies may also be procured from the BALTIMORE NEWS CO.. Ballin 



BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered u Srcond-Clus Matter it the Baltimore, iUrrUnd, Pottofflc*. 



Vol. XXV.-No. 277.] 



BALTIMORE. MARCH. 19 14. 



(Price. 25 Cents 



CONTENTS. 



Remarks on Cases Received in the Henry Phippa Psychiatric 
Clinic. 

By Davis K. II: am rsos, 51. D 

Essential Sialorrhea in a I>"l', Cured by Excision of I 
ti.l Submaxillary and a Portion of the Sublingual I 
(Illustrated.) 

By ions W. (in i;i mm s\. M. 1) 

Observations Following the Use of Collargol in Pyelography. 
(Illustrated.) 

By fi. n W Vest, M. D 

Koplik'.- - ng "ii the Tonsils of aChild Subsequently 

Found to be Anaphylactic t" Egg-Albumen. 

By Sydney R. Mil leb, M. D 

A Brief History of Quarantine. 

By W. W. Pobd, M. I) 



(Illual 

Bj i. A. Hiivmi i ii. M. h . and \. i 

In Uemoriam. Reginald Bebei I 

By W. S. I ii win MM 

1 

Bj P :. M. I». ■ . • 

Dr. .1 ii 1 1 1 >— Pi 

Bj David I. M icht, M. D 

ohna Hopkins 1 1 . •— i ■ ^ t , 
Intel 
[Db. I>. R. Hook i ■ and Mu. J. D. 5a 





REMARKS ON CASES RECEIVED IN THE BENR1 
PSYCHIATRIC (LINK . 



MINT- 



During the eighl months fr May L to D II, 1913, 

in which The Benry Phipps P 

operation, 23c 

•In per 

land, fifteen or 3ix per cenl Maryland, out 

more, nnd the r< maininj 

The P 

idy and diagnosis oi 
for the 
from t] 

tient. 
The numlx 
the limit of what we wi 
tfdering the care and caution needed in I 
l . Many applicati 



• Paper read at a meeting of the Baltimore City Hi 
February 6, 1913. 



i 'win K. II t. D., 

■ 
■ 



70 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 277 



important point of distinction is: Does the patient or at least 
the family show a reasonable spirit of cooperation? 

To give you a very summary idea of the type of cases it 
will suffice to say that among the 238 cases received, 

14 women and 40 men had organic disorders. 

22 " " 17 " were cases of various psychoneu- 

roses. 

23 " " 18 " were cases of depression. 
6 " " 21 " were cases of excitement. 

35 ■ " " 21 " were cases of dementia pragcox 

and allied states. 
6 " " 11 " were cases of toxic psychoses. 

4 " "9 " were cases of constitutional psy- 

chopathic disorders. 
In only 8 of these eases was commitment resorted to. 

Public opinion still makes a very exaggerated contrast be- 
tween simple mental difficulty and insanity, and unfortunately 
many physicians tend to bewilder the public still further by 
using that very misleading term " borderland case." It 
seems to be a wide-spread misconception that only so-called 
"borderland cases" are admitted to the Psychiatric Clinic; 
another misconception is that only acute cases are received, 
and a third and rather negligible one is that the Clinic is 
chiefly a place for the training of defective children. 

The name " borderland " seems to me to be a very dangerous 
one, and one very fruitful of error. I suppose that it is its 
ambiguity that is so appealing — as the term eczema is in skin 
diseases — and on that account it is used to denote cases in 
which the diagnosis is more or less doubtful. One's experi- 
ence either with the psychoneuroses or with the psychoses 
proper need not be extensive before one begins to appreciate 
that there is no definite dividing line between these conditions, 
and that too frequently the patient tends to get quite an 
erroneous view of his condition which is hard to eradicate. The 
line of divison lies chiefly between cooperative and non-cooper- 
ative states, and not between any supposed standard of sanity 
or insanity. 

Our main opportunity for progress in combating mental dis- 
orders is to facilitate as much as possible the admission of 
voluntary patients during the stage of capacity to cooperate — ■ 
a tendency which is well exemplified by the numerous volun- 
tary admissions to all the progressive institutions around us. 
The family physician more than any one else is the best 
person to point out to the families and patients how success 
or failure in the treatment of a case depends to a tremendous 
extent upon the degree of cooperation. 

It will not be necessary to discuss the general methods of 
work with our patients, the special treatment of the specific 
cases, the treatment for drug and toxic cases, the hydro- 
therapy, gymnasium, and occupation treatment, and the ef- 
forts to help the patients to attain to n mental readjust- 
ment. But it may be of some use to depict briefly a few eases 
in which the cooperation of the family physician would be of 
the utmost importance, and a few others illustrating the 
ransre and aims in the treatment of cases calling for a mental 



readaptation. Some of these cases may also suggest how im- 
portant it is to make a very close and diagnostic study of the 
symptoms so that grievous mistakes may be avoided. 

A young married woman, 30 years old, was admitted to the 
Clinic on May 19, 1913, with a history of having lost weight (50 
lbs.), of persistent vomiting, air hunger, and occasional catheteri- 
zation. She was admitted to a quiet ward, but owing to her 
strenuous objections had shortly to be moved to a private room. 
She lay quietly in bed with a smiling expression, and talked freely 
about her complaints. She frequently would take deep inspira- 
tions, followed by a long sighing expiration and said: "When 
I breathe naturally it does not satisfy me, I must take deep 
breaths — it seems as if the breath just goes to here " (pointing to 
the middle of the sternum) . As soon as one could get her interested 
in a conversation, however, her respiratory difficulties consider- 
ably abated. In addition to her respiratory difficulties she refused 
to take anything to eat except a little cracked ice and milk from a 
medicine dropper. A careful examination of her physical condi- 
tion failed to elicit any basis for her complaints. The history of 
the case in brief showed that she had been a healthy child, who 
apparently had developed normally, and married at the age of 19 
years in 1902. In June, 1905, 3 years after marriage she was 
admitted to the Maternity Ward of the Johns Hopkins Hospital, 
and was at that time 5 months pregnant; but, what is of more 
immediate interest to us, it is also noted in the history that she 
showed considerable respiratory difficulty, especially in the pres- 
ence of a doctor or nurse. These symptoms, even at that time, were 
diagnosed as being neurotic in origin. 

Following the birth of her child on November 15, 1905, she 
remained well for a very short time, but then commenced to com- 
plain of vague pains, on account of which she underwent three 
operations — in 1908, 1909, and January, 1913, for adhesions. In 
September, 1912, however, vomiting, which soon became persistent 
in character, developed. This vomiting was at first thought to be 
due to another pregnancy: but, after that diagnosis had been ruled 
out, pelvic adhesions were blamed for the vomiting, which was 
considered to be of reflex origin, and so finally in January, 1913, the 
last operation was performed. Following this operation she did 
not vomit for 15 days; she returned home, but 3 days later vom- 
iting again started so that until the time of her admission to the 
Clinic she had been existing on a small quantity of " lozak " or a 
little ice-cream. 

During all these months at home she had been confined to bed, 
and made life unbearable for everyone in the house; her husband's 
capacity as a workman was seriously interfered with, and her 
family physician would be summoned both night and day to con- 
sole her and to administer morphia so that she might get a little 
sleep. 

No time was given us to make an analysis of this case, but from 
the history which has been given, many psychogenic features are 
evident. During the two and a half days she was in the Clinic she 
was exceedingly discontented, asked to be taken home all the time, 
and owing to the fact that those who were closely associated with 
her would not take a definite stand, the patient had to be dis- 
charged. The case clearly shows how important an early diagnosis 
of psychogenic factors would have been, and how necessary the 
firm advice of the family physician. 

A second case was that of a young married woman, 23 years old, 
who on admission had a twitching movement of the left side of her 
face, frequently protruded and withdrew her tongue, and lay in 
a somewhat trance-like state, usually with her eyes half closed. 
She looked pale and anguished, and frequently put her hand over 
the region of her heart. She answered questions in a sing-song, 
irrelevant way, and repeated the same thing over and over again. 
At times she tended to assume an opisthotonos position, and 
frequently tried to vomit. She did not react to pin pricks anywhere 



Mai;, n, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



n 



over the body or face, willingly put out her tongue to be pricked, 
but her corneal reflexes were present on both - 

The history of the case showed that three months previous to 
her admission to the Clinic the patient's sister had died Id a 
hospital from nephritis. The patient had been great 
this sister, frequently talked about her, and following bi 
visited her grave every day, rain or shin.'. About one month aft. r 
her sister's death she consulted the family physician for 
complained of all the symptoms from which her sister had Buffered, 
and thought too that she had nephritis. Two months later and two 
days previous to her entrance to the Clinic she complained of pain 
In the left side of her abdomen, refused to talk, would hold her 
breath at times, and twitching started in the left side of her face 
and in both arms. Two days following admission t! 
much better but refused to cooperate in a thorough analysis of her 
case, said that she did not want to stay in a I 

bad died in one, and consequently five days after admission the 
patient was taken home by her relatives much improved, but far 
from having learned to understand and protect herself for the 
future. 

A third case which emphasizes the same points as the p 
two was that of a young married woman of 30 years of aj 
was admitted to the Clinic in an excited, ballnclna 
which she saw God and felt compelled to do everything thai 
her to do. She seemed fearful, blamed herself for having 
told about a clandestine love affair with a physician and begged 
God not to send her to hell. 

The history showed that she had been a healthy girl who had 
developed normally. In 1910 she married, but owing to a 
ismus had never been able to have sexual relations with her 
husband, which was a source of considerable dissatisfaction to her. 

For about 10 clays before admission she had a fever with a 
temperature elevation varying from 103° to 104° F., for which no 

te cause could be determined. No mental s> u ; 
thems' lii's until 2 days previous to admission when irnne 
after receiving communion she began to talk about her sins having 
been forgiven, told how the family physician had shown al 
for her. and of how she had had two children fifteen minutes 
apart without any pain. Later because God told her to do 
things she became very violent and abusive. 

During her six days residence in the hospital the patient Im- 
proved considerably, but then the husband de ; 
insisted upon taking her home, even though the 
believed that she had actually seen and talked to God, and while 
■be still maintained that she heard voices tellin. 
things. 

cases I suppose would 1"- called bj man] " 
lnml " cases, I it tl ■ ature about them all li 

their total hick of appr 
that in itself - 

view of such cast -. It seems to • 
least the mil'. . in which 

■ 

and of the family physician, 
two physiciai 

^'ich patiei - 

the situation an.! 

an and pati< at. U 
who mo~t nnforti I 

trance to the < llinic that they will i ol 
"real mental patients." hut with other "boi 
themselves, and when tie ir rap 



of rap] 

an.] ii 
fain i I;. 

■ 

■ 
- t.. enter him on 

know . 

attitude, w I 

him on the day ;." 
■ 
patients. 
I i 

dmitted in an n" 

unpardonab ■ 

tit for wh. 

if We 

Clinic i 

of hnv:: 

■ 












72 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 277 



The patient described herself as always having been of a secre- 
tive nature and an exceedingly conscientious student while pre- 
paring herself for work as a missionary. It seemed impossible to 
get at the basis of her trouble simply by straightforward talks, 
and therefore association tests and an analysis of her dreams were 
undertaken. By means of this it was soon revealed that her 
fainting attacks had occurred in relation to the intense con- 
flict about her auto-erotic behavior which had troubled her since 
infancy. The attacks were usually precipitated by some external 
reference, c .g., social problems, difficult work, or imminence of her 
secret knowledge being discovered. After the general biological 
aspects of the natural instinctive life had been explained to the 
patient, and a plan of readjustment had been outlined and par- 
tially carried out, the patient was tremendously relieved. She was 
discharged 14 days after admission with a new point of view and 
with a safe and sound understanding of how to handle herself. 

Here then was a case which had Dot reacted to general 
medical measures, but in a short time an excellent result was 
obtained by means of procedures which demand the training 
and patience of the specialist. 

Before concluding, I want to cite still one more case to 
show how it is not the acute cases only which react to 
treatment, but also how occasionally long standing cases when 
subjected to intensive treatment by a careful going over of 
the causal factors may show a remarkable improvement. 

A young lady, 27 years old, was admitted to the Clinic on June 
27, 1913, in a rather inaccessible and impulsive condition. She 
kept repeating the same thing over and over again, continually 
said that she must go home and whenever anyone entered or left 
the ward, made a bolt for the door. She smiled and giggled in a 
stereotyped way, showed a great deal of facial grimacing, and 
could not be got to cooperate in a satisfactory mental examination, 
usually replying to questions with such an answer as " I don't 
know — I must go." She could not give any definite account of how 
she had been during the last two years. She seemed puzzled by 
the whole situation, would not recognize physicians whom she had 
known formerly, and apparently seemed the victim of inaccessible 
imaginative ruminations and blind impulses, with the characteris- 
tic features of dementia prsecox. 



The history of this case showed that this patient had always 
been a conscientious, quiet girl, who in some ways might have 
been characterized as precocious. She was brought up in absolute 
ignorance of sexual matters, and at school was told of a number 
of things which she felt that she ought to have known, and in 
consequence of which she accused her mother of having exposed 
her to ridicule. Previous to this, in 1904, she is described as hav- 
ing two tantrums of laughing and crying of short duration. In 
1905 she went to school in Europe, but then became discontented, 
was very nervous, and while on board the ship returning home 
claimed that she was pregnant, and that the ship surgeon had 
taken advantage of her. Immediately after landing she was put 
in a private institution, where she is described as having been 
suicidal and impulsive, and having had a number of delusions. 
In 1907 some improvement occurred in her condition which lasted 
until 1911, when she again passed into a state of fancies, refused 
nourishment and kept repeating the same thing over and over 
again. 

Here was a patient whom everyone would be inclined to 
designate as an absolutely hopeless case, but in whom a re- 
markable improvement has taken place during her residence 
in the Clinic. She is now able to employ herself in many use- 
ful ways, goes shopping, and behaves in general like a normal 
person. The full knowledge of the factors in the patient's 
life and of her reactions seemed to justify the patient's re- 
ceiving hospital treatment, which was made possible because 
the parents were willing to cooperate in every way. It goes 
without saying that especially the period of improvement and 
convalescence is of the greatest importance for intensive treat- 
ment and for the laying of a safer foundation for the patient. 

Enough has now been said to show how important it is to 
get away from using terms such as " borderland," " acute," 
•'' chronic," " insane," and " not insane," and that the only sat- 
isfactory basis on which patients can be received is one of 
willingness to cooperate, if possible, on the part of the patient 
and above all things on the part of the family. 



ESSENTIAL SIALORRHEA IN A DOG, CURED BY EXCISION OF THE 

PAROTID, SUBMAXILLARY AND A PORTION OF 

THE SUBLINGUAL GLANDS. 



By John W. Churchman, M. D. 
{From the Laboratory of Surgery, Yale University.) 



In an exhaustive study of sialorrhea by Andre, 1 essential 
sialorrhea is said to be very rare, " if indeed it exists." It is 
defined as a neurosis in which sialorrhea is the only or pre- 
dominating symptom and is said to follow traumatism or a 
slight infection, as in a case of Ball's, in which the condition 
developed after a cervical adenitis. 

In the case here reported, sialorrhea of the most extreme 
type developed without apparent cause ; it was accompanied by 
advanced and progressive asthenia and cachexia; excision of 
the glands was followed by complete cure of the sialorrhea and 



1 Andrfe: De la sialorrhSe. Paris Thesis, 1S98. 



restoration of the moribund animal to normal; and examina- 
tion of the excised glands showed no changes save an increase 
in size. The somewhat vague term, essential sialorrhea, seems 
therefore sufficiently justified as descriptive of the condition 
present. 

The case was referred to me by a veterinarian, Dr. H. L. 
Tower, of New Haven. The animal was a Boston bullpup, a 
much-prized family pet. He had been healthy at birth, but 
shortly afterward began to drool saliva. At first this was the 
only symptom, but anorexia gradually supervened; and soon 
attacks of vomiting came on, the immense amounts of saliva 
swallowed causing constant gagging and frequent expulsion of 



THE JOHNS HOPKINS HOSPITAL BULLETIN, MARCH 




Fig. i Condition ol dog before operation. 




Kn 

glanda from a normal pn] 





Ellenberger .and Baum, showing I 

1 Parotid gland 

2. Submaxillary gland 

:: Sublingual gland aboral portion. 

ml • ir:t I portion 
1. 2 and ■'■ • 




Flo. 6 Lou powi 
illary gland : </. f r< i I 
normal pup. 



March, 1914.] 



JOHNS EOPKINS HOSPITAL BULLETIN. 






the saliva from the stomach. The animal refused t 
spiritless and was dying of asthenia and starvai ii 
On admission the dog, an affectionate little animal, was 

little more than skin and bones. He weigh 
Fig. I, which really fails to do justice to th< i maciation). He 
was quite weak, moving about languidly in Bearch of a sunny 
spot to lie down in. The jaws were constantly dripping saliva 
and the bed made for him was kept soaked. Every little while 
Urge amounts of saliva v, d. He could be made to 

take food only with difficulty, and was altogether a pitiable 
object to behold. Abdominal examination was negative and 
no signs of paralyses or other nervous lesions were discovered. 
Greatly enlarged salivary glands could be felt beneath the 
lower jaw. reaching in a crescent from the root of one ear to 
the root of the other. No chemical analysis of the saliva was 
made; nor was its ferment coefficient determine.!. 

Under ether, excision of both parotids, both submaxillaries 
and both sublinguals, was done. The oral portion of the sub- 
linguals was left (see Pig. 2). The glands were evidently 
enlarged (><■<■ Pig. 3), but were otherwise unchanged. The 
postoperative convalescence was without event. The wound 
healed nicely and there was almost no general reaction. 

For a few days following operation a rather more than 
norma! amount of saliva was secreted, but nothing thai could 
be called sialorrhea was observed. The dog's bed remained 
dry. there was no gagging or vomiting; and on the tenth day 
the dog, though still weak, was able to be taken home. Hen 
rapid recovery began and ha- since continued. Salivation lias 
ceased entirely: the dog is in every reaped normal. He runs 
and plays actively, i ats well, and now weighs . nearly 

twice what he weighed on admission to the lab 
and 5). lie is still small in frame. 

The literature of sialorrhea completely n 

by Andre. ' In account i jibility of his 

publication and the rarity and 
be useful to presenl a \n.lrc"s findi 

If sialorrhea be cl • the follow- 

ing types may be re •■_ i ized : 

ntial sialorrhea. B] this term is urn 

in which abundai 

or predominating symptom. It 
-ts. 
ous sialorrl 

depem 

a. Epili ■ 

b. Hysteria. Mai of tb 

ilivary flow may i 
emotion, a sharp odor, an 

and make i: 
Bloody salivatioi 
the b 

c. Nearest 

d. Exophthalmic goitre and n 

e. Rabies. 



orrhea dm I 

a. Paral; 

b. Di» a :' thi m iulla : 

i. I. 
ii. P muscular atn 

laryn- 

mellt. 

d. Diseases of the brain : hemiplej 

al paralysis. 

e. M 

chondria. 

f. Affections involving the cran particularly 

the facial. Sialorrhea onlj occurs when the 

■iiral. for di 
decrease in salivary b© retioi 
due to thi :.ral inhibil 

•ion. In tic douloureux the Balivarj 
may accompany, follow or replace the painful 
crisis. 
•I. Sialorrhea with 
a. I 1 

i. Diseases of the buccal 

tin-, dentition in infanl 
ii. Stomach. Sialorrhea may accompany 
chlorhydria. In some of tl 

mulates in I 
to be followed ! 

iii. [ntestinal pan 

iv. hi-, a- s of the pai 
v. D 

In « i rhea may a 

in the genital I it the 

monthly periods and particularly - 
nancy (" This 

j. With 

■ 



n 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 2'i 



in the condition of secretory activity which expresses itself 
clinically in sialorrhea. So far as I am aware no resection 
of the glands has previously been done for this condition; and 
a description of the specimen removed in this case is therefore 
given. 

There was obvious macroscopic enlargement of the salivary 
glands, which formed, as I have said, a crescent reaching from 
ear to ear. The comparison of the glands removed, with a 
similar specimen from a healthy pup of about the same size 
and age is shown in Fig. 3. The glands removed weighed 
28.2 gms. ; the normal glands 7.5 gms. When examined with 
the low power, the alveoli with their basement membrane are 
seen to be retracted from the interstitial tissue. This is not 



due to atrophy of the alveoli, which are well developed, nor to 
atrophy of the individual cells, which seem to be as large as 
those of the normal gland. The interstitial tissue is actually 
diminished in amount and forms a much smaller proportion 
of the whole section than in the normal gland. The inter- 
alveolar spaces are, therefore, more evident and the glands 
less compact in structure than the normal glands. There is no 
definite change in the high power picture of the secreting cells, 
nor of the demilunes. The mucous cells are large, the lumen of 
the alveoli very small, the nuclei lie at the base of the cells, and 
the protoplasm fails to stain. The picture, strangely enough, 
is that of the loaded or charged state usually associated with 
freedom from secretory activity (see Fig. 8). 



OBSERVATIONS FOLLOWING THE USE OF COLLARGOL IN 

PYELOGRAPHY. 

By Cecil W. Vest, M. D., 
Late Resident Gynecologist, The Johns Hopkins Hospital. 



Abdominal surgeons and urologists are often called upon 
to diagnose renal conditions and tumors or to exclude the upper 
urinary tract from the other organs considered. In this field, 
as in all other branches of medicine, anything which will aid in 
differential diagnosis is eagerly employed. Eecently the plan 
of injecting the renal pelvis with collargol and then taking an 
X-Eay picture has been used in urinary clinics. From such a 
radiogram, the outline of the upper urinary tract can readily 
be made out, and this is of marked value in determining the 
size, shape and position of the renal pelvis and ureter. 

For the past three years this method has been followed in 
the gynecological department of the Johns Hopkins Hospital, 
and our attention has been called forcibly to symptoms 
and conditions, which at times follow the use of collargol. 
In many of the public ward and dispensary cases so treated 
here, no symptoms whatever have been noted as a result, but 
a few patients have caused us some uneasiness by their re- 
actions. 

The technique used by the author has been practically uni- 
form in all cases. After catheterizing the ureter desired and 
measuring the capacity of the renal pelvis, the patient is 
made ready for an X-Eay picture; then the renal pelvis is 
injected, the photographic exposure made and the collargol 
allowed to run out, so that it does not remain in the renal 
pelvis more than two or three minutes. The injections * are 



* To avoid possible injury to the kidney from an injection made 
under pressure, the plan of allowing the fluid to run into the renal 
pelvis by gravity has been tried. An instrument for this purpose 
is shown in Oehlecker's 1 article; it is quite simple, consisting of a 
glass measuring cylinder from the lower end of which a piece of 
rubber tubing about 4 ft. in length leads to the renal catheter. The 
cylinder can be placed at any desired height. 

Thomas, 2 of the Mayo Clinic describes a similar instrument for 
the same purpose. A Y-shaped tube is attached to the lower end of 
a titrating buret. To one end of this tube is attached a piece of 
rubber tubing 4 ft. in length. A needle to be inserted in the renal 



made slowly and carefully with a piston syringe. When the 
patient first feels a fullness or tightness in the side, the injec- 
tion is stopped. In order that as small an amount as possible 
of the collargol might remain in the pelvis, for the past six 
months we have irrigated it with sterile water. A 15 per cent 
solution of collargol is used ordinarily, but a 10 per cent solu- 
tion has been tried in a few cases. . No difference in the symp- 
toms has been noted with the weaker solution, while a better 
shadow, especially in fat patients, is obtained with the stronger 
solution. Tennant f used a 25 per cent solution in a second 
injection. 

The collargol is never sterilized and is always thoroughly 
shaken before the injection. In many cases the material was 
warmed before using. The solution is usually used within one 
or two days after preparation, but in some cases it had been 
kept for ten days or two weeks in a tightly stoppered bottle 
from which evaporation was prevented. 

In the histories of the six cases that I report, the constitu- 
tional disturbances noted are all recorded. The chief com- 
plaint in the injection, whether with water or collargol, of the 
renal pelvis is pain, which occurs probably in one-fifth of the 
cases. The pain is persistent, often lasting from one to three 
days, while in one of my cases it was necessary for the patient 
to remain in bed ten days following the injection. Nausea and 
at times vomiting are associated with the renal pain. In three 
cases there has been a rapid rise of temperature following the 



catheter is fastened to the other end of this tube. The other arm 
of the Y connection empties the buret which is supported by a 
telescoping stand. 

f Here : the author has graphically shown by photographs and 
micro-photographs the presence of collargol in the kidney sub- 
stance. At operation two weeks after injection an infected area 
about 2 inches wide was found to be infiltrated with collargol and 
the capsule covering this area was lifted from the parenchyma by a 
layer of collargol. This mass extended down to the renal pelvis 
and was resected without going into the pelvis. 



Mm;, ii. 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






n. These i 
three days tx Fore the catheterization, and each had a 
temperature. In Case VI the verified rectal ten 
the third day following the injection \».i- 102.4 I-'.. « 
the fourth it was 104° F. 

The urine of th< ore the injection was i 

Followini.' it. it is not unusual to find white blood-cells and 
hyaline and granular casts which may persist for foui 

Ubumen is also pr< - ni in definite amounts 
lengths of time. Cases II and 111 showed -mall am. units when 
discharged and Case VI 3 after thi ii 

In the five cases operated upon, the 

noted in the kidney or retroperitoneal tissui I there 

was an escape of approximately 1"> cc. of .lark brown fluid when 
the kidney was exposed, while in another a small am. unit was 
found in the peritoneal cavity. In Case VI the n 
abscess was undoubtedly causi d by th ollargol 



Qpol v 



kldne) 

dark br 

were d. ■ ; . ma] in 

"ii tl. •• 
mproved from t : 
day. VI ! • 
and Ik. i 
infusi.'i 
and drowsy. 
Ni. ant 

blood. J mi. ■ 5, \V t 
granular casts voided. Joi 

The cow 



z'^^Mmm^^^^^Mm^^^^^^m^^^^^^^^^M'^\ 




v__:\i 






Case II.— Cyn. No. 19227. Both kidneys In 

9 dayB. No 

which was noted al th 

jection. Assoi iated with thi 

periu 

Ni. arini «vas al any time not< d in thi 

nor did thi ca urinarj odor. Win th 

I from the 1 
■ 

kidn. 

renal fat been found ■ 
- ■ 

.ml upper portion of 1 1 1 
• il.le. but no 

for the purpose of stu 
All ex. eptu _ ' aa No. Iht 

by the author. 

1 Gyn. N... 184H 
■■•inf.— Pain in the 
painful urination. May 28. patient v. 



temperature 1 ■• - 

■ 



76 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 277 



No mention is made of the method of injection used in these 
cases. 

Prof. Rovsing (Copenhagen) does not use collargol in his 
cystoscopie work, preferring to make his diagnoses by other 
means. (Personal communication.) 

Case II. Gyn. No. 19227. Age 18. White. 

Complaint.— Vain in right side of abdomen. April 11, both kid- 
neys catheterized. 6 cc. of collargol injected into the right pelvis 
and 11 cc. into the left. X-Ray picture taken. Following the ex- 
amination, the patient had quite severe pain in each side which 
lasted until the second day. Temperature eight hours after injec- 
tion, 100.2° F. No operation. Urine. — Both kidneys the same. 
Sp. gr. 1004. Albumen absent. A few epithelial cells. April 13, 
patient has a " soreness " in each hypochondrium. Temperature 
102.6° F. Urine: Catheterized specimen. — April 14, sp. gr. 1015. 
Albumen present. Reddish yellow sediment and masses of R. B. C, 
and a few W. B. C. Granular and hyaline casts. Considerable 
tenderness in left hypochondrium. Temperature 102.8° F. W. B. 
C, 8120. April 15, sp. gr. 1010. Albumen present; also R. B. C. 
and W. B. C. No casts. Condition improved. Temperature still 



/_*.. 



SM 



'zm%mm$\wmxmu\m%mmmm& 




Case IV. — Gyn. No. 1S978. Left kidney injected. Temperature 
elevated 8 hours after injection. 102° F. on 3d day. 

elevated. Patient remained in the hospital for ten days longer 
when she was discharged feeling quite well. Wassermann test 
negative. Calmette tuberculin tests, 1 per cent and 5 per cent, 
negative. When patient left the hospital, there was a slight trace 
of albumen, and some blood cells noted as present in the urine. 

Case III. Gyn. No. 19121. Age 30. White. 

Complaint. — Pain in right side under costal margin. March 3, 
right kidney is in descensus, the upper pole being quite readily 
palpable. The ureters were catheterized, the urine from each side 
being negative. 21 cc. of collargol were injected into the right 
renal pelvis and an X-Ray picture taken. After the injection a 
catheterized specimen of urine from the right kidney showed some 
albumen, no casts, and a few red and white blood cells. Oper- 
ation. — March 6, suspension of the right kidney. The kidney was 
slightly stained a deep brownish color. There was also a slight 
discoloration of the perirenal fat. Convalescence uninterrupted. 
A positive amount of albumen was found in the urine after the 
operation, which amount was present upon discharge, March 27. 
Both specimens were voided. No casts. 

Case IV. Gyn. No. 18978. Age 45. White. 

Complaint. — Pain in left half of abdomen. Left kidney was 
movable, slightly tender and lower half palpable. January 9, 



ureters were catheterized and 14 cc. of collargol was injected into 
the left renal pelvis. The urine from each kidney was normal. 
There was marked elevation of temperature three days following 
the injection. Operation. — Fourth day after injection, January 13. 
Suspension of left kidney. The kidney and perirenal fat at the 
operation were found to be deeply injected, these tissues having 
a deep brown color. There was a small amount of serous material, 
stained the same color, about the kidney. A small sinus which 
drained the perirenal area persisted at the lower angle of the 
incision until the end of the third week. Patient was discharged 
February 12, well. 

Case V. Gyn. No. 19142. Age 33. White. 

Complaint. — Dull aching pain under right costal margin and in 
right lower back. Right kidney quite movable and in descensus. 
It can be depressed to the anterosuperior spine and to the median 
line. Left kidney normal. March 11, 30 cc. of collargol were in- 
jected into the right kidney and an X-Ray made. Patient had quite 
severe pain for six hours following injection. March 12, urine, 
clear. Operation. — March 12, suspension of the kidney. Appendec- 
tomy. There was a small amount of dark colored material (collar- 
gol) in the perirenal tissues. The pelvis was large and boggy but 
the kidney was normal in size and outline. The kidney and peri- 
renal tissues were seen to be stained a deep brownish color. There 
was a small amount (approximately 2 cc.) of black fluid in the 
peritoneal cavity. Urine. — March 13, albumen present; many 
W. B. C. and R. B. C, and fine and coarsely granular and hyaline 
casts. Convalescence uninterrupted. This case is of interest 
because collargol-like material was found in the peritoneal cavity. 

Case VI.* Gyn. No. 19249. Age 32. Black. 

Complaint. — Pain in right abdomen. April 21, right kidney 
catheterized. 10 cc. of collargol injected and an X-Ray picture 
taken. April 22, patient had nausea and vomiting yesterday and 
to-day. April 24, patient is fairly comfortable but has some pain 
in the lower right abdominal quadrant. No muscle rigidity. Tem- 
perature continues elevated since last night, 102.5° F. W. B. C. 
16,800. April 25, continues practically the same. W. B. C, 21,200. 
Temperature 104° F. Operation. — April 26, both tubes and the 
appendix removed. There was a mild chronic pelvic inflammatory 
disease. The abdomen was opened through a median line incision. 
There was marked discoloration (a deep brownish and in parts 
blackish) noted throughout the right half of the pelvis and abdo- 
men, extending to the lower pole of the kidney. This discoloration 
was entirely retroperitoneal. The adherent appendix was removed. 
A drain was placed through the cul-de-sac. Patient had a con- 
tinued elevation of temperature, for the most part between 102° 
and 103° F. and at one time 105° F. This condition continued 
for 12 days after the operation when the temperature fell, remain- 
ing for a week at about 100° F. During the next ten days there 
were daily elevations of temperature, varying from 100° to 103. S° F. 
Suspecting the discoloration of the retroperitoneal tissues to be 
the cause of this disturbance, an incision was made in the right 
flank. There was an immediate escape of about 2ozs. of thick 
yellowish pus which contained definite fecal material. Digital 
exploration was carefully made to make sure no further pockets 
existed and a drain was placed in the incision. Fecal material was 
noticed on the dressings on the second day. The fistula persisted 
for 11 weeks. During the last three weeks of this period the 
fistulous tract was given a continuous irrigation of tap water five 
hours daily. In the week after the second operation the tempera- 
ture remained between 102° F. and 104° F., but gradually fell. 
In the six weeks following there were numerous elevations to 
103° F., twice to 105° F., and twice to 106° F. (All temperatures 
over 101° F. are rectal and over 103° F. are verified.) Widal 



* A case quite similar is reported by Oehlecker in his interest- 
ing article. In our case a first radiogram was negative for stone. 



March, 191 1.] 



JOHNS BOPKINS HOSPITAL BULLETIN. 






and blood culturea negative. Haemoglobin 6S p>r 
blood examination negative On the LlStb day alter the Bi 
ation she was discharged well. Urine. — April 19lh on aci< 
sp. gr. 1021. Albumen absent Few W. B. C, No < 
April 22, sp. gr 1020. Albumen absent. Cellular and hralii 
No R. B. C or \V. I! C. ( catheterised specimen i April 26 
1021. No albumen. Many hyaline and many Dne granular and 
cellular casts. No R. B. C. (voided specimen). April 27, after 
operation, sp. gr. 1019. Slight trace of albumen. Many fine granu- 
lar, cellular and hyaline casts. No W. B. C or R B 
Ized specimen I. There was a trace of albumen in all the 
nations of the urine during the patient's stay in the hospital. 
There is no doubt but that the retroperitoneal necrosis and 
in this case followed the widespread dissemination of collargol 
noticed at the first operation. 

The unusual symptoms in t towing injec- 

tions of collargol. and especially the course of the lasl i 
worthy of record. 



aminal .. . B. i '.. l; 

granu Li 

while in a third :i I 

In t i . 
but it - 

.m'iI to run 
amounts and uiuli r 
A freshl} > 

It is no essary tl 
by those using th - 

■ 

I 



C^Cll 



/r /f •?* 



x 3 J* j) 



z\miHnnmwKU$immz%H$mmm^\$m$m&$ts$&mH8.i\n%i ■ 




r ., 



i 






• • 



'.' 



.**»• 



••• 



Caai VI.— Gyn. No. 19249. Right k i . 1 1 1 • 



Retropi : 



V 
and perirenal tissu 
in the peritoneal cavity. The kidney 

re colored 'lark brown or bluw 
edematous. The amoui I 
■ 

i 
Tli<- tini" betw( ei thi 

Both 10 |" r cenl and ' 

• ■ 
Pain may 1"- qu 
r 10 days. 

perature, 10S 
toother. 

While no phritis has : ■ 



.•inn' 
in pyi 

■ 



78 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 277 



KOPLIK'S SPOTS OCCURRING ON THE TONSILS OF A CHILD SUB- 
SEQUENTLY FOUND TO BE ANAPHYLACTIC TO EGG-ALBUMEN.* 

By Sydney K. Miller, M. D., Baltimore, Md. 

The following case is reported for two reasons : First, because 
of the unusual and misleading symptoms at the onset, and sec- 
ond, for the reason that it presented, it is thought; character- 
istic Koplik's spots in a manner hitherto not described. 

Present Illness. — On the evening of March 29, 1913, I was 
hastily summoned to a neighbor's home by a telephone mes- 
sage, saying, " The baby is choking to death." I found the 
child, a girl of ten months, seated on its mother's lap, very 
cyanotic, breathing rapidly, and with a to-and-fro stridor that 
was audible as soon as one entered the door of the house. This 
condition had come on without warning within the space of 
about ten minutes, and while in the mother's arms; she was 
positive that the child had swallowed nothing. For some three 
or four days the baby had been unusually restless, fretful and 
hard to feed, symptoms attributed by the mother to teething. 
There had been no cough, coryza, or conjunctivitis. The baby 
was a full-term infant of normal delivery and breast-fed. 

Physical Examination. — Temperature, 104.5° F. Pulse, 
1G0. Bespiration, 60 to 70. The eyes and ears were quite 
negative. So far as could be determined the lungs were clear 
on percussion and auscultation. Aside from its rapidity 7 , the 
heart seemed normal in size and action. The skin was clear, 
hot, and dry. 

The most interesting finding was in the throat, which was 
examined with the aid of a pocket electric light equipped with 
a Tungsten bulb, which furnishes a white light. The entire 
buccal and pharyngeal cavity was of an intense dusky red 
color; no Koplik's spots were to be seen on the lips or cheeks; 
the uvula was swollen. There was not the slightest evidence of 
a membrane in the throat. The tonsils, however, were remark- 
ably swollen and succulent, nearly touching each other in the 
mid-line when the child gagged : on each tonsil there were 
visible some 25 or more small bluish, semitransparent, elevated 
bodies, averaging considerably less than the size of the head 
of an ordinary pin ; three were visible on the anterior pillar on 
one side; the majority of them showed a minute white dot in 
the center of the otherwise bluish-gray structure. The appear- 
ance was that of minute vesicles, peppered over a diffusely red 
base. The structures in no way suggested a follicular tonsil- 
litis; indeed, I had no notion of, nor time to speculate, con- 
cerning their identity. Smears, made while the child was gag- 
ging, subsequently showed no Klebs-Loeffler bacilli, nor were 
the spots described above in any way perceptibly damaged in 
the process of swabbing the throat. 

The child was with difficulty given an effectual enema, fol- 
lowing which her feet were placed in a hot mustard bath, and 
a steam kettle was started in the immediate vicinity. Attempts 
to induce vomiting wire ineffectual. About half an hour after 



* Read before the Johns Hopkins Hospital Medical Society, 
May 5, 1913. 



starting the foot-bath, or about one hour from the time of 
onset, there was decided improvement: the respirations had 
fallen to 35 or 40, the stridor was less marked, the pulse slower. 
Simultaneously with the relief of symptoms there occurred, 
first on the forehead and face, a dusky, reddish mottling, and, 
almost as one watched it, this eruption became more and more 
outspoken, so that within three hours from the time of invasion, 
the child, now absolutely free from respiratory distress, was 
literally covered from head to toe with a rash characteristic of 
measles. Exhausted, the baby fell into a deep sleep. 

The next morning the temperature was 103.5° F. The face 
was distinctly swollen and the conjunctiva; quite red. The 
rash was outspoken, hyperemic, and easily palpable under the 
skin. There now was a cough, and definite signs of a bron- 
chitis over the right chest. Examination of the mouth again 
showed a total absence of Koplik's spots on the cheeks or lips ; 
the elevations on the tonsils were somewhat larger and whiter 
in the centers, though each one remained discrete. By the 
following day these spots had practically disappeared; that is, 
within 4S hours from the time of onset, the tonsils, meanwhile, 
having subsided to a nearly normal size and appearance. By 
evening of the third day the temperature had fallen to 99° F., 
and the rash had commenced to fade, though leaving behind it 
a rusty discoloration of the skin, still visible two weeks after 
the onset. There was slight, but definite, desquamation asso- 
ciated with pruritus. The child made an uneventful recover)'. 

Exactly two weeks prior to the sudden attack above described, 
the baby's sister,four years of age and also my patient, had come 
down with measles. She had had three days of prodromal 
sneezing and coryza, and some conjunctivitis, before I saw her; 
during those days the two children had played together and 
slept in the same room. The sister had a severe attark of 
measles, complicated by an otitis media. There were other 
cases of measles in the neighborhood, and a serious epidemic 
was prevalent in Baltimore. These facts, taken in conjunction 
with the clinical course of the disease, fully justified, it is 
thought, the diagnosis of measles, and the opinion is advanced 
that the eruption seen on the tonsils was an aggregation of 
characteristic Koplik's spots in an unusual location. 

The typical enanthem of measles, first adequately studied by 
Henry Koplik, 1 of Xew York, in 1896, is described by him as 
follows : . 

On the mucous membrane lining the cheeks and lips we see a 
distinct and pathognomonic eruption. This consists of small ir 
regular spots of a bright red color; in the center of each spot is the 
interesting sign to which I wish to call attention. In strong day- 
light we see a most minute bluish-white speck. These minute 
bluish-white specks in the center of a reddish spot are absolutely 
pathognomonic of beginning measles. I have never met them else- 
where, and when once seen they are a certain forerunner of the 
skin exanthema. These bluish-white specks are sometimes so 
delicate that they can be seen only in a strong window light. No 



March, L914.] 



JOHNS BOI'KINs HOSPITAL 1:1 I.I.I .Tl N. 






one has ever called attention to these bluish-whit' 

forerunner of the skin eruption. Their background j s the Irregular 

red spots referred to above. They cannot be mistaken tor sprue, 

for they are not so deeply white, nor are they as larKe as sprue 

spots, anil sometimes we must, as 1 said, look sharply an< 

the mucous membrane of the cheeks to find them. These bluish- 

whit.' specks surrounded by a red area are found, as I - 

the mucous membrane of the cheeks and lips and not on I 

or hard palate. Sometimes only a few red spots exist with their 

central bluish points, a dozen or more, anil again these whitish 

specks may cover the whole lining membrane of the cheeks and 

lips. If these bluish, white specks on a spotted background are at 

the height of their development, they never become as white and 

opaque as sprue spots, and therefore can be easily differentiated 

after having been once seen. Nor do they ever coab 

plaque-like In form. They always retain their punctate Character 

If the mouth has been washed these spots may have been rubbed 

off, and then the appearance is lost. 

As the exanthema on the skin appears and spreads, the eruption 
on the mucous membrane inside of the cheeks and lips b 
diffuse and the characters of a discrete eruption or spotting dis- 
appear, and we have an intense general redness which is simply- 
dusted over with myriads of these bluish-white specks. This 
being so, It will be seen that this eruption of bluish-whit. 
on a spotted or red background is of the great) Bt value at I 
outset of the disease, before the appearance of the eruption; also 
at the beginning and height of the skin eruption. When the skin 
eruption or exanthema is at its efflorescence, the buccal eruption 
begins to fade and gradually disappears, even while the exanthema 
is still out. In the later stages of the fading skin eruption the 
phenomena described above are no longer seen. 

In a personal communication Dr. Koplik slat'-: "The 
- enanthem, when at its height, can he seen on the 
mucous membrane, the lips, fauces, roof of the moutl 
junctiva?, and larynx; Kopli 
describe them." I »r [lowland states that he ha- • 
spots on the tonsils; and I'r. von i'irquet. to whom 1 told mj 
experience, gave me a similar answer. In a fairly exhaustive 
search through the literature, it ha- been thus far ■ 
■ n of any ai 
ribed in nearly every other locality, including the 
es. 1 1 was aggestei Dr. Koplik thai I 

of Rotheln, or ' I 
Intasche " of Porecheimer an. I 'I noma 

Tin- i- t.-r-. I] ■ :■ 

n mi the uvula -.!■ 
the hard ; it is 

Bemble Kopli ry much, hut fail 

show the minute hlui-h-v. 
prominent, however, in this case. 
been prevail nt hi 

: 

tainlv mi ' with in R 

■ 

features make the d 

riot m.-r.-l. 
crypts was manifi -t bj thi ir rath 
appearance, small 



• Dr. Koplik. 



« 

simplex. 1cm ah.. ■! on tl 

not oncomm 

eruption, or a little earlii r. Tl 

that a 
true angina herpel 
through the usual I 
never closelj i i iher. little ; 

during 
the short period • 
ruled out. In view of tl; 
conclude thai ntly runnii 

of measles, true Ki 
confined to the to' 
within two da 
• Ither interesting and 

First, the unusually acul isel witl 

obstruction. Laryngeal diphtheria, 

oedema of thi 

consideration. All of these conditions were ru i 

rapid disappearance of tin- laryngeal syn 

doubtli - 

the glottis. Holly, 

initial laryngeal symptoms u 
patients \ar\ ing m age from ■ 
all the sympl 
Her * Btates that thi 
ity. particularly in 

pseudo-croup ma) usher mil' 

i hildhood," 

nd ha- a h 

Bymptoi 

nary catarrhal lai 

■ 

alarm • 



80 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 277 



of measles, makes the italicized statement that " a complete 
development of the enanthem inside of a single day speaks 
against measles.'* Yet, even if his ingenious hypothesis of 
progressive intracapillary agglutination of the causa tivi 
of measles by specific anti-bodies, advanced to explain the 
nature, initial location and subsequent spread of the enanthem, 
be true, one may still conceive of a sudden, explosive-like dis- 
semination of agglutinins and rapid fixation of antigen 
throughout the entire body, manifested, as in this case, by 
speedy and complete development of the eruption. 

Finally, experience in this case strengthens the widely preva- 
lent idea that a hot bath, given to " bring out the rash," has a 
decided beneficial effect. Certainly, the result here was most 
remarkable, though mere coincidence cannot be ruled out. 
ITeulmer, in speaking of cases with severe laryngeal symptoms, 
states: "They are effectually influenced by a suitable anti- 
phlogistic therapy." 

It is hoped that verification of these unusual findings may 
ultimately be forthcoming, or that errors in diagnosis, not 
patent to the author, may be revealed. 

On the day prior to that on which this report was read, it 
was accidentally discovered that the child in question was 
markedly anaphylactic to egg-albumen; this was made mani- 
fest by alarming laryngeal distress, fever of 103° F., and the 
rapid development of an urticarial rash that literally made the 
child's features unrecognizable. These symptoms came on 
within about a half hour after feeding the child some egg- 
white and orange juice, and quickly subsided under treatment 
precisely the same as that used at the onset of the attack of 
measles. Though the tonsils were swollen, there was not the 
slightest evidence of an eruption upon them or any other part 
of the buccal cavity. Similar negative findings occurred dur- 
ing a subsequent milder anaphylactic reaction, purposely 
induced. 

As a result of questioning, it developed that on the very 
evening of the day on which the child's illness commenced it 
had been given egg-white for the fust time, so far as is known, 
in its life, a detail which quite naturally had never entered the 
mother's mind as being in any way associated with the severe 
symptoms described. While there exists 710 reasonable doubt 



as to the genuineness of the attack of measles, the egg-white 
anaphylaxis introduces a new factor which makes it quite im- 
possible to say to just what the alarming manifestations at the 
onset were wholly due. The entire illness may have been 
measles alone, in an intense form, as was thought ; on the other 
hand, despite the apparent lack of previous sensitization, ana- 
phylactic phenomena, by a curious coincidence may have 
ushered in, and considerably hastened the clinical manifesta- 
tions of measles. In any event, it seems unlikely that anaphy- 
laxis bad any share in causing the tonsillar eruption thought to 
be that of Koplik's spots. 

A von Pirquet test performed with egg-white and suitable 
controls induced a speedy and marked local reaction associated 
with a mild constitutional disturbance. It was subsequently 
found that a constitutional reaction followed the administra- 
tion of one teaspoonful of a mixture composed of one pint of 
water plus one drop of egg-white; a like amount of albumen 
diluted with one quart of water was tolerated perfectly. Xo 
anaphylaxis resulted from the administration of yolk alone. 
Commencing with the dilution which failed to produce a re- 
action, the child was given gradually increasing amounts of 
solutions of increasing strength. The dosage was always one 
teaspoonful given three times during the day; the result has 
been that, in a period of about three months, the child has been 
desensitized to such an extent that one dram of pure egg-white 
is now taken with impunity and the von Pirquet test remains 
as negative as are the controls. 

I wish to express my appreciation for opinions given me by 
Dr. Koplik of Xew York, and Dr. von Pirquet, formerly of 
Baltimore; and to thank Dr. Howland, of this clinic, for his 
kindly criticism of this report. 

REFERENCES. 

1. Koplik: Arch. Pediat., N. Y., 1896, xiii, 918-922; Med. Rec, 
N. Y., 1898, liii, 505; Med. News, N. Y., 1899, lxxiv, 673. 

2. Forcheinier: Arch. Pediat., N. Y., 1898, xv, 721. 

3. Roily: Handbuch d. Inn. Med., Mohr u. Staehelin, 1912, i, 
65-98. 

4. Huehner: Modern Clinical Medicine, 1910. 

5. Still: Common Disorders and Diseases of Childhood, 1910. 

6. Holt: Diseases of Infancy and Childhood, 1912. 

7. von Pirquet: Ztschr. f. Kinderheilk., 1913, vi. 



A BRIEF HISTORY OF QUARANTINE.* 

By W. W. Ford, M. D., 
I iate Professor of Hygiene and Bacteriology. The Johns Hopkins University. 



Although the first enactment for the delay and isolation of 
travelers was adopted in the 15th year of the reign of the 
Emperor Justinian, A. D. 54?, and a sort of detention had 
been known and practiced in the Orient since the 7th century, 
quarantine in the modern sense may be said to have originated 
in Italy in the 13th century as a result of the invasions of 
plague from the Levant into Europe. How frequent these 

* Read May 16, 1913, before the Medico-Chirurgical Faculty of 

Maryland. 



invasions were is indicated by the fact that from 900 to L50G 
A. D. plague appeared in Europe sixty-five times with dread* 
ful ravages and terrific loss of life. The fear inspired by 
these visitations led the Italian cities, then the centers of 
trade between Europe and the Orient and dependent upon 
this commerce for their prosperity, to begin the enforcement 
of drastic regulations at their ports to prevent the importa- 
tion of the dread disease by the incoming vessels. Venice 
appointed three commissioners of health in the year 1-5S4. the 



Mabch, 191 1. 1 



JOHNS HOPKINS HOSPITAL BULLETIN. 



-i 



lirst year of the Black Death, increasing the numbi i 
in the next century. Ber example was followed by 1 
me year, by Reggio in Modena in 1374, b] L 
in 1374, and by Milan in 1399. Maritime quarantine 
in L403 in \- with the establishment of a detentii 

pita] on an island adjoining the city for the isolation of all 
- from the Levant for a period >•!' 10 days. For this 
an old almshouse, known as the Hi 

was employed and from this usage ran ax moden 

lazaret or lazaretto. Genoa followed the examp 

: in establishing a lazaretto and in 1 176 tl 

hospital of Marsi illes, then almost empty a- a result of the 
dying out of leprosy, was converted into a plague hi 
It is worthy of not'- that whereas thi arantine was 

! against plague the isolation of individuals inflicted 
with certain diseases was by no it idea. Tl. 

tion of lepers was a will established practice at this time, it- 
origin dating from I ; [»'riod< of the world's history. 
About the year 1490, or probably a few years later, if we 
accept Ivan Block's view that syphilis was brought back by 
the sailors returning with Columbus on bis Becond voj 
the new world, an ineffectual effort was also made to check 
the invasion of lues into Northern Europe. 

In the year 1526 the greatest lazaret of early times was 
erected in Marseilles on the island of Pomegue adjoining the 
city, and here the most riiri'l and strict quarantine of the 
old world was set up. loiter sanitary regulations for the 
whole of France were issued by Colbert, minister t 
XIV. on August 25, Ids:!, and the Hoard of Health of Mar- 
Beilles was given almost absolute power. 

In 1485 Venice had adopted the rule that all vi 
from infected ports i tained for a period 

during which time they must lie in harbor without int. i 
with land or other ter this period they could ili>- 

charge goods or passengers. The simpler n tiding 

ships back to their port of departure was manifestly injurious 
to trade and the practice of permitting them to 1 
40 days detention was clearly . 

commerce. The important relation of quarent )■ 

merce, so much emphasized by the English authoriti 

sed from the first Wh 
pioneer in the establishment of quarantine 
Marseilles that the model quarantine station of tl - 
isvelopecLone far mon mp rtant, indeed, than thai 
According to Fischer' all incoming vessels hen 

I with a health pass (bill of health i or pa ■ ■ 
was to be filled out by a trusted official of the p, ri 
at the port of departure. On this pass must 
condition of health might be in the countri 
which the ghi i which the 

Acre of 4 kind? : 

1. /' when the I 

irely satisfai 

2. r ■ .me from infect 
but no cases of illness exi-- 



from p - 

i. /' 
of departure and the ship had 
hoard. 

In addition to | 
themselves, theii 
carried were Bubji 
board were divided into 
tible, an. I a 
had to [»■ reported. Finally .< 
adopted for the Oriental porta 
which had great influence upoi 
enforced. Volken 

non-suspicio ! from harbors n 

health were satisfactory, Class I. wen 
ships with the >aiiie conditions hut from barboi 

■ 
departure. Class II. v.. 
harbors where plague might I ■ 
had arrived from 

Constantinople, t llass til, wen • eta aed 
tine after a prei ioua exposure of all wares to the air for three 

Finally if oases of ,\i- 
gers were detaini i 

side of the ship a row of planks was remold to perm 
tion ( ,f the ship's con! 

: he had to undergo a new mi 

plete healing of the bubw -. Whenevi : a new 

ippeared the 
to a new quarantine, but after a third 
ship and all it- contents were but i 
station a lazaret was i stablished for 

the well ale! ■ 

great loss of time and monej and wot 

quarantine ship- \ 

the regulations co ■'■' tx 
The quarai founded upon tie 

tial dis 
world. ., 
With th< 

what i 

1 

■■■ 
I 



82 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 277 



in the 19th century reached its maximum possibly in Spain 
and Portugal where special regulations were carried out to 
prevent the entrance of yellow fever from the New World. 
Here we see the transfer of the center against which nations 
quarantined from the Levant to South America. The largest 
. lazarette in the world was established at Lisbon, on a hill 
opposite the Belem tower, 4 miles from the city,, at a cost of 
$1,000,000 to the Portuguese government. It consisted of 
seven pavilions arranged in a semicircle with the convexity 
towards the river. It was under the Department of the 
Interior which managed it at a loss and let out the contract 
of feeding and housing the passengers to the lowest bidder. 
At this station quarantine was imposed on all ships, pas- 
sengers, and cargoes coming from Brazil, the time varying 
from 5-7 days according to whether the Brazilian port was 
infected or suspected. A bill of health was issued to the 
captain of the vessel by the Portuguese consul at the port of 
departure giving the number of deaths from yellow fever 
during the past 8-10 days. Quarantine could be lifted when 
■an absolutely clean bill of health was presented, which, how- 
ever, rarely happened in the old days, since yellow fever was 
endemic in most cities in Brazil up to the end of the 19th 
century. During December, January and February the 
baggage and cargo of incoming vessels only were subject to 
detention on the theory that the virus of yellow fever could 
not develop at Lisbon, the passengers being permitted to go 
on shore at once with their hand luggage. For the rest of the 
year all passengers from Brazil were sent to the lazaret to 
remain there the alloted time, their effects being aired and 
fumigated or disinfected. Certain articles, including cotton, 
hair, hemp, letters, parcels, hides, fresh meat, wool, linen, 
skin, feathers, and silk were regarded as susceptible. All 
these were fumigated with chloride of lime, and the inside 
of the ship was washed with chloride of lime or other disin- 
fectants. This rigorous quarantine was a concession to popu- 
lar opinion, since a terrible epidemic of yellow fever broke 
out in Lisbon in 1857, with 19,000 cases and 6,000 deaths, 
traced to a tainted ship and cargo from Rio. The quarantine 
practiced at Lisbon was copied faithfully at the Azores, at 
Madeira and the Cape Verde Islands. The old quarantine 
traditions were also maintained at two chief lazarets in Spain, 
one at Vigo on the Atlantic Ocean and another at Port Mahon 
on the Mediterranean Sea. These were known as " foul laz- 
arets." Certain ports, as Havana in ordinary times, and all 
ports in cholera epidemics (i. e., when cases of cholera existed 
there) were known as "foul ports" and all vessels from such 
places were compelled to enter these stations for quarantine. 
Only a " quarantine of observation " lasting 3-6 days could be 
imposed at other ports. 

Turkey and Greece likewise held to the old traditions of 
quarantine with lazarets at the Piraeus and in the Darda- 
nelles. The Lazarets in various Mediterranean, Adriatic, and 
Levantine ports were also maintained, including Malta and 
Gibraltar where the machinery of the old-fashioned quaran- 
tine still exists and can be used in cholera times. 



The classical rigid quarantine which had been in vogue 
throughout the entire world was gradually given up except in 
a few areas such as those mentioned, and by the year 1886 
existed in but one or two places with its pristine rigor and 
severity. This was due to several factors chief among which 
may be placed the influence of England and the growth of 
the modern sciences of bacteriology and protozoology. As 
early as 1815 England abolished quarantine, directing her 
efforts towards an improvement of the sanitary conditions of 
her ports and substituting the system of revision or inspection. 
This system took definite form in an order of the Local 
Government Board in 1873 according to which no vessel was 
detained or refused pratique unless there was a communicable 
form of sickness on board or had been during the passage. 
It was the duty of the officers of custom to question the 
captain as to any eases of contagious disease among the ship's 
company or the passengers. If such existed, report was 
made to the local sanitary officers who inspected the vessel, 
detaining all on board till the inspection was made, the sick 
removed to the hospital and disinfectants applied. This prin- 
ciple was accepted by the Sanitary Conference in Vienna in 
1871, and was adopted by all European maritime states except 
Spain and Portugal. 

As early as 1847 France created six medical posts in the 
Orient at Constantinople, Smyrna, Beyrouth, Alexandria, 
Cairo, and Damascus, the officers at these cities having the 
especial duty of keeping their government informed of the 
sanitary conditions there. The work of these French sanitar- 
ians was really the occasion of the first sanitary conference 
held in Paris in 1851. This was further necessitated by the 
growth of commerce between countries and the difficulties 
encountered in the application of the principles of the 
quarantine of detention. It has been followed by a number 
of other conferences which, in the main, have not led to as 
great an improvement and advance as was to be expected. 
Changes in quarantine laws looking toward simplicity and 
effectiveness of operation have come not as the result of inter- 
national change of opinion, but as the result of friction 
between powers in enforcing quarantine regulations at a 
time of threatening epidemics. The first international sani- 
tary congress was held in Paris in 1851, eleven powers sending 
delegates, Austria, Great Britian, the Roman States, Sardinia, 
Sicily, Spain, Greece, Portugal, Russia, Tuscany, and Turkey. 
A code was prepared for uniform action, but only France, 
Portugal and Sardinia were willing to sign it. s Another 
conference was held in Paris in 1859, a third in Constanti- 
nople in 1866, and a fourth in Vienna in 1874. At this last 
the new principle of inspection advanced by the English 
sanitarians was adopted. According to this principle all 
vessels were to be examined at the port of entry to determine 
the presence of disease. Sick individuals only were to be 
detained, the well allowed to continue their journey. This 
change in system was regarded as necessary in view of the 
enormous commerce and travel extending over the entire world. 
It was evident that quarantine stations to provide for all 



March, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






passengers and goods regardless of the point from which they 
came would either be of enormous expense and a great burden 
in ordi live or the detention would develop into 

a mere formality. Added to tins n that the 

quarantine stations themselves would become foci of in 
In 1892 a conference was held in Venice which rest; 
the production of a sanitary code which H by the 

European nal rding to this a ship Bhould be 

rely from its port of departure, but 
length of time which ha 
the presence on it • 
be established by medical in-' 
into three groups. < 
as had had no cases of disease at the tin 
during the voyage. S 

which cases had occurred, but not within the past few days 
before debarkation, the free period between the 
the day of arrival b than the ii 

□ question, i 
as had cases on beard at the time of arrival or had ha 
during ' lat the incubation tin:' 

disease had not pase 
arrival, the possibility thus remaining that la1 

□ the incubation period might still lie present. This 
conference had little influence in pr 
uniform regulations by di tie rent count 
oretical standpoint. Hut I 

at Hamburg which showed that many of the old quarantine 
regulations were absurd, the greatest injury being 
German commerce by injuriou As a 

result an International < held in Dresden :■ 

which established common rules for handlr 
epidemics. The Dresden lit only with choli 

the measures to be adopted on land and along inten 

). It first brought out thi of an intern 

■ion of the app 
epidemic form or as 
new principle was adopted in :• 
a medical control and obeerval on 
infection, without n 
them in any one particular pla 

This i- manifest ;• ■ 
bubonic plague, which for yean bad i 
indeed to bavi disappeared from th< 
appearai 
ingyear it thr 

remarkable how quickly the worl 
primitive col 
tnS y and in Ms 
by cannon shot and in M 
to leave ; 
to another international - 

iruary 16, 
new knowledgi 
regard to v - 



l. The in. 

1 and which the ! 
'■ 
the inb 
administrai 

5 
At ■■ 

' i 

parallel, the outer 
1089. All provini 
reman 

and later thi 
cholera from 
Btretched along thi 

■ 
jankaja. with 1700 inhal 
extended to I 
Bet up Burro 

tljankaja wi 
citizens rein 

,i round 7/ir 

;i city of in. 

■ 
In 1-- rdon militaire or Dp by 

Italy a 
the follow n 

Spain. 

irly known 

: to with l- 

country duril 



S4 



JOHNS HOPKINS HOSPITAL BULLETIN, 



[No. 277 



the pari of othei countries and greater difficulty will be en- 
countered in the lifting of embargo. 

2. Quarantine regulations are not applied to the entire 
country but only to the area where the epidemic exists (cvr- 
conscription territoritUe contaminee). An infected area is 
that point where cases of disease appear. Ten days after the 
last case is diagnosed, provided proper precautions be carried 
out, the area in question is again opened to free and unre- 
stricted commerce. All vessels which have left an infected 
port five days before the breaking out of disease are to be 
regarded as free from suspicion. 

3. Preventive measures must be carried out before the de- 
parture of the ship from an infected port and during the 
voyage. Passengers and crew must be supervised by medical 
authorities before departure, individuals with suspicious 
symptoms being left behind. Dirty clothing and objects of 
personal nature must be disinfected before departure. This 
usually may be limited to passengers of the third class and to 
the ship's company, since it has been shown that, in general, 
individuals belonging to the better walks of life seldom carry 
diseases like cholera or plague. Ships must be cleaned and pro- 
vided with drinking water from an uninfected and unsuspi- 
cious source before leaving port. 

4. During the trip careful medical inspection of all indi- 
viduals on board must be carried out and proper disinfection 
applied when suspicious cases occur. For certain classes of 
vessels, particularly pilgrim ships and emigrant ships, a ship's 
doctor and an apparatus for steam disinfection are obligatory 
provisions. 

5. Measures in the port of entry depend upon the results of 
the medical examination of incoming vessels. Unsuspected 
or unsuspicious ships are allowed to go free at once after the 
doctor's visit (libre pratique) provided five to ten days have 
elapsed between the time of departure and time of arrival, 
five days for cholera and ten days for plague, the maximum 
incubation period. By shorter journeys this time is to be com- 
pleted in quarantine. At the discretion of the quarantine 
officer all non-suspected ships may be treated as suspected. 
All articles on board such as old or dirty clothing and personal 
effects must be disinfected if the physician deems them likely 
to convey infection. Suspected ships must be inspected by 
the quarantine physician, all rooms occupied by cholera or 
plague patients must be disinfected together with all dirty 
clothing and personal effects. All bilge water, water ballast 
and drinking water must be discharged and a new supply 
obtained from an unsuspicious area. Passengers and ship's 
company must be kept under observation 5-10 days (depend- 
ing on the disease), and during this time the landing of the 
crew is to be limited as far as possible. Passengers may be 
allowed to continue their way but must be kept under police 
supervision till the end of their journey. If the ships be 
actually infected by the occurrence of cases of disease on 
board the sick must be transferred to quarantine hospitals, 
and the dead bodies interred with all possible precautions and 



all other persons kept under observation either at the quaran- 
tine station or at such places as they may select. Thi> obsraH 
vation must last five days for cholera and ten days for plague. 

Wares or Goods. 
According to the Venice Conference the following materials 
are infectious " (marchandises misceptibles) : clothing and 
underclothing, rags, refuse, used garments, carpets, hangings, 
laces, hair, raw skins, animal wastes and unclean wool. For 
cholera certain articles of diet are also susceptible especially 
milk, butter, vegetables and fruits. The transposal of infec- 
tious material from an infected area is forbidden. The reten- 
tion of wares in quarantine as formerly practiced is now given 
up, but all infectious material is to be at once disinfected with- 
out foolish formalities, such as the disinfection of letters. 
(The same rule would probably apply to money.) 

Quarantine of Pilgrims. 

The great danger to Europe which rose from the various 
bands of Mohammedan pilgrims to Mecca passing through the 
Suez Canal and the recognition of the part they had played 
in earlier times in the dissemination of disease led the Paris 
Conference of 1894 to establish special rules for these indi- 
viduals as regards Asiatic cholera, and the Venice Congress 
of 1897 adopted similar rules for plague. According to these 
rulings all pilgrims are to be examined before departure from 
home and their effects disinfected. To accomplish this prop- 
erly a limited number of ports are selected from which pil- 
grims are allowed to depart for Mecca, and individuals with- 
out money to defray the expenses of the trip are not permitted 
to leave. Pilgrim ships must always be provided with a doc- 
tor and an apparatus for steam disinfection. Overcrowding 
should be avoided, cleanliness insisted upon and a good supply 
of food arranged for. In addition to these general regulations 
applicable to pilgrims before departure, the Egyptian govern- 
ment now requires that each pilgrim from Egypt should have 
a pass with his correct name and address without which he 
cannot again land in Egypt. This is especially designed to 
prevent the return to Egypt of irresponsible vagabonds, wand- 
ering about from point to point, objects of charity and a 
danger to the community. 

Pilgrim ships are detained in quarantine at a number of 
points. Vessels from the South are quarantined at Kameran 
(or Zameran) on the Arabian side of the Bed Sea, 200 miles 
within the Straits of Bab-el-Mandeb. This station is under 
the control of the Turkish Government and has usually been 
regarded as hopelessly inadequate. Ships from the North are 
examined either at Wejh on the coast of Arabia, half way 
between Jedda and Suez or at El Tor on the Sinaitic side of 
the Gulf of Suez. The station at El Tor under the control 
of the Egyptian Government is entirely satisfactory. There 
20,000 pilgrims can be eared for. The station lies on the 
west coast of the peninsula of Sinai on the land side, com- 
pletely shut off from the adjoining desert by a high wire fence. 
Disembarkation is possible only by landing bridges, so that 



Mabch, r.M i.| 



JOHNS BOPKINS >SPITAL BULLETIN. 



the station is completely isolated, "hi landing the pi 
are passed into the disinfection halls which are -• 
clean and dirty sides. Here on the dirtj 
must completely dis i douche bath (what a ti 

a pilgrim!) while their clothing and effects are dis 
Transferred to the clean si.le the pilgrims are pri 
with their disinfected clothing and divided up i nt> > 

tachments are kept under obsi 
a period <>f time varying from three days, if no cases of plague 
or cholera existed at Hedjaz, the poinl from which the. 
bark, to eighteen days if cases of i 1 "- disi a-' did ■ ■ -t there. 
Should a case <>!' disease break out in any Bectii 
grims. this section only must be quarantined again for 
eighteen days from the date of isolation of the last . 

The quarantine station at El Tor is directly under the 
authority of an Egyptian International Commit 
saniiaire tnaritimc 1 1 quaranlinaire d'Egypte, which also 
maintains a station I'm- passenger ships at Moses' Wi Us on the 
Sea. Special regulations are enforced at tie-,, stations 
for all vessels which pass the Suez Canal. Every .-hip is sub- 
■•> medical inspection. Should si, ur they 

are transferred to isolation hospitals ; it the quarantini 
and the parts of the ship contaminated by them disi) 
The other past ithei retained in quaran- 

tine if no doctor or apparatus for steam disinfection !><■ on 
board or may remain in the vessel in the latter event. After 
five to ten days freedom from d dp is allow, 

through the Suez Canal (transU en quarantine) hut. must 
not come in contact with the shores of the canal. 

Quarantine >r emigrants >imilar in chars 

or pilgrims are now maintained at a oum I 
particularly in Germany. One of the most com 
is that of the Eamburg American Line in Hamburg. 

w i im i\ mi United Si 

The first conferem e in the Dniti 
a ran tine regulatio 
in Philadelphia ii ' oned by the 

the year before. Other.- foil, 
and in Is.','.' hut nothing ' 

[form regulations in thu i ountry, the • 
continuing to eir own quarantix 

their own laws, until the pat 
Act of February 1 tied " An \ I 

tional Qoarantii i P 
Upon the Main., I : 

national system oi quaranl (jned primarily 

■ d assist i 

Government through thi 
Public Bealth Service, has assumi d • ontrol 
tine stations in this country 
operating nearly all the b 

nine seaboard with the • 
and Baltimore. Bp to 1881 thi 



quaranl 

S 
theria, 
of timi 
quaranl 

any di» 
ter. whii 

public health. Ii. | 

,iu- fever, yelloM 

I >■ 

the Bealth < >ffii er. Thi unifon 
Health - 
smallpox, ■ 

- : Mil I. I'.v 

It i- evident from tin- brief hist 
quarantine that thi 
and had little or I 
strictly they wen 
quently got through quarantii 
the sanitary or military cordon wi 

i out in thi 
the protection afforded Prussia by i 
the Russian frontier. The failun •■' 
the din 

only whin I 
point when 

n-i-t upon 

began • 

link- in the chain o 

should 

influence in this n 
the discover) of I 
the di 

and l\, 
and thi 



8fi 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 277 



pneumonic form it is the individual himself who is dangerous, 
the infection spreading from person to person through the 
agency of the plague-laden sputum. In bubonic plague 
entirely different conditions are met with. The individual 
himself is not dangerous. It is the infected rodent popula- 
tion from which the disease passes to man chiefly through 
the medium of insects (the rat flea for instance) against which 
quarantine measures must be directed. Bacteriology, however, 
has solved the problem of but two of the five great quarantin- 
able diseases of the world. For two of the other three at least 
protozoology has furnished the clue. The investigations in 
this science which have led to the discovery of the important 
facts really began with the demonstration by Sir Patrick 
Manson that the disease filiariasis produced by the nematode 
worm Filaria sanguinis hominis is transmitted to man by 
the bite of the mosquito which harbors the parasite. This 
discovery was followed by the work of Theobald Smith on 
Texas fever of cattle who showed for the first time in the 
world's history that a protozoan disease was transmitted by 
an insect host, in this case the cattle tick. As a result of these 
investigations it became possible for Walter Bead and his band 
of devoted followers to prove that yellow fever, the scourge of 
the New World as plague had been of the Old, is carried only 
by the female form of Stegomya fasciata. The clothing, the 
dejecta and the personal effects of yellow fever patients are 
entirely without infectivity. It is now an old story how the 
application of the work of Eead, Carrol, Agramonte and 
Lazear enabled Wood and Gorgas to drive yellow fever out of 
Cuba, and Gorgas to keep the Panama Canal Zone free from 
this disease. Without this knowledge the Panama Canal 
could not have been built and the United States was just as 
surely doomed to failure as was the Eepublic of France. 
Furthermore this knowledge of the epidemiology of yellow 
fever has enabled the southern ports of the United States to 
keep this infection out of America and, in the few instances 
in which it has found entrance, notably in New Orleans, 
and in Brunswick, Georgia, to eradicate it without great loss 



of life. Finally it has now been shown by the work of Nieolle in 
Algiers and by the investigation of Pickets, Anderson and Gold- 
berger in Mexico City that typhus fever is also insect-borne, 
the hosts of the unknown parasite in this case being the body 
louse (Pediculus vestimenti) and the head louse, (Pediculus 
capitis). With smallpox we are still in the dark as regards 
the ultimate cause but have in the Jennerian vaccination an 
efficacious method of protecting the population and wiping 
out the scourge. Many problems must yet be solved, however, 
before quarantine can be perfect. The greatest needs relate 
to diagnosis. There is now no method to establish beyond 
dispute a diagnosis in a suspected case of yellow fever. This 
must still be done chiefly by elimination. Anderson and 
Goldberger, however, have given the world the method of 
diagnosing typhus fever by the inoculation of guinea pigs, a 
characteristic reaction occurring with all cases of this disease. 
The problem of bacillus carriers is also an urgent one 
especially in the case of cholera. In this infection Dunbar of 
Hamburg has shown that apparently normal individuals may 
harbor and excrete the bacillus and are capable of causing 
widespread epidemics, a discovery which Koch hailed as 
next to the discovery of the vibrio itself, the most important 
to be made in the epidemiology of Asiatic cholera. Whatever 
else may be needed in a quarantine station the services of a 
competent bacteriologist, with special training along certain 
lines and an up-to-date bacteriological laboratory with special 
equipment for making diagnoses of plague, cholera, and 
,typhus fever, must be regarded as essential, as well as the 
presence in quarantine of expert physicians who can recognize 
with some certainty smallpox and yellow fever. 

BIBLIOGRAPHY 

1. Ewald: Social Medizin, 1911, I, 27. 

2. Vblkers: Vierteljahrschrift fur gerichtliche Medizin, 1904, 
XXVII, 3. 

3. Journal of American Medical Association, 1913, LX, 193. 

4. Gotschlich: Kolle und Wassermann's Handbuch der patho- 
genen Mikroorganismen, 1904, IV, 1. 



NEW PUBLICATIONS. 



The following six monographs : 

Free Thrombi and Ball-Thrombi in the Heart. By J. II. 
Hewitt, M. D. 82 pages. Price, $1.00. 

Benzol as a Leucotoxin. By Laurence Selling, M. D. 60 
pages. Price, $1.00. 

Primary Carcinoma of the Liver. By M. C. Winteenitz, 

M. D. 42 pages. Price, 75 cents. 



The Statistical Experience Data of the Johns Hopkins Hos- 
pital, Baltimore, Md., 1892-1911. By Frederick L. 
Hoffman. LL.D., F.S.S. 161 pages. Price, $2.00. 

The Origin and Development of the Lymphatic System. By 
Florence E. Sabin. 94 pages. Price, $2.00. 

The Nuclei Tuberis Laterales and the So-called Ganglion 
Opticum Basale. By Edward F. Malone, M. D. In 

press. 



are now on sale by The Johns Hopkins Press, Baltimore. Other monographs will appear from time to time. 



Mabch, 1914.] 



JOHNS HOPKINS BOSPITAL BULLETIN. 






TATTOO MARKS FOR THE [DENTIFICATIOIS OF \MM Ms l\ 

LABORATORIES. 

J''\ J. A. ih nnk i 1 1. M, d., and A. P. Joni s, M. D. 

the Uunteriatl Laboratory of 1 . .- . ■ / hi Johns Hopkins University. ) 



Various methods have been employed for the identi 

of animals in laboratories. 




Tattookd Inner Surface "i Rabbit's Bab 



For the larger animals, tags and detailed descriptioi 



been relied upon, and for the id 

guineap 

fully dee 

■ liable than any of the means hithi rf 

trials of other phv mark, 

which is made while the animal is under the influence <>f the 

India ink. a No. 

only articles required for th( | e little 

on. The inner side of the an 
95 ]" r I and dried wit! 

is sharpened to a point The clamp bolder, 

ami tho eye of the needle ■ India ink into 

if is dipped. ; 

with the sharpened eye-end of the ; 

into the skin at an angle of, perhaps, 

We I iting this method of indelibly mark 

animals for several months and are well pleased with it. 



IN MEMORIAM. 

REGIN \U> HEBEB III/.* 
I:. \'. , - T win. M. D., 
Professor of Clii • Johnt Eopleint 1 



It is a sad but grateful opportunity, th 
today to pay an affectionate tribute to the memorj of I 
and valued master. 

It is not far from thirty yean ago, th 

ay, that we -at in the precipitous amphil u 
then new school building m Boylston Street, am 
his brilliant talks. Xo one who heard thi 
tures could have failed to carry away a deep im] 
strength, the ability, the learning of the man I 
remarkable l< narkable in form and 

models of clear and pn 
in language. 

been so chosen that it. and it alone, could fill its 
ulating hours whii 

of the importance of precision and accur. 
and thought and • 

Fitz was not an 



•Read at a Memorial Meeting at the Harvard Hi 

Boston, Mass . November IT, 1913. 



out or mtribu- 

■ 

important and valuable. His habil 

n thought, 
Bition gave him that p 
i 

atly unrelab 
picturt 

that this 01 

■ 

Of win 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| No. 27JJ 



for the first time, the vision of the medical world on the true 
nature of the inflammatory processes occurring so commonly 
in the right lower abdominal quadrant, and showed, convinc- 
ingly, that the seat of primary disturbance, in the great 
maji rity of instances of this nature, lies in the appendix 
vermiformis. And along with this demonstration, he set forth 
in a masterly manner the clinical manifestations of the disease. 

This publication came at a time when the world was well 
prepared. Everyone recognized that Fitz had, as it were, put 
his finger on the spot. Once set forth, the pathological and 
clinical sequence of events seemed almost obvious — obvious as 
are so many great truths when once they have been clearly 
enunciated. The sharp light thrown by Fitz on this common 
and perilous pathological event brought it about that our 
countrymen were fully ten years in advance of the rest of the 
world in their comprehension of this process, and in their skill 
and efficiency in the care of the patient. 

How many human beings owe their lives to-day, more or less 
directly to Fitz, no one can tell. Surely, it is no small number. 

There has been one curiously paradoxical sequence of this 
great contribution. The word " appendicitis " employed by 
Fitz in the course of this article was immediately seized upon 
by the public and has entered into universal use, but not 
without bitter protest from some who still shudder at its 
etymological hybridism. 

It is an amusing thought that of all men, Fitz, the most 
careful and accurate, should have been the target of irritated 
critics, because of the introduction into medicine of what 
they regard as an ill-constructed word. 

The practical importance of the facts set forth in this first 
contribution has, it has often seemed to me, somewhat over- 
shadowed the brilliancy of the later work. In his studies on 
the appendix, the truth seemed so nearly ready to emerge of 
itself that the medical public grasped, immediately, the sig- 
nilicance of the exposition. The lectures on acute pancreatitis, 
on the other hand, treated of a subject of which little was gen- 
erally known, even anatomically. The analysis of the carefully 
collected pathological material, the discriminating consider- 
ation of the clinical features and the final synthesis of the defi- 
nite, convincing clinical picture of the disease, acute pancrea- 
titis, was truly a great achievement. 

How well I remember the demonstration by Virchow, nearly 
a year after the delivery of the Middleton Goldsmith lectures, 
after I had seen acute pancreatitis recognized clinically and 
confirmed at necropsy — how well I remember the demon- 
stration by Virchow of the organs from a case of disseminated 
fat necrosis with sequestration of the pancreas, accompanied 
by the observation that these instances were pathological 
curiosities. With what pride I sought him out and made him 
familiar with the little pamphlet which set forth so clearly 
and so simply the clinical aspects of the disease ! 

How vivid is the memory of Fitz's recitations and dem- 
onstrations ! What student who attended them can forget 
the charm of that subtle and incisive, but yet humorous and 
not unkindly irony — or rather, perhaps, that ironical face- 



tiousness which so disconcerted some of his pupils and 
colleagues, and so delighted others; which was, I am sure, 
highly beneficial to many who did not fancy it at the moment. 

One did not go to sleep in Fitz's demonstrations ! 

By nature of a careful and judicious temperament, he was 
a strong man. and had the strong man's love for discussion, 
argument, opposition. Just and tenacious of his opinions as 
a strong man should be, his firm mind was not easily shaken. 
But firm though his mind was, it was ever open to recognize 
and welcome and embrace the new truth. This very attitude 
of apparent opposition was one of Fitz's most stimulating 
qualities, inciting his associate, whether student or colleague, 
to keener and more efficient effort. 

At the necropsy table he sought to induce the clinician to 
express a definite opinion as to the nature of the case, and, 
where there proved to have been any failure wholly to appre- 
hend the character or extent of the pathological process, he 
often pointed out the omission in diagnostic procedure or the 
error in reasoning which had been responsible for the incom- 
pleteness of the diagnosis. This most instructive and valuable 
habit was trying to some over-sensitive colleagues. But Fitz 
was consistent ; he did not spare himself. While yet pathologist 
at the Massachusetts General Hospital, he used to visit, in the 
surgical wards, patients on whom an abdominal section was to 
be performed, in order that he might compare his bedside 
observations with the results of surgical investigation. His 
opinions he was always willing to express, far more willing, 
sometimes, than those in attendance upon the patient. This 
habit must have been of great assistance to him as a consultant 
in later years ; as an example to the house officers it was invalu- 
able. 

Fitz's peculiar keenness of intellect inspired, at first, in 
certain of his students, an admiration and respect not untinc- 
tured with fear — something akin to the Ehrfurcht of our 
Teutonic brethren. But the element of fear dissolved into 
love with the first personal contact. How simple and gracious 
was his reception of the student who, perhaps, with some 
misgiving, sought his counsel in private! His unfailing 
kindness and thoughtfulness, his friendly interest and wise 
advice so freely and generously given, meant more to some of 
us than words can express. 

To not a few of his students, his teaching and example were 
the great inspiration of their school days, and to most of 
these men this inspiration has been a. lasting and a growing 
influence. There must be many who owe to him their best 
ideals in medicine, and surely, there are others of his pupils 
who have been, as have I, so jealous of his regard that any con- 
sciousness of lapse or shortcoming has been inevitably asso- 
ciated with the sting of the thought that they were unworthy 
the confidence of Fitz. 

It is very strange and sad, the thought that all this wealth 
of wisdom and learning and experience so slowly and pain- 
fully acquired through a long and active life, has vanished 
in a moment. It leaves one with a sense of immense empti- 
ness and vacancy and waste. 



Mahch, 191 !.] 



■loilNs HOPKINS HOSPITAL Ml I.I.I.IIV 






Bui he has lefl to mankind a large legacy in his 
making contributions, and with his student* 
remains ever present, embodied in their Is. If 

in shaping their 
might have wished, ent influence will long endure. 



TWO MEN: 
GEORGE ALEXANDER GIBSON 
HUGH ANGUS STEWART.* 

By W. S. Thayer, M. D., 

Professor of Clinical Medici iu Hopkins 

University. 

there came to as from Edinburgh, a 
man who desired to spend a year at work such as might 
him to prepare the thesis aecessar] For the acquisition of hi> 
doctorate in medicine. This young Scol brought with him 
letters from his former master in Edinburgh, a man distin- 
guished in his profession and very dear to his friends. The 
affection that the pupil always showed toward his master and 
the almost loving interest with which the master inquit 

bis pupil on those 1 -are occasions when it was <■ 

fortune to be thrown with him, have brought it abo 
!. in some ways very different, have been 
associated in my mind. 

By a e, both of tl full of 

life and strength and vigor, 1 thin a few months 

of one another. 

The world was ill able to spare them. 

I cannot refrain from saying, at I 

ster from whom Hugh Stewart drew mui : 
ration, the man who gave him that advice which brought him 

duated in medii i 

of M. D. in 1881. [n 1874 he had ale 
the same university. A 
able fellow, he soon attaint d en inence as a prai 
er, and In- visits 
■ 

many lean 
medical literature were numerous and valuable. G 

man of unusual | 
j 

perimental work, hut hi 
forcefu 1 

fellow ni' n. a power alwa 
lating. ' I 

clean-cut features might havi - ■ 
century portrait, and thi 



* Remarks made on the occasion of I 
tablet to Hush Aneus Stewart, M D., O lun 
November !"■. 1913. 



in him 

in his libra 

. 

chuck 1 - 

whom he loved to quote : in 
Btudents, or about his more than I 
of lit"'' was in him and rai 

rounded him. W 
ear wai 
unexpectedly humi 

him. There 

him with warm admiral 

s 

natural clinical ability, 

his pu] 

nal contributioi s to mi 

he has upon those about I 

Freed by his nature from the blinders of vanity and pride, 

such a man knows and wi 

well a< thosi 

■ i the youth 
; 
and as f 
to him. 

■ 

■ ■an labo 

we cai 

3t 

education. I 

■ 

nourisl 
all the 

and t;. 

1 



90 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 277 



mules which had been imported from the United States. I 
regret to say that his opinion of the moral character of those 
mules was such as to inspire a distrust which I was never 
able wholly to shake, as to the business probity of those of 
our countrymen who had been instrumental in furnishing 
these important engines of war. 

Quiet and modest as was his demeanor, he was one of the 
strongest and most self-sufficient characters I have ever 
known. His problem once chosen, he went to work with an all- 
absorbing energy and persistency. Remarkably resourceful, 
he rarely asked assistance or advice. He framed his own 
plans, devised his own instruments and pursued his problem 
to its end in an orderly and systematic manner. During his 
first year in Baltimore, he carried out, in Dr. Hirschfelder's 
laboratory, the excellent piece of work on the pulse and blood 
pressure changes in aortic insufficiency, which earned him his 
degree of M. D. and a gold medal. 

After returning to Edinburgh to receive his well-earned 
honors he came again to Baltimore in the fall as my assis- 
tant. His duties in this capacity were numerous and not 
always easy, but he found time, nevertheless, to carry out 
some exceedingly interesting and ingenious experiments which 
apparently demonstrated that the circular muscle fibres below 
the aortic and pulmonary valves enter into contraction slightly 
later and remain in contraction somewhat longer than the rest 
of the ventricular muscle. In the course of this work, he 
showed remarkable mechanical ingenuity in devising a deli- 
cate instrument for the graphic registration of these muscular 
contractions. Why these experiments were not recorded 1 
have never known. Stewart was not one who rushed into 
print and it is probable that he felt that there was still some- 
thing lacking to make the demonstration complete and his 
results unassailable. 

He was an admirable assistant, ready, understanding, far- 
seeing, and he soon showed himself to be a man of excellent 
clinical judgment. His most valuable qualities were, I should 
say, his self-sufficiency and his independence. Deferential, 
never obtruding his opinion, he always knew his own mind, 
and if the opportunity offered, he expressed his views, whether 
or not they agreed with those of his superior officer. He was 
fond of argument, showing, in rather high degree, an in- 
clination to take up opposition to any sharply enounced 
proposition, a tendency which was so striking in an honored 
leader of the medical profession in America, whose untimely 
death we have so recently had to mourn — my dear old master 
and friend, Dr. Fitz. But there is no more valuable habit 
of mind than this when it is associated with a fundamentally 
open and judicial temperament; it is an attitude which, as I 
have often said of Fitz, is characteristic of the strong man — 
and Stewart was a strong man. 

I can see him now: We were perhaps discussing some 
question of interest, and, in my enthusiasm, I had expressed 
my views at some length and rather positively. Stewart had 
listened with perfect deference but when I was done, he would 
lower his head a little, as if he were about to charge some 
obstacle, and in a quiet, determined manner, with a slight 
Scotch accent, he would say, " I don't think so " — and he 



was generally able to give good reasons why he did not think 
so. 

After a year's service as Assistant Resident Physician, 
Stewart became Assistant in Pathological Physiology in the 
Johns Hopkins University, and a Fellow of the Rockefeller 
Institute. During this year, he carried out with Dr. King 
some important experiments in which it was shown that the 
toxic element of the bile, that which causes the lowering of the 
blood pressure and the slowing of the heart, lies in the pig- 
ments and not, as is still so commonly asserted, in the salts. 
Following this, Stewart published an interesting note on " The 
Dextrose Consumption by the Isolated Perfused Human 
Heart." 

In 1909, he left Baltimore to become the Associate of Dr. 
MacCallum, as Assistant Professor of Pathological Anatomy 
in Columbia, and it was with most sincere regret that we 
parted with him. That which he accomplished in these last 
four years, I need not tell you. 

Stewart had always desired eventually to enter into clinical 
medicine, and alongside of his experimental study in the 
laboratory and his teaching, he kept in touch with the patient 
at the bedside in St. Luke's Hospital. In medicine his 
especial interest was in the study of the circulatory system, 
an interest stimulated, undoubtedly, by his work with Gibson. 
The list of his valuable contributions shows how consistently 
he pursued the course that he had chosen at the outset. 

To all he seemed a man of exceptional promise, one who 
must surely have made his mark. 

The master, essentially a clinical observer, had impressed 
upon the pupil the desirability, in the new day, of preparing 
himself for a career in medicine by years of fundamental 
study and research, that he might be fitted properly to direct 
the many activities of a modern medical clinic. And there 
were few men in America better fitted for such a career than 
was Stewart at the time of his death. Reserved, undemonstra- 
tive, retiring as he was, it was not difficult to see that Stewart 
was a man of really deep feeling and of rare loyalty. For 
Stewart was a man — a man in the purest and best English 
sense of the word — a man on whom one felt instinctively that 
he could rely in any emergency. And after all, is it not this 
which means most to us in this world ? What skill, what bril- 
liancy, what powers, what accomplishments move use as do 
those qualities of sturdy and efficient self-reliance and courage, 
and honesty and directness which go to make a man ! What 
triumph of genius stirs us as deeply as does the simple story of 
a Scott and an Oates ! 

And with all his ability and his talents, it is this inde- 
finable essence of manliness that appeals to us most profoundly, 
as we think of the fine fellow in whose memory we meet today. 
There are few of us who knew him who, in our hearts, have 
not more than once said, "Would that I were a little more 
like Stewart ! " 

LIST OF PUBLICATIONS OF HUGH ANGUS STEWART. 

Stewart (H. A.): A Case of Aortic and Pulmonary Incompe- 
tence, Complicated by Pericarditis with Effusion. Edinb. M. J., 
1906, n. s., XIX, 507-513. 1 pi. 



March. 1!»1!.] 



JOHNS HOPKINS liosiMTAl. BULLETIN. 



■.-I 



Stewart (H. A.): Experimental and Clinical Investigation of 
the Pulse in Aortic Insufficiency. Arch. Int. Med., Chicago, 1908, 

I, 102-147. 

King (J. H.) and Stewart (H A.i: Effect of the Injection of 
Bile on the Circulation. J. Exper. H., Lancaster, Pa., and X Y . 
1909. XI, 673-685; also Tran Assn. Am. Pliys , Phila . 1909. XXIV. 
396-409. 

Stewart (H. A.): The Dextrose Consumption by the Isolated 
Perfused Human Heart. J. Exper. M , Lancaster, Pa., 1910, XII, 
59-66. 

Stewart (H. A): The Cause of Cardiac Cohypertrophy. Proc. 
Soc. Exper. Biol, and Med.. N. Y.. 1910-11, VIII. 13. 

Stewart (H. A.): An Experimental Contribution to the Study 
of Cardiac Hypertrophy. J. Exper. M., Lancaster. Pa., 1911, XIII. 
187-209. 4 pi. 

Stewart (H. A.) : The Influence of Salts of Calcium and Potas- 
sium on the Degree of Hypertrophy Produced by Adrenalin In- 
fection in Rabbits. Proc. Soc. Exper. Biol, and Med., X Y . L911 

II, IX. 7. 

Stewart (H. A . i and Harvey I S. C.t: Variations in the Re- 
sponse of Different Arteries to Blood Serum and Plasma. Proc. 
Soc. Exper. Biol, and Med., X. Y., 1911-12, IX. M 87. 

Stewart ill. A.i and Harvey (S. C): The Vaso Dilator and 
Vaso Contractor Properties of Blood Serum and Plasma. .1. Exper 
M., Lancaster. Pa., 1912, XVI, II 

Stewart (H. A.) : The Mode of Action of Adrenalin in the Pro- 
duction of Cardiac Hypertrophy. J. Path, and Bacterid. , Cam- 
bridge, 1912-13. XVII. 64-81. 2 pi. 

Stewart (H. A): On certain Relations between Lipoid Sub- 
stances and the Adrenals. To appear in the transactions of the 
XVII International Medical Congress. 



DR JULIUS PRE1 

By 1 Ir. I 'win I. M LCHT. 

I am happy to have the privilege of addressing a few word- 
to this society about one who is probably unknot 
you, and yet one with whose work every student o 
of medicine should be familiar. I am referring in particular 
to the students of medical nisi 
word. Those who are interested in th 
into two groups. Weha hand, men who a 

of cherishing the memoi 
excellent old local worthy, or of son 

in the line in which th< 
the other hand, we find 
wo maj style them, ph '■ 
tory of 

m of \ iew, 
one, of the! i 

■ 
the other nations and ra 
tbrtunat 
those o: 

superficial one. Tl 

and Arabic medicine. Althi 

this field have from timi 



•Read before the Johns Hopkins Hospital 
Dec. 8, 1913. 



which they i 

hand, or by wme one unfamiliar with 

Tims, for 
Biblical and 
lished in l 860 bj W . 
appearing u 

iliar with I 
literature. What thai means can hai 
who knows not hi i 

briefness, but little, but 

the rich gig] 

the pii til the 

ation of tie " I .1 ulius 

. Ill 1911, lint v. 

hensivi . 

class physician on the one hand, and a Semitic 

philoloj 

on the oth.-r. It 

away, and of his work that I wish b 
Julin D in a small 

in the Mark of Brandenburg, Prussia, in 
through the publi 

■ i the gymnasium at Prenslau, wl 
himself by hi- brilliant scholarship. Upon gradual 
went to study medicine in Berlin, and there upon tl 

.tied an inti 
■ 

■ 

town • 

learn.: 

3 

tuthor of on 

: in the 

short 1;. 

will -! 



■ 



rk 



92 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 277 



I should earnestly recommend every one desiring to trace 
the history of some medical subject hark into antiquity to 
consult this book. There are but few subjects in medicine 
upon which it does not touch. Here is a brief resume of its 
contents : 

The first chapter treats of the physician in general, his 
position, education and training. 

The second chapter contains extremely interesting data on 
anatomy and physiology, covering over one hundred pages. 

The third chapter treats of general pathology and therapy. 

The fourth chapter deals with special pathology and therapy. 

The fifth chapter is on surgery. Here we have a descrip- 
tion of various kinds of wounds, different operations, sleep- 
ing medicines, etc. 

The sixth chapter deals with diseases of the eye. 

The seventh chapter contains some extremely interesting 
information about ancient dentistry. 

The eighth chapter is on diseases of the ear. 

The ninth chapter is on diseases of the nose. 

The tenth chapter describes a number of nervous affections, 
epilepsy, hysteria, headaches, palsies, sciatica, etc. 



The eleventh chapter is devoted to a consideration of some 
psychiatric conditions. 

The twelfth chapter treats of skin diseases. 

The thirteenth and fourteenth chapters deal with gyne- 
cology and obstetrics. 

The fifteenth chapter is a discussion of materia medica and 
pharmacology. 

The sixteenth chapter is a very important and interesting 
one on legal and social medicine. 

The seventeenth chapter is a treatise on hygiene. 

The eighteenth chapter is on dietetics. 

Last but not least important of all, the book contains a com- 
plete bibliography. 

I do not intend to take more of your time, by going into a 
detailed description, but if these few remarks may serve to 
impress upon your memories the title of this book, I am sure I 
have not spoken in vain, and I know that it will be a most 
acceptable tribute to the memory of my friend, its author. 



PROCEEDINGS OF SOCIETIES. 



THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY. 
November 8, 1913. 
Interpretation of the Auscultatory Blood Pressure Sounds. Dr. 
D. R. Hooker and Mr. J. D. Southwobth. 

The accuracy of KorotkofFs method for the determination 
of diastolic arterial blood pressure in man has been questioned 
on the ground of clinical and experimental observations. The 
authors obtained a graphic registration of the vascular sounds 
by the use of a telephone and capillary electrometer (method 
of Einthoven and Gehik) and compared them with a syn- 
chronous graphic record of the excursions of the lever of an 
Erlanger sphygmomanometer. In sixteen records from four 
normal individuals there was perfect- agreement between the 
two records for the points of systolic and diastolic pressures. 
Several of these records were exhibited. Tests of the delicacy 
of the method of sound registration convinced the authors 
of its reliability; and they therefore concluded that, at leas! 
in the cases observed, the auscultatory method is reliable for 
the determination of the diastolic as well as of the systolic 
arterial blood pressure in man. 

DISCUSSION. 

Dr. Barker: Since the appearance of KorotkofFs publica- 
tions we have been using the auscultatory method of deter- 



mining bliMid pressure in the clinic here, especially for the 
diastolic pressure. Dr. Hirschfelder and I were very interested 
in the method and found it clinically accurate. At our 
request Drs. Engle and Allen controlled the method with the 
Erlanger instrument. They found the maximal pressure to 
be entirely accurate when determined by the auscultatory 
method ; the minimal pressure agreed within 5 mm. of mer- 
cury. The method is not applicable in cases of aortic insuffi- 
ciency on account of the sound audible over the artery even 
when no pressure is applied in the cuff. 

There has been some dispute as to the exact moment which 
corresponds to the minimal pressure. As the minimal pres- 
sure is approached on the way down from the maximal pres- 
sure one hears first certain murmurs over the artery, then a 
sudden accentuation of the sound, a little lower an enfeeble- 
ment of the sound, and then a disappearance of the sound 
altogether. The last three phases do not cover a variation 
of more than a few millimeters of pressure so that for clinical 
purposes it is really unimportant which point of the three is 
chosen to represent the minimal pressure. It would be inter- 
esting, however, for scientific purposes to determine by Dt. 
Hooker's method which one of these three points corresponds 
precisely to the minimal pressure. 



JOHNS HOPKINS HOSPITAL BULLETIN. 

The Hospital Bulletin contains details of hospital and dispensary practice ; abstracts of papers read and other proceeding 
of the Medical Society of the Hospital, reports of lectures, and other matters of general interest in connection with the work 
of the Hospital. It is issued monthly. Volume XXV is now in progress. The subscription price is $2.00 per year. 

(Foreign postage, 50 cents.) Price of cloth-bound volumes, $2.50 each. 

A complete index to Vol. I-XVI of the Bulletin has been issued. Price 50 cents, bound in cloth. 



March, 1914.] 



JOHNS Ilol'KI -P1TAL BULLETIN. 






NOTES n\ m;w BOOKS. 



Manual of Human Emhryolorjy. Edited by Franz Km 
Franki.yv S. Mail. In two volumes. Volume II, wll 
illustrations. $in.00 {Philadelphia and London: J. B. Lippin- 
COtt Company. / 

The editors explain In the preface that the delay of more than 
one-half of a year beyond the expected time of publication of this 
volume is partly due to the fact that the sections on the heart, 
blood vessels and sense organs were completed by others than 
those who originally undertook the work of writing them. In 
justice to some of the authors in the matter of literature references. 
It should be stated that their articles were finished more than a 
year before the publication of the book. 

Dr. Streeter discusses the development of the nervous 
under four subdivisions: (1) Histogenesis of nervous 
(2) Central nervous system, (3) Peripheral nervous system, (4) 
Sympathetic system. 

In the description of the structure of the neuroglia and partly 
in the histogenesis he follows the work of Hardesty. In I 
cussion of the various theories of the histogenesis of i 
proper credit is given to Harrison's work, which Streeter 
as proving that the outgrowth theory of Hlfi is con 
derives the sheath cells from the ganglioi advocates the 

theory that the T-shaped processes of ganglion cells are due to 
branching rather than to approximation by unequal growth of the 
perikaryon. Contrary to former opinion, he considers that a 
neurolemma is present on the nerve fibers of the central i 
system. 

In referring to the optic evagination as constituting tl 
ball," he makes an erroneous use of the term. We notice the omis- 
sion of the epithalamus in the list of the derivatives of the dien- 
cephalon and the inconsistent use of the terms ventral, dorsal, 
anterior and posterior, diencephalon and thalamencephalon. 

Streeter favors the views that the rhombic grooves are branchio- 
meric rather than neuromeric. as hitherto considered. 

On page 40 the lamina !■ n of as forming the 

anlage of the rhinencephalon and on page 47 line 7 he - 
depression for the organ of sni' 11 appears lateral to the lamina 
terminalis." and on i "in embryos under four 

old the rhinencephalon can only be recognized as the space I 
the lamina terminalis and the internal ridge formed by the corpus 
striatum." 

He is in agreement with Patterson that the dorso-median 
of the spinal cord is, to some extent at least, formed bj 
tion of part of the neural canal. 

The description of the development of the pltuitai 
bodies is not very satisfactory u 
sprouts " is certainly open to objection. 

In the development of the Interforehrain rommis 
follows the descriptions of Smith and Marchand. If 
that the term fissure in contradistinction to sul 
the Sylvian and longitudinal will probably no- 
Is no consideration of the development of the Individual I 

The description ol 
Hies Is based chiefly on tl 
the case of the cranial i 
followed so far as no 
as ectodermal in orisin without any reservation. 

A few minor erroi 1. as the omission ol 

on page 56. line 4. and the incom 

The subject on the who!- 
of vision and is quite satisfactory. Many of the num- i 
tlons are original. 

Zuckerkandl. who is especially well Qtti 
contributes a short 



chromaffin or) 

tnpatho- 
chromaffin tissue and rails attention I -al im- 

portant 

mat*. 

Fra ' • of the 

organ- i 
not sen that an unpaired olfactoi 

• Ith Ills as • 
of the ]■■ 
origin, and ol 

destroyed in the adult bj frequently n 

Is called to th. i s t and 

by hypertrophy form tumor-Ilk- of the 

section on the nose folio ,nd Inadequate account of 

malformations in tl on. The Illustrations are drawn 

largely from Peter and Killlan. 

In the section on I .intalns 

that all attempts it> 
Invertebrate I to the 

fact that all ca f cololwma cannot I failure 

of the closure of the chorlolda -it and 

lcrraal 
outer layer of the optic cup. and the description of Fleischer and 
Matys as to the development of the larhrymal paasagi 
I to the lack of a sal tunt In man •■ 

ment of the ocular muse lis and U lllty of a much more 

complete study of thi 
throwing light on tl.- 

The n I W. His. Jr 

middle ear. and Hi-' and S 

of the aurlcli 
credulity of the antJ 

the embr] 

In thi il F. T. 

mouth and I' 

on. 

sbowlm 
from Johl 

• 
addition. 
In t! 

■ 



94 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 277 



as possibly a rudimentary internal gill. Stohr's view that the 
lymphocytes of the tonsil are derived from epithelium is favored, 
and that the carotid fcody is from the chromaffin system rather than 
branchiogenetic. He introduces the term ultimo-branchial body 
for the lateral part of the thyroid. The statement that the widely 
divergent opinions of various authors concerning the condition 
of the post-fetal thymus is due to accidental involutions during 
illness is not a satisfactory explanation to the writer. On page 
467 the term cervical is used by mistake for cortical. The reader 
of this section is left with the impression that our knowledge of 
the subject is in an unsatisfactory condition. 

Grosser considers the lung anlage symmetrical and in this 
disagrees with the work of Norath and Flint and believes that 
no final statement can at the present time be made as to Whether 
the branching is monopodial or not. The illustrations are numer- 
ous and drawn from several sources. 

The development of the blood and vascular system is treated by 
several authors. Minot contributing the part on the blood, Tandler 
dealing with the heart, Evans with the vascular system, and Sabin 
the lymphatic system. 

Minot justly arraigns the present nomenclature of the blood cells 
and blames the clinicians largely for the unscientific terminology. 
He boldly discards the old terms and proposes an entirely new one, 
dividing the erythrocytes, a group term, into the ichthyoids, 
sauroids and blood plastids (non-nucleated form). He considers 
the primitive mesamceboids as the ancestors of all blood cells and 
therefore red and white corpuscles arise monophyletically. He 
states clearly what we know and do not know about blood develop- 
ment. The leucocytes are divided into 

r non-granular 
■\ ["fine granules 

I granular J coarse granules 
I degenerating 

Eosinophile granules he considers devoured fragments of red 
blood cells and not endogenous in origin. He holds the opinion 
that genuine blood platelets occur only in mammals and follows 
Wright's theory of the development of the platelets. On page 511, 
line 13, evidently by is intended for but. On the whole this section 
is the most original in the methods of presentation, most stimulat- 
ing in ideas and one of the best in the book. 

Tandler largely follows Mollier on the early development of the 
heart and Born on the later development. He describes in great 
detail the bends, twists, constrictions, etc., but does not always 
state the age of the embryo in relation to the development stages 
described. On page 42, line 2, the term fibrous is hardly a good 
histological term as used here. The histogenetic changes are not 
very thoroughly considered and a brief discussion of the anomalies 
of the heart would be a desirable addition. On page 543 the text 
reference should be fig. 377, instead of 397. 

The section ou the development of the vascular system contrib- 
uted by Dr. Evans is, to a large extent, original and is a very ex- 
cellent presentation of a difficult subject. The illustrations are 
numerous and for the most part very good. The introductory part 
is a general discussion of the origin of blood vessels, and the second 
part deals with the special development of the vascular system and 
chiefly with the main vascular trunks. He considers that it is 
impossible yet to give a decisive answer to the question of the 
origin of the blood vessels in the body, but his account indicates 
that already considerable is known and that recent additions are 
extensive, especially as indicating the method of transformation 
of the primitive blood vessels into the adult type. 

He formulates the fundamental conception of the development 
of blood vessels essentially as follows: Blood vessels tend always 
to be laid down in multiple capillary anlage rather than single 
trunk-like forms, and the trunks are made by the preservation and 
enlargement of some vessels, while the others disappear and 



hydrodynamic grounds determine what part of the plexus shall 
be preserved as vascular trunks. The strong growth of a region 
drawing the blood to it, and the tendency of the blood stream to 
take the shortest path, constitute some of these hydrodynamic 
factors. 

The following errors were noted : On page 606 T. a. of the plate 
subscription is lacking in the legend of the illustration. On page 
588 we notice the incorrect spelling posses; on page 641, 
perisodactyle ; on page 643, cerical, and on page 690, branchial for 
brachial. On page 641, line 12, upper is a very poor substitute for 
dorsal. 

The chapter on the development of the spleen and lymphatics by 
Dr. Sabin will be especially interesting to American anatomists who 
have followed the controversy as to the method of lymphatic de- 
velopment. She adheres steadfastly to the sprouting theory. We 
notice on page 740 the error in synecytium. This article is well 
illustrated and is a satisfactory presentation of the subject. 

W. Felix, in a long section of some 230 pages, gives a very 
elaborate discussion of the development of the urinogenital organs. 
The illustrations are numerous and many are original. He con- 
siders that the first six pronephric segments show dysmetamerism 
and that the pronephros is better developed in man than any other 
mammal, lacking only the internal glomerulus. 

On page 800 we find the statement that the pronephros extends 
from the fifth cervical to the third thoracic segment, and on page 
819 that the pronephric tubules are never found caudal to the first 
thoracic segment. An elaborate table is given showing the length 
of the mesonephros expressed in segments and the number and 
position of the mesonephric tubules. Also attention is called to 
the important fact that a cystic kidney may be due to a failure of 
the terminal collecting tubules to find and fuse with the interme- 
diate tubules. The post-fetal growth changes of the kidney are de- 
scribed and finally kidney malformations are discussed. The view 
Is held that in man the bladder is ventro-cloacogenic rather than 
allantoidogenic, and that there is no internal descent of the testis 
or ovary. We note that no embryological explanation for ectopia 
vesicae is offered. 

The volume closes with a discussion by Keibel of the interde- 
pendence of the various developmental processes, accompanied 
by a comparative table. A literature list follows each section 
throughout the book. 

This volume is even less adapted than the first as a text-book for 
students, but as a reference book it is unquestionably a classic and 
should be in the hands of all anatomists and biologists. Mistakes 
are few and there is little for criticism and the reduplication 
which is a natural result of multiple authorship is not excessive. 
Anatomists everywhere will regret that Dr. Mall is not a contrib- 
utor to this volume. 

Oxford Medical Publications: Gout. By James Lindsay, M. D. 
$1.50. (London: Henry Frowde and Hodder <£- Stroughton, 
1913.) 

American physicians and medical students, who have few op- 
portunities to see cases of gout, will find this work in excellent 
resume of the subject. In a brief but clear and comprehensive 
review of the subject the author brings out the essential points in 
his discussion of its aetiology, pathology, symptoms and treatment. 

Headache. By Dr. Siegmund Auerbacu. Translated by Ernest 
Playfair, M. B. $1.50. (London: Henry Frowde and Hodder 
& Stroughton, 1913.) 

Symptoms are not as frequently or carefully considered by stu- 
dents as diseases, but a thorough study of a symptom may often 
elucidate fully the whole trouble. How many physicians or stu- 
dents, when a patient complains of headache, really stop to con- 



Mabch, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






sider what this symptom may indicate — how it 

are affected, etc. Headache is only a certain form of pain, and 

pain no matter where situated is but a symptom, and prat 

must learn to look at it so, and remember that every symi I 

its cause, and that he will not euro the cause by simply eliminating 

the pain with some form of an; 

common we are all apt to consider it but a 1 1 

rarer instances where the pain is persistent or Bevere, and as a 

result our treatment of h».; ruently worse than I 

all, for we treat it without due thought. For 

clans, who haven't a clear idea of the various forms and nature oi 

headache, and how it should be treated, this well-written < 

of Auerbach will be most helpful. The following is his cl 

tlon of headaches: A. The more independent forms (migraine, 

neurasthenic, rheumatic I : B. Those associated with di 

individual organs i brain, special s. nses, digestive tract, kli 

C. Those in general diseases; and D. Contractions of different 

forms. The book is not too long for a busy doctor to read through 

with care, and yet the subject is so lucidly handled as to give the 

reader a very clear idea of not only its variety, but its importance. 

The Modem Hospital. By John Allah Hobksbt, U D., and Rich- 
Aim E. Schmidt, Architect Illustrated. (Philadelphia and 
London: IV. B. Saunders Company. : 

This volume of over 600 pages is an exhaustive work on the 
inspiration, architecture, equipment and operation of hi 
The authors have treated the subject in detail and t 
"The Surgical Operating Room," " Business Management" and 
" Purchase of Supplies " are especially good. 

In a work of this kind it is doubtful if the authors should enter 
into the description and detail of the administration of ai 
ics, of the uses of hydrotherapy and of minor surgical technic. 
Such subjects are more in the realm of therapeutics am! 
than of hospital administration. In many instate 
seems to be a lack of finality of discussion in certain .- a 
leaving the reader in doubt as to the correct course to i 
More space could well have been given to the subject ol 
service and outpatient work — branches of hospital admii. 
which have, of late, assumed large proportions. 

\t the same time the book fills a longfelt want. The illustra- 
tions are very good. I 
an interesting manner. 

Medical and Surgical /.•.;/<// n a) I'hihi- 

d-lphia. Vol. I. (Philadelphia: 
1913.) 

It is a pleasure to note the ap] 
from this hospital. All larg< 
similar volumes annually, for in I 
work secures a recognition, which It would i 
tain. The larger numtx r this volumi 

and a few of them b 
of them are Illustrated, and thi r 
tive of different parts of the hospital. I 
worthy of this well-known and highly • 

A Manual of Otology. rt> 

tion. ; 

and Philadelphia 

The merits of this manual have long sine 
the profession, and the present edition, with ne* l 
continue its popularity, 
subject is attractive, and makes I 
student and general practitioner, who is ol 1 1 - 
tlons on the ear. 



Oenito 

M i> n; 

Though the word | book, 

yet in t 

;\ work. 

simply indicating . 

book i! so far 

as Portner an 

The tlli; • 

cmncli 

graph is omitted four W( I 

as printed in 

;. I.I. I! II 

This is a set 
he can learn readily what 

■ 

il 'men- 
tions, but " is an attempt to put I 
of the law relating to I the reason fof 

Mr. Mitchell takt a up t 
fessional evidi tract, civil and criminal 

of the profession, remuni r I 

qualifications. Tie 

what are his rights on main of ; 

■ 

mpltclty, « U 

The h 

| v . M I i 
diction 

■ 


















96 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 277 



of cancer. It is fortunate for specialists that these very handsome 
books are sold at such a comparatively cheap price. Both volumes 
contain numerous fine illustrations. 

The Microtomist's Vade-Mecum. By Arthur Bolles Lee. Seventh 
Edition. $4. (Philadelphia: P. Blakiston's Son d Co., 1013.) 

This is a book every microscopical laboratory worker will find 
most useful to have close at hand. Lee has complied practically 
all the useful methods of staining and preparing microscopical 
specimens, and keeps his well-known work up-to-date by including 
all the* newer means that have proved themselves of value. It is 
excellently well arranged and has a good index so that its users 
can readily find what they need, and if they so desire look up the 
original papers in which the methods are described. 

International Clinics. Vol. III. Twenty-third Series. 1913. $2. 
(Philadelphia and London: J. B. Lippincott Company.) 

The largest clinic is by Gwyn of Philadelphia on the " Treatment 
of Pneumonia"; it is an interesting paper as showing the results 
achieved with different forms of treatment during one winter at 
the Philadelphia Hospital. 

Daniel of London writes at length on " Gastrointestinal Tox- 
aemia," and Abrams of San Francisco writes on the value of the 
concussion of the seventh cervical spine for stimulating the heart- 
reflex, what he calls his method of " vertebral reflex therapy." 

All the clinics treat of subjects of perpetual interest from one 
point or another to the physician and surgeon, and introduce to 
many readers new methods of treatment which may help to make 
their practice better if carefully studied. 

Diet in Health and Disease. By Julius Friedenwald, M. D., and 
Joiix Ruhkah, M. D. Fourth Edition, Thoroughly Revised 
and Enlarged. $4. (Philadelphia and London: W. B. Saunders 
Company, 1913.) 
This is the most helpful book on the subject in English for the 
general practitioner and student, and can be warmly commended. 
The new edition is evidence of its wide and well-deserved popu- 
larity. It is dedicated to Sir William Osier, and its fitting place 
on the bookshelf, is next to the latter's " Practice of Medicine." 

Obstetrics for Nurses. By Joseph B. DeLee, M. D. Fourth Edi- 
tion, Thoroughly Revised. $2.50. (Philadelphia and London: 
IV. B. Saunders Company, 1913.) 
It is evident that this work has found favor with nurses or it 
would not appear in a fresh edition; but for them it seems to us 
too long and too detailed in parts, while for students ^although 
not primarily written, yet considered by the author as valuable 
for them, the book is insufficient. It is a pity that both the author 
and publishers show so little taste in the illustrations; even in a 
medical work to open on such a frontispiece as is here found is 
not artistic, and others of the drawings might have been made 
more comely. 

Essentials of Prescription Writing. By Caey Egglestox, M. D. $1. 
(Philadelphia and London: W. B. Saunders Company, 1913.) 
The " essentials " are here compressed into very brief space, 
too brief for the book to be really useful except to those who desire 
only the merest outline. It is not nearly so good as Mann's small 
work on the same subject which has long been the standard, and 
is short enough. 

Gray's Anatomy: Revised and Reedited. By Robert Howden, 

M. B., etc. Illustrated. (Philadelphia and New York: Lea & 

Febigcr, 1913. i 

There is probably no American or English text-book in any 

branch of medicine so deservedly popular as Gray's Anatomy, or 



one that has passed through so many editions. This is a new 
American from the eighteenth English Edition. The essential 
alteration adopted by Howden is the use, practically throughout, 
of the B. N. A. He has added some new illustrations, and made 
some changes in the arrangements of the paragraphs on Surface 
Anatomy. It is to be hoped that until some better anatomy is 
written, which is not a likely probability, that Gray's will remain 
henceforth without further changes. There is a danger that more 
changes would injure it. His anatomy was a masterpiece, and to 
tamper with such a work is likely to do it harm. It would be 
interesting to know what opinion Gray would have of his work 
in its present form. The adoption of the B. N. A. is undoubtedly 
to be commended. The other changes will or will not be approved 
in accord with the individual reader's feelings. 

Diagnosis in the Office and at the Bedside. By Hobart Amoby 
Hare, M. D. New (7th) edition, thoroughly revised and re- 
written. Illustrated. $4. (Philadelphia and New York: Lea 
d- Febiger, 191',.) 
Under a somewhat altered title Hare's well-known work appears 
for the seventh time, somewhat abbreviated because practically all 
laboratory methods of diagnosis purposely have been omitted. 
The book has been appreciated in the past, and will continue to be 
in the future, for the author's method of presentation is one that 
is attractive to many students. This " Diagnosis " is a useful 
clinical guide. 

Treatment of Internal Diseases for Physicians and Students. By 
Prof. Noreert Ortnek. Edited, with additions, by Nathaniel 
Bowditch Potter, M. D. Translated by Frederic H. Bartlett, 
M. D. $5. (Philadelphia and London: J. B. Lippincott Com- 
pany, 1913.) 
Although it does not appear on the title page, yet this is the 
second English edition of this work, from the fifth German, which 
has been so much altered by the author, that the new English issue 
is materially different from its predecessor. The chapters on 
children's diseases have been entirely rewritten, and the English 
scale of measures is supplied alongside of the French, and Fahren- 
heit scale is used to record the temperatures noted in this book. 
The editor has added many notes as well as a chapter on neuras- 
thenia. This is a work which students and general practitioners 
will find an excellent guide to the treatment of internal diseases. 
It is safe and sound, and sufficient drug therapy is indicated 
to meet the needs of any practitioner. 

The Physician's Visiting List for 191!,. $1.25. (Philadelphia: P. 
Blakiston's Son & Co.) 
This useful note-book, well suited in size and shape to be carried 
in the pocket, is always timely in appearance. The country prac- 
titioner will find it of service, as he drives from one patient to 
another, for all sorts of notes, and for reference, as it contains 
numerous tables, which are not always at one's fingers' ends. 
Diagnosis of Bacteria and Blood-Parasites. By E. P. Mixftt, 
M. D. Second Edition. $1. (New York: Hoeber, 1913.) 

There should be no call for such a work as this; it is too small 
to be of any real value to an honest student of this subject. There 
is only one illustration and that a wretched one of the malarial 
organism. 

Radium and Cancer. By Louis Wickham and Paul Degrais. 

Translated by A. and A. G. Bateman, M. D. $1.25. (New 

York: Hoeber, 1918.) 
This brief presentation of the effects of radium on various forms 
of cancer, illustrated by many photographs, is a helpful manual 
for the radiologist. Dr. Wickham lectured in this country several 
years ago, and explained what could be accomplished with radium 
when skillfully applied in various ways in the treatment of can- 



Maw. H. 1914.] 



.IOHNS llol'KINs BOSPITAL BULLETIN. 






cer. In " Radium and Can. - very remarkabli 

he and his confrere have obtained by their brilliant manipulation 

of this dangerous remedy. 

Modern Problems of Biology. By Charles Sedowii k Misot, LI.. D., 
etc. Illustrated. $1.25. (Philadelphia: P. Blakitton't 
& Co.. MS.) 

Incomplete, since they are presented in a condensed form 
lectures, delivered at the University of Jena by l>r. Minot. offer 
much of living interest to the reader, whether sciential or layman. 
Who is not interested in the questions of immortality, death, and 
sex even when considered from a purely scientific point ol 
These are a few of the vital problems of biology which Minot dis- 
cusses lucidly and learnedly. 

A Manual of Surgical Treatment. By Sib W. Watson Chi ^ m . Bart, 
F. K. S., etc., and F. F. Bi bghasd, F. R, C. S. in Five Volumes. 

(Philadelphia and Veto York: /.. <i u Febioer, 

The fifth and hist volume of this excellent system is of thi 
high quality as its predecessors. It is a valuable work and one 
which will appeal to a large body of surgeons. It is not too 
bulky, and yet covers the general field of work in a verj 
hensive and satisfactory manner. The original authors hai 
ably aided by their assistants Drs. Legg and Edmunds. Tin- pub- 
lishers are to be complimented on this handsome product i 
press. 

of the Breast. By Chables Banett I.o, kwood, F. K. C S. 
(Eng.). V'. (London: Henry Fronde and Hodder & Stough- 
ton. MS. < 

Quite from his own experience the author has composed this 
book, which, due to the introduction of case hlstorli 
type as the body of the text, is from one-third to one half larger 
than need be. The author's results compare well with i 
most operators; there are a few, perhaps, who could show a 
greater list of recoveries. The work is of interest as the exp 
of one able surgeon's thoughts and results in a most important 
branch of his art 

Artificial Parthenogenesis and Fertilization. By J 
$2.50. ago Press. MS. > 

It is somewhat strange that this work appeared originally In 
German, about four years ago, and that Ami nta have 

had to wait so long for an English edition. In the n 
ever, Loeb has had the opportunity to add to his first publication, 
so that in its new form the reader on 
author's most brilliant and Inti 

has long since been universally admired and praised by all 
of following his investigations, and this volume Bhoi 
ality of his thought, and skill ll "d diffi- 

cult problems. The book is a real addition i 
of fundamental Importance to various bl 

Tear-Book of the PUc) 
». Y.. 191 I. 
The appearance of this third volume is modest and 
tive. The Pilchers are to be complimented on it 
a noteworthy index of the work 
small private hospital. The papers Included • 
surgery, and discuss topics of Interest to all .-urgi-ons. It is an 
excellent proof of the general advaie 

surgeons working together should issue a report of their work an- 
nually. 



Surgia! 

: this work I 
Kven with the limits of the writ • v ill. as 

it has alreadj 

Mr. Ma.. 

The work is well illn I 
•1 it ion toil', comparatively small numb 

surgery on thi 

md Mental '■ 
emlni by Wn 1 1 ui 

A. White, m. D., Sup< i 
for the Insane. Washington, D ra Eli Jeli 

A. M . M. 1 1., l'h 1 1 . Adjunct l'r.-i 
Mind and Nervi 

Illustrated. Per vi 

d< .',' I 

Had psychiatn ni I 
study of medicine there would bardl] 
system, but bappll] 
■ • have their 

11 as In health, and ' 
as also many other i 
from an entirely new poll I 
public, and « 

a comprehensive and abli - 
■ 

'nine w ill ii I | public 

official.-. 

purely medical it la a pity t 
burled, so to 
anxious to inform i 

ly to find them. 1 
problems, delinquency and crime, Imi 
some written by m 

i ntlflc to be n adllj undi • I 
intelllgi 

■ 

author 

ti d In this treat 
gratulnted nn havll 

high. 

■ 

of thi 

' 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 277 



works, for few writers have the proper sense of proportion. Dr. 
Norris has used 2300 references culled from 20,000 found cata- 
logued only in the last ten years. Had he written a treatise on this 
subject from his own experience it would have had a more dis- 
tinct value. As a comprehensive work it can be recommended 
to all who have time to read it; even the layman will find in it 
chapters of interest, touching on gonorrhoea from a sociological 
point of view — one of its sides which, within a few years, has 
assumed a much greater importance than it formerly held. The 
disease, with its rarer complications, is well presented, so that 
also as a work of reference this book has value; but its size, cost, 
and weight (for which the publishers are responsible) will ob- 
struct its merits being generally recognized and appreciated. 

Studies Concerning Glycosuria and Diabetes. By Frederick M. 
Allen, M. D. (Cambridge: Harvard University Press.) 

In a volume of over 1100 pages, with a bibliography of nearly 70 
pages, but no index, a most unfortunate lack, Dr. Allen presents 
the results of three years of study on these conditions. The work 
is not for students but for specialists and laboratory workers; it 
covers, however, a ground which has not been before really 
elaborated in any work in English, so that the need of such a 
volume and a smaller, more practical one is undeniable. As a 
result of his investigations the author believes " that the cure of 
diabetes is now a feasible experimental problem." We trust that 
the work of others may prove it so, and that Dr. Allen may have 
the pleasure and satisfaction of seeing his studies become the 
foundation of the proper treatment of these most troublesome 
conditions. The solution of this problem depends more on the 
laboratory worker than the clinician, and its complexity is shown 
by the difficulty of its solution in spite of all who are working to 
solve it. A study like Dr. Allen's, even if it is not confirmed, is a 
valuable piece of work from the negative side, and so, although 
the author may be disappointed in finding that his results are not 
so important as he had hoped, he may find consolation in the 
thought that he is none the less helping others to find the right 
path. 

The Catarrhal and Suppurative Diseases of the Accessory Sinuses 
of the Nose. By Ross Hall Skillern, M. D. $5. (Philadel- 
phia and London: J. B. Lippincott Company, 1913.) 

This book of Dr. Skillern's was gotten together for the use of 
students, and is an admirable work for this purpose. It is well 
illustrated with original drawings which clearly bring out the 
points they are intended to show. 

The anatomical descriptions are well written and concise, and 
not merely a re-hash of the material contained in the works on 
general anatomy. 

The most commendable thing about this book, however, is the 
numerous references to the original articles. They are given at 
the foot of each page, and include all the best and most recent 
German, French and English publications on this subject. This 
feature alone makes it the most valuable text and reference book 
on this subject that we have as yet seen in the English language. 

It is much to be regretted, however, that the author does not 
lay more stress on the relation of the infections of the accessory 
sinuses to general systemic disorders and diseases. 

Only a small percentage of medical students become " special- 
ists " in the diseases of the nose and throat, but eacli and every 
one should know that gastrointestinal disturbances may result 
from the swallowing of pus; that anaemia, arthritis and nephritis 
may all have their origin in an unsuspected chronic infection of 
one of the accessory sinuses; and that many of the disturbances 
of the optic and oculomotor nerves are secondary to obscure in- 
fections in the nose. 



Pathology: A Manual for Teachers and Students. By W. J. 
Councilman, M. D. (Boston: W. H. Leonard, 1012.) 

Professor Councilman has introduced several new features in 
this manual of pathology, most conspicuous being the absence 
of any illustration, and the presence of several blank pages fol- 
lowing each chapter. Illustrations were omitted because the 
author feels they too often represent carefully selected areas for 
the illustration of a point, more commonly an individual inter- 
pretation. The blank pages are inserted that the student may 
make personal notes and drawings of objects studied, thereby 
helping create his own text-book. 

Many protocols of autopsies are included presenting typical 
morbid processes assisting the student to correlate the lesions as a 
disease of an organism rather than of a single organ. 

The infectious diseases and special pathology of organs are con- 
sidered with more fullness than subjects whicli seem to the author 
to illustrate principles of less wide application. 

After most chapters suggestions are given which serve as a 
guide to the experimental production of lesions considered. 

The manual is of convenient size for class and laboratory work, 
consisting of 393 pages exclusive of blank pages. 

It will be found a valuable book for the student in correlating 
and preserving his observations. 



Diagnosis of the Malignant Tumors of the Abnormal Viscera. By 
Professor Rudolph Schmidt. Authorized English Version by 
Joseph Burke, M. D. $4. (New York: Itebman Company, 
1913.) 

The work is divided into three parts — a general, special and 
case histories. In the special part the author considers carci- 
noma of the stomach, large intestine, liver, gall bladder, pancreas, 
malignant tumors of the kidney, and atypical malignant abdom- 
inal growths. Throughout this useful guide, Dr. Schmidt tries 
" to emphasize the most important factors of suspicion," as 
well as "the symptoms which appear first"; and by the use of 
case histories adds much to the value of his book, since he Is 
hereby able to trace the history of the patient through the hands 
of physician, surgeon, and pathologist. For a young clinician 
the work affords much that is of real interest and help. 

Problems of Genetics. By William Bateson, F. R. S. Ilustrated. 
$4. (New Haven: Yale University Press, 1913.) 

A most interesting series of lectures, presented under the 
Silliman Memorial foundation, on species and variety. It is not 
adopted to the general reader, but specialists in biology will value 
highly Professor Bateson's presentation of the subject. The 
problems of genetics are many and varied, and their solution is 
extremely difficult, but of vital importance to physicians, and it is 
a pity that there are so few medical men who are able to follow 
and comprehend such a work as this, which demands a wider 
range of scientific knowledge than most of them have. 

A Text-Book of Biology. For Students in Medical, Technical and 
General Courses. By William Martin Smallwood, Ph. D. 
Illustrated. $2.75. (Philadelphia and New York: Lea rf 
Febiger, 1918.) 

Dr. Smallwood's text-book will doubtless be popular, it is 
abundantly and elaborately illustrated, is not too long, and gives 
the medical student such information as he most needs and a 
good foundation to build upon. The author shows the practical 
connection of biology to medicine, which is required to interest 
the student. Had medical students, as a class, a better grounding 
in biology they would be more capable physicians, but this un- 



Makcii, 1914.] 



JOHNS HOPKINS BOSi?ITAL BULLETIN. 






fortunately tliey do not see until too late, and so lose something 
which is very essential to their development of intelligence and 
culture. 

Modern Medit ini : Its Theory ami Practice. In original con- 
tributions by American and foreign authors. Edited by Sut 
Win mm Osleb, Bart, M. IV, F. R. S., and Thomas M 
II D. Second Edition Thoroughly Revised. (Philadelphia: 
Lea <£ Febiger, 1913.) 

Vol. 1.— Bacterial diseases: diseases of doubtful or unknown 
etiology, nonbacterial fungus infections, the mycoses. 

The ap] the first volume of the new edition of 

Modern Medicine six years after the beginning of the first edition 
is evidence enough that this work lias been and is still in d 

The new edition is to be condensed into five, instead of seven, 
volumes and its price proportionally reduced, so that it may have 
a wider distribution among the English speaking profession. In 
physical appearance the new volume is a very great improvement 
on the original edition; the page is larger with better type and 
paper, and the illustrations are quite in a different class from the 
very poor productions in the first edition. The number of pages 
in the volume is also considerably increased, and, last but not 
least, we have a much more acceptable binding. 

The subject matter in the first volume covers a good part of 
volumes I and II of the earlier text, revised to date with the addi- 
tion or expansion of some subjects such as the articles on i 
and trypanosomiasis which have assumed a new import 
the last few years. 

There will be those who regret the elimination of the historical 
paragraphs and, to a large extent, of the bibliographies. In fact 
it is one of the most important functions of a system b 
collections of the literature to date. 

Be this as it may. however, there is no doubt that the work is 
one of the best systems in English and will meet the demands of 
the greater part of the profession fully and so justify the success 
it has had and will continue to enjoy. 

Der Pru Von Dr. 

. ( ; i i ■ i -. 
I ' / / i 

In this monograph nhoi tully and wit' 

pathological material, d< scribed with sufficient detail. The in- 
vestigation is directed mainly upon the relations of tul" 
pulmonary foci to the adjacent tuberculous lymph 
brings extremely strong evidence for the view that the pulmonary 
focus Is always the primary one. The Involvement of the lym- 
phatic system can always be shown to be secondary although the 
demonstration is at times accompli bed onlj bj the ma 
taking dissection. This is confirmatory of the work of K II 
Albrecht, although many clinicians still hold that the I 
bronchial lymph nodes are first infected, and the 
after, through the nodes, by reti 
ion however now seems uni 
the pulmonary focus, Ghon holds decidedly t" 
He believes also on the basis of I 
striking tuberculous foci 
■ 
invasion of the tubercle bacillus has » 

ind Bealth:With oi 

The Macmillan Con 

A plea is entered for the use of psych. I 
as it is believed that one of the r 
minister to (ill the needs of man. 
failure of medical men, and occasions an 



Those religious worl 

i. It might 

• 
cause other w i 
and OOI 
harm than gi 

The book I ad baa little I 

it. The author is ma 
Chrlsti 
than he Is when 1 

Trai 

In his Introdui don, Dr 
ame an 

: Freudian I 
timely and valuable, and 
author and i 

' 
as to include normal dream life, wit, t 
tion of the Instlncl of sex, and still ■ 
certain psychoses, m \n..l p 
mythological, and bu| 

it is pointed ont hovi ini\ • • 
against the Frt adit 

unfailing sexual etlolog] it li ihown bi thy and 

■ indiv tduals are Ini lint ml 1m 

portam 
no problem; the others I 

r the t' rm i 

■ 

function. • 

i hlldhood. 

ntatea. 
i th Ujp 

era! Pi 

This volumi 

day to find SO 

work, and h 

ate: 

rllnlco 



100 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 277 



THE JOHNS HOPKINS HOSPITAL REPORTS. 



Volume I. 423 pages, 99 plates. 



Volume II. 570 pages, with 28 plates and figures. 
Volume III. 766 pages, with 69 plates and figures. 
Volume IV. 504 pages, 33 charts and illustrations. 
Volume V. 480 pages, with 32 charts and illustrations. 

The Malarial Fevers of Baltimore. By W. S. Thayeu, M. D., and J. 
A Study W o( T 8ome 1 F'aUl Cases of Malaria. By Lewellys F. Barker, M B. 

Studies in Typhoid Fever. 
By William Oslee, M. D.. with additional papers by G. Blumeb, M. D., 
Simon Flexneb, M. D., Waltee Reed, M. D., and H. C. Paesons, M. D. 



Volume VI. 414 pages, with 79 plates and figures. 



Volume VII. 537 pages with illustrations. 



Volume VIII. 552 pages with illustrations. 



Volume IX. 1060 pages, 66 plates and 210 other illus- 
trations. 

Contributions to the Scienoe of Medioine. 
Dedicated by his Pupils to William Henry Welch, on the twenty-fifth 
anniversary of his Doctorate. This volume contains 38 separate 
papers. 



Volume X. 516 pages, 12 plates and 25 charts, 

Structure of the Malarial Parasites. Plate I. By Jesse W. Lazear, M D. 

The Bacteriology of Cystitis, Pyelitis, and Pyelonephritis in Women, with 
a Consideration of the Accessory Etiological Factors In these Condi- 
tions and of the Various Chemical and Microscopical Questions 
involved. By Thomas R. Beow.n, M. D. 

Cases of Infection with Strongyloses Intestinalls. (First Reported Oc- 
currence in North America.) Plates II and III. By Richard P. 

On the Pathological Changes in Hodgkln's Disease, with Especial Reference 
to Its Relation to Tuberculosis. Plates IV-VII. By Dorothy M. 
Reed, M. D. „ „ 

Diabetes Insipidus, with a Report of Five Cases. By Thomas B. Fdtcheb, 

Observations on the Origin and Occurrence of Cells with Eoslnophlle Gran- 
ulations In Normal and Pathological Tissues. Plate VIII. By W. T. 
Howard, M. D., and R. G. Peekins, M. D. 

Placental Transmissions, with Report of a Case during Typhoid Fever. By 
Frank W. Lynch, M. D. .„,,»» 

Metabolism In Albuminuria. By Chas. P. Emerson, A. B., M.p. 

Regenerative Changes in the Liver after Acute Yellow Atrophy. Plates 
IX-XII. By W. G. MacCalldb, M. D. 

Surgical Features of Typhoid Fever. By Thos. McCbae, M. B., M. R. C. P. 
(Lond.), and James F. Mitchell, M. D. 

The Symptoms, Diagnosis, and Surgical Treatment of Ureteral Calculus. 
By Benjamin R. Schekck, M. D. 



Volume XI. 555 pages, with 38 charts and illustrations. 

Pneumothorax : A historical, clinical, and experimental study. By Charles 
P. Emebson. M.D. _ _ 

Clinical Observations on Blood Pressure. By Henry W. Cook, M. D., and 
John B. Brioos. M. D. _ „ _ _ 

The value of Tuberculin in Surgical Diagnosis. By Martin B. Tinker, 
M. D. 

Volume XII. 548 pages, 12 plates and other illustrations. 

The Connective Tissue of the Salivary Glands and Pancreas with Its De- 
velopment In the Glandula Submaxlllarls. Plates I-III. By Joseph 
Marshall Flint, M. D. 

A New Instrument for Determining the Minimum and Maximum Blood- 
Pressures In Man. Plates IV-X. By Joseph Erlanoer. M. D. 

Metabolism In Pregnancy, Labor, and the Puerperlum. By J. Morris 
Slemons. M. D. , _ , „ 

An Experimental Studv of Blood-Pressure and of Pulse-rressure In Man. 
Plates XI and XII. By Joseph Erlanoer, M. D., and Donald R. 
Hooker, A. B., M. S. 



Typhoid Meningitis. By Rufus I. Cole, M. D. 

The Pathological Anatomy of Meningitis due to Bacillus Typhosus. By 
William G. MacCallum, M. D. 

A Comparative Study of White and Negro Pelves, with a Consideration 
of the Size of the Child and Its Relation to Presentation and 
Character of Labor in the Two Races. By Theodore F. Riggs, M. D. 

Renal Tuberculosis. By George Walker, M. D. 



Volume XIII. 605 pages, with 6 plates, 201 figures, and 
1 colored chart. 

Studies in Genito-T/rinary Surgery. 
The Seven-Glass Test. By Hugh H. Young, M. D. 
The Possibility of Avoiding Confusion by Bacillus smegmatls (Smegma 

bacillus) In the Diagnosis of Urinary and Genital Tuberculosis. An 

Experimental Study. By Hugh H. Young, M. D., and John W. 

Churchman, M. D. 
Urethral Diverticula In the Male. By Stephen H. Watts, M. D. 
An Unusual Case of Urethrorrhagla. By H. A. Fowler, M. D. 
Paraurethritis. By John W. Churchman, M. D. 
Use of Ointments in the Urethra In the Treatment of Chronic Urethritis. 

Hugh H. Young, M. D. 
Treatment of Stricture of the Urethra. By Hugh H. Young, M. D., and 

John T. Geraghty, M. D. 
The Treatment of Impermeable Stricture of the Urethra. By Hugh H. 

Young, M. D. 
The Treatment of Bacterluria by Internal Medication. By John W. 

Churchman, M. D. 
Use of the Cystoscope In the Diagnosis of Diseases of the Prostate. By 

Hugh H. Young, M. D. 
Chronic Prostatitis. An Analysis of 358 Cases. By Hugh H. Young, 

M. D., John T. Geraghty, M. D., and A. II. Stevens, M D. 
Modern Method for the Performance of Perineal Lithotomy. By Hugh H 

Young, M. D. 
Operative Treatment of Vesical Diverticula. By Hugh H. Yodno, M. D. 
Case of Double Renal Pelvis and Blfld Ureter. By Hugh H. Young, M D. 
Pyonephrosis Due to Bacillus Typhosus. By Hugh H. Young, M. D., and 

Louis C. Lehr, M. D. 
The Use of the X-ray In the Diagnosis of Renal and Ureteral Calculi. By 

F. H. Baetjeb, M. D. 
Nephritis and Ha?maturla. By H. A. Fowler, M. D. 
The Microscopic Structure of Urinary Calculi of Oxalate of Lime. By 

H. A. Fowler, M. D. 
Cystlnuria with Formation of Calculi. By H. A. Fowler, M. D. 
Post-Traumatic Atrophy of the Testicle. By John W. Chubchman, M. D. 
A Description of the Dispensary for Treatment of Genlto-Urlnary Surgical 

Cases at the Johns Hopkins Hospital. By Hugh H. Young, M. D. 



Volume XIV. 632 pages, with 97 figures. 

Studies in Genito-TJrinary Surgery. 

The Treatment of Prostatic Hypertrophy by Conservative Perineal Pros- 
tatectomy. An analysis of cases and results based on a detailed 
report of 145 cases. By Hugh H. Young, M. D. 

Recto-Urethral Fistula. Description of New Procedures for their Pre- 
vention and Cure. By nuGH H. Young, M. D. 

The Early Diagnosis and Radical Cure of Carcinoma of the Prostate, being 
a study of 40 cases and presentation of a radical operation which 
was carried out in four cases. By Hugh n. Young, M. D. 



Volume XV. 542 pages, with 87 illustrations. 

Twelve papers on pneumonia. By Drs. Chatard, Fabyan, Emerson, 
Marshall, McCrae, Steiner, Howard and Haines. 

A Study of Diarrhoea in Children. By J. H. Mason Knox, Jr., M. D., and 
Edwin H. Schorer, M. D. 

Skin Transplantation. By John Staioe Davis, M. D. 

Epidemic Cerebrospinal Meningitis ami Serum Therapy at the Johns Hopkins, 
Hospital. By Frank J. S laden, M. D. 



Volume XVI. 670 pages with 151 figures. (Now in press.) 

Studies In the Experimental Production of Tuberculosis In the Genito- 
urinary Organs. By George Walker, M. D. 

The Effect on Breeding of the Removal of the Prostate Gland or of the 
Vesicula? Semlnales, or of Both ; together with Observations on the 
Condition of the Testes after such Operations on White Rats. By 
George Walker, M. D. 

Scalping Accidents. By John Staige Davis, M. D. 

Obstruction of the Inferior Vena Cava with a Report of Eighteen Cases. 
By J. Hall Pleasants. M. D. 

Physiological and Pharmacological Studies on Cardiac Tonicity In Mam- 
mals. By Percival Douglas Cameron, M. D. 



The set of sixteen volumes will be sold, bound in cloth, for ninety 
dollars, net. Volume II will not be sold separately. Volumes I, HI, 
IV, V, VI, VII, VILT, X, XI, XII, XIII, XIV, XV, XVI will be sold for 
$5.00, net, bound in paper, and $5.50, net, bound in cloth. Volume IX 
will be sold for ten dollars, net. 



Orders should be addressed to The Johni Hopkini Press, Baltimort, Md. 



The Johns Hopkins Hospital Bulletins are issued monthly. They are printed by the LORD BALTIMORE PRESS, Baltimore. Subscriptions, S~00 
a year {foreign postage, 50 cents), may be addressed to the publishers, THE JOHNS HOPKIXS PRESS, BALTIMORE; single copies iciU be sent by 
mail for ticenty-flve cents each. Single copies may also be procured from the BALTIMORE NEWS CO., Baltimore. 



BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered u Second -CUm Milter at tb« Baltimore, MtrvUnd. PoatoOc*. 



Vol. XXV.-No. 278. 



BALTIMORE, APRIL. 1914. 



[Price. 25 Cents 



CONTENTS. 

PAOI 



A Clinical Method for Studying Titratable Alkalinity ol 
Blood and It- Application to Acidosis. 
By A\in:iw Watson Sellabds, M. D 1"1 

Borne Errors in thi Pulmonary Tuberculosis. 

By Lawrason Brown, M.D II! 

Observations on the Protective Enzymes of the Body (Abder- 
balden). 

By Erm st G. Gbbv, M. D. . 1 IT 

Principal Types of Micro-Organisms in Baltimore Milk. 

By I-. P. RnrppEx, M. 1) 1-- 



Bacteriological Findings in Baltimore II 

Bj Moans .lost pn, B. S 



Brief N^t.- on tin- Baltimo 

B\ M \K.miui hut/ 






The Johns Hopkins Hos] I 
Two i .i-- of Helmintbemesis (from the ""t Patient D* 
partmi ni ••: I he Johns Hopkins Hospital) [Di David I 

M M HT.] 



v CLINICAL METHOD TOR STUDYING TITRATABLE Al.kAI.IMn OF 
THE BLOOD AND ITS APPLICATION TO ACIDOSIS. 



In the investigation ol tl tremi lj varied properti 

functions of the bl 1 considerable attention has been i 

toward the chemical analysis of its fundamental 
methods have been developed for I 
and quantitative estimation, not ouh ol mi ommon 

constituents, but also for son* 

in relatively minute amounts. However, the deten 
I 
emical reai tic . 
tin. tlv different principles have been util 
• 
Is, howe\er. hav. 
ti..n which i- require! .linn-ally, bul I 
from an experimental stand|x>int. 
[nasmucl 

... used in I 
advisable. In its si 

Bpon the phvs 

hydroxy] ions which il 
hardly more alkalii • I 

■ i 
behavior toward indicati 



|:. \.:> ^ i:l>-. 

Assistat ' "'- Hoplrin* //• i 

of the M 

or bases. Although normal 
toward a few ind 

acid, tl 
From • 









102 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. '.'78 



that the hydroxy] ion content of the blood varies but slightly, 
even under extreme pathologic conditions. This relatively 
constant value of the hydroxy] ion concentration is maintained, 
in part at least, at the expense of the titratable alkalinity. 
Eowever, the detection id' changes in the titratable alkalinity 
is difficult and unsatisfactory. The purpose of the present 
paper is to consider a method for detecting such changes and 
its application to clinical conditions, especially to acidosis. 
There are a variety of conditions in which the possibility of 

an acidosis has I n suggested, more especially in certain of 

the nephropathies and anaemias, in eclampsia, and other com- 
plications of pregnancy and in several of the diseases of chil- 
dren, as in rickets and in the gastrointestinal disturbances." 
Instead of examining for certain specific acids in each of these 
conditions, it would lie much more satisfactory if a method of 
general application could be evolved which would not require 
the isolation and recognition of the acid in question. The 
determination of the tolerance to sodium bicarbonate affords 
such a method with the reservation, however, that the effect of 
renal lesions on the validity of this procedure has not been 
determined. Any methods for the detection of acidosis which 
depend upon the examination of the urine, may readily lie 
inapplicable in the presence of renal disease, and, unfortu- 
nately, many of the conditions in which acidosis is suspected 
are complicated by disturbances of renal function. 

Of the methods which have been proposed for determining 
the titratable alkalinity we need not consider the indirect pro- 
cedures, such as the determination of the carbon dioxide con- 
tent or the changes in the spectrum upon the addition of acid. 
Direct titration with some of the ordinary indicators has given 
the most suggestive results. As a type of this method we may 
consider the titration of blood serum against a standard acid 
with one of the azo dyes as an indicator. This group of indi- 
cators is extremely sensitive to alkalies, and apparently the 
underlying object in the use of them is to measure the full 
value of the titratable alkalinity. One of the principal objec- 
tions to the procedure is that the end-point is extremely un- 
satisfactory. The protein of the serum is largely responsible 
for the interference with the end-point, but the removal of the 
protein would remove one of the important sources of titratable 
alkalinity. Furthermore, the maximal differences that are 
observed between normal and pathologic sera are without any 
striking significance. This necessitates the measurement, 
under unfavorable conditions, of small differences in the quan- 
tity of acid required for neutralization. 

To obviate the difficulties of the titration methods it would 
seem desirable to develop a purely qualitative method in which 
all normal sera would react distinctly alkaline, whereas the 
pathologii sera would be distinctly acid to a given indicator. 
In the attempt to obtain such a result, the following depart- 
ures from the usual titration methods were considered : 

1. The selection of an indicator to which tin- scrum of all 
normal individuals is acid, depending upon the conversion of 
the acid carbonates of the blood to normal carbonates in order 



= See Ewing: Arch. Int. Med., 190S, II, 330. 



to obtain an alkaline reaction in normal individuals. The 
variation in the reaction of the blood toward different indica- 
tors is due, principally, to the sodium bicarbonate which it con- 
tains. This salt reacts as an acid to certain indicators, such as 
phenolphthalein, and as a base to others, notably methyl 
orange. However, on boiling, carbon dioxide is driven oil' and 
the normal carbonate is formed. The latter hydrolyzes in 
water and reacts as a base to all indicators. Thus, the content 
of sodium bicarbonate in normal blood is sufficient to explain 
why the serum reacts as an acid to phenolphthalein, but, after 
diluting with water and boiling, it will react sharply alkaline. 

2. The removal of the interfering protein from the serum 
with the purpose of determining definite changes in the titrat- 
able alkalinity rather than the measurement of the total titrat- 
able alkalinity. 

3. The substitution of another solvent for water to reduce 
the amount of hydrolysis ami ionization. Before sodium car- 
bonate can react with phenolphthalein, it must ionize and 
hydrolyze. These changes take place very readily in water, 
but by substituting some other solvent it might be possible to 
reduce these changes to such an extent that a trace of carbon- 
ate would give no reaction, whereas the amounts normally 
present in the serum would give a pronounced reaction. 

From these considerations it is conceivable that conditions 
might be obtained in which all normal blood would be distinctly 
alkaline, whereas pathologic blood in which a definite diminu- 
tion of sodium bicarbonate had occurred, might be distinctly 
acid under the same conditions. The basis of such a test would 
be essentially qualitative rather than quantitative. The feasi- 
bility of such a procedure has been tested in the following 
ways, namely : 

1. Experiments with serum in vitro. 

2. Experimental production of acidosis in lower animals. 

3. Investigation of clinical conditions. 

Selection and Preparation of an Indicator. — There have 
recently come into use a large number of indicators whose end- 
points change at varying concentrations of hydrogen and 
hydroxyl ions. Phenolphthalein is one of the most convenient 
of those which change to an acid reaction at a comparatively 
low concentration of hydrogen ions. The ordinary dun id 
preparation was employed for all qualitative work, using a 
\Jo solution in absolute alcohol. Later, for quantitative 
measurements, sufficient alkali was added to give a faint tinge 
of color to a large bulk of solution with the expectation that 
the colorless monosodium salt would change more readil) to 
the red disodium salt than the acid itself. As a routine. 3 
drops of either solution were employed ; this indicator is such 
an extremely weak acid that accurate measurement proved to 
he unnecessary. 

Removal of Protein ami Sell ction of Solvent. — The removal 
of protein and the substitution of another solvent for water 
was combined in one step by precipitating the serum with 
alcohol. The removal of the protein avoids any interference 
with the end-point and at the same time removes a definite 
fraction of alkali-yielding substances which are probably fairly 
persistent, thus affording the possibility of obtaining a more 



Aran., 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






sensitive test than could be secured vrith the, aqueous dilutions 
(if th«' whole serum. The removal of ah traces of protein was 
not attempted, hut practically complete removal was o 
by precipitation « ith absolute ethyl alcohol. 

Experiments in Vitro. The purpose of the tests in vitro 
was to determine w hether the addition of minimal quant 
mill to serum could be detected by the use of phenolphl 
under conditions in which the titration- by the usual meth- 
ods would not reveal the addition of the acid. To I cc. quan- 
normal human scrum increasing quantities of stand- 
anl sulphuric an.] wen added. With the lower quant 
acid, sufficient water was added to make a final volume • 
of the mixture of acid ami serum. The following observations 
were made on the-,, specimens: 

1. Reaction of the residue afti r incineration in platinum. 

-'. The reaction alter diluting with water and boiling. 

■ i. Precipitati f the protein with alcohol and the i 

of the alcoholic filtrate. 

For the incineration in platinum the specimens wen 
at dull red heat. The residue was dissolved in water and the 
reaction tested to phenolphthalein. For the aqueous tests the 
mixture of serum and acid was diluted with about live part- .•! 
water and, after boiling freely for a minute, the reaction to 

phenolphthalein wa- tested. For the tests after re val of the 

proteins, 2 cc quantities of the mixture of acid an. I 
were added, drop by drop, to 25 part- •>! absolute ethyl alcohol. 
The mixture was then shaken thoroughly and filtered. The 
filtrate, after the addition of phenolphthalein. and with 
washing of the precipitate, was evaporated to dryness 
water hath. 

Tie examination of a few spe< imens was sufficient to 
mine the characteristics ■>! the reactions which » 
uinler the-.- conditions. The reactions with normal -era were 
essentially -nuilar to the behavior of -odium hydroxii ■ 

phenolphthalein under the sai onditions. The a 1 

lilt rati' upon eon. entrain. i a steam hath, rapidly too 

deep red color. This color wa- dependent upon the t. ■ 
lure of the solution, for upon rapidly cool it 
color faded markedly or disappeared completely. Tin- 
took place inn Mat there wa- tun. for tin 

arbon dk» ir, ami wa- due ap] 

diminished dissoi iation with tin- lowering i 
Upon evaporatioi I ue retain* d I 

for many hour-. As a t _ht hours In at 

steam hath -• 
quantity of a. el w.i ■ 
rapid h ■ 
• 

but tin- addil 
Lastly, tie.-- 

i the pvaporut ion or upon the aildit 
residue. In • 

dilution of the serum would _ 
nolphthalein. 

Pure sodium hydroxi 
em which corresponded to t>. 



when ail.!.-.: I ; U | M> „ 

evaporation to tli 

■ ■!' phenol])l I 
hydros 
four hour- on a steam Lath. On hi 

ill two 

or three hours. 
Tin- results of tin 

ompared with the usual titi 
serum. <>f tin- various 
with .' 

feasible for clinical purposes, and in tl 
gators it ha- given rathi n raits. M 

variations ha in the up]. I 

eeilure. Of 1 . dimethylan 

reagent i i- recommended bj St 

tin- technique devised l>\ Wright ' for the quantitative 
titration of serum « ith • < 

quantity of serum which is required. Inasmuch 
quantities of serum were avilable in thi 

titration- wi l it in tl i. 

routine applies to all the results w I 
which are recorded in this paper. 

serum was diluted with water until th lor of tl 

dlv eliminated : usually about loo ■ 

quired : '■'• to I • t r- ■ 

ilcohol were used. The addition of \ 10 
a. nl was continued until the distim t yellow of t! • 
agent, not only had deep 
definite pink shad. 

this change that tie - 
dilution than \ to. Indeed, 

taincd, hut I 
of acid effected only a very gradual 

all -ha 

and fi 
Prom 

« ith a? 
under 

I 

i 






104 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 27$ 



mals in order that it might be tested under conditions in which 
a simple definite acidosis of known etiology could be estab- 
lished. For this purpose acidosis was produced by the admin- 
istration of mineral acid. Among the various possibilities of 
this experimental acidosis the two extreme effects that might 
be produced are: (1) the carbonates in the blood may diminish 
under the administration of acid, or (2) such a condition may 

TABLE I. 

Addition of Acid to Sekum in Vitro. 

first specimen. 







Behavior toward phenolphthalein. 




CC N/25 acid 


After 


removal of protein. 


1-10 dilution 
of whole se- 
rum in water. 






In alcoholic 
solution. 


Residue after 
evaporation. 


In aqueous 
solution. 


residue 
in water. 


None 


Red 


Red 7hrs. 


Red 


Red 


Red 


0.05 


Red 


Red 1 hr. 




Red 




0.10 


Red 


Red 15 min. 


Red 


Red 




0.15 


Red 


Red 15 min. 


Red 


Red 




0.20 


Red 


Red 15 min. 


Red 


Red 




0.25 


No color 


Red 5 min. 


Red 


Pink 


Red 


0.5 


No color 


No color 


No color 


Trace 


Red 



SECOND SPECIMEN. 



None 


Red 


Red 6 hrs. 


Red 


Red 




0.25 


Red 


Red 15 min. 


Red 


Pink 




0.4 


Red 


Red 5 min. 


Red 


Red 




0.45 


Red 


No color 


Red 


Pink 




0.5 


No color 


No color 


Pink 


Pink 




0.6 


No color 


No color 


No color 


No color 


Red 


0.7 


No color 


No color 


No color 


No color 


Red 


0.75 


No color 


No color 


No color 


No color 


Red 


1.0 


No color 


No color 


No color 


No color 


Red 


1.5 








No color 


Red 







THIRD SPECIMEN. 






0.25 


Red 


Red 


Red 


Red 




0.5 


No color 


No color 


No color 


Pink 




0.75 


No color 


No color 


No color 


No color 





FOURTH SPECIMEN. 



0.25 


Red 


Red 


Red 


Red 




0.5 


No color 


No color 


Trace 


Red 




0.75 


No color 


No color 


No color 


No color 





be incompatible with life, a fatal effect resulting before the 
carbonates arc appreciably reduced. 

in case the carbonates do not diminish in the blood under 
the administration of acid, the question would arise as to the 
source of supply which could furnish sufficient carbonates or 
other alkali-yielding substances to meet the relatively large 
amounts of acid which it is possible to introduce into thi 
It is readily conceivable that the blood might draw on the 
other tissues of the body for carbonates ami death might result 



from the exhaustion of these tissues before the blood itself was 
markedly depleted. On the other hand, in case a definite re- 
duction in the bicarbonate content of the blood takes place, 
there are a number of compensatory mechanisms by which the 
respiratory processes may be continued. 

Some experiments were undertaken to determine whether, 
upon the introduction of acid into the body, sufficient changB 
takes place in the blood serum to give it a neutral or acid 
reaction to phenolphthalein. Hydrochloric acid was admin- 
istered through a stomach tube to rabbits after the manner 
of the original experiments of Walther. 5 A 10% solution in 
water of absolute hydrochloric acid was kept as a stock solu- 
tion and this was diluted to i% before use. Walther esti- 
mated that 0.9 gm. of hydrochloric acid per kilo per day was 
fatal for rabbits (approximately 25 cc. of a normal solution). 
For the production of an acute acidosis, I have used quantities 
of 0.5 em. per day. In some experiments this was divided into 
two doses, one of which was given in the morning and the 
other in the afternoon. 

For the examination of the serum with phenolphthalein the 
following routine was used throughout the remainder of the 
experiments described in this paper. The description is given 
in some detail, inasmuch as there are a number of minor fac- 
tors which might definitely affect the results. 

The serum was usually examined at the time of collection, 
especially in the important cases. In some instances it was 
stored in the refrigerator, but the examinations were always 
made within twenty-four hours after the time of collection. 
Absolute alcohol was chosen in preference to 95%, partly on 
account of its freedom from organic acids and also to reduce 
the amount of water in the reaction mixture to a minimum. 
In order to test its neutrality 0.1 cc. of N/200 sodium hydrox- 
ide was added to 25 cc. of alcohol, using 2 to 3 drops of 
phenolphthalein as indicator. The mixture was evaporated to 
dryness and the residue, on taking up in a few drops of water, 
gave a distinct color. For the incinerated specimens, a drop of 
serum was ashed at dull red heat in a platinum crucible. The 
residue was taken up in water and a few drops of phenolphthal- 
ein were added. The preparations with water were made 
in 1-10 dilution and boiled in a test tube over the free flame 
for one minute or more. In the case of normal sera a pink 
color appeared immediately upon the addition of phenolphthal- 
ein. In other cases it frequently happened that preparations 
which were colorless at first would develop a trace of color on 
standing for five to ten minutes. Such a behavior was some- 
what unexpected, since phenolphthalein in aqueous solutions 
fades mi cooling, owing to the absorption of carbon dioxide 
from the air. However, the preparations of normal serum in 
water also failed after several hours at room temperature. 

High dilutions of normal sera in water, even 1 to 1000, 
usually gave a distinct color with phenolphthalein after boil- 
ing. As a rule, however, 1 part of serum was added to 10 parts 
of water. At this dilution, comparatively little precipitation 
of protein takes place on account of the alkali which is presi nt 
With a slight excess of acid, the solution remained compara^ 

•Walther: Arch. i. exper. Path. u. Pharmakol., 1S77, VII, 148. 



April, 191 I 



JOHNS HOPKD ISPITAL BULL] 



n»: 



lively clear on heating, but after approximate neutral 
by -mall quantities of acid, abundant precipitat 
occurred on heating on account of the la< k of alkali for t } ■<- 
formation of the soluble alkali albuminate. This pn 
occasionally interfered with the detection of faint tri 
color, since a practical]) solution would sometimes 

become faintly j >ink ii] »»>n high dilution; the result* 
hardly be misleading, however, as the interference 
and the source of this interference depends upon the • 
of alkali. 

For the preparations with alcohol, 1 cc. of serum «a> added, 
drop by drop, to •-'•"> cc. of absolute ethyl alcohol. The mixture 
was then shaken thoroughly and filtered into an evaporating 
dish. Perfectly dry apparatus, <>r apparatus washed with abso- 
lute alcohol, was used throughout in order to exclude all water 

from the mixtun except that which is contained in the l>l I 

Berum. Without washing the precipitate, 3 or I drop- of phe- 
nolphthalein were added to the filtrate and evaporation to dry- 
ness was carried out on a steam hath (not over 100 C). 
Only a minimum amount of steam was used during the 
evaporation in order to avoid, as far as possible, the • i 
absorption of water vapor by the alcohol. The method of 
recording the results requires careful explanation. In the 
preparation of the experimental mixtures, many gradations of 
titratahle alkalinity were produced. The variations in the 
behavior of phenolphthalein with bases in aqueous and in 
alcoholic solution fortunately offers the possibility of di I 
nine of the gradations. The alcoholic filtrate at the moment 
of goinj: to dryness approaches an aqueous solution on account 
of the water added with the serum. In many i .:-■ 

solution remained colorless till this point was n 
In these cases the residue, however, instead of retaining its red 
color on the water hath for several hour-, usual!] 
within five to fifteen minutes. 

In a series of examinations, where a great variety of tran- 
sitional ur, it is obvious that there will be 
crable variation in the minor detail- of the results that are 
obtained. However, it has not seemed necessar) oi bi 
to attempt to describe all of these details; onlj the mi 
nifieant changes have been noted. For many rea* 
desirable to attempt to record shades of color, rl 
is obviously necessary to distinguish 
personal equation does not come into consideral 
example, in chow i ases where a pronounced red or .. 

cernibli I nk is obtained. In c piling I 

tahular form, the term " no "lor" is usei 

to the -hade- of red and pink. In ma 

dry residue was tinged with yellow, presumably oi 

the lipoids of the serum. The 

phenolphthalein m< t the 

treloracid. Some of the most pron 

with N 200 sodium hyi 

distinct diffi r< n< ■ between the an ■ 

for the test spei im< ns at 

attempt was made to measure 

present. It i- not pss i I 



results in • 

mens at neutral or faintly a< id to 

phthali 

i \iu.i: ii. 

I Ml HI Ml - ! • 

11 UIH'T I 









collfrli \ 

- 



. Pilli«lrtB 

... 



In.lcobolp. ........ •rpppilpp 

• .tr, 



No coloi 



Pi 

No color 









1 






o.s 
















- 


No color 












.'• hr- 


pp. ns 




So color 







1 


Nonr 














CM 


6b». 












o.ts 














O.tt 


Ohr. 












o.ts 










Ilrl 







0.1b 




O.Si 


Bhri. 

























' 






' 


















No color 



















































•. 

















■ 



106 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| No. 278 



and alcoholic solution, and in the presence or absence of pro- 
tein, offers the possibility of the ready detection of several 
different grades in the diminution of titratable alkalinity. 
These reactions with phenolphthalein may be listed tentatively 
as follows : 

1. Persistence of red color in either alcoholic solution or dry 
residue for several hours. 

2. Absence of color in alcoholic solution or transient appear- 
ance of color in the residue, but with good coloration in aqueous 
solution. 

3. Total absence of color in alcoholic solution, in the residue 
on evaporation or after the addition of water, but with distinct 
color in the aqueous solution before removal of protein. 

4. Total absence of color in all stages including the aqueous 
dilution without the removal of protein. 

These stages would, of course, merge gradually into one 
another. 

For convenience the sharper changes may be outlined as 
follows : 

BEHAVIOR TOWARD PHENOLPHTHALEIN. 



After removal of protein. 


Without removal of 
protein. 


In alcoholic 
solution. 


Residue after 
evaporation. 


In aqueous 
solution. 


1-10 dilution of whole 
serum in water. 


Alkaline 




Alkaline 




Alkaline 


Alkaline 


Alkaline 




* 




Alkaline 


Alkaline 


Neutral 




Neutral 




Alkaline 


Alkaline 


Neutral 




Neutral 




Neutral 


Alkaline 


Neutral 




Neutral 




Neutral 


Neutral 



•Color discharged on evaporating to dryness and heating for a few minutes. 

From the results which are recorded in Table II, it is evi- 
dent that a comparatively early grade of acidosis can be 
detected merely by the qualitative changes in the reaction of 
the alcoholic fraction of the serum toward phenolphthalein. 
These changes took place before the development of any clini- 
cal symptoms. Nevertheless, it was necessary to use rather 
large amounts of acid before sufficient change occurred in the 
blood to be detected by this method. Thus, Walther found that 
the introduction of 0.9 gm. of hydrochloric acid per kilo of 
body weight per day was fatal for rabbits. In this series it 
was necessary to introduce at least 0.5 gm. per kilo per day to 
obtain a definite effect, while in one case twice this quantity 
was necessary. In the advanced stages of this experimental 
acidosis the increasing frequency, and especially the increased 
depth of respiration served to compensate in part for the loss 
of alkali. 

Walther observed that in experimental acidosis, death took 
place while the blood still remained slightly alkaline to litmus. 
The same holds true for all of the animals in this series. As 
regards phenolphthalein, however, the functions of the body 
may continue, for a limited time, although the serum after 
heating reacts neutral or acid to this indicator. The acid 
reaction to phenolphthalein of the alcoholic filtrate from the 
serum does not mean that the bicarbonates are absent from the 
serum itself, but rather that the fraction has disappeared 



which is removed in the alcoholic filtrate. In some instances 
the heated aqueous dilution of the serum remained colorless 
with phenolphthalein. Such sera, however, are not wholly free 
from alkali-yielding substances : upon incineration of these 
specimens in platinum crucibles at low red heat, the residue 
when taken up in water reacted strongly alkaline to phenol- 
phthalein. although the aqueous dilutions upon boiling were 
neutral or acid in reaction. Death occurred m all cases while 
the serum was still strongly alkaline to phenolphthalein after 
incineration. 

The essential feature in this series of animals consists in the 
demonstration of definite changes in the reaction of the blood 
as a result of the effect of acid in vivo, as well as in vitro. 
Much larger quantities, however, were required to produce a 
corresponding effect in the animal body than in vitro. Thus, 
1 to 2 {■{■. of X/100 acid per 1 cc. of blood serum in vitro pro- 
duced an effect corresponding to the action in vivo of the 
equivalent of 1400 to 3000 cc. of N/100 acid per kilo of body 
weight. Of course, it is not possible that the acid which was 
introduced was distributed equally through the various tissues 
of the body and it is impossible to say just what proportion 
acted directly on the blood itself. It is evident, however, that 
relatively enormous quantities must be introduced into the 
body to produce the same effect upon the blood as are produced 
by minimal quantities acting in vitro. 

In considering the clinical application of this method, it is 
hardly necessary to note that the experimental results were 
obtained under conditions which differ markedly from those 
arising spontaneously in man. In the first place, the intro- 
duction of a mineral acid by way of the alimentary tract is 
rather different from the formation of organic acids in the tis- 
sues and from defective elimination of acid salts by the kid- 
neys. Moreover, it is well known that the herbivora react in a 
different manner from the carnivora toward the mineral acids, 
while it is supposed that the omnivora constitute a somewhat 
intermediate group. 

In order to test the applicability of this method to clinical 
conditions, examinations were made in normal individuals, 
in cases of diabetic acidosis and unknown conditions where 
acidosis was suspected. Of the unknown conditions, attention 
was directed primarily toward the study of the nephropathies. 
In the series of diabetics some supplementary tests were car- 
ried out in order to facilitate the interpretation of the results 
obtained with phenolphthalein. The complete list is as fol- 
lows : 

I. Examination of the urine: 

1. Determination of the ammonia coefficient. 

2. Estimation of the acetone and /3-oxybutvric acid, 

by Shaffer's method. 8 

3. Titration of the acidity by Folin's method.' 
II. Examination of blood serum : 

1. Titration with N/10 acid against Tbpfer's re- 

agent. 

2. Behavior toward phenolphthalein. 



" Shaffer: J. Biol. Chem., 1908, V. 211. 
; Folin: Am. J. Physiol., 1903, IX, 2G5. 



Aim; 1 1.. 1914.1 



JOHNS HOPKINS HOSPITAL BULLETIN. 



10; 



III. Determination of tin- effecl of the 
venous injection of sodium bicarbonate upon th< 
tlir urine, i. »■.. the tolerance to bicarbonate. The • i 
nation was < arried oul according to a principle which i- • 
analogous to the work with sug stiniating the 

amount which must he introduced into the body 

■: tin' urine. lender certain conditions, whei 
■ •r carbonates are introduced into the body, 
able quantity may be stored In-fore any excretion tak. • 

• I clearly that the cause and the manner of this 
may vary with different substances, and also for the 
sanii- substances under different conditions. Throughout this 
paper the term "tolerance" is used in connection with bicar- 
bonates without any reference to the explanatory factors which 
an- involved. In the discussion of ' tremely 

convenient to have a general term which may be Pi 
unknown conditions without regard to the underlying 
nation. For example, the expression, "toleranci 
is used freely in the literature in a general sense, for it do$s 
not explain in detail the fate of sugar which i- retained in the 
body. However, both the -mrars ami bicarbonates havi 
important features in common. Tim-. Uith of them mi 
qucntly be stored in the body essentially for use as such, i. e., 

• •hydrate and alkali. One of the striking diffi 

• these two substam • - i onsists in the fact that relatively 
large amounts oi sugar can be added to the diel 

person before any excretion take- place, whereas the addition 
of a little bicarbonate results in its prompt excretion in the 
urine. Thus, the differences between the two substai 
in ]iart. only differ e. It would Beem to the author 

impropriate to retain the term "tolerance" for 
genera] sense with either alkalies or sugars. In case th< 
nation of the unknown • a quently forthcoming, then 

it would he helpful, if pi term which would 

1h' explanatory for the case under consideration. Obviously, 
such a • Many difficult 

in the cm-.- of the >ui:ar-. several fa. i^r- may tx 
the explanation of e ami. mon 

that the relative importance of the-, factors may vai 
time to time ii a given individual. Intheci 
certainly no conclusive •■• idem • has beet offen •! which would 
enable one 1 ' • itplanation i 

Consequently, it ha >med 

•• toleram e " in a general sei 

term until the ex plana! 
Palmer and Henderson' recent 

ii of bicarb idied by di • 

centration of the urine in hydrogen and 

the U- 

riduals who require more than l gm. of • 

uormal. Practii ally identical 
pimply by the use of litn i 
sodium bicarbonate was determined which if req 



mixed • 

found that 5 
found i 

■ Ha- perm it tc .1. and tl 

each patunt. 
In thi 

sted tec litmus paper. In thof i Ii the 

was not dist inctly acid or all 
boiled thoroughly in ordi 
normal carbonate. The mildi i 

■ 
given by mouth through a glass ml* 
r the intravi 
ition in wati 
tec i. oil CC. at [TiT.r-.-cii— of about 
cautioi 

lions during -ten I le bladder • 

diately before thi 
the reaction of the urine was I 
the bicarboi 

l-'ccr the series of ncphropatl 

Hows: 
I Examinatioi i : 

1. I '■ • 

2. 'I 

method. 
Ill 

1. Titral with 

2. Bcha> i rum toward : 
[II. Detei 

omitted inasmui l> a 
of carbohydi 

III the 
under I 

In t! 

unknot 

■ 

other I 

of tile ' 

thirl;. 



Palmer and Henderson: Arch. Int , XII, 15 

Sellards: Johns Hopkins Hosp Hull. 1912, XXIII. 






108 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 278 



appeal till after heating for six or eight hours, and in all 
cases there was a distinct pink visible for at least one hour. 
The change in color is so gradual and so slow in normal cases 
that it would be impracticable to set any exact time limits for 
its disappearance. 

It would seem evident from those data that in all normal 
individuals the unheated alcoholic filtrate of the serum is neu- 
tral, or slightly acid, to phenolphthalein, and becomes alkaline 
upon heating. The individuals on which these tests were made 
included all ordinary ages, except the first decade of life. 
However, the subsequent tests on pathologic cases did not in- 
clude any children. .It seems most improbable that healthy 
children would show any marked variation from the adult in 
such fundamental characteristics as the alkalinity of the blood. 

The first series of pathologic conditions which were tested 
was a group of seven diabetic patients, in four of whom (A, B, 
C and D) acidosis was present, while in three others (E, F and 
(i) it was absent. Of the acidosis cases, two (C and D) were 
in an advanced stage with all the typical signs. The other two 
were in an earlier stage without clinical signs and without any 
definite increase in the excretion of acetone and related bodies, 
or of ammonia. The diagnosis of acidosis in these two cases 
was based on a well-marked increase in the tolerance to sodium 
bicarbonate (on intravenous injection). The behavior of their 
titratable alkalinity is shown in Table III. 

TABLE III. 
Cases of Diabetes. 



Urine. 




!S 






Blood serum. 






















■e. 


a 


a 
1 


!2^ 


If 

to U 




Behavior toward phenolphthalein. 




After removal of protein. 


1-10 dilu- 




< 


X 


< 


11 
c 3 


H 


3 






tion of 

whole 

serum in 

water. 


O 


In alcoholic 
solution. 


Residue 
after evap- 
oration. 


In aqueous 
solution. 


A 


5.5 


5.6 


0.010 


0.04 


40 


0.8 


No color 


No color 


Pink 


Pink 


B 


6.3 


6.1 


0.011 


0.10 


30 


0.9 


No color 


No color 


Red 


Red 


C 


4.5 


11.7 


2.20 


3.3 


50+ 


0.7 


No color 


No color 


Faint pink 


Faint pink 


D 


4.0 


16.4 


3.20 


10.5 


80+ 


0.8 


No color 


No color 


Faint pink 


Faint pink 


i: 


3.5 


6.0 


0.100 


0.26 


5 


0.8 


Red 


Red 




Red 


r 


4.0 


5.7 


0.135 


0.38 


10 


0.9 


Red 


Red 




Red 


: 


3.0 


3.4 


0.412 


0.21 


10 


0.8 


Red 


Red 




Red 



In Table III the behavior of the serum toward phenol- 
phthalein parallels the tolerance to sodium bicarbonate and 
bears no constant relation to any of the other factors recorded 
in the table. The parallelism between the behavior of the 
serum to phenolphthalein and the increase in the tolerance to 
bicarbonate in two patients (A and B) justifies the diagnosis 
of acidosis in these cases, if one considers acidosis to be an 
impoverishment of the body in bases. Moreover, the total 
daily output of ammonia averaged 0.4 to 0.5 gm. per day in 
each ease and did not exceed the normal range of 0.4 to 0.6 gm. 
daily. We have, therefore, the existence of a definite acidosis 
without any appreciable increase in the relative or absolute 
excretion of ammonia. The behavior of the titratable alka- 



linity was investigated in a group of nephropathies, selecting 
primarily those cases which show an increase in tolerance to 
sodium bicarbonate. The special object in view was to deter- 
mine if the bicarbonate in these cases is retained on account of 
an acidosis or if it accumulates in the body on account of the 
inability of the kidney to excrete it. 

There are a number of features which make it probable that 
this increased tolerance is to be explained by a deficit of bi- 
carbonate in the body. Nevertheless, it is equally clear that 
no crucial evidence from any standpoint has been obtained for 
the determination of this question. One suggestive point is 

TABLE IV. 
Cases of Chronic Renal Disease. 

in L'R.EMIA. 



3 






Blood serum. 




S3." a 

< 


Behavior toward phenolphthalein. 


After i 


emoval of protein. 


1-10 dilu- 
tion of 
whole 

serum in 
water. 


In alcoholic 
solution. 


Residue 
after evap- 
oration. 


In aqueous 
solution. 


160+ 


0.6 


No color 


No color 


No color 


No color 


40+ 


0.9 


No color 


No color 


Pink 


Red 


30 + 


0.6 


No color 


No color 


No color 


Pink 


70 


0.8 


No color 


No color 


No color 


No color 


30 


0.8 


Pink 


0) 


Red 


Red 


30 


0.7 


No color 


No color 


Pink 


Pink 


40 


0.9 


Pink 


0) 


Red 


Red 



EXTREME CASES. 



H 


3.0 


3.7 


70 . 


0.6 


No color 


No color 


Pink 


Red 


1 


3.1 


4.2 


80 = 


0.8 


No color 


No color 


No color 


Red 


J 


2.5 


2.6 


70 2 


1.0 


No color 


No color 


No color 


Faint pink 


K 


2.0 


8.7 


80 


0.8 


No color 


No color 


Red 


Red 


L 


2.0 


11.6 


40 


7 


No color 


No color 


Red 


Red 



Ol TSPOKKN CASKS. 



4.0 


7.1 


30 2 


0.0 


Red 


0) 


Red 


1.5 


11.8 


30 = 


1.0 


Red 


P) 


Red 


2.7 


3.0 


20 = 


1.0 


Red 


(') 


Red 


2.4 


2.2 


10 = 


0.8 


Red 


Red 




1.8 


4.0 


10 = 


1.3 


Red 


Red 





Red 
Red 
Red 
Red 
Red 



1 Colorless after five minutes. -' By ingestion. 

that the urine of a nephritic which has been rendered alkaline 
by large doses of bicarbonate is, after the return of the acid 
reaction, rendered alkaline again by much smaller doses of 
bicarbonate than were necessary originally. It lias been sug- 
gested that this fact constitutes an almost crucial test, proving 
the existence of acidosis." It is obvious, however, that these 
results are open to another explanation. Thus, in the case of 
substances which are known to be retained in the body on 
account of renal lesions, it is characteristic that they are not 



'- Palmer and Henderson: loc. cit. 



April, L914. 



JOHN'S BOPKIXS [osPIT.W. Ill i.I K'l'lN. 



LOg 



retained quantitatively when large amounts are intro 

imt after a certain maximum ha- been reached excretion eom- 

- in the .a-.- ••' practically all Bubstai 
quently. when an acid reaction of the urine returns after the 
alkalinity following a massive injection <>! bicarbonat 
obvious that the effect of an additional small dose of bicar- 
bonate cannot form a crucial test for distinguishing 
acidosis and retention. Table IV shows the behavior of !■ 
renal disease. <<( tin' chronic diffuse type tested during 

a stage of L r 1 cardiac compensation. 

In analyzing Table IV. the most significant feature is the 
general parallelism between the reaction of the blood to 
phenolphthalein ami the tolerance to sodium bicarbonate. 
The following outline, compiled from Table IV. illustrates 
this feature: 

BKHAVlni: OF SERUM TOWARD PHENOLPHTHALEIN. 





After removal of pr<"t i-in. 




lotion of 
whole 
si rum in water. 


Range of toler- 
ance to 

donate 


No. of 
casts 
tested. 


In alcoholic 
solution. 


B 
evaporation. 


solution. 


■2 


Alkaline 


Alkaline 


Alkaline 


Alkaline 




10— 


5 


Alkaline 


• 


Alkaline 


Alkaline 




8) to 40 


3 


Neutral 


Neutral 


Alkaline 


Alkaline 






o 


Neutral 


Neutral 


Neutral 


Alkaline 








Neutral 


Neutral 




Neutral 







•Red color discharged in a few minutes by heat on water bath. 

In this outline two cases (B and ('. Table I V i an 
omitted, Bince the bicarbonate was discontinued in those 
patients presumably long befon their tolerance was reached. 
Duly the nephritic ease- are included, as it is not unlikelj that 
the relation between the react ion of the blood and the tolerance 
to sodium bicarbonate may vary according to the etiology "I 
the acidosis. This possibility is suggested by the tw 

diabetic acidosis (Table III, C and D), which did not 

show extreme changes in the hi 1. although the test 

made during the day on which these patients died, i 
Table IV. i- omitted because of the hepatic syphilis, sii 
tain feature- of hepatii gest the possibilit; 

acidosis. In this ilightlj higl 

one might expect from the blood chai 

Tin- gradatioi - of changes in the blood a- given in I 
line can only i..- i lassified in a very general way. It 
that, with accurate quantitative measuri men! 
changes, their parallelism to the alkali toll i 
more definite. This relationship between tin- titrate 
Unity and the increased tolerance to bases indii it 
latter i- due. m part at least, to a defii it of the bodj 
It i- rather more difficult to decide whether tin- ■ 
sole factor involved in the production of tin- ini ream 
aiue. It i- quite conceivable that in addition to I 
there may 1»' an inability of the injur 
bicarbonate. Tin- question i an ■•• 

changes that take place in the 1.1 1 upon tin- inti 

bicarbonate and their relation to I 



in the 

Unity of tin would 

expect that the further introduction of would 

change the ur 

there i- Buppn ssion of ! 

i high tolen 
sodium bicarbonate were studied to determine whet 

i hanges in the hi I ami in the ur- lultane- 

ou-ly. The results are given in Table V. In • 

which the bicarbonate was ad istered by mouth, 

given in In gm. quantities tin. 
of each specimen of urine to litmus wae 
specimens wi n h morning befoi 

bicarbonate. In cases where intravenous a. Inn: 
employed, the blood sample was taken before esu h inji I 

1 M-.l.l \ 
Kn H l i.i im Aiimimmiuii.is 01 Kit \iui'«\ \T( BJOS mi 

TlTHWWIM Al.KlllMII n» till BLO 
\I>MIMSTI!A1|..\ in HOI Til 



Sodium 
bonati 



Interval 
aince last 
administrs 
tionof hi 
■ trl .<»■ 



Of serum toward (ihenolphthaleln. 






■ I SI" 

10 gm 

SO gm. 
«0gm. 

30 gm. 

M tm 
10 gm. 



15 hrs. 

10 lir.. 
4 hrs. 

18 hrs. 
3 hrs. 

18 bra, 
I bra. 



No color 
Trace color 












wnwir 



























Plat 









Reaction ol 






iHimi'. 










80 gm. 




Sogm. 




U gm 






tlhrs. 


tigm. 




*ngm 









' 





















110 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| No. 378 



reason of renal retention. Indeed, it would seem very striking 
if, in cases where there is partial suppression of the ordinary 
substances, such as dyes, salts, sugars, and water, that the 
bicarbonate alone should escape partial' suppression. A quan- 
tity such as 5 gm., however, would be without any clinical 
significance in comparison with the total amounts which were 
used. 

Some evidence has been collected in regard to the rapidity 
with which the increase in tolerance to bases returns after the 
administration of bicarbonate. The period required for the 
return of the increase in tolerance is so long that only a few 
cases were available for investigation. 

TABLE VI. 
Duration of the Effect of the Administration of Bicarbonate. 





First test. 


Interval 

between 

tests. 


Second test. 






Behavior of blood serum to 
phenolphthalein. 


Tolerance 




Tolerance 
to bicarbo- 
nate 

(grams). 




After removal of protein. 


bonate 
(grams). 




In alcoholic 
solution. 


Residue 
after evap- 
oration. 


In aqueous 
solution. 




H 


70 
80 
70 
30 
20 


2 weeks 
2 weeks 

2 weeks 
4 days 

3 clays 


Red 

No color 
Pink 
Red 
Red 


Red 

No color 

(') 
Red 
Red 


Red 
Red 
Red 
Red 
Red 


10 

40 
20 
10— 
10— 











1 Colorless in five minutes. 

These data indicate that the effect of the bicarbonate lasts 
for a relatively long period as compared with diabetic acidosis. 
Moreover, in the cases in uraemia in which massive injections 
were used, there was no evidence of rapid neutralization of the 
injected bicarbonate. These considerations are of special 
interest from the standpoint of therapy. 

Conditions Other than Nephropathies. — Some additional ex- 
aminations were made in conditions which are of interest in 
connection with nephritis and uraemia. One of the more 
important features is the study of the various combinations of 
cardiac and renal disease. Especial attention has been given 
to two groups of cases, namely, ( 1 ) in which an acute cardiac 
decompensation has brought about a temporary impairment of 
renal function; and (2) that group in which renal lesions have 
brought about a more or less permanent impairment of the 
cardiac compensation. The various tests for renal function 
have been employed by different observers to differentiate these 
two groups; it would seem that those substances would be 
particularly unsuitable whose excretion is markedly interfered 
with by an impaired circulation. On the other hand, the more 
favorable tests would be those which depend upon a long- 
standing kidney lesion. In this connection it is interesting 
to note that the excretion of phenolsulphonephthalein is defi- 
nitely reduced during a break in cardiac compensation, whereas 
the rest nitrogen of the blood rises but very little, even during 
long cardiac insufficiency. The changes in the titratable alka- 
linity in the chronic nephropathies require a long period for 
their development and, a priori, one would not expect such 



changes to occur in cases of pure broken compensation. Four 
patients were tested who were crucial cases for determining 
the effect of a cardiac break upon the titratable alkalinity of 
the blood. All of the four cases were in the stage of acute de- 
compensation. This was accompanied by marked cyanosis. 
Two of these cases subsequently recovered sufficiently to return 
to their homes. The other two were tested when in complete 
coma, in extremis, during the last day of life. In these two 
cases the diagnosis was confirmed at section. In all four of 
these cases the behavior of the blood serum to phenolphthalein 
was distinctly normal. It is apparent that this procedure offers 
a certain amount of information in the differentiation of car- 
diac and renal cases. However, the exact limits of its value 
could only be determined by the examination of a large series 
representing a variety of cases. 

Of the other conditions in which there is a dyspneeic coma 
without diabetes, pernicious anaemia is especially interesting. 
Seven cases of anaemia were examined. Three of these were 
secondary to haemorrhoids. The other four were pernicious 
in type, two being outspoken cases, while the third (A) was in 
comparatively good condition. The general results were as 
follows : 

TABLE VIT. 
Cases of Anaemia. 
pernicious an.emia. 









Toler- 






Hemo- 


ance to 




Red cells 


globin 


sodium 


Case. 


per cmm. 


% 


bicar- 






normal. 


bonate, 
igrains) 


A.... 


1,800,000 


47 


10— 


B.... 


1,900,000 


39 


70 


C... 


900,000 


20 


40 


D.... 


1,600,000 


35 


60 



Behavior of serum toward 
phenolphthalein. 



After removal of protein. 



Red 

No color 
No color 
No color 



orati< 



Red 

No color 
No color 
No color 



Red 
Red 



Red 
Red 
Red 

Red 



SrX'ONDARY AN.EMIA. 



E .... 


2,300,000 


20 


30 


No color 


No color 


Red 


Red 


F.... 


3,000,000 


40 


10— 


Red 


Red 


Red 


Red 


a .... 


2,100,000 


35 


30 


Red 


(') 


Red 


Red 



1 Colorless after five minutes. 

These cases of anaemia show that, in addition to the im- 
poverishment in cellular elements and of haemoglobin, the 
titratable alkalinity is often reduced. Furthermore, in these 
seven cases the change in titratable alkalinity bore more rela- 
tion to the grade of anaemia than to the type as determined 
by the morphological and etiological factors. All of these 
cases, except the milder pernicious one (A), showed a trace of 
albumin and a few casts in the urine. It would seem clear, 
however; that the changes in titratable alkalinity were due to 
the anaemia, since an even more definite grade of nephropathy 
gives rise to no changes in the titratable alkalinity of the blood. 

On the other hand, the anaemia of the nephritic cases was 
altogether insufficient to account for the change in titratable 



April 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



111 



alkalinity. In some of the eases, with thi 

bicarbonate and with extreme change in titrata 

tin- red cell count and haemoglobin were no! reduced more 

than a fourth of the normal. 'The results wen 

independent of the red cell count and haemoglobin 

that it was n..t > onsidered ne essarj to r» ord these in i 

of nephritic cas< s. 

\ few miscellaneous cases were observed in which the 
titratable alkalinity proved to be of interest. On 
a man. 55 years old, was admitted to the hospital in coma with 
■ history of anuria for 1"> hours and a record >>f chronic 
nephropathy extending over 35 years. The respiratioi 
deep and regular, but were not increased in frequency, and ex- 
piration was not prolonged. The mucous membranes »■ 
mal in color. Ten cubic centimeters of urine were obtained bj 
catheter. An abundance of albumin and a variety of casts wen 
present. No additional information could be obtained on fur- 
ther examination. The diagnosis lav between anemia ami 
cerebral hemorrhage. An examination of the blood Berum 
showed a normal condition as regards real nitrogen and titrat- 
able alkalinity, The secretion of urine commenced in 
hours, the albumin and casts disappearing almost complete h 
within a few day-. Later a history was obtained of partial 
paralysis "i shorl duration m the left arm. coming on about 
two weeks before admission to the hospital. The subs 
record of this case confirmed the diagnosis of 
haemorrhage. 

In a second instance, the patient was a man of 15, who had 

some knowledge of medii me. A definite nephritis of i I- 

grate grade was known to have existed for.several years. This 

patient suddenly developed attacks of dyspnoea chara 

by comparatively rapid respiration, without cyanosis, and with 

subjective (symptoms of air hunger. Tl 

physical changes n the chest, the irregulai 

ami the absent e of any relation to ph) sical ■ 

that they were neurotic in origin. Nevertheless, 

hility of an an hungi r due to renal 

eluded clinically without further observation Tie 

nation of the blood serum at tin- tii bowed i 

■ in titratable alkalinity. The residue a 
ation of the alcoholic extract did not lose 
.after heating for 1". minut 
indicate a diminution ; titratable alkalinity whii 
far t light 1 1 

Brandenburg ' divides the ;> 
two fractions. Tin 
This i- small in amount and . • 
of the blood. Tie- - ■ oi I 
which is bound to the proteii 
ond fraction i- siihjei I 
■•mate- an- r. la- 
alcoholic nitrates from serum poinl 
elusion, for it i- largely the 
by the alcohol. The d\» 



eat, for th< 
ticularl) to • 
of the blood. 

iiniti/. 

qualitat 

tion to quantitati in the 

inaccurai j of all p 

of tin - 

end-points obtained with the ii 

serum. 11 removal of : 

of the ihili. ulti. - with tl 
It would seem that the 

phthalein after removal of the protein should 
of expression in some quantitative form even though minute 
quantities of alkali are band 
themselves for clinical purposes, such a- din 
metric measurement, determination of the dilul i 
the i olor disappears in the l • 

determination of the minimal amount of i hIii.1i 

will suffice to give a color reaction in thi 

A number of titral 
lowing technique : 1 cc. of serum was diluti 
Bolute alcohol and the mixture filtered after thon 
Twentj ■ ul> 

a water hath and taken up in lOcc. of wati 
centimeters of \ |?5 sulphurii 
in order to t it rate smWqueiltly for tl 
the disappearance of color. Tin- titi | 
boiling temperatui 
nolphthalcin. The number of cubii 
phuric mid which were neutralised bj tl 
table nJkalinity of tin 
of a normal solution, or 
of the titratable alkalinity whii h i- 
filtrate. Norma] serum, undei 

i 
■ 
mal to 

slight amoui I 

i linical 

■ 



Emerson: Clinical Diagnosis. II 



112 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 278 



Physico-chemical Reaction of the Blood. — The work 
throughout this paper has been confined to the titratable alka- 
linity of the blood. The study of the physico-chemical reaction 

of the blood in health and disease did not seem appropriate 
under the present conditions for two reasons: In the first 
place, although investigators are not yet fully agreed as to the 
accuracy of either the colorimetric or the electric measurements 
of physico-chemical reaction in the presence of protein, yet 
the concensus of opinion is that the reaction of the blood under- 
goes comparatively little change even during an acidosis. The 
most recent work from Sorensen's " laboratory with improved 
methods for electric measurement indicates that the compen- 
satory processes of the body are sufficiently effective to main- 
tain a comparatively normal physico-chemical reaction of the 
blood, even during an acidosis. In addition to the uncertainty 
which still surrounds the application of the physico-chemical 
methods in the study of the reaction of the blood, it is evident 
that the observations on the titratable alkalinity offer a much 
simpler procedure for clinical purposes. Moreover, the weight 
of evidence tends to show that it is the titratable alkalinity 
rather than the physico-chemical reaction which is subject to 
variation and which consequently is of importance from a 
clinical standpoint. This view was suggested by Folin ™ at an 
early date and at a time when the first application of physico- 
chemical methods to the blood were frequently interpreted as 
indicating that the older titration procedures were erroneous 
and should be abandoned. 



1. Changes in the titratable alkalinity of the blood occur 
which give rise to distinct qualitative differences in the re- 
action of normal and pathologic sera to phenolphthalein. 
Conditions are readily obtained under which the blood serum, 

"Sorensen: Personal communication. 

"Folin: Trans. Ass. Am. Phys., 1907, XLIX, 128. 



during an acidosis, is neutral <>r acid, whereas under the same 
conditions all normal sera are strongly alkaline. 

2. The less severe grades of diminished alkalinity can be 
detected in a qualitative way from the behavior of sera before 
and after the removal of protein and by the selection of a 
solvent, such as alcohol, in which the ionization and hydrolysis 
of carbonates are diminished. The effect of protein and of the 
solvent upon the reaction permit a variety of combinations of 
these factors for detecting varying grades of diminished 
alkalinity. 

3. Definite changes in the titratable alkalinity occur in 
experimental and spontaneous acidosis, in certain nephropa- 
thies, and in some anaemias. The method also affords infor- 
mation of value in the differentiation of certain obscure comas. 

4. Cases of diabetes occur in which the excretion of am- 
monia and of acetone and related bodies is normal, but the 
titratable alkalinity is decreased and the tolerance to bases is 
increased. This affords proof of a definite impoverishment in 
bases in these cases. 

5. Changes -in the titratable alkalinity are accompanied by 
corresponding changes in the tolerance of the body to fixed 
bases. 

6. The titratable alkalinity is of important biological sig- 
nificance, while the available evidence indicates that the 
physico-chemical reaction of the blood is maintained at a fairly 
constant value, even in outspoken grades of acidosis. 

?. The parallelism between the diminution in titratable 
alkalinity and the increase in tolerance to fixed bases in dia- 
betes and in the nephropathies affords crucial evidence that 
■ this increase in tolerance is due practically altogether to a 
deficit of the body in alkalies or alkali-yielding substances. 
The questions as to whether such a condition constitutes an 
acidosis will be discussed in a subsequent paper. 

It is a pleasure to thank Dr. Lewellys F. Barker for an 
interest in this work which has been very helpful. 



SOME ERRORS IN THE DIAGNOSIS OF PULMONARY TUBERCULOSIS.* 

By Lawrason Browx, M. D.. Saranac Lake. X. Y. 



It is a curious psychological fact that the mistakes of 
another practitioner, when narrated with a more or less com- 
plete medical history, rarely impress the listeners in any way 
other than avoidable. 1 was well aware of this when I impru- 
dently suggested to Dr. Hamman that I would speak to you 
to-night of some of my errors in diagnosis and mention a few 
made by other men. The only medical man who has made no 
mistakes is the second or third year medical student just enter- 
ing upon his clinical work. Some of these mistakes of mine 
would never have been made had the patient and myself been 
able to enjoy the privilege and co-operation of such ah 
staff as you have here. The limitations of private practice 
must be experienced to be realized. The physician must in 
many cases depend entirely upon his own powers of observation 



* Read at a meeting of The Laennec, a Society for the Study of 
Tuberculosis, The Johns Hopkins Hospital, January 26, 1914. 



for such assistance as he can command in a small town among 
poor patients. 

A hint from a wide-awake colleague, a member of the house 
staff or from a keen nurse, may recall to mind another case 
that makes the diagnosis clear. I shall present to you a num- 
ber of brief histories of patients and endeavor to help you to 
see how I fell into error. I am fully aware that many men. 
keener of observation than I, would have had more data upon 
which to base judgment and so probably have avoided these 
pitfalls. 

I have no doubt that I was taught in my classes in physical 
diagnosis that muscle sounds could in rather thin muscular 
subjects simulate rales, but when I told a medical student a 
few months after my graduation that his disease extended over 
the posterior of both lungs I had forgotten this fact, and later 
learned that he had a just discoverable apical lesion which has 
remained healed for thirteen years. 1 had never grasped the 



April, 1914.1 



JOHNS HOPKINS HOSPITAL Bl I LETIN. 



113 



fad that shoulder fricti ■mild lead mi that a 

patient hail pleurisy in the interscapular region, bul 
Swallowing can produce -<>un>N in tin- upper ch< 
resembling rales that I had to learn that fact also. It t 
inanv years to learn that disease could »■ n i ~t for a time 
physical signs and that not infrequently a- tin- patii 
proved the physical sien* became much mon 

I still make yearly some mistakes in regard t" the pr 
or absence of a pleuritic effusion. The signs seem t< 
gome cases, n hen limited in area, to !»■ very difficult of interpre- 
tation, anil tin- needle i~ of course the only test, an.! t 
is not infallible. More difficult Mill is it to determine whether 
or not any fluid remains in the chest after repeated aspirations. 
I shall narrate the history of a case a little later where 1 found 
it most difficult to decide. The heart may not Im' displai 
the si.lt* not increased it 

1. Some ten or twelve years ago I had referred to me I >:■ 
the physicians in the Johns Hopkins Dispensary, B pati 

had been acutely ill with what Beemed like the grip, She hail. as I 
now recall it, no temperature but Bomi cough and expectoration 
and riles all over the posterior of one lung and the upper half of 
the opposite. She applied to me for admission to the Adirondack 
Cottage Sanitarium and 1 refused her. one month later when 1 
re-examined her, to my astonishment I found her lungs normal 
An acute proa BS was clearing up irregularly cm the two sides. 

2. One hot afternoon some ten years ago 1 was called t<> a little 
back room to see a poor woman, thirty live or forty years of age, 
with high fev. r. \ ■ry pale and weak. She was said to have tuber 
culosis and I immediately Buapected an ai ate miliary tuberculosis 
The lungs showed no definite Blgns on repeated examlnatli 

a very few glands were slightly enlarged and I finally ■ 

her admission into the Reception Hospital, whi curring 

at Brat in thi diagnosis of pulmonary tuberculosis, Dr. Baldwin 

made a diagnosis of Hodgkin 

microscopic examination of a gland excised after 

...lit seven year- ago I 1907 > a young man. agl 
under treatment by me for pulmonary tuberculosis off and on for 
two years. Tubercle bacilli were present in the spin inn 
returned home and I 

lues. One year later he had son. rvtcal glands 1 

which were said to be tuberculous \ year after this, I 
after I had seen him. he again, saying 

fever of lo4 F, for I On examination, t 

the neck was yen evident and about it wen 

The right upper and middle lobes were infiltrated 

slight advanci 

nation was neg 

reflexi Ibly a trihv Increased. Poui 

ind twitching 
and at night (so tl e nura< 

ind no Kernig Igi VI 
meningitis ol which I wa 
obtained data which I I 

to normal. The sputun 

for an occasional trace of albun 
cast the ai 
globin. 3600 li 
count 

■nail monon i 
tlonals 3.6%. On the 7th 
showed only 3'.''. of P 
nuclears and transltionals and • 
weeks later a similar blood pictui 



culture 

ture rose gradu til ■ 

again thought lay* of 

pyrexia the I ind the 

a third attack with a temperatui 

days, during which bj 1 ir S \\ 

a diagnosis ol Hodgkin'a 

enlarged, the liver d ■ gland" 

wen palpable in the axllli i. r 

I had sufficient data ' 
why tie lltant ami I I 

everytti 

1. In August. I'.U 1. a I 

came !• te had begun, to f. . i badl) (• i 

VioUSl) i He- sister had had pulmonary t. 

covered. Three weeks previously he had bad ntgl I 

' and I. it weak V 
Catakills he ■ ame to Bar 
had lost weight and ills general condition 
monary examination showi d signs of fluid i pr< \ louslj dli . 

to the level of the third rib and third \. III- 

sputum contained no tubercle bacilli and tie ur 

albumen and a '• in byallne CBStS He had eontinii. 

tng about 100 to l"l P He ■■ 

tluld never showed an} tubercle bacilli either bj anim.il 

tlon or by staining However I thought tie 

CUlOUS pleurisy and tread. I l.im tCCOrdlngl] 

three months after his arrival. In the 

third right Intercosl 

and softer I dlagni 

Incised the swelling but could get no pus v llttli 

appean 

axllhe and above and below 

The mental C lltlOD of the pathnt R 

■ 

finally largelj i li ared up Th< 

.nil mon Irregular \ Ml 

21, and In a differential COUI I 

phlhs • ' 

I thought ' 
but in ' 



114 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 278 



were sent to the Adirondack* for tuberculosis. In two the 
superficial glands and spleen were enlarged and the diagnosis 
should have been made and the patients kept at home. In the 
other three the superficial glands did not enlarge at all or only 
very late in the disease. An indefinite onset followed by pleu- 
ritic effusion and fever is likely to lead anyone astray. When 
enlarged glands occur in a tuberculous patient and do not 
recur after removal or remain very small, it is not easy to 
diagnose lymphadenoma. I have no doubt a number of cases 
have escaped me, but to-day I am on the outlook for such 
cases and that, I believe, is a large factor in their correct diag- 



5. In the winter of 1912, a school teacher, fifty years old, from 
the Middle West was sent to me suffering from pleurisy with 
effusion. I immediately took it for granted that a diagnosis of 
tuberculous pleurisy had been made, as I believe it had. He com- 
plained of great pain over the left anterior costal margin and a 
fast pulse. One brother died of tuberculous laryngitis. He denied 
lues and tripper, but had pneumonia when a child. Fourteen 
months before he saw me he had been treated on account of the 
pain for indigestion. Not improving he went to Battle Creek 
where fifty ounces of a clear fluid, of low specific gravity, con- 
taining no pus, were withdrawn. He returned home and tried to 
but could not continue work. One month previous he had nearly 
lost the use of his left side, and since then the left palpebral 
orifice has been smaller than the right. Hoarseness then occurred 
and loss of weight and strength. His appetite was poor and 
bowels very constipated. He had slight expectoration. A radio- 
graph was said to show a thickened pleura and some intrapul- 
monary disease on the left with scars of an old tuberculosis on 
the right. He stated that he had had little or no temperature but 
that his pulse was fast and he was slightly short of breath and 
slightly aphasic. His chief complaint was pain at the left 
anterior costal margin, so severe that he could sleep only when 
he lay on his back and then only when he took analgesics. The 
left side was depressed, moved less, showed loss of vocal fremitus 
and almost flatness over most of the side. The breathing was 
distant, the vocal resonance decreased and there were a few 
scattered rales. There were possibly a few fine rales in the outer 
third interspace on the right. The heart was not misplaced. The 
sputum contained some tubercle bacilli ten days after arrival and 
the urine was normal. Three weeks later his voice became more 
husky and weak, due to a paralysis of the left recurrent laryngeal 
nerve. Two months later, after a dry tap in front, 400 cc. of a 
reddish brown fluid with many polymorphonuclear and few mono- 
nuclear cells were aspirated posteriorly. A differential blood 
count was normal and when five months after arrival the liver was 
found enlarged, a negative Wassermann was obtained. There were 
no glands except one the size of a hazel nut in the left axilla which 
decreased in size. The patient returned home and as my diagnosis 
of malignant tumor of the lung and pleura was not acquiesced in, 
a laparotomy was done and revealed a liver studded with carci- 
nomatous nodules. He died a few days after the operation. As I 
said at first I thought the patient had tuberculous pleurisy but as 
the other signs developed the diagnosis seemed untenable. He 
may have had pulmonary tuberculosis also as tubercle bacilli 
were found in the sputum at the Adirondack Cottage Sanitarium 
or some mistake may have occurred as at no other time were they 
ever demonstrated. 

This case and the ease of the clergyman with Ilodgkin's dis- 
ease show how easy it is to be misled by the presence of fluid. 

6. Two years ago a woman, aged 50, the mother of two children, 
was referred to me for treatment. One brother died of tumor of 
the lung, otherwise the family history was negative. Thirty 
years previously she had had for about three years, attacks of 



bronchitis lasting about two or three months each. Her health 
continued good until one and a half years ago when the left 
breast was removed and the axilla cleaned out for a typical 
mammary carcinoma. She was then well until about eight weeks 
previously she had a slight haemoptysis and had ever since raised 
blood streaked sputum in which tubercle bacilli were found. A 
few physical signs were discovered at the right apex and the 
lymphatic glands in the right cervical region were found enlarged. 
Pleurisy in the right infraaxillary region developed three weeks 
previously and the temperature rose to 100.5° F. and 101° F. Fol- 
lowing this the temperature varied from normal in the morning 
to 100° F. at night. Three weeks previously her right knee began 
to pain her and continued to do so. The finding of tubercle bacilli 
convinced the hospital authorities that she had pulmonary tuber- 
culosis and her attending physicians were considerably chagrined 
as they had not discovered them on several examinations. When 
she came under my observation June 29, 1912, she was in bed 
expectorating blood and had a slight elevation of temperature. 
I kept her in bed and only at the end of a week did I examine her 
lungs, for the blood spitting continued. A few scattered rhonchi 
were heard over the upper lobe of the right lung. The examina- 
tion of the sputum and urine were negative and I thought the 
patient was probably tuberculous with possibly carcinomatous or 
tuberculous glands in the neck on the side opposite the former 
tumor. Two weeks (July 12) after arrival the breathing was 
noted as being slightly distant and broncho-vesicular above the 
left clavicle but no dulness could be made out. Four days later 
(July 16) the breathing on the right was puerile, on the left 
distant over the front but of good quality. On the left back there 
was dulness, more pronounced below. The breathing was less 
marked than on the right and after coughing a few sonorous rales 
were heard. The heart sounds were more widely transmitted than 
normally. The cough had now become spasmodic and suggested 
intrathoracic pressure and she had difficulty in breathing. The 
next day there was dulness over the greater part of the left lung, 
with flatness below, whispering broncophony was audible to the 
fifth rib and eighth vertebral spine, but vocal fremitus was less- 
ened. The breathing was distant. Three days later a dry tap was 
obtained. On July 2S, the knee was put up in crinoline. The next 
day double vision occurred and several days later a marked 
internal strabismus of the left eye occurred. Later vomiting 
occurred frequently. From this time on the symptoms gradually 
increased until weakness lessened them. The only point of in- 
terest which developed before her death on September 3 was that 
she had attacks of premature cardiac contraction, apparently 
ventricular in origin. Her headache would increase and the pulse 
drop from 132 to 60 and in one-half hour rise to 120. On one occa- 
sion it dropped to 38. I diagnosed secondary carcinoma of the 
lungs, cervical glands, brain and knee, but the autopsy performed 
by Dr. Krause revealed a hypernephroma on the right side with 
metastases to the left lung, two or three to the right lung, to the 
liver, left kidney, right knee and a few nodules in the mesentery 
• and retroperitoneal tissues. The brain and neck were not ex- 
amined. A few weeks ago, the sections from the mammary carci- 
noma were examined by Dr. W. G. McCallum, who pronounced the 
tumor a typical carcinoma. 

7. A youth, aged 19, from New Jersey, applied for admission to 
the Adirondack Cottage Sanitarium last summer. His family 
history and his previous history were unimportant except that he 
lived under poor hygienic conditions and was closely associated 
with a boy friend who was tuberculous. About six or seven weeks 
before admission (March, 1913) he began to lose appetite, weight 
and strength, had a slight cough and suifered from languor. One 
and a half months later he had night-sweats, fever and sputum. 
On arrival in Saranac Lake one and a half months before admis- 
sion he had temperature of 101° F., night-sweats and physical signs 
interpreted as due to enlarged bronchial glands. After admission 
he grew worse and was transferred to the infirmary where his 



An.n. I'M l.i 



JOHNS HOPKINS HOSPITAL BULLETIN 



temperature ranged from 97° 

to normal: his pulse varied from 100 t 

16 to 28. On October 12, seven months after onset, his li 

were 38,000 and the polymorphous 1. ■ 

showed a shadow In the mediastinum, about i; 

some diffuse consolidation in the lower part of the right In 

some consolidation about the hilua of the left lung Th- 

the right was markedly dull below the sixth verti 1 r 

breathing somewhat exaggerated m • r the whole front, t 

resonance normal, a few fine rales were heard at thi Inm 

the fourth Interspace and moderately coarse rales belon the fourth 

vertebral spine. On the left the note was byperreaonant i 

lower front, the breathing slightly distant over the faonl 

scattered moderately coarse rales after coughing were heard over 

the front and fine rales to the third vertebral spin. Tl 

ing day a fluoroscopic examination confirmed the radiograph and 

showed the posterior mediastinum to !»■ U 

mediastinal abscess was made and the Introduction of . 

was considered. The second day following there wai 

the right of the sternum extending over most of the left front, the 

vocal resonanet was increased and the breathing markedly 

ikened. The patient expectorated some dark clotl Of blood. 
The urine examination was negative and the purulent gputum 
never showed any tubercle bacilli. The radiograph Bhowed that 
the whole mass had shifted slightly to the left At this i 
mediastinal abscess was diagnosed and the patient r 
surgeon who diagnosed malignant growth. After Beveral d 

• rvation a thoracotomy revealed sarcoma of the mediastinum 
and left lung which was continued by histologic examlnatii D 
piece of excised tissue. I should have made this diagl 
sudden change in note led me astray as well as the aharplj 
right border of the X Kay shadow and the positr. • I some 

medical men. 

In these three cases of maligi ai I ti >r of the lui 

pleura, it is curious that in two tubercle l>a< ilh w< 

■ but never again in the s]iutum. One patient might 
hail a tuberculous focus in the lung, hut in the other it was 
axcluded at autopsy. The pleuril 

e of tubercle Iwcilli in the sputum and thi 
easily mislead anyone in the lir-t case, wh ■ 
of tubercle bacilli in the sputum in I 
think of anything else than a pulnio 

■■ nding pin • I liis, but th< 

thorities wen 

they yielded. When a ■ 
authorities with a d 
the sputum, it is well to 
their laboratory has 

ever, probabl) • urred with us. \\ hen I 
pulmonary tuben ulos • . • 
the ,![.,_ putum. I 

bare d 4 wrnephroina, but the 1 

an.l had 1 felt the turn..! I would. I 
it a metastasis, I r i 

■t rare m : I 

8. A lawyer, aged :.t. complaining 
consulted me some si 
mediate family had suffered fn • 
tory dlsordi ra T le 
he had had a slight cough for ■ 
While he had been exposed, no 1 
of four years before I saw hii 
strength, but recovered and w.^ 



r a ft-w 

Ian had 
found tubei 

con.liti 

slight d 
murmn: 

fremitu 

Ing was 
• tourtti 

and fifth Interapai e and fr 

1 made a diagnosis of pulmonary lutx ■ v.milna- 

tlons of the sputum 

■rmal His pnlmi HI* 

rmal, puis, fj 
arrival 

tup and pain In I 
phlebitis occurred One month later when I 

normal, he hai 
chair and !•• ■ 

I fluid that ■ 1 
diagnosis of acute dial 

|fat be 

died suddenly tul 

arch which had foil. art. r\ well 

The Ini ■ 

phlebit , in hi* 

sputum which his 1 

real tubercle bactllL 

I do 

9. Last month thi 

tarium • 

; ilmonary tuben nil 

had In" 

spring 

return trip t» • idi ill « 

both ll 

• 

■light 1 

and l... 
Impuli 









116 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 278 



time. Babinsky's sign was present in both sides. The blood 
pressure was systolic 115 mm., diastolic 70 mm. A spinal punc- 
ture revealed a bloody fluid not under much pressure. The second 
day after the onset she moved, her right arm but developed 
stertorous breathing and died that night, having been uncon- 
scious most of the day. Autopsy revealed a haemorrhage into the 
left lateral ventricle and some over the convolutions about the 
fissure of Rolando. Her heart showed a chronic mitral lesion and 
a beautiful acute endocarditis. In the right lower lobe was a firm, 
dry patch about 5x5 cm. and on section like hepatization, but con- 
taining air, while the rest of the lung was oedematous. There was 
no tubercle. This patch could have given some signs and misled, I 
believe, several physicians. 

What had happened was, I suppose, as follows: An embolus 
had lodged in a small branch of the middle cerebral artery lead- 
ing to a silent area of the brain. This area had softened and 
with absorption of the embolus or after the formation of an 
aneurysm, rupture had slowly occurred and the blood oozed out. 
I do not see why an apical infarct might not lead to mistakes 
in diagnosis. I heard of a patient who was admitted to a large 
New York hospital, as she had heart disease and the pulmonary 
tuberculosis was too advanced in the apex or apices for treat- 
ment in the Adirondack Cottage Sanitarium. As her heart 
condition improved her lungs finally cleared up completely. 

10. In the summer of 1911, a woman, married, aged 29, from 
Pennsylvania, sent for me and complained chiefly of pain in the 
back. The family history was negative and the previous history 
unimportant. She lived under good hygienic conditions and had 
never been about cattle or stables. The present illness began 
about ten months previously with an indefinite attack which was 
attributed to a floating kidney. Two and a half months later 
( March, 1910) she went to Augusta, Ga., for six weeks. After her 
return she began to cough, but only slightly at first. The follow- 
ing fall (November, 1910), she was so weak she went to bed for a 
five months rest cure. This followed by a six weeks visit to 
Cambridge Springs resulted in a gain in strength and weight, but 
with the hot weather of June the cough increased and she felt 
worse. In July, eighteen months after the onset, she noticed a 
painful and tender swelling over the right lower thorax pos- 
teriorly. Disease of the spine or rib was diagnosed, but no fluid 
was obtained on puncture. In August when I saw her she com- 
plained chiefly of pain in her back. She was very thin, weak, 
nervous and with marked pallor. The heart was apparently 
norm?! and not displaced. The right side was much contracted, 
moved less, with much increased vocal fremitus to the third rib. 
There was some dulness over the back, most pronounced below 
the seventh vertebral spine and bronchial breathing to the clavicle 
and third vertebral spine and opposite the fifth and sixth vertebral 
spines with increased vocal resonance. Moderately coarse rales 
were heard over the side on coughing. On the left the vocal 
resonance was somewhat increased in the axilla. There was 
marked rigidity of the spine, tenderness over the ninth and tenth 
dorsal vertebrae and brawny swelling along the spine from the 
eighth to the twelfth dorsal vertebrae. I informed the husband 
that she had extensive disease pf the lungs, probably tuberculous, 
and also in all probability disease of the ribs or vertebra?. The 
temperature ranged from 99° to 100.5° F. and the swelling slowly- 
increased in size and softened in the center. About this time 
marked rigidity developed in the right abdominal muscles. The 
urine was normal. , The leucocyte count at this time was 15,000, 
the differential about normal. I had a surgeon see her and he 
though she had empyaema, probably tuberculous in origin, and 
advised aspiration, saying there was nothing wrong in the abdo- 
men. A few drops of bloody, glairy fluid were obtained on aspira- 
tion which on examination contained no tubercle bacilli, but some 



Gram positive cocci and rods with some Gram negative ovals. 
About this time the patient acknowledged that she had a little 
sputum which was negative for tubercle bacilli. In September, two 
months after her arrival in Saranac Lake, the swelling was incised 
and under the skin a curious, rather friable, stringy, bloody tissue 
was found which bled freely. The abscess contained bloody, 
glairy, rather thick, tenacious pus, full of minute, sulphur yellow 
particles, slightly less than one millimeter in diameter. They 
proved to be actinomycotic granules, and the organism was culti- 
vated later and found in the sputum. She died May 12, 1912. I 
should have suspected actinomycosis sooner but this was only the 
second case which I have ever seen. The first was a patient in the 
Johns Hopkins Dispensary. 

11. In the summer of 1912 (August 24), a married woman, aged 
41, wife of a professional man, came to my office saying her lungs 
were diseased. The family and previous history were unim- 
portant. The present illness dated from November, 1911, nine 
months previously when she had a " cold " and was in bed with 
cough and expectoration for two weeks. She said she had had 
night-sweats, fever, some hoarseness, pain on the front of the 
chest, shortness of breath, loss of weight and strength, and cough 
and expectoration. She had spat blood-streaked sputum, but 
thought it might be due to whooping cough, which she might have 
contracted from her adopted son. The temperature was 99.6° F., 
pulse 128, respirations 20, her general condition was poor and she 
had slight pallor. She said no tubercle bacilli had been found in 
her sputum. The pulmonary examination showed rhonchi to the 
third rib on each side and to the fifth vertebral spine on the right, 
as well as fine rales to third rib on the right. I promptly made a 
diagnosis of pulmonary tuberculosis and put the patient to bed. 
During the next month she remained in bed, had a temperature 
ranging from normal to 101° F., pulse 88 to 116, usually 100, and 
respirations 20 to 26. Her cough was severe and the sputum at 
times was slightly blood tinged but contained no tubercle bacilli. 
The lungs cleared up and only an occasional fleeting rhonchus was 
heard. She was very erratic. Her brother came to see her five 
weeks after her arrival and told me of a marital infection with 
lues. Two Wassermann's were positive and a couple of intra- 
venous injections of salvarsan brought the temperature to normal 
and the patient returned home and has been well since. 

12. Several years ago a married woman, 27 years old, the mother 
of four healthy children, consulted me, complaining that she had 
high fever (103-105° F.) much of the time for three years. Her 
family and previous history were negative. Three years pre- 
viously, while nursing a child with typhoid fever, she began to 
have fever and was treated for typhoid at first and later for 
malaria. As the fever persisted she was sent to Asheville and 
then kept in bed for months. The temperature finally reached 
99° F., but on return home it again rose and her physician sent 
her to me. She had lost strength and had night-sweats, but her 
weight was normal, her bowels regular. The temperature in the 
office was 100.8° F., pulse 116 and respirations 24. The general 
condition was good and there was only slight anaemia. The heart 
was not enlarged, the abdomen negative, the urine normal and 
there was no sputum. The lungs were apparently normal and a 
gynecological examination was negative (W. Griffith). Both she 
and her husband denied all symptoms of lues. I referred her to 
Dr. Futcher who told me the Wassermann reaction was positive, 
but the temperature did not become absolutely normal for a time. 
She, however, made a complete recovery. 

13. About ten years ago, a farmer, married, aged 47, from New 
York State, consulted me as he had had repeated haemoptyses. 
One aunt died from tuberculosis. He had had cough and expecto- 
ration for thirty years, dry pleurisy as a boy and pneumonia many 
times. His present illness he dated two years previously, when 
he had his first haemoptysis. He had had slight hoarseness, much 



Aran,, 1914.] 



JOHNS HOPKINS HOSPITAL 111 I.I.KTIN. 



in 



cough and expectoration, some shortn. 

of strength. He was slightly pale, had 

puis.' in; and had lost nine pounds In weight The physical 

nation revealed only a few moderately coal 

seventh vertebral spine on the right. The urine 

hyaline and granular casts and the sputum was repeatedly and 

always negative for tubercle bacilli. Pneumococcl and h 
bacillus were looked for but the results were Inconclusivi 
patient finally decided to remain permanently in Saranai 
1 saw him off and on for blood spitting and he was fairly well, 

still with cough and expectoration, until the fall of 1910 .-, 

had cholecystitis and during convalescence hemorrhage into his 

internal capsule on the right, which caused in a 

death. The autopsy showed besides these complications, a chronic 

bronchiectasis of the right lung. 

This case shows the fallacy of always accepting haemop- 
tysis as due to pulmonary tuberculosis, but only his history at 
first could have excluded pulmonary tuberculosis and thai was 
only aegative evidence. 

14. In the summer of 1910, a broker from New York. I 
consulted me as he had had fever and I. It badly. His famil;. and 
personal history were unimportant. Three months |.r. \imis to his 
arrival in Saranac Lake he had a rather atypical attack which 
resembled pneumonia and had not been well since Malaise had 
been pronounced and cough, expectoration, fever, nighi 
shortness of breath and pain in his right side were marked. Once 
or twice he felt as if his right lung was choked up. He went from 
place to phi. .• and early in August came to see me. His tempera 
ture was 100.8 V . puis.- 120, general condition poor. On exam I 
nation, dulness was marked over his upper lobe with bronchial 
breathing and vocal resonance markedly increased. Fii. 
were heard over the back and a few over the lower hack on 
The relative heart dulness apparently extended to the right of the 
sternum. There was pain radiating to the right shoulder when 

re was made on the abdomen. The sputum 
at times tinged with blood but always negative for tubercle bacilli 
The urine was normal. 1 felt uncertain about the dlagm 
had a colleague see him with me, He made a diagnosis of pul- 
monary tuberculosis. During the month he was under m> 

tion the physical signs remained normal on the left sidi . but on 

the right, the dulness Increased slightly, the breathing i 

lower two-thirds of the ch. pronounced and mi 

coarse and fine rales w.re present over the side Pneu 

were found in the sputum and I wanted to give him s 

which he refused to take He then went to Montreal « i re a little 

later a radiograph showed a cavity The ph] 

and hyperesthesia developed below the third rib ami si 

third vertebral spin.-. Operation t ed, butnotdi 

the pulmonary abscess Jointed about the fourth rib under i 

ula. A pure culture of pi 

sank gradually and died 



I should l 
but ma 

mind until lal 
condition licing tul 

sent to lie from V .v \ • : 
ture and .it tine - -light COUgh 

to 101 1". for many moi.i men in 

Philadelphia and New York In the latter dtj she f. II 
hands of a BUrgeOO who i nslform 

cartilage t,, the pub.- but found 
■ 

might have a tuberculous pulmonar. 

always normal and nothing abnormal ol ■ found 

anywhere The urine, the blood (Including 

were apparently Dl gatlvt 1 
and then as it did not at: 

get up In short, the temperature persisted foi 
months and flnall] 

miliary tuberculosis could not be w \.r an 1 

know, w.-ll to day. 

A physician who lives m a health r<-..rt for puln 
tuberculosis and limits his practice largel) to that 

• unity for in.. 
a iii.ui in general practice has. < In the other hand 
fall into the error of thinking that ever) patienl has without 
question pulmonary tuberculosis. Fourtoi 
man) patients roach us in the final si 
day the problem i- changing and we are kepi but 
endeavoring to prove that some of oui 

tuberculosis. Wi all other disease pulmo- 

nary tubert ulosie than the op: 

■ 
tuberculosis an.! t- begin at once I 

of a few of m\ iiu-' 

brief!) cas< II 

. ardiai 

o\er tllelll I -ee tli.it in 

1 knew, hut I 

■ 
■ 

it. It 
w ithoul 
which I 



observ moNS on the proj i cm e enz^ mes of i he bodi 

\i;i>i.i;iiau>i:n . 

'■' 



idy of the Abderhaldi i 

■ 






'I wish to express my greatest appreciation to Pr 

for encouraging this work and for I 

which to carry it out I ■: 

Paul Wegefartfa and I Chandli i ■• 

plying me with materials 






118 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 21$ 



















TABLE I. 


























• 












Case 

No. 


Clinical Diagnosis. 


I 
E 


si 


E 


1 

J: 


s 


•p 


1 

El 


B 

— 
Eh 


1 

>. 

Eh 




> 
O 


1 
o 


c 

c 

> 


fci 
> 

3 


3 


1 

s 

Cm 


•a 


1 

•a 


to 

-7 


1 

1, 
I 


1 


1 

2 


1 
5 


— 

1 

- 




fcr 



< 


a. 





















O 




























































-"- + 




























+ 









































































1) 




+ 








+ 





















































+ 



+ 




















































++ 




++ 










































11 ! 
























































± 


















+ 















































































++ 




































































































































































++ 








18 





















































40 










c 











































8 






















n 






























41 









+ 













+ 
































































































31 





















































22 









































+ 










25 






++ 

















































33 













































II 






30 


































1) 












16 
























ii 














'I 


















15 





















































51 


















1 t 


+ 






+ 






















53 

















































27 




+++ 


++ 


+++ 







































60 






















































69 














± 









± 







+ 






























24 












































28 




+ 














II 
































68 
























+ 


+ 
























35 






















± 
































50 




















































34 













































± 




++ 




49 



















































29 




+ + 











































7 























































70 






± 




































11 




t + 



















































April, i;>i4. ] 



JOHNS BOPKINS HOSPITAL BULLETIN. 












- 









J.'"' BtrnmalODI Serum an. I liver 



Myomata 

Preemancy, Sd month 1 

Chronic appew licit is 

Polyarthrit is 

Health? 



Carcinoma cervix, 

Hypophysis. pol> glandular 

Pregnane.* . 

i I 'ITU 

Kiulomctritis 

Amenorrhea, hypopituftari 

Carinonu. Laet 

Abdominal adhesions 



Cirrhosis, liver 

Necrosis, phalanx toe 



Carcinoma, cervix 

Chronic app 

Preirnancy, time t 






Serum n 









..the Abderhaldi i 
work was performed ii 
t.. whom 1 ,un indebti 
daring this period that varyii 
interest ami !i\. : 
of rach ferments 
Heilner and Petri ' havi | 
placed themselv. - 01 
trine. 






"Heilner u. Petri, Munch med. '■' 






120 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 278 



given also, together with certain conclusions drawn from the 
earlier portions of the work. 

The method used was that described by Abderhalden. Tis- 
sues as fresh as possible were cut into small pieces and washed 
with 0.8 per cent NaCl solution. They were then boiled in dis- 
tilied water containing a trace of glacial acetic acid and 
changed and boiled in distilled water until a negative ninhy- 
drin reaction resulted. 

Before each separate test the amount to be used was again 
boiled in ten times its volume of distilled water and the filtrate 
tested with ninhydrin. About 2 gm. of the organ and 1-1 cc. 
of hemoglobin — free serum were used. These were incubated 
for 18 hours at body temperature. 

The membranes were carefully standardized, using the same 
serum and peptone solution for each set. Occasion was taken 
to frequently retest such sets. Care was exercised to use only 
perfectly clean utensils. 

Manifold errors in the first months of work demonstrated 
the following points: It is essential that the organs be fresh ; 
great care is necessary in standardizing the membranes and in 
retesting the sets frequently ; it is absolutely necessary that the 
organs be blood-free; paradoxical results appear to indicate 
some error of technique such as undoubtedly crept into the 
investigations of Heilner and Petri: the serum must be 
hemoglobin-free, fresh and sterile, and collected several hours 
after meals: a non-specific cleavage of the protein in question 
usually depends upon the presence of blood corpuscle elements : 
liver, for example, is very hard to prepare free from blood: 
controls are necessary for each serum and for each organ. 
Observing the above precautions such controls have always 
been negative. 

As vet we are not familiar with the part played by acute 
and chronic inflammatory processes in stimulating or hin- 
dering the formation of the ferments under discussion. Thus 
far we do not clearly understand the part played by poly- 
glandular and polyvisceral disturbances in the formation of 
antiferments. 

Thirty-seven sera from a variety of patients were tried with 
placental tissue. Twenty-two were from women not pregnant, 
and of these no serum reacted positively. There were twelve 
sera from women clinically pregnant. The tests were all 
positive in these cases with two exceptions. One serum, Xo. 31, 
was from a questionable case of pregnancy. It reacted strongly 
with cat placenta, but not with the human material. The 
error possibly lay with the placental preparation, which was 
immedately discarded and new material prepared. Another 
serum. No. 11. gave a negative test at first, but three weeks 
later broke down the same placental preparations — human and 
cat. Four sera from carcinoma cases were se1 up \\ ith placenta. 
Only one. No. 35, gave a feebly positive reaction. 

With kidnej tissue Erom man. dog or cat. sixteen different 
sera were tried. Of these four had nephropathy histories. No. 
21, a cardio-renal ease, with syphilis, and Xo. 3, from a patieni 
in diabetic coma, gave slightly positive reactions. Another 
cardio-renal. No. 7, and a case of chronic nephritis. No. 19, 
did not react at all. No. 53, from a cardiopathic patient, gave 
a negative reaction. 



Sixteen sera were tested with normal human thyroid. No. 
69, from a case of probable internal glandular disturbance, 
gave a feebly positive reaction. With Basedow tissue 6 sera 
were used. Four had no clinical histories of thyroid disturb- 
ances. No. 51 was from a case of outspoken Basedow disease 
and definitely broke down the tissue. It did not affect normal 
thyroid. No. 69 (see above) yielded a negative test. Xo. 24, 
from a nervous patient with a struma, reacted negatively. 
Ten sera were tried with prepared adenomatous thyroid tis- 
sue. Of these three gave some result. No. 24 (see above) and 
Xo. 35 (hypophysis tumor) yielded feebly positive results. 
No. 51 (see above) definitely broke down the adenomatous 
tissue. 

Three sera were tried with dog thyroid. All gave negative 
tests. 

With normal human ovary twelve sera were used. Three of 
the tests resulted positvely: Xo. 24. thyroid struma: No. 51, 
Basedow disease; and Xo. 60, probably internal glandular dis- 
turbances. Three sera were used with tissue from a cystic 
ovary. Only one, Xo. 36 (pregnancy), reacted — feebly posi- 
tive. 

With tissue preparations from human, dog and cat livers 
twenty sera were tried. No. 21 (cardio-renal witli syphilis), 
Xo. 14 (carcinoma of the stomach with marked liver necroses), 
and Xo. 68 (varicose veins) yielded positive results. Four 
of the negative sera — Xos. 25, 26, 28 and 6 — were from preg- 
nant cases. Two sera — Nos. 14 and 82 — came from patients 
with carcinoma. The first reacted and the second did not. 
The donor of serum Xo. 38 had cirrhosis of the liver with 
ascites. 

Ten sera were set up with preparations of normal pancreas 
tissue. Two were from nephritic cases and three from diabetic 
patients — one in coma. In no instance was the tissue broken. 
down. 

Adrenal gland preparations were used with nine sera. The 
tests were all negative. 

In thirteen different cases (three pregnant sera) there was no 
serum which acted upon muscle tissue preparations. 

Si\ sera were used against myoma tissue. Two cases — Nos. 
44 and 50 — had uterine myomata. In no instance was there 
a positive reaction. 

Ten sera were tried against preparations of human blood. 
The positive reacting specimens were: Nos. 46 (polyarthritis) : 
43 (perirectal abscess) : 19 (24 hours after a laparotomy) : 22 
(ti days after plastic operation on axilla) ; 4 (24 hours after 
curetage and repair of cervix) : and 3 (diabetic coma) feeble 
reaction. 

With preparation of adeno-carcinoma of the ca?cum ten 
sera were used. Of these live had clinical (and pathological) 
carcinoma. Three yielded positive results. Two, Nos. 30 and 
62 (from carcinoma cases) gave no reaction. Six sera were 
tested with lymph gland metastasis preparations. All re- 
sulted negatively. Two of these. Xos. 39 and 14, were from 
patients with carcinoma. One serum, Xo. 33, was from a case 
id' carcinoma of the tonsil. Six sera with a scirrhus carcinoma 
preparation (from the breast) yielded negative results, except 
one ease. Xo. 34. which was feebly positive. 



April, 1914.] 



.loiixs llnl'KIXS OSPITAL BULLETIN. 



181 



A beef hypophysis preparation was set up with ••!- 
of tin 1 latter, four were from dyspituitarj cases. Tl n 
negatn ■ 20 and 16). ( >ne reacted pos 

35). 

BLOOD FERMENTS FOLLOWING TRANSPLANTATIONS 

li, December, 1912, a case in thi if the 

Johns Hopkins Hospital was operated upon — tellar 

d — for an hypophyseal cyst. The patient man 
a Byndrome of hypopituitarism, with accompanying diabetes 
insipidus. Several months later, because of the marked pitu- 
itary insufficiency, a second operation was undertaken, con- 
sisting of ;i subcortical implantation of the hypophys 
newborn child. Improvement in the glandular signs appeared 
fnr a short time. Subsequently, however, the features of the 
hypopituitarism became marked, and the patient finally buc- 
cum bed. 

The approvement noted was attributed by the operator to 
either the material contained in the glandular transplant or 
to the Becretion manufactured by the transplant itself during 
n- period of absorption. Could the graft have survived in- 
definitely it seemed plausible that the patient might have re- 
covered, in part at least, from the Btate of hypopituitarism. 

Similar negative results were obtained by Bxner' in trans- 
planting the hypophysis in rats. 

The laws governing the viability of epithelial transplants 
are still v< ry oba ure, in spit.' of much work in this direction. 
The literature yields opinions, however, nearly unanimous in 
the view that homo- and hetero-transplants of the paral 
gland are absorbed ultimately as foreign material.' II I- 

BteadV dog, which maintained g I health with a parathyroid 

autograft approximately 1 mm. in diameter, is a Btril 
ample of it- kind. 

In brief we may mention the follow ing as some of I 
ble factors in the failure of sui h transplantation work. 

l. A " Verhungern " of the transplant.' 

v. \ ti>\i> action of the transplant on the host. Such 
dition i- found in certain cases of bl I transl 

:;. a toxic action of certain constituents of the 
upon the graft. 1 

e lack of an u degree of deficient 

of the gland in qui 

5. A trop 

6. An immunity reaction— in the sense oi an 
reaction/ <>r othei 

The fad that at first the transplants frequent 
vascularized and only later 
permanent interference with the bl I Bupply ii 



Kxner, A.: Deutsch. ; 
'Lelschner, H.. and Kfihler, It Ar.h f. kiln Clilr 
169. 

'HaJsted. \V. S.: J. Exp. Med . 
•Schone-Marburg: Wien kilt 
' Axhausen. G.: Med. Kllnlk.. 1 
•Halste.l. \V 8 J. Exp Med 
•Schone-Marburtc: toe. Cit 



I 

may sun ive transplantation in 

ate, pi a part, 

answers the fifth point a 

probably fun llv without their 

after a temporary suppression of thi 

The -• ond, fourth and sixth points maj tinder 

the heading 

Murphy" -a mechanisn nd rapidit] 

action depend upoi 

prompt and violent the more foreign thi duced. 

Murphy think- t; at this defei 
developed rather than one naturallj present in 

Russt II " has Bhot» n that t 
multiplied in a normal rat for more than n 
rat previously immunized the graft was rapidh 
Furthermore, Lambert and Ham 
that rat and mouse tissues will grow almost as well in 
from an alien as from the nati [f the animal, how- 

ever, from which the plasma is obtained is previously im- 
munized with the In ing cells of the foreign 
will inhibit or actually prevent anj bucIi activity. 

In view of the protective ferment mechanism of the body 
demonstrated by Abderhalden in other Belt ations 

above mentioned suggested a p lytic action on the 

graft of antienzymes developed in the host follow 
plantation. It appeared conceivable that thi 
graft considered above caused the formation of pro! 
enzymes which, in turn, brought about its ultimate absorption. 

patient had pn ■ ived glandular tl 

both intravenously and by mouth, we are able to 
-urli glandular administration ma\ have ■ 
for the ultimate survival o rjn pituitary I 

With tin- idea in mind an endeavor was made I 
derhalden technique in detet tii 
be present after I 

The liver was cl 

■ 

periment. I 

•1..11 and thi 
for ferments breaking down h 

In the first di 
liminai 

In D 

muscle I 



' 



122 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 278 



the liver tissue were held accountable for the failure in this 
experiment. 

In Dog II about 15 gm. of liver were removed from a re- 
cently killed dog, cut into small pieces and implanted under the 
rectus muscle. Three days later the serum was set up with dog 
and cat liver tissue. They both reacted positively. 

In Dog III about 15 gm. of liver were removed from a dog, 
cut into very small pieces and implanted under the rectus 
muscle of the donor. After five days the serum was tested 
for proteolytic ferments. It reacted with dog, human and cat 
livers. 

In Dog IV about 15 gm. of liver were removed as in Dog III, 
cut into fine pieces and transplanted under the rectus muscle 
of the same animal. With dog, cat and human liver prepara- 
tions the serum reacted after five days. 

In Dog V about 10 gm. of liver tissue ground up in salt so- 
lution (from another clog) were injected intraperitoneally. 
Three days later enzymes were present in the dog's serum 
capable of breaking down dog liver. 

Human placenta was used as a control in these dialysations. 
Such controls were always negative. 

These results seem to indicate that liver tissue, under certain 
circumstances, when transplanted into a dog, acts as foreign 
protein in the animal's circulation and stimulates the formation 
of proteolytic enzymes capable of digesting it. Transplants 
of this nature, then, have to cope with protective ferments de- 
veloped in the body of the host. 

Between the experiment as carried out in Dogs II, III and 
IV, and the experiment represented by Dog V there is no es- 
sential difference other than one of quantity. Where the 
gland tissue has been reduced to a semi-fluid form we expect 
it to have a greater capacity for stimulating the formation of 



antienzym.es than an equal mass of gland tissue sectioned into 
pieces. Just so a transplant of less proportions, an hypophysis 
for example, probably brings about a protective ferment for- 
mation of comparatively limited extent, a formation entirely 
commensurate with its size. There is every reason to believe 
then that the process is the same in each case. From these con- 
siderations we are fairly safe in concluding that a small graft 
as well as a larger one is capable of stimulating the formation 
of a protective mechanism in the body of the host. 

Since the subcutaneous," intraperitoneal, 15 and oral admin- 
istrations " of protein all stimulate the formation of ferments 
capable of breaking down such a protein into its cleavage prod- 
ucts, it is clear that procedures of this nature, if instituted 
before or during a transplantation, will serve to aggravate the 
antiferment formation evoked by the graft itself. 

CONCLUSIONS. 

1. The results of this work agree with the conclusions of 
those investigators who have found that the Abderhalden fer- 
ments are specific. 

2. In transplanting epithelial organs it is necessary to re- 
member that such a procedure stimulates the formation of 
antiferments in the host : and, in the case of glands, it is im- 
portant to avoid any preliminary intravenous or subcutaneous 
feeding — perhaps oral also — of the substance, since such ad- 
ministrations encourage the development of protective enzymes 
on the part of the host. 



"Frank, E., u. Rosenthal, F. : Miinchen. med. Wchnschr., 1913, 
LX, 1594. 

,s Fuchs, A.: Miinchen. med. Wchnschr., 1913, LX, 2230. 

"Bauer: Wien. klin. Wchnschr., 1913, XXVI, 1109. 



PRINCIPAL TYPES OF MICRO-ORGANISMS IN BALTIMORE MILK. 

By L. P. Siiippen, M. D. 
(From, the Laboratory of Hygiene and Bacteriology, Johns Hopkins University.) 

on inconstant properties of the media employed, and which 
are frequently of so elusive a nature as to be incapable of de- 
scription. On the other hand stress has been laid upon those 
biological activities which are usually constant, and whose 
presence or absence may be indicated by positive or negative 
characters. 

The samples of milk examined were collected from small 
shops in the northeastern part of the city, with the exception 
of two specimens obtained in bottles from local dairies. Plates 
of agar were poured at once and the predominant colonies 
picked up after twenty-four to forty-eight hours incubation at 
37° C. The samples of milk were also incubated for twenty- 
four hours, and a second set of plates made from which colonics 
were also picked. When for any reason there arose suspicion 
of a mixed culture, plating was again resorted to. or whenever 
the colonies were so numerous that there seemed danger of 
transferring a mixed culture, the colonies themselves were 
again plated, and well separated colonies transferred to agar. 



During the past year an attempt has been made to describe 
ami classify the most frequent and important organisms found 
in Baltimore milk. Tiie studies on pasteurization now being 
made in this laboratory, and the attempt to demonstrate the 
setiological relationship between certain intestinal infections, 
notably typhoid fever and the summer diarrhoea of children, 
and an impure milk supply, render such a study of great im- 
portance, as it is manifestly impossible to determine the fate 
of pathogenic organisms or to explain the effect of heat of 
various degrees on milk without some notion as to the bactei ia 
which predominate in the milk in any given communitv. 

The organisms which we have encountered have been de 
scribed as Ear as possible in such a way that their identifica- 
tion by other workers in this field may be comparatively easy. 
No great care has been expended upon descriptions of colonies 
in agar or gelatin, or the manner of growth of the organisms 
in these media, on shades of pigment, or upon a number of other 
properties of bacterial growth which are variable, and depend 



April, 1914.] 



JOHNS BOPKINS HOSPITAL BULLETIN. 






Tin' organisms from these agar growths were then in 
into litmus milk, gelatin, potato and Deutral broth, and into 
dextrose, lactose, and saccharose l>r«itli in fermentation tubes. 
With certain organisms which failed to grow well in broth, 

which the various sugars were added, « 
fur the fermentation tubes. Of the media mentioned 
the least value from the standpoint 
Btancy and clearness in description, but was used thro 
ts importance in a few instances, and out ol 
to former dea riptions. 

Only twelve different samples of milk were studiei 
no attempt was made to isolate and describe all thi 
bacteria existing in milk, and it was found that the common 
types were encountered in the first few specimens examined. 
The later samples revealed the same organisms, or variants of 
e differing in no very important details. About fort] 
different strains were isolated, and we believe that these in- 
clude the most common varieties of bacteria existing u 
more milk. 

The organism most frequently encountered, and th 

which seemed to exist in the greatest numbers corresponded to 
a type described by Giinther and Thierfelder," Leichmann,' 
ami others as a bacterium, and by Grotenfeldt' and ol 
a streptococcus, and which is commonly known a* /• 
'. lactis acidi, and as Streptococcus laclicus. 
Great confusion exists in regard to this organism on account 
of the fact that different investigati 

. while others have given a Minilir name to a distinct. 
separate species. Thus Hueppe ' bas named /.'. m 
organism which grows like /;. coli, produce- gas ,p 
forms -pore-, and peptonize- milk, and Grotenfeldt and Zopl ' 
independently have di -eriheil bacteria indistinguishable from 
l!mt. arogenes and /■'. coli which they bav< called B 
/•/< Hci, and Perkins : has taken this type, and made it a 
subdivision of the Priedlinder group. At the presi nt tine 

•ii /.'. acidi lat lid has very little i 
at all it should apply undoubtedly to the organ 
by Hueppe, which stows luxuriant!] 
in dextrose, and which 
li.i, l. ■> U gula, and '.v 

Perkins differ- from the latter only by its inabil I 
rose. 
The other type w predominai I 

more milk, >wn as B. 

very faintly on agar, pi 
luthors i- a ' . 

Giinther and Th • 
it. but errom - inism with I 

ibed by Hu< 
the dilfereii, 
the organisn 

ti, iof II u. 

Giinther and Thierfeldi 
teriiim. later calli 
Ii. in ie 

authors continuing to apply I 
which should bear the former 



To make i 

well shown by tl 

ther and T 
Bjnonyms I 

■ 
probably identical « ith it. 

In addition, the curious ; 

liniann made the - I 
evident from the literature that tie 

isms of identical cultural cha im, the 

other a streptococcus, or else that thi 
of a sit differently u I 

observers. Thus Leichmann Lft named the bacterium 
ther and Thierfelder /■' 
l • . K-tcii." and Schierbeck 
same organism as a bacterium. Hut Krus 
to the resemblance which it bore t" tl"- pneui 

-;ed that a hotter term would 
though he acknowledged that rod-shaped font 

Then Grotenfeli inn " and Freudi 

scribed strepl i w hii h seem identical with t' 

cut lacticus of Kru-e. and finally Marpmann" 

elltly the sail r^aiil-ln >'/■' 

• ven by K • 
generally adopted, and has found its way into 

hook-, hut has th. ■ 

nil form, and ol placing the 

of Btreptococi i, tl 

the Sti On 1 

avoid the use of tl 

■ 
tnted the n 
Neumann i 

other and Thierfi 
them 

men o 

ant type in 

drop n 






I'M 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 278 



pairs, short chains and clumps all added to the picture of a 
contaminated culture. But repeated platings failed to change 
this appearance, so that it is evident that hut one organism was 
present. 

(•n the other hand other strains when examined in the same 
way seemed at first glance to be genuine diplococci or strepto- 
cocci, and at first the writer thought it possible to classify the 
various cultures into two distinct types, one a polymorphous 
bacterium, the other a streptococcus. But careful search 
always revealed streptococcus forms in the bacterial type, and 
bacterial forms in the streptococcus type, while so many strains 
were intermediate in character that finally the writer was 
I'm icd to the conclusion that no definite line could be drawn 
between the two varieties. 

When examined in smears stained with gentian violet the 
likeness to streptococci became even more marked. The rod- 
shaped forms under these conditions appeared mostly as diplo- 
cocci, and as noted by Kruse resembled closely the pneumo- 
coccus. In milk the various strains also appeared as diplococci 
and as short streptococci, and in plain broth and in the sugar 
broths long chains were frequent. 

All of the strains isolated agreed in growing faintly on meat 
extract agar, in producing no haemolysis on rabbit blood agar, 
in being Gram positive, in showing no motility, nor capsules, 
nor spores, and in being facultative anaerobic, growing even 
better in the stab than on the surface of agar. In addition, 
they grew at a temperature of 20° C. as well, though more 
slowly than in the thermostat at 37° C. This important fact 
was early recognized by Kruse lc - in his discussion of the rela- 
tionship of this organism to the pneumococcus. 

The colonies in agar appeared at the end of twenty-four to 
forty-eight hours in the thermostat as minute pin points and 
pin heads, which, under the microscope, appeared homogene- 
ous and translucent. Some strains grew in broth in the form 
of a flocculent precipitate without turbidity, while others pro- 
duced a faint cloudiness in this medium. On potato there 
could he observed at times a barely perceptible growth ; at other 
times no visible reaction could be perceived. Xone of the 
strains liquefied gelatin, though they all grew well along the 
line of the stab. In regard to milk, the action was variable, as 
has also been noted by Kruse.' 1 Sometimes this medium was 
coagulated with a strongly acid reaction and reduction of the 
litmus after twenty-four hours in the thermostat. At others 
only a slight, though permanent, acidity was produced, even 
at the end of two weeks or more. At first this was thought to 
indicate definite strains, but it was found that the power of 
coagulating milk was not a constant quantity with this bacter- 
ium. When a culture which possessed this quality was plat I 
it was observed to give off strains which failed to coagulate the 
milk, though otherwise identical witli the original organism. 
and one culture which at first failed to coagulate, after several 
month's growth on agar assumed this power. 

The action of the organism upon dextrose, lactose, and sac- 
charose broth was found to vary with its power of growth in 
these media. But when agar was used as a base the result lie- 
earn, constant for each particular strain, and consisted in all 



cases in the production of acidity in dextrose and lactose. In 
saccharose some strains caused acidity, while others did not. 
No gas was ever observed. 

When injected subcutaneously into rabbits and guinea pigs 
in large doses no apparent harm resulted. A number of guinea 
pigs and rabbits were thus treated with broth emulsions made 
by scraping and washing the growths of freshly isolated strains 
from twenty-four hour slant agar cultures. At the end of 
four weeks these animals seemed as healthy as ever. 

The viability of the organism was tested by transplanting 
every month from agar slant to agar slant for one year. Under 
these conditions the organism continued to live, and four 
strains so kept gave at the end of this period the same reactions 
as at the beginning. A fifth strain which at first failed to 
coagulate milk later was able to do so. 

The thermal death point of these strains in milk was roughly 
estimated after nearly a year had passed from the time of their 
isolation, and strangely enough was not found to be uniform. 
Thus four of the cultures were killed when transferred to milk 
and immediately heated in a water bath kept at 60° C. for 
fifteen minutes. A fifth strain when repeatedly treated under 
identical conditions survived a temperature of 65° C. for fifteen 
minutes, hut. was killed by 70° C. for the same length of time. 
Morphologically, this latter culture belonged to the strepto- 
coccus type of Bad. guntheri and seemed to be otherwise 
identical with types whose thermal death point was under 
60° C. The fact that one strain showed in milk a thermal 
death point of between 65° C. and 70° C. would indicate that 
some strains of this organism are capable of surviving pasteuri- 
zation. 

On account of the importance attached by many departments 
of health to the presence of streptococci, and especially of the 
Streptococcus pyogenes in milk, and because of the resem- 
blance which this organism bears to Bad. guntheri, it may he 
well to consider here the question of the identity of the two 
species. Kruse 1 - - first called attention to the great similarity 
existing between the lactic acid bacterium of Leichmann and 
the Streptococcus lanceolatus, and proposed for the former the 
term Streptococcus lacticus. Heinemann 17 in a recent paper 
states that " the Streptococcus lacticus agrees in morphologi- 
cal, cultural, and coagulative properties with pathogenic, fecal 
and sewerage streptococci," and further concludes that " since 
Streptococcus lacticus is invariably present in market milk, 
and in fresh milk collected with good precautions, the sanitary 
significance of streptococci in market milk will need further 
investigation." 

With this latter statement we agree thoroughly, but in our 
opinion there do exist definite morphological and cultural dif- 
ferences between Bad. guntheri (called S. lacticus by Kruse 
and Heinemann), and the Streptococcus pyogenes, which is 
evidently the organism meant under the term " pathogenic 
Streptococci." This point is important from a public health 
standpoint. For if S. pyogenes agrees in its morphological 
and cultural properties with Bad. guntheri, it is evident that 
the identification of S. pyogenes becomes impossible. And 
since Bact. giintheriis practically always present in milk, even 






April, 1914.) 



.loiINs EOPKINS HOSPITAL BULLETIN. 






<>f hi^rli quality, it follows that the isolation of an orj 
having its cultural and morphological proper! 
have any sanitary significance. 

But according to our observations Baci. giintheri and S. 
pyogenes show the Following differentia] points: 

First. Morphologically />'•!</. giintheri usually presents 
some rod-shaped forms w hen examined in a hanging drop made 
from an agar slant, and some strains show very little resem- 
blance to streptococci under these circumstances. S. p 
on the other hand is commonly a definite streptococcus under 
such conditions. 

Second. Baet. giintheri never hemolyzes blood agar in our 
experience. S. pyogenes usually does so. 

Third. Bad. giintheri lives for at least a month on meat 
extract agar kept at room temperature. S. pyogenes on this 
medium under these conditions dies in about ten to fourteen 
days, .T even in a shorter period of time, and indeed maj not 
grow at all. 

Fourth. Bad. giintheri grows on favorable media at a 
temperature of 20 c ('. S. pyogenes requires a higher tem- 
perature. 

Fifth. One of the .-trains of Bm l. giintheri isolated by the 
writer possesses .1 thermal death point of between 65 C. and 
70° C. S. pyogenes has a thermal death point of 54° C. 
according to Sternberg'' and Bartmann." At times it may he 
possible to differentiate the two organisms by tins means alone. 

Sixtli. Some observers Btate that Bad. giintheri i- not 
pathogenic for rabbits and guinea pigs, although others differ 
m regard to this, Heinemann admits " thai streptococci 

freshly isolated from milk, apart from those originating fr 

mastitis, do not possess high virulence," hut claims tl 
property may he acquired. In the writer's experieno 
/niitlu ri is oon-patbogenic for rabbits and guinea pigf 
when inoculated in huge doses from freshly isolated -tram-. 
8. pyogenes when freshb isolated usually is pal 

iinals. 

In addition, it should he remembered that much of the con- 
fusion existing in regard to the various prop I 
jii/ogetirs may arise froi I Met that many of the 
cultures recovered from tonsils, the mucous membram 

mouth, and other ■- touched by milk, with «he 

giintheri i- readily confused, \ery possibly may be in 
/;./< /. giintheri, and tine N . /"/"■: 

If these observations a 
may he identified and - 

seems universally presenl in milk, and which it so 
-emhle-. In consequi I 
the typical morphology and cultural 
should have somi significance from a public health »\ 
But it must he admitted that s 
resemble eai h othi 
morphologii al features tliat 

culture til. \ , .III died olll\ al 

In addition, the tv 

distinguishable in milk by morpholi § 

time- presenting minor differ) ;. 



mation. In ., m ,|i, 

made solely on th( lamination must be 

dubious m . harai ter. 

i hich m in., 
uilar to /,'.;. /. gunthi ■ i. and tor thi- 

here. This organism, which probab 

with the one ineiit 1 by Conn " U 

found three time- in fres milk, ami on t » 

the predominant type present. It 

semhled the ha. tcruil type of Bad. giintheri, and like the 

hi'ter - inn,- presented the appea nixed culture. 

At times when examined in a hanging drop made from an 
agar slant preparation many of the form- seemed to bl 
fat rods with rounded ends. Others were -.> -h..rt as to ap- 
rcular, and v.t other- were beyond doubl rather thin 
bacilli. Short chain- were common. Like Baet. guniheri 
the organism was Oram positive, and possessed neithi 
sules, nor the power ol spore formation. At iir-t u ■] 
to he Don-motile, hut after several month- growth on agar there 
was observed a definite rotatory motility quite distinct from 
Brownian motion. « hich placed it definitely in the i lass of the 
bacilli. Culturally the organism differed from Baet. giintheri 
by it- action on litmus milk, in which it produced no apparent 

change, and upon lactose agar in which it caused no acidity. 
otherwise it was identical with the saccharose fermenting 
t\ p.- of Baet. giintht ri. 
After Bad. giintheri, wlmh is ..i constant ... currem • in 

Baltimor. milk, the most frequently .• untered sinj 

ganism was Bacterium atrogenet (Escherich) Uigula L< * i /•' 
lactis vrogenes). It wat present in hall I ol milk 

examined, twict m fresh, and four tunes in .incubated milk. 
It i- significant that half the specimens did not reveal the 
organism on the plate-, and n i- reasonable to conclude that 
it was either lacking from t .■ samples, or, what i- more prob 
able, present in comparatively, small numbers, since T ' 
-m.- of tin- bacterium are large and ».l' 

and not readily ovei looked. I 
. al morphologii >i and . ultural under 

the microscope w Ik in a milk pri 

encapsulated ha. t. rium, 1 1 

. oagulated milk without 
tin. produ< . ■' 
carbohvdrati 
m the Friedlandt r 

scribed 

In ai 
with thi 



126 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 278 



when first isolated were quite devoid of motility, even in 
18-hour cultures in broth, and such organ isms naturally 
resembled the Bacterium acidi lactici (Perkins) of the Fried- 
lander group. But with the exception of one strain all such 
cultures developed definite motility after cultivation in the 
laboratory for a time, and were thus clearly to be regarded as 
/;. coli, and the one strain in which no motility was ever demon- 
strated failed to show any mucoid growth on agar, and at no 
time could we determine in it the presence of capsules. This 
culture we came to regard as representing the B. coli immo- 
bilis of Germano and Maurea, 21 since it has all the cultural 
reactions of B. coli communis of Escherich, but is devoid of 
motility. Then an organism which was identified as II. zenkeri 
(Hauser) Migula lc - * (B. proteus zenkeri) was obtained three 
times, once from fresh and twice from sour milk. This was 
characterized by branching colonies on agar, and a branching 
penetrating growth on an agar slant and in gelatin. It was 
positive to Gram, was motile, and showed no spores. On potato, 
it produced a dirty brown growth ; gelatin it failed to liquefy, 
and milk it rendered alkaline, without coagulation or peptoni- 
zation. In dextrose, lactose, and saccharose broth it produced 
neither acidity nor gas. Xo characteristic cultures of B. 
proteus vulgaris, nor of 11. proteus mirabilis were ever isolated. 

In addition to these well-marked types, a number of non- 
pigmented, non-spore bearing bacteria were isolated whose 
characteristics we usually associate with the organisms of the 
intestinal tract, and for this reason are described in this paper, 
although they cannot be said to occur frequently- in the Balti- 
more milk. These bacteria present great difficulty in proper 
classification. They have doubtless been described by other 
observers as occurring in milk, but if so the descriptions are too 
inadequate or indefinite to be made use of. They correspond 
closely to species described by Ford " ! as existing in the in- 
testinal tract, and while the absolute identity of the two sets of 
organisms, one derived from the intestinal coutents, the other 
from milk, cannot be proven, we prefer to follow the descrip- 
tions given by this author. These organisms were as follows: 
Bacterium oxygenes, isolated in one sample of sour milk; 
Bacterium cceci, isolated from one sample of fresh milk, and 
Bacillus chylogenes, which was found as the predominant 
organism in one sample of milk, both when fresh and sour. 

Bad. oxygenes was Gram negative, showed no motility or 
capsules, and formed no spores. It had the appearance of B. 
coh on agar, produced a luxuriant growth on potato, and made 
broth turbid. It failed to liquefy gelatin, and "coagulated 
litmus milk with the production of whey and of a pink color 
that seemed to indicate acidity. Yet neither in lactose nor 
saccharose broth did it form any acidity or gas. In dextn 
broth it produced acidity without gas, and in this differed from 
the Bad. oxygenes of Ford, which made this medium alkaline. 

B. c(eci like the preceding was Gram negative, formed no 
spores nor capsules, and showed no motility. But on agar it 
appeared translucent and moist, and on potato and in broth it 
failed to grow visibly. It liquefied gelatin slowly, and pep- 
tonized milk with an alkaline reaction, and without coagula- 



tion. In dextrose, lactose, and saccharose agar it produced 
neither acidity nor gas. Except in regard to motility this 
organism corresponded very closely to the B. cceci of Ford. 

B. chylogenes was of especial interest, since it appeared in 
large numbers in the one specimen of milk in which it was 
found, and indeed seemed to be the predominant organism. It 
was Gram negative, possessed no capsule, formed no spores, 
and was violently motile. All of its reactions were very slow 
in forming, appearing only at the end of from three to ten 
days. On agar the bacillus at first grew faintly, but later re- 
sembled B. coli in its general appearance. It flourished lux- 
uriantly on potato, and produced turbidity in broth. It lique- 
fied gelatin, ami coagulated milk. It produced neither acidity 
nor gas in lactose and saccharose. In dextrose it formed 
acidity without gas. It will be seen that this organism cor- 
responds to the B. chylogenes of Ford, except for its growth 
on potato. 

Associated with these organisms may be placed a species 
which occurred in half the samples of milk examined, five times 
in fiesh specimens and once in an incubated specimen. Al- 
though it was never the predominant organism, it was a clear- 
cut variety, with definite cultural reactions, and was com- 
paratively easy to recognize. In its cultural reactions it closely 
resembled the B. fcecalis alkaligenes of Petruschky, from which 
it differs in regard to motility, morphology, and Gram reaction. 
It also resembled the organism described as B. No. 06 by 
Conn lc * and the B. Troilii (Bad. lactis longi b) mentioned 
in Mat/.usehita, lc f with which perhaps it may best be iden- 
tified. 

Examined in the hanging drop this organism appeared as a 
rather fat bacterium, about twice as long as broad, with 
rounded ends and without motility. No capsule was demon- 
strated. When stained by the Gram method it retained the 
gentian violet. On agar its growth resembled closely that of 
B. coli. Its colonies in this medium after twenty-four hours 
incubation appeared as minute pin points and pin heads, 
opaque when deep, delicate and translucent on the surface. 
However, in forty-eight hours these grew r to be quite large, 
and were often indistinguishable from those of B. coli. In 
gelatin and on potato it likewise resembled B. coli. causing no 
liquefaction of the former medium, and forming a moist, 
heavy, brownish growth on the latter. But in milk and in 
the sugars employed its action was quite different. In these 
media it produced no acidity. No gas was formed in dex- 
trose, lactose or saccharose, and litmus milk inoculated with 
this organism gradually became more and more alkaline, 
but was never peptonized, or coagulated. In meat extract broth 
it usually failed to grow, although one strain succeeded in 
producing a slight turbidity in this medium. 

A variety of this bacterium was found on three occasions 
in fresh milk. It differed from the more common type in 
producing acid in dextrose, and in causing no visible growth 
on potato. 

The most difficult organisms to classify satisfactorily, and a 



* P. 54. 
f P. 376. 



April. 1914.] 



JOHNS HOPKINS OSPITAL BULLETIN. 






group encountered with great frequency, being in fi 
to B. leichmanni in this 

occi. By fur the larger number resembled closely the 
pyogenic staphylococci, from which often they could 
ferentiated only by 'heir manner of growth on agar, .1 
beristic very difficult to describe clearly. The various strains 
belonging to this type differed but little in cultural reactions, 
and could 1"' included in one group whose various m 
arc apparently identical with the organism described I 
merman " 3 from water ( .1/ 

from air (Microi its aureus). For convenience of descrip- 
tion, they will !»<• placed in one group, which will be named 
after thi si isolated by Zimmerman {M. 

One or more members belonging to this general t\ 1 
isolated from ten specimens of fresh milk oul 
examined, but wire never the predominant organism, I 
occasionally occurring in large numbers. The different strains 
agreed in being ■ Iram positive, and often showed a variation in 
size and in intensity of color when stained with the ordinary 
anal in e dyes. It was not unusual to see in a smear from a 
arefully plated culture forms so markedly different in 
size and in depth of staining that it was impossible t«> believe 
in the purity of the preparation. Yet invariably subs 
plating failed to change this appearance. At the present time, 

eral months growth on agar, this peculiarity 
appeared, and only rather large staphylocci are found in the 
cultu 

The various strains appeared on agar plates as large, 
opaque, white or yellowish colonies. On agar slants tl 
luxuriantly, at first white, but later often turning to 
yellowish tinge, the agar its* U assuming a brownish color. In 
gelatin liquefaction along the Hue of the Btab was produced in 
from forty-eight hour- to ten days, while on potato there 
usually appeared in twenty-four hours a flat, white or 
i>h growth, at times faint, at others profuse, probably ■ 
ent upon rome unknown factor in the ingredient 

In milk the different members of the group va 
what, for while the majority 

medium wit! "ii of so much whey that pi 

tion wai indeed have been pn 

others producei n 1 soft icid coagnlum, with Httli 
whey. 

All of thi • lity without 

-. and l.i. ii.-- agar, but in saci har 
icidity in twenty -four hours, othen 
lays incubation. 
The only other coci us found mor 

eour f the 1 jam 11 I 

■ 
group in it< manner of growt 
tural reactions, but differ 

a. The former mediun 
late, while gelatin it liquefied in tl • 
than along the In • 



but could not 
cina forms pi 
For tin- reason am 

variety oup. 

Tin 
commoi isting in t! 

growing aerobically at bo 

Bui 111 addition, thi 

and in, 

ilar to those found in the air ami water. Tl 

mi onstant, and thi 

milk cxamii 
varieties, but it was fell that their rarity and 
their detailed description a matter of lit' 
it i> worthy of note that on tv 
the predominant type in curdled milk, In 
numerous than lint. gi'm then, and thai 
though the predominant type m curdled milk, yet fai 
isolation to produce any but an alkaline reaction upon this 

mediuni. 

This \ea-t grew rather faintly upon agar, pro, 
meiit. and was t Irani positive. It failed to liq 
and made milk alkaline in much tl 

■■roth it pro 
ami gas, which cons 
lactose broth neither acidity 

T 1 other varii I 
..in- sample of curdled mi ntical with t : 

except tor 11- .!■ tion upi ind milk, i 

ilhlted. whili 
both acidity and | 

.(IN 

l. Tin most 

mm. I 

■. 

first 

from tl. - 1 

■ 



128 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 278 



tered during the examination, and it seems possible that this 
organism deseribed as occurring frequently in milk may cor- 
respond to the B. coli immobilis of Germano and Maurea. 

(J. Other organisms resembling B. coli in many ways may lie 
isolated from time to time, and sometimes are the predominant 
type in the sample of milk collected. Their identification 
presents great difficulties. For the sake of clearness they have 
been regarded and described as identical with some of the 
rare organisms found in the intestines. 

7. A bacterium resembling B. alkaligcnes in its cultural re- 
actions, but perhaps best spoken of as Bad. Troilii, is quite 
common in fresh milk in this vicinity. 

8. The micrococci in milk are found in such great variety 
that any satisfactory classification is difficult to make. The 
majority may be grouped together as the cremoides type first 
described by Zimmerman. They are organisms apparently 
derived from air and water, and usually are recovered from 
fresh milk. 

!>. The remaining organisms isolated, while presenting in- 
teresting features in special cases, are too inconstant and 
usually too few in number to make their description a feature 
in a paper of this character. 



BIBLIOGRAPHY. 

1. Gunther and Thierf elder: Arcii. f. Hyg., 1895, XXV, 164. 

2. Leichmann: Centralbl. f. Bakteriol., 1896, Pt. 2, II, 777. 

3. Grotenfeldt: Fortschr. d. Med., 1889, VII, 124. 

4. Hueppe: Mitth. a. d. k. Gsndhtsanite, 1884, II, 309. 

5. Grotenfeldt: See Matzuschita: Bact. Diag., 1902, 370. 

6. Zopf: See Chester: Manual of Determ. Bact., 1901, p. 149. 

7. Perkins: J. Infect. Dis., 1904, I, 264-265. 

8. Matzuschita: Bact. Diag., 1902, p. 374. 

9. Fliigge: Mikroorganismen, 1896, II, 356. 

10. Liebmann: See Matzuschita: Bact. Diag., 1902, p. 374. 

11. See Heinemann: J. Infect. Dis., 1906, III, 174. 

12. Kruse: Centralbl. f. Bakteriol., 1903, XXXIV, 737-738. 

13. Migula: Syst. d. Bakteriol., 1900, II, 39, 42. 

14. Chester: Manual of Determ. Bact., 1901, p. 65. 

15. Lehmann and Neumann: Atlas and Principles of Bact. 
Trans. 2 Ed., 1901, II, 223. 

16. Bartlett and Murphy: Comm. Mass. M. Soc, 1912, XXIII, 456. 

17. Heinemann: J. Infect. Dis., 1906, III, 181-182. 

IS. See Hiss and Zinsser: Text-book of Bact., 1910, p. 341. 

19. Heinemann: J. Infect. Dis., 1907, IV, 88, 92. 

20. Conn: Classification Dairy Bact. Report, Storrs (Conn. 
Agricult. Ex. Station), 1899, p. 53. 

21. Matzuschita: 1. c. 450. 

22. Ford: Studies from the Royal Victoria Hosp., Montreal, 
1903, I, 4-95. 

23. Chester: I. c, 93, 99. 



BACTERIOLOGICAL FINDINGS IN BALTIMORE OYSTERS. 

By Morris Joseph, B. S. 
[From the Laboratory of Hygiene and Bacteriology. The Johns Hopkins University.) 



While but a few cases of typhoid fever have been traced with 
clearness to the use of oysters contaminated with sewage — 
such cases occurring, as a rule, in epidemic form as reported by 
Conn 1 — the opinion has been gaining ground that much of 
our winter typhoid fever has its origin in sewage-polluted bi- 
valves. This opinion is strengthened by the careful studj of 
the occurrence and distribution of the cases of typhoid fever 
in such a city as Washington. The recent observations of 
(Jorham, 2 however, throw some doubt upon the wisdom of 
attributing winter typhoid to this source, for he has shown 
that during cold weather oysters go into a condition of rest or 
hibernation, when the ciliary movement ceases and feeding 
does not occur, and the oysters become practically Tree linn, 
sewage organisms, even when lying in sewage-polluted beds. 
A bacteriological study of the oysters sold in Baltimore was 
undertaken, therefore, to determine whether they contain 
organisms derived from the intestinal tract and whethi i 
content in bacteria varies with the season of the year. 

Twelve different lots of oysters, with live in each lot. were 
examined. They were purchased in various shucking houses, 
where they were said to come from four different areas — Chesa- 
peake and Lynnhaven hays and the York and Rappahannock 
rivers. This examination indicates the quality of oysters at 
the time the\ are sold, mid not at the time of collection. The 
methods employed were those adopted by the Committee on 



Standard Methods of Shell Pish Examinations of the American 
Public Health Association. When the oysters were collected 
at the shucking houses, certain oysters with deep bowls were 
purchased and carried to the laboratory, where five of the most 
suitable were selected for examination. The outside of the 
shell was first thoroughly washed with running water to free 
it from dirt and then allowed to dry in the air. It was then 
sterilized by exposure to the free flame, especially along the 
thin edge, after which the oyster was opened with a shucking 
knife, also sterilized in the free flame. The mother liquor or 
shell juice was immediately drawn off in sterile pipettes and 
dilutions of 1-10, 1-100 and 1-1000 made up with sterile water. 
From these dilutions dextrose fermentation tubes were planted 
to determine the presence of fermenting bacteria, intestinal in 
origin, and agar plates poured to determine the approximate 
number of bacteria in each oyster. Finally, those fermentation 
tubes, in which an active evolution of gas had taken place, 
were plated and characteristic colonics transferred to agar. 
Colonies were also transferred from the agar plates used foi 
making the counts to agar and both sets of cultures identified 
by means of the ordinary culture media. 

In determining the quality of the oysters examined the 
standard method already referred to was followed. By it the 
oysters are scored in the following manner: The presence of 
Bacillus coli or some other gas producer in each of the five 



April, l'.'l LI 



JOHNS HOI'KIN 'SPITAI. BULLETIN. 






iai:i.i: i. 
Bai rERiOLOGii vi Booking oi Baltimore Otstebs ■ 



l AB1 



tnt] .lute. 



Rapi>ali«nii'»'Wl:n 
er. Lot I. I"-'-'' 



Chesapeake Ba 3 
Lot I!. ll-2-'12. 



York River, Lot 
III, 12-3 12. 



Rappalianntx-k. Lot 
IV. 1-14-1S, 



York. Lot V. 1-20- 1 

•13, - 

3 



Rappahannock, Lot 
VI. I-O-'IS. 



peake, Lo1 I 

\ II. 2-3r'13. 



Lynnl ' 

"\ III • 



«ake, Lot 1 

IN. 2-ll-'13. 







. 









II 


547 


1(H) 




11 









100 




+ 




ion 




+ 




100 




+ 




|HI> 




+ 




100 




+ 




100 






s 









10 


6.700 


+ 




100 


20,133 


+ 




100 


0,560 


+ 




too 


24,466 


+ 




100 






- 


111' 









10 


Nil count. 


II 




111 


Do. 










Do 










Do. 


II 




l> 


Do. 




n, ,. r . 


20 









II 




II 




111 












12, 


II 




II 




(1 













111 









II 


No count. 







II 


Do. 


II 




II 


Do 


n 




III 


Do. 


11 




II 


Do 






10 




11 




II 




n 














11 


' 


n 




1 




11 




1 






- 








101 




11 






























I 










n 




II 


■ 






Lynnhaven, Lot V 
2 l» '13. 



Rappahannoi k. Lot 
XI, 1 I "13. 



Rappaliamiork. Lot 
Ml. I 16-'13. 






1" 




II 




III 


I 000 


100 
















III 




II 


1 00a 


100 


12 000 




11 ,000 






ioo 




100 




I'M) 




100 


10 IKKI 


100 




- 





• The lunn . I 
taken too liter.,: 

for belli ■ 






oysters in any lot is given a value which represents tin 
rocal of the greatest •liliit i«>ii in which tin 

For example, if gas 1- present in h diluti f 1-10, I 

merical value for the oyster 1- 10; it present in a dilul 

1-lini u 1- 100. The numerical val iters in 

each lot Bre added, in order I 

fur that particular time of the year. The tests upon ■ hich the 

score is based are only presumptive ones, but in 1 

confirmed b\ the cultm 

quentl 

ml' t" tin- method and 1 
■ 
A number 
ing the result I 

il findings 
are in 
out of the i" 






■ 






130 



JOHNS HOPKINS HOSPITAL BULLETIN. 



|\"o. -278 



condemned by the most rigid standard. When it is remem- 
bered that some time necessarily elapses between the time of 
collection and time of sale, during which period the micro- 
organisms in the oyster have an opportunity to multiply, 
these findings must be regarded as pretty favorable. 

The most striking point brought out in this table is the dis- 
tinct change in the character of the oysters, according to the 
time (if the year. Thus in the early fall the scores were high, 
in the cold weather of midwinter low, and again high in the 
spring. This is indicated by striking an average for the various 
lots of oysters as is done in the following table: 

TABLE II. 
Seasonal Variation of Bacterial Findings. 

Average Average Average 

Source. Fall W r inter Spring 

Score. Score. Score. 

Rappahannock 100 15 405 

York 245 10 No exam. 

Chesapeake 500 10 No exam. 

Here it may be seen that during the cold winter months the 
scores of the three lots of oysters examined at different seasons 
are all low and the oysters free from contamination. These 
results confirm in a general way the opinion of Gorham and 
raise a serious question whether the typhoid fever which oc- 
curs in Baltimore during the cold months of winter can 
reasonably be attributed to oysters. Finally, it may be noted 
that there is a distinct correlation between the number of bac- 
teria in each oyster and the number of gas producers as de- 
termined by the fermentation tube. A low bacterial count is 
associated with absence of fermentation, and a high count with 
a fermentation produced by considerable fractions of a cubic 
centimeter. This seems to indicate that the increase of bacteria 
which the various oysters show is in large part due to a multi- 
plication of the intestinal organisms and not to an increase of 
the ordinary water species. This correlation between bacter- 
ia] count ami fermentation is indicated in Table III. It should 
be noted that no such correlation exists ordinarily in milk, as 
we have shown in a previous paper.* 

Varieties of Microorganisms Found in Baltimore. 

Many of the oysters examined revealed the ordinary spore- 
bearing and pigmented bacteria which are characteristic of 
water and have no significance in this connection. In addi- 
tion a number of non-spore-forming, non-pigmented species 
were isolated from time to time. These organisms were w'orked 
over with care and their cultural peculiarities established on 
the usual media. In some instances their identification pre- 
sented no difficulties. Thus Bacillus coli was obtained 14 times 
in 1? oysters with positive fermentation tests. It had the 
classical reactions of motility ami decolorization by Gram's 
stain, acidifying and coagulating milk, failing to liquefy gela- 
tin, producing indol, and fermenting the carbohydrates with 
the evolution of a gas consisting of a mixture of hydrogen and 
carbon dioxide, with an excess oi the former. Organisms dif- 
fering from Bacillus coli by their gas formula, producing an 
exec ss of carbon dioxide over hydrogen and thus corresponding 



to Bacillus cloaca of Jordan, were obtained five times. They 
differed from Jordan's Bacillus cloaca in not liquefying gela- 
tin, hut should probably be included in this group. 1 Their 
acidification and coagulation id' milk was also much slower 
than that of Bacillus coli. Bacillus alhaligenes of Petruschkj 
was isolated from one oyster. This organism also presents no 
difficulties in its recognition, since its alkaline reaction in 

TABLE III. 
Correlation Between Fermentation and Bacterial Count. 



Lot No. 


Sample No. 


Bacterial 
count. 


Dextrose 
dilution 1-10. 


Fermentation 
1-100. 


I 


1 


*2,833 










2 


2.103 










3 


.547 










4 


2,. -.33 


+ 


+ 




5 


1,033 








II 


1 


03,866 


+ 


+11 




2 


3,91 in 


+ 


+ ! 




3 


75,660 


+ • 


+ = 




4 


57,666 


+ 


+ ls 




5 


2:1.333 


+ 


+Ji 


Ill 


1 


*fi . 700 


+ 







2 


20,133 


+ 


+ 




3 


9,560 


+ 


+ 




4 


24,466 


+ 


+ 




5 


2,560 


+ 


+ 


V 


1 


12,000 





.0 






80,000 


+ 







3 


12,000 










4 


1.-,, 111 ill 










."> 


39,000 








VIII 


2 


11;, 000 


+ 







3 


2."), Ill 10 


+ 







4 


1,132,000 


+ 


+ 




5 











X 


1 


3 , 000 


+ 
+ 







3 


1,000 







4 


3.(100 


+ 







5 


1,000 








XI 


1 


14,000 


+ 


+ 




2 


13.000 


+ 







3 


1,000 










4 


12,000 


+ 


+ 




5 


11,000 


+ 


+ 


XIF 


1 


13,000 


+ 


+ 




2 


*5 1,000 


+ 







3 


16.000 


+ 


+ 




4 


10. 000 


+ 


+ 




5 


S.000 


+ 


+ 



•Indicates where gas should have appeared in one or both dilutions, but failed. 
These exceptions only number 3 out of 38 samples tabulated, approximately 8%. 

mills and its failure to liquefy gelatin or to act upon any of the 
carbohydrates place it quite definitely. In addition to these 
well-defined species, a number of forms were encountered 
which presented some difficulty in classification. The most 
frequent of these was an organism with some of the reactions 
of Bacillus coli and others of Bacillus cloaca. Thus it splits 
up the carbohydrates in the same manner as Bacillus coli, with 
a gas preponderating in hydrogen over carbon dioxide, and 
acidifies and coagulates milk with great rapidity. It thus 
resembles Bacillus coli. At the same time it causes a rapid 
liquefaction of gelatin in a funnel-shaped growth along the 



April, 1914.] 



JOHNS HOl'KI -IMTAI. IULLETIN. 






line of inocculation, resembling 

ism is identical with the organism isolated by Ford and Wat- 
son' fro • more city water and described b> I 
a liquefying fermenter. It was isolated R\ r work 
and was a well-defined species. In addition, we round on 
various occasions bacteria which agreed in their cultural rc- 
of the rarer intestina finally 
in the intestinal trai i ! 
important of these were : /•' ■• '• rii 

acidifying anil i lagulating milk, producing no liquefacti I 

gelatin and grow ing only in Ihe opi n bulb of the fermentation 
tube; /•' ■■ ■ us oryphilus. acidifying and coagulating milk, not 
liquefying gelatin «nd producing acid from dextrose growing 
in the • the fermentation tube ; two Bpet ies identi- 

fied as B i • and as /.' acidify- 

ing and coagulating milk, liquefying gelatin and producing 
acid from dextrose, wil growth in the closed arm in ■ ! 
Imt without it m the other. While these organisms were found 
«>n hut a few occasions, their cultural reactions w 
tinet and the re well marked. Whether they have 



time. S 
and pr 

which • 
that tl 
which M 
above. In I 

BIBLIOGRAPHY. 

■ XI. VI. 471 

1 1 mii: Am. .1- Pub I II, 24 

:: Prescotl and Wlnslow 
edition, 

4 Ford Jo i Hi pklm Ho p. Bu 191 
Jordan: J Hyg . 1903, ill. l 

-il and V?at will. 

t Ford: sui(li>> from the Royal \ 
Vol. l. ' 



BRIEF NOTE ON THE BALTIMORE CITY WATER 

By \l iRJOiui In 

'■••In. 1 he ./'.'ims Hopkini 



Iii a recent pap r b; Ford and Watson * it was poinl 
that the chemical treatment ol the Gunpowder water, tl 
source of the Baltimore City supply, had not resulted in as 
greal a diminution of intestinal bacteria as waa ti 

from the cxpei ie ! othi n tii -. The numb 

in the water was markedly diminished, but the fermenting 

»ms continued to appear « I 
January 1 a different method of applying the i 
inent waa adopted, alum being added first, followed 
hypochlorite of .odium. This treatment of t ; 
applied at the Montetx i 
It seemed of inter -I 
city water to determine 
applying I I resulted in 

III the 

out over a period • 
entirely different from 
oratory. During I 
prisingh Ii 

centlll 

.iin. I in the plates and on no 

The t 

seen in chemically treated wati 
drawn fron 



• Ford and Watson: Jol i 



I 

active fermentatioi 

on two 

only the ordinary 

ordinal 
anaerolx 

- 



132 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo.27| 



'ROCEEDINGS OF SOCIETIES. 



THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY. 

October 1. 1913. 
Two Cases of Helminthemesis (from the Out-Patient Department 
of the Johns Hopkins Hospital). Dr. David I. Mac iit, In- 
structor in Medicine, The Johns Hopkins University. 

The following two eases which I had occasion to study ;it 
the Johns Hopkins Dispensary la>t summer are sufficiently 
exceptional to deserve reporting. 

Case No. F. 8193. — J. W., male, white, married, age 25 years, 
American, farmer. Was admitted to the Dispensary June 19, com- 
plaining of "indigestion, pains in the stomach, and vomiting of 
worms." 

Family History. — Negative. 

Past History. — Negative. Bowels have been regular prior to the 
present illness. 

Present Illness. — Has been suffering for the past four years from 
indigestion, which takes usually the form of irregular pains more 
or less severe, of variable duration, coming on especially after 
eating. His bowels are irregular, usually constipated, necessi- 
tating the use of Epsom salts. Appetite, however, has always 
remained good. Has lost 15 lbs. in weight, in the last three months. 
For the last four weeks appetite has been ravenous. " The more 
I eat, the more I want," as he says. In spite of the good appetite 
he has lost weight, been nauseated, and vomited a number of 
times in the latter part of the day. 

Three weeks ago, after severe retching, he vomited a worm, 
which he described as having the appearance of a fish worm. He 
never noticed any worms in the stools before that time, but has 
since. Feels weak, and complains of pains around the waist line. 

Physical Examination. — Looks thin, pale, and feverish. Tongue 
heavily coated; foul odor from the mouth. 

Temperature 100.5° F. Pulse, 120 to the minute, regular, of 
moderate volume and tension. 

Heart and Chest. — Negative. 

Abdomen. — Flat and symmetrical. No tenderness on pressure, 
no masses felt. Liver and spleen not enlarged. Stomach is dis- 
tended by gas and rises high in the left axilla. 

Urine contained no albumin or sugar. 

Diagnosis. — From the history of the case, a provisional diagnosis 
of ascaris infection was made. 

The patient was given 1 gr. doses of santonin, and two days 
later brought some ten or twelve full-size specimens of ascaris 
lumbricoides which he had passed, thus confirming the diagnosis. 

Case No. F. 5242.— R. K., female, white, married, age 21 years, 
was admitted to the Dispensary on May 19, 1913. Her complaint 
was " tapeworms." 
• Family and Past History. — Negative. 

Present Illness. — In December, while in the early months of 
pregnancy, patient was vomiting frequently. One day after a 
violent retching she vomited a portion of a tapeworm. Becoming 
terribly frightened she called to her mother who ran to her assist- 
ance and pulled the worm out of the patient's mouth. The seg- 
ment thus expelled was about one and a half yards long. Follow- 
ing the shock of fright, the patient had a miscarriage. Two days 
later she passed two long pieces of worm per rectum, and has 
since then for half a year been passing small segments in the 
stools. 



At present patient complains chiefly of weakness and nervous- 
ness. She sleeps well and has no pains. Appetite is not very 
good; bowels are irregular. No spasms or convulsions. No more 
vomiting. 

Urine. — No albumin and no sugar. 

Diagnosis. — From the history of the case a provisional diagnosis 
of tapeworm was made. This was confirmed by the therapeutic 
test. The patient was given two V2 drachm doses of oleoresini 
aspidii and two days later brought a jar full of tapeworms. On 
examination of the segments it was found to be a taenia saginata. 
The head could not be found. 

The above two cases are remarkable for the vomiting or 
expulsion of intestinal parasites by mouth, complained of in 
both, which we may term " Helminthemesis." Vomiting of 
worms is not unknown, and yet is considered a rare occur- 
rence. The commonest cases on record are those of ascaris 
lumbricoides. This nematode may wander into various organs 
of the body and cases are reported of its getting into the 
mouth, the nose, the larynx (causing fatal suffocation) and 
even the Eustachian tube. (Eulenburg: Real Encyklopadie 
der Gesammten Heilkunde. 1896, X, 269, etc.) 

Vomiting of tapeworms or their segments, however, is a 
very much rarer occurrence, and only very few such cases have 
been reported. Only five instances have been collected in the 
great work on Animal Parasites by Davaine. (Traite des Ento- 
zoaires. Paris, 2d ed.) Mosler and Peiper ( Xothnagel's 
Handbuch, 1897, VI, 58) write: nur ausserst selten isi d& 
Abgang von Proglottiden beim Erbrechen gesehen worden. 
My second case undoubtedly belongs to this class. That abox* 
tion should have been induced by the shock is not at ali sur- 
prising, and recalls one of the cases quoted by the above writer. 
where a peasant was seized with a vomiting spell, and expelled 
part of a worm by mouth. A physician tried to pull out the 
rest, but the poor fellow, frightened, thought that his bowels 
were being drawn out and would not allow it. 

In this connection I have analyzed all the cases of tapeworm 
and ascaris infection admitted to the Johns Hopkins Dis- 
pensary in the last eight years. 

I have found in all 65 cases of taenia infection, and nine 
cases of infection with ascaris lumbricoides. Of the 65 t;vnia 
cases, 42 were diagnosed as taenia saginata. one was hothryo 
cephalus latus, and in the remaining cases the species was not 
stated. It was interesting to note that the majority of tape* 
worm cases ( 42 out of 65 ) were in women, and the ages of the 
patients were almost all below 10 years. Vomiting as a symp- 
tom is noted only in five out of the 65 cases, or 7%, a figure 
rather less than that given by Stiles (Osier's Modern Medi- 
cine 1. .~>iiii). Of the ascaris cases there was only one case Old 
of the nine that gave a history of vomiting, and all of thesi 
cases with the exception of one were in children, unlike the 
one 1 described, which occurred in an adult. 






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BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered u Second-Clua Master at th* Baltimore. Maryland. I' 



Vol. XXV.-No. 279. 



BALTIMORE, MAY. 19 14. 



(Price, 25 Cents 



CONTENTS. 



Iloidal Gold Reaction in the Cerebrospinal Fluid, illln- 
trated.) 
Bj Sydney R. Mii i us. M. D., and Robebi L. Levy, M.D 

1 Features of Acidosis and Their Occurrence in 
■ Renal l>i-' ase. (Ilhisl 
Bj Ai'iii" vVatso Sellabds, M. D. . . . .Ml 

The Work of the Out-Patient Department of the Henry Phippn 
Psychiatric Clinic. 
Bj C. M m i ii Campbi i.i . M. n 






Dj -Ir..] 

Bj 1.1 l>M, Ii. \\ HII II > m. \| h 

Louis B 

Bj M. i ii mi ro IM 

The Jo Hospital Mi 

m itli i >il of < henopod iun 
mens) Robi n i . Levy, Ml'. 

.... 



THE COLLOIDAL GOLD REACTION IN THE CEREBROSPI1S \l III 1 1 ». 

Bj SYDNEI Ii'. Mm 

i of Internal Vedicine, Th( Henry Phippt I 

■ ipitol. i 



1. Is i 
lamination of I linal fluid i~ essential in 

ly nt man\ m urolojrii nl am 
Prom it much infonnati 

ibtained, while receul ?tndi< - 
ami Klli-.' indicate thai it is n val 
i)f treatment, particularly tin 

and i posil 

and Halliburton ' and oth< i - proi 

blems. Pari 
the form and combinal 
ami abnormal flu - I' 
failed • 
same 

- 
of doubtful clinii ^ 

■ 
empirical state, quite apart from tin 

nded with many difficult • - and 



•Read before the Johns Hopkins 
March 2, 1914. 






spinal fluid 

Raid - 
from it. 









134 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xn. 279 



tein-comples group reaction, though it is commonly accepted, 
when positive, as Indicating an increase in the globulin con- 
tent of the fluid. That globulins in abnormal fluids constitute 
only a part of the precipitate caused by one-half saturation 
with ammonium sulphate can readily be demonstrated. Al- 
though positive in from 95$ to 100$ of luetic infections of the 
central nervous system. Phase I alone does not enable one to 
differentiate between luetic and n<>n-luetic conditions. It is 
incorrectly stated that the intensity of the reaction is always 
greater in the specific infections. While these three tests meel 
most of the requirements of clinical diagnosis, they tell us 
nothing concerning the factors responsible for their causation. 

The present report deals with one of the recent tests applied 
to the spinal fluid, in which colloidal chemistry plays the 
leading role. In view of the wide range to which the rela- 
tively new- subject of colloidal chemistry is applied, and the ex- 
actness of the laws which control and determine colloidal reac- 
tions, and their extreme delicacy, it is not surprising that this 
science should have found a place in clinical laboratory 
methods. If the predictions of such investigators as Ostwald 
are to be relied upon, we may ultimately expect to learn most 
concerning the aggregation of living protoplasm, the laws 
which govern immunity, the basis for the Wassermann reac- 
tion, etc., by the use of colloidal chemistry and allied sciences. 

The foundation for the present test was laid by Zsigmondy 12 
in L901. Having worked exhaustively with solutions of col- 
loidal gold, he attempted with success to use it as a mean- for 
the quantitative estimation of protein substances. It was well 
known that colloidal solutions of gold or other metals air 
precipitated or "coagulated out - ' by electrolytes, this coagu- 
lation depending upon the degree of concentration as well as 
the valency of the electrolytes employed. It was also recog- 
nized that colloids are electrically charged and that two op- 
positely charged colloids mutually precipitate one another, 
though only in definite quantitative amounts. If these 
amounts are exceeded in one way or the other, no precipitation 
occurs. Zsigmondy discovered that solutions of protein- give 
protection to colloidal solutions of gold up to a certain point, 
and he determined the so-called Goldzahl for various protein 
substances, by which is meant the number of milligrams of 
the protein employed," just sufficient to prevent the precipita- 
tion of 10 cc. of colloidal gold of a percentage of .0053 in the 
presence of 1 cc. of 1(K XaCl solution. By this method n can 
be determined whether a given protein is absolutely pure, or 
granted this is the case, how much is present in a given solu- 
iinn. In attempting to apply this gold protection method to 
the study of the proteins of the spinal fluid, Lange. 13 in 1912, 
discovered that instead of securing protection, quite the re- 
verse occurred, particularly in conditions in which the spinal 
fluid contained an abnormal amount of protein substance, 
notably in the syphilitic diseases of the central nervous system. 
Moreover, he observed that the reaction which occurred took 
place within certain dilution limits which seemed to he mure or 
less specific, thus making possible, by means oJ colloidal solu- 
tions (if gold, the differentiation between syphilitic ami i- 

syphilitic conditions. Since that time, the tesl a- u 



various observers has yielded fairly consistent results, which 
will be discussed in more detail in another portion of the 
present report. 

2. Apparatus and Solutions Required. 

A. Glassware. 

For the preparation of all reagents required, the following Jena 
glassware is necessary: 

1. Flasks: 1000 cc, plain and distilling, the latter provided with 
side glass outlet tube. 

2. Certified graduates: 25 and 1000 cc. 

3. Beakers: 1 and 2 litre sizes. 

4. Liebig condensers: all glass. 

5. Glass stoppered stock solution bottles, 2 litres. With the 
exception of the condensers, all glassware is rinsed with strong 
HC1, followed by distilled water and hot air sterilization for 30 
minutes. Condensers are cleaned with steam and rinsed by the 
first 200 cc. of the distillate, which is subsequently thrown away. 

In the actual performance of the test there are needed: 

1. Test tubes: 120x12 mm., thick walled. 

2. Certified pipettes: 1, 10, 25 cc. 

The tubes are cleaned each time by boiling in 10% potassium 
bichromate solution, and then in distilled water, using a brush 
when necessary, to remove all traces of precipitated gold from 
the sides and bottom. After sterilization they should be kept in 
a suitable dust-proof glass container until used. It is important 
to avoid contamination of the tubes by alkaline cleaning mix- 
tures. Pipettes, rinsed in an automatic washer, are dried with 
alcohol and ether and sterilized in a pipette box. Confusing re- 
sults will be avoided if a suitable supply of glassware is reserved 
solely for use in the test. We are convinced that upon the i are 
with which the cleaning ami sterilization of glasswan is 
out depends the success of the preparation of the gold solution and 
tin- reliability of the entire reaction. 

B. Solutions Required. 

(1) Distilled Water. — The preparation of the distilled water is 
the most important stage in the making of colloidal gold solu- 
tions. Ordinary tap water and ordinary distilled water are both 
unsuited for preparing the reagent. Freshly distilled water, re- 
ceived in a sterile flask provided with a side glass connecting 
tube, is immediately redistilled and used within two or three 
hours; if allowed to stand much longer the water seems to ac- 
quire properties which render it unfit for use. No rubber stop- 
pers or connections should be used in the distilling apparatus. 

(2) NaCl Solution (0.4%). — This solution, made with doubly 
distilled water and Merck's " Blue Label " sodium chloride, keeps 
for a long time, but it is desirable to prepare it at least every 
two weeks. There seems to be no advantage in making this dilu- 
tion each time from a stock 10% solution, as recommended by 
some authors. This particular strength is used because it causes 
no coagulation of colloidal gold. At the same time it is of suffi- 
cient concentration to hold globulins and nucleo-proteins in solu- 
tion. Spinal fluids diluted with water exert no action upon a 
gold solution. 

i :: i Colloidal Gold Solution. — The ingredients required to pre- 
pare this indicator are: 

a. Doubly distilled water. 

b. Gold chloride crystals ( yellow).! ,, ,, .. _, 

, Merck s Blue 

c. Potassium carbonate. L. , , ,, _ 

„ ,. Label Reagents. 

d. Formalin. 

One litre of water is heated to 60° C. in a sterile Jena beaker. 
At this temperature 10 cc. each of a 1% aqueous solution of gold 
chloride and a 2% solution of potassium carbonate are added 
synchronously and thoroughly mixed at once. From this point 
the solution is heated as rapidly as possible, by using a four or 



May, I 



JOHNS EOPKINS HOSPITAL BULLETIN. 






six flame Bunsen burner, until a temperature ol al 

. is reached. The flame is turn. .1 
beaker are iiriskly agitati 
r. aqueous Bolutlon ol rormalin are gradually added. The pr< 
vloualy clear, color! -s liquid al 

tion. with reduction ol the gold to a colloidal Btate, Bhowi 
production of a beautiful play of colore Th< resultant Bolutlon 
should meet the follow ii.. 

1. Color: A rich brilliant red with an orange glint whl I 
in thin layers. Thi or blue Bhadi 
be avoided. 

2, Such solutions must be absolutely clear and tran 
when s. in from any angle by any |] 

al fluorescent layer is an Indication tor 
■ 

inge in the physical propi i 
lng ability of good solutions. 
4. They do not dialyse or dill I 
:.. Protect! d fron evaporatl n sui b s i 
for an indeflniti lengtl light and ro 

|» ra! 

>;. With normal spinal fluids, such solutions give no r 
while with a paretic fluid completi occurs in th< 

first 4 

Other methods for the siandarizalion of cold Bolutii 
i so that workers may always emplo] 
parable indicator. Occasionally, a solution meeting all of the flrel 
uirements, will fail absolutely to read with a known 
abnormal spinal fluid: the cause for this is not known to us. We 
ther reducing ch as glucose and tannin. 

hut with results Inconsistent and generally unsattsfactorj 
tempt to "doctor up" a solution which fall 
■ rst two requirements. Provided due can If 

on of the water and the cleaning of i' 

■ iloidal solutions can always be obtained by the 
[bed. 

('. Ti ISAL F*L1 10. 

preferabl) 

.in. should no* be boiled prior to use 

d by drawing through them distilled 
cohol and ether, alter which they are sterilised in 
^ h two smal 

■ d with tie 

Every needle must be examined frequi 

■ 

If the pr 
it must 1 ■ 

though Wi mined all Bp 

■ 






Fig. 1. 

Lumbar 

Puncture 

Outfit 



into ii 

fluid are now add) 

the dilution is inn 

dilution of spinal fluid from the Oral 



Milts in .: Bin U r ■ ti ■ r dllui 
eight tubes, i" dilutions In all 

nth tub 

■ 

loldal - 
slble; otherwl 
tluid is appro* i 

making 

carry ou 

following morning, I 

peratun 

against and the tubi 

Una] readings with artificial liu-ht should 

■ 

I. Til 

slon value ol ti Iloidal gold 

the maximum pn 
par- tli fluid i, coi Isting In con i 
aiently by the flgun 
occur, runnn 

: blue, to which numerical valui 
shown In 1 tor the 



Piluhoni op 
C.S. fluid 




CI 




o 




o 


a 


9 




5 

* - 


5 


Colorless 
























1 


Tble or 
Graq-Blue 
























3 


T3lue 






r— 


—T 
















:. 


or 

Purple 






f 


A 
















1 


Red- 




/ 






\ 














. 


/ 






S 


. 


r— 






■ 






lng mi' 



mum it. 



136 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| ISTo. 279 



Pilurtons of 
CS. fluid 


o 


o 




o 

CD 


O 

o 


o 


O 


o 

CO 
CN 


o 


o 

CNi 


o 


5 


Colorless 
























ZL 


Pale or 
Graq-Blue 
























3 


Blue 
























2 


Lilac or 
Purple 
























1 


Red-Blue 



























Red 

























Fig. 3. — The reaction in meningitis with typical VerscMebung 
nach oben. 

3. From observations herewith presented we feel that the curve 
in dementia paralytica is sufficiently constant to justify the intro- 
duction of the term " paretic zone." This zone comprises the 
first 3 to 6 tubes, in which the reaction is characteristically of 
the " 5" type (Fig. 4). 



Pilurions of 
C.S. fluid 


o 


o 

M 


o 

T 


CO 


CD 


o 

K3 


O 

o 


o 

CO 


o 

CM 


O 


o 

o 

CO 


5 


Colorless 
































^, 


4 


Rale or 
Graq-Blue 










s 














3 


Blue 
























2 


Lilac or 
Purple 
























1 


Red-Blue 



























Red 































Fk;. 4. — The characteristic curve of general paresis. 

5. Nature of the Reaction. 
The exact nature of the reaction, it must be admitted, is 
not known. This is necessarily the ease, since the exact com- 
bination and nature of the protein substances which may 
occur in the spinal fluid under normal or abnormal conditions, 
have not been determined. Lange is inclined to interpret the 
reaction as an indication of the occurrence of different qualita- 
tive mixtures of protein substances rather than of a true 
quantitative increase in one or otheT of the protein constit- 
uents. There is considerable evidence in favor of this view, 
since the strength of the reaction apparently bears no con- 
stant relation to the amount of protein present, as revealed by 
the ordinary tests. Other writers, as Zaloziecki, 1 ' are inclined 
to view it as an immunity reaction, more or less analogous to 



the "floecule reaction " of Porges and Meier," Hermann and 
Perutz '" and others, used as a diagnostic test for luetic condi- 
tions. Exponents n( colloidal chemistry rather incline to the 
idea that the color changes are induced by variations in the dis- 
persion value of one or more colloidal substances present in the 
spinal fluid. No attempt has been made by us to prove which, 
if any. of these theories is correct, but merely to determine 
whether or not the test is of sufficient value to warrant it< 
adoption as an aid to clinical diagnosis. 

6. Routine Followed. 

The present report is based upon the examination of 210 
spinal fluids secured from 171 cases.* 

All fluids have been subjected to the following routine ex- 
amination : First, a quantitative estimation of the cells has 
been made as soon after withdrawal of the fluid as possible, 
usually within ten or fifteen minutes. We have used a dilu- 
ting solution consisting of distilled water, 50 cc; glacial acetic 
acid, 2 ce. ; and methyl violet, 0.1 of a gram. This stains the 
nuclei of the cells with sufficient clearness to permit of a fairly 
accurate differential count at. the same time that the quantita- 
tive estimation is made. In all instances counts have been 
made with the Fuchs-Rosenthal counting chamber. Second, 
increase in the protein content has been tested for by the Ross- 
Jones method. In our experience this test has yielded results 
which are both trustworthy and easily obtained. Third, the 
Wassennann reaction has been carried out by one of us on all 
spinal fluids and on specimens of blood from the same patients 
when available. Every fluid and serum has been tested with 
at least two, and in many instances with throe. aatigenSj 
namely, a plain alcoholic extract of the human heart, a similar 
extract, strengthened by the addition of .4^ cholesterin. and 
an alcoholic extract of syphilitic liver. It should be noted in 
passing, that in the great majority of the cases the results 
obtained with these three antigens have been parallel. There 
have been, howexer. undoubted cases of syphilitic infection in 
which the cholesterinized antigen alone has given a positive 
result, the other two antigens yielding an absolutely negative 
or, at most, a 1 + inhibition. Such cases are indicated in the 
reports given below. Fourth, the colloidal gold reaction. 

7. Tabulation of Results. 
Detailed case reports are herewith presented. The numbers 
1-10 under Gold Reaction refer to the dilutions previously de- 
scribed. A star indicates that the fluid was sent from an out- 
side source. Wassennann reactions positive with a cholesterin 
antigen only are indicated by the letter C. A cell count of 
ten or over has been regarded as a pleocytosis. 



* The rapidity with which we have been able to secure this 
number of observations is due in large part to the hearty co-opera- 
tion received from the various members of the medical, pediatrical 
and dispensary staffs of this hospital, to whom we express our 
greatest appreciation. It is also a pleasure to acknowledge the 
receipt of numerous spinal fluids from the Manhattan State Hos- 
pital, through the kindness of Dr. Cheney; from the Central Islip 
Hospital, Long Island, through Dr. Wescott's help; and from the 
City Detention Hospital at Bay View, through the co-operation of 
Dr. Kenneth B. Jones. 



Mat, r.'i U 



•lollNs BOPKINS HOSPITAL BULLETIN. 






rABLE I. MISCELLANEOI S (iROI P 












lo.... 



.....to.... 






...lo.. 






Ill 






■ 



t 






' 
































1 








1 










































. 








.....lo. . 

































































































































































■ 



■ 
II 



ru:i.i 









- 
- 













i 



i 
■ 






138 



JOHNS HOPKINS HOSPITAL BULLETIN. 



["No. 27S 



TABLE IV. CONGENITAL LUES. 



B. (7).... 

C Ml, .. 

C. (20)... 
C. (23.... 
II. I HH|.. 
M. (70)... 
S. I in, , 
S. (103).. 
S. ( KM).. 
Y. (127).. 



Cerebro-spinal fluid. 



\\ K. 



Negative. 

lo.... 

Posil ive.. 
Negal ive. 
....do ... 



...do. 
...do.. 



•_':: 



do.. 



1 Negative. 

1 Positive.. 

2 Negative. 



Cold reaction. 



J 1 000 

3 in 

1 i" 



0000 

I 000 

oopo 

,, i,n 

ii 



5 injections Neosal- 

injections Neosal- 
varsan. 
>astic paraplegia. 



TABLE V. SECONDARY LUES 



Pr. (151). 
F. (32)... 
J. (56) .., 



P. (85). 
W. I 125). 



Cerebro-spinal iluid. 



'In lo — 



Clobulin. 



Faintly + 
Negative. 
Positive . 

Negative. 
....do... 



Gold reaction. 



Condylomata. 

Mucouspatches ; boni 

pains. 
Mucouspatches : a lo 

poecia ; papulai 

eruption. 
Papular eruption. 

Mucous patches. 



TABLE VI. TERTIARY LIES. 







Cerebro 


spinal fluid. Gold 


reaction. 




( ase No. 


W. 1!. 










Blood. 












Remarks. 






YV. R. 


'_ 


Globulin. 123 1 




10 




.1. A. 1 153) 


Posil ive.. 


Negativi 


Negative. OO'OO 


00000 


i in u mesaorl i- 
tis. 
ii Lues not suspected. 


C. (16)... 


....do.... 


....do ... 


i 


....do ... 2333 


2 1 l) (I 


I.i.;: 


....do.... 


lo.... 


2 


lo ... 0001 




Aortic an, 


G. (37)... 


....do.... 


....do.... 


I 


....,lo ... 2 3.3 2 





Gumma of palate 


H. (12)... 


VI 


....do.... 


3 


....do ... 00 


i, ,, u i, i) 


n Treated sei ei i 


H. (It)... 


I',, ,, ive 


lo.... 


5 


lo. ... 00 


u on ii n 


o Latent case. 


H. (49)... 


Negative. 


lo.... 


6 


....do.... 122 1 


,, ,1 ,: 


n Thorough i reatment. 


J. (155) .. 




1 . 

Positive. . 


5 


....do.... ii 'I n i 


i 




K. (60)... 


....do.... 


\r-,,l l\ e. 


2 


....do... 


n i 


\l. (83) 


....do.... 


....do.... 




lo.... 132 


1 II 'I I \,,ll 1, 11 


W. (120).. 


....do.. . 


lo.... 


:■: 


lo.... II I) 1)11 


II II 11 ii 1! 


' 


\.ii..|i..' . n 



TABLE \ll. TABES DORSALIS. 



H. (5i)).. 

J. (55).. 
K. (61).. 
L. (65) . . 
M. (82).. 
P. (.89).. 

1'. I 

I!, (nil.. 
W. (124) 



Positive. 
...do... 



.do.... 

' re. 

Negal ive. 
Positive.. 



' lereb) o-spinal fluid. 



Positive.. 
Positive.. 

Positive.. 

Negal h e, 

Positive.. 
Negal ive. 



....do.... 
Negative. 



Positive.. 
Negative. 



Gold reaction. 



1 23 4 56 7S9 Hi 



' i , it , :i , enous dose of 
"606" between ex- 
aminations. 

Intra-spiuous treat- 
ment. 



Treated case. 
Extensive treatment. 



Treated Bince B99. 

1 intravenous injeo 
tion of "606" be- 
tween examinations 



TABLE VIII. CEREBROSPINAL LUES. 



Cerebrospinal fluid. 



C. (21)... WVnk pos- 

itive. 

D. (26)... Positive.. 

F. (152) do.... 

*F. (34) . . Not done. 



W. Ii. S Globulii 



H. (47).. 
L. (67).. 
M. (75). 
Q. (HI).. 
R. (06).. 



Positive 
Negativ 

Positive 
....do.. 



lo... 

Positive., 
....do.... 
....do... 
Negative, 
Positive.. 
Negative, 
. Positive.. 



R. (98) do.... 

R. (99)... Negative. 



Ni'iiatt' 



T. (113).. Positive.. Positive.. 107 ....do 



( I i i n 1 1 J 
positive. 

2 Positive.. 

5 Negative. 
4S Positive.. 

t ....do.... 
50 ....do.... 

3 F a i n 1 1 y 

positive. 
35 Positive.. 

7 Negative. 

i3 Positive.. 
8 

2 Negative. 

27 Positive.. 



V. (137) do ... 

*W. (144) do.... 



...do ... ....do... 

...do I 15 do.. . 



Gold reaction. 



1 2 3 4 5 6 7S j in 



Vigorous specific 
therapy. 

.6salvarsan previous- 
ly. 

Congenital syphilis. 



Congenital case. 

Optic atrophy ; luetic 

history. 
Bilateral abducens 

palsy. 
Hemiplegia : treated 



Intra-spinous treat- 
ment. 

Kpik'i'til o r in a I - 
tacks. 

Intensive "61)6" ther- 
apj : spastic para- 
plegia. 

Luetic aortitis. No 
nervous sy stein 
s, mptoms. 
ivanced case. 



TABLE IX. GENERAL PARESIS. 



Case No. 


W. I). 
Blood. 


Cerebro 


spinal fluid. 












W. R. 


i 


Globulin. 


T. (5).... 


Positive. 


Positive.. 


57 


Positive.. 


F. (5).... 


....do.... 


....do.... 


27 


....do.... 


M. (5).... 




....do.... 


39 


....do.... 


Ba. (5) . . . 


....do.... 


....do.... 


12 


....do.... 


Be. (5)... 


....do.... 


....do.... 


13 . ..do ... 


Tr. (5)... 


....do.... 


....do.... 


17s lo..,. 


P. (5).... 


....do.... 


....do.... 


I'll ....do.... 


H. (5).... 


....do.... 


....do.... 


lis I...... 


G. mi.... 


lo.... 


....do.... 


2 W e a It 1 v 


B. (6).... 


....do.... 


....do.... 


positive. 
6 Positive.. 


O. ii',,.... 


....do.... 


....do.... 




W. (151). 


....do.... 


....do.... 


16 


....do.... 



Gold reaction. 



1 2 8 4,5 6 78 9 1" 






May, 1914.] 



.lollXs HOPKINS BOSPITAL BULLETIN. 






l\\i;i.K IV GENERAL PARESIS. Continued. 



■pinal Buld 



\. I 0MPOS1 l I I VBI 









3 

•B. (182). 



.....lo.. 



H. (139) . 



....do.... 

....do.... 
....do.... 



..do... 





Positive . 




J. (57)... 






K. (58)... 


.....lo.... 




L. (147).. 










....do.... 






















....do.... 




















- 






T. (111).. 
































































...lo.. 






lo., 















I 





















.... 






. 












I 












- 






































1 








- 









- . \ \ \ ; . - 
\ Mi-, i . 

finding normal spinal fluid. 
• ! precipital 
conditions, presuraabl 

I!. Pi 1:1 I l \ l '• 

Iii i«ii of eight examinations madi 

that the supernatant Bui 
turbidity and the 
maining tu 
The anomalous <■ 

bacilli o 

firms ! 

■ 

1 1 



140 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 279 



de astrated in the blood in practically every instance, and 

was present in one hundred per cent of the cases constituting 
the present series. 

E. Secondary Syphilis. 
Reactions in the " luetic zone " occurred in four out of five 
cases. Eicke reports positive results in 60 of 136 examina- 
tions, at times even in the absence of pleocytosis and Phase I. 
This tends to support the view that syphilis, even in its early 
stages, is an exceedingly diffuse process, and emphasizes the 
importance of repeated lumbar punctures on all syphilitica. 
in the hope of detecting the earliest manifestations of meta- 
luetic disease. 

F. Tertiary Syphilis. 
In eleven cases, comprising instances of latenl syphilis, 
gummatous lesions and vascular manifestations, a reaction in 
the luetic zone occurred in four. In none was there any de- 
mons! rable clinical evidence of central nervous system involve- 
ment. Several of the individuals were elderly men. who had 
had their primary infection many years before, and who, in 
all probability, will never develop cerebrospinal syphilis, tabes 
or paresis. 

G. Taises Dorsalis. 

All .showed luetic curves. With three exceptions, these 
were of moderate intensity, yet definite. This is contrary to 
the statement of Kaplan and McClelland. 1 " who find in this 
group either no reaction at all or at mosl a very weak one in 
the first three tubes. 

Though clinically a tabetic, Case II 50 may well be in an 
early stage of tabo-paresis, in which cases we have always 
found a reaction of the paretic type. In two instances, strik- 
ing changes in the curves followed minimal amounts of 
therapy. 

H. Cerebrospinal Syphilis. 

Thirteen of the fifteen fluids examined reacted in the 
luetic zone, six with fairly marked intensity. 

Eicke, and Jaeger and Goldstein ~° state that the reaction in 
cerebrospinal lues may simulate that of paresis, differing from 
the latter in that it appears only after standing for several 
hours. We have had no difficulty in differentiating the reac- 
tions in these two groups of cases. 

I. General Paresis. 

The series exhibits a striking uniformity of results, in that 
all of the 49 cases gave characteristic paretic curves. 

The more advanced cases clinically have shown the most 
striking tests. \1. 69, aged 5, a ease of juvenile paresis, gave 
a typical reaction. That the reaction tends to remain un- 
changed both during remissions and after intensive intraspin- 
ous therapy, is in harmony with the " Wassermann fast " 
condition of the blood and spinal fluid observed in most 
instances of 1 W. 122 alone bas show a a mi 

diminution in the intensity of the gold reaction coincident 
with outspoken clinical improvement. 



9. Summary and Conclusions. 

1. The colloidal gold test is essentially a laboratory method. 
It can be performed rapidly and with a minimal amount of 
spinal fluid. 

2. Extreme care in the preparation of reagents and the 
cleaning of glassware is imperative. 

3. Normal fluids give negative reactions. 

1. The test is of no aid in the diagnosis of purulent or 
tuberculous meningitis. 

•"i. It has no advantage over known laboratory procedures 
in the diagnosis of congenital syphilis. 

6. Beactinns in secondary and tertiary syphilis are incon- 
stant. Their significance when present is not known. The 
statement that they indicate the earliest stages of central nerv- 
ous system involvement lack's proof. 

7. The positive reactions observed in the majority of cases 
of tabes and cerebrospinal syphilis are nut characteristic. 

8. We feel that the reaction peculiar to paresis is suffi- 
ciently constant to warrant its use as an aid in the differen- 
tiation of this condition from others with which it might be 
confused. 

it. It is possible that the test may prove to be more sensi- 
tive, than are those at present employed, as an indicator of the 
results of specific therapy in syphilitic diseases of the central 
nervous system. 

10. Much may be expected from the application of colloidal 
chemistry to the study of biological problems. 



REFERENCES. 
N. York M. J., 1912, XCVI, 53. 



J. Exper. 



1. Swift and Ellis: 
Med., 1913, XII, 331. 

2. Dandy and Blaekfan: .1. Am. Med. Ass., 1913, LXI, 2216. 

3. Dixon and Halliburton: J. Physiol., 1913, XLVI1, 215. 

4. Kafka: Neurol. Centralbl., 1912, XXXI, 627. 

5. Szabo: Ztschr. f. d. ges. Neurol, u. Psycliiatrie, 1913, XVII, 
145. 

6. Abderhalden: Abwehrfermente des tierischen Organismus, 
3d edition, 1913. 

7. Alzheimer: Zentralbl. f. Nervenheilk. u. Psychiatrie, 1907, 
XXX, 449. 

. 8. Szecsi: Ztschr. f. d. ges. Neurol, u. Psychiatrie, 1914, XXII, 
345. 

9. Nonne: Syphilis and the Nervous System ( English transla- 
tion), 1913, Lippincott. 

10. Ross and Jones: Brit. M. J., 1909, I, 1111. 

11. Noguchi: Serum Diagnosis of Syphilis, 3d edition, 1912. 

12. Zsigrnondy: Ztschr. f. anal. Chem., 1901, XL, 697. 

13. Lange: Berl. klin. Wchnschr., 1912, XDIX, 897. Ztschr. f 
Chemotherap., 1913, I. 11. 

14. Zaloziecki: Deutsche Ztschr. f. Nervenh., 1913, XLVI1 and 
XLVIII, 783. 

15. Porges and Meier: Berl. klin. Wchnschr., 1908, XLV, 731. 

16. Hermann and Perutz: Med. Klin., 1911, VII, 60. 

17. Eicke: Miinchen. med. Wchnschr., 1913, LX, 2713. 

18. Grulee and Moody: J. Am. Med. Ass., 1913, LXI, 13. 

19. Kaplan and McClelland: J. Am. Med. Ass., 1914, LXII, 511. 

20. Jaeger and Goldstein: Ztschr. f. d. ges. Neurol, u. Psychia- 
trie. 1913, XVI, 219. 

Plaut, Rehm and Schottmiiller: Leitfaden zur Untersuchung 
der Zerebrospinalfliissigkeit, Jena, 1913. 

Sippy and Moody: Tr. Ass. Am. Phys., 1913, XXVIII, 720. 
(Through delay in its publication, this article was not accessible 
until after our paper had gone to press.) 



Mat, 19] k] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



THE ESSENTIAL FEATURES OF \< [DOSIS LND THEIB OO I RREN< I 

IN CHRONIC RENAL DISEASE. 



By Anhukw W v 



OUTLINE, 

I. General Discussion of \.i.i. 

1. Misuse of the term mi ill.- .-in.-, ol tree acid in the blood. 

2. Impoverishment of the bod; in Dzed baa 

the definition of acidosis. 

II. Evidence of Acidosis In Renal Disease: 

1. Clinical picture of air him. 

.' Diminution of carbon dioxide in the alveolar air 

mges in the body fluids: 

rease In the acidity of the urine. 

h. Decrease in the titratable alkalinity of the blood. 

4. Increase in the tolerance to blcartx 
III. Evidence that the Increase in Tolera 

i.losis: 

1. Determination of carbon dioxide content of the blood 

2. Titratable alkalinity and real nitrogen of blood serum 

3. Comparison of the excretion by the kidney of bicarbonati 

and those substances whose excretion is sup 

pressed by renal lesions. 
1 Examination of Intestinal contents tor blcaxboi 
IV Evidence that the Essential Feature of Acidosis is an Impo 

verishment of the Body In Fixed Bases Resulting 

In: 
1. Decrease in the carbon dioxide of the blood. 

D the titratable alkalinity of the Mood serum 
3. Increase in the tolerance to fixed b 
4 1'iireliability of the ammonia excretion as a criterion "f 

acidosis. 

5. General methods of detecting aci.! 

V. Clinical Significance of Acidosis in Renal Disease wi" 

.ptoms of iir 

of acidosis. 
i Relation to sail action and I 

Of the etiology of thi 

- 
tion, ni 



RDS, 

' ! 

on of tk> 
differentiates it n on sharply from 

hunger of dis 

anemia, it wi 

Until. 1 

therapy in n 

neutral - 

planation of I rring in tir:. 

a LL • Ioxsid 
The q 

natur 
ally many obi 
in tin • 

lie fundami i 
Peril 
of the tl 

pean lit< 
in the blood 

Howi 

i- due 



1 12 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No.27«j 



alkali-yielding substances. The essentia] feature of the defini- 
tion of acidosis has been stated clearly by Naunyn 3 under the 
term hypalkalitat, by Emerson,* who uses the term "alkali 
starvation.'" and Palmer and Henderson,' who use the term 
" depletion of bicarbonate from the blood." It would seem 
necessary, however, to include other tissues, as well as the 
blood, since, in the absence of evidence to the contrary, it must 
be considered that there is a general deprivation of the body in 
bases. It is. of course, possible that there may be a localized 
increase of hydrogen ions in certain tissues of the body, hut 
in the circulating blood these would always meet with hydroxy] 
ii. ns tor their neutralization. Magnus-Levy" has emphasized 
especially that in diabetic acidosis there is an increased accu- 
mulation rather than an increased formation of acids. A 
clearer statement of this position would be that there is not 
even any increased accumulation of acids, but that in acidosis 
the acids are destroyed largely by neutralization, whereas in 
health they are destroyed largely by oxidation. 

From these considerations it is seen that the underlying 
principle of acidosis is a general impoverishment of the body 
in bases. This may be brought about by a variety of methods 
such as : 
1. Simple starvation ; i. c. the withholding of bases from the 

food. 
'2. Disturbances of acid formation and elimination. 
3. Loss of alkali as such during excessive purgation. 

The acidoses have been classified into two groups ; namely, 
the absolute acidoses in which there is an increase in acid, and 
the relative types in which there is a loss of alkali as such from 
the body. However, in both cases the end result is the same; 
that is. there is an impoverishment in bases and not an in- 
crease in acid in either case. Consequently, it would seem 
that there is no real distinction between the so-called relative 
and absolute acidoses, and that the two conditions are essen- 
tially the same. If it is necessary to subdivide the acidoses, 
they could be classified according to their etiology, or the 
effects which they produce, but it is not desirable to subdivide 
the principles upon which the theory of acidosis rests. 

Evidence of Acidosis ix Xephropathies. 
The study of acidosis and the evidence for its occurrence in 
the nephropathies, will be considered upon the basis which has 
just been outlined. Among the newer arguments which have 
been brought forward the most important is the analysis of 
the alveolar air. Straub and Schlayer ' found a definite 
lowering of the carbon dioxide content of the alveolar air in 
advanced stages of nephritis. This factor is, of course, de- 
pendent upon the carbon dioxide of the blood. It has been 
studied rather less than the other signs of acidosis and the 
authors do not draw any final conclusions from their data. 
Recently, a publication appeared by Lewis, Ryffel, Wolf. 
Cotton and Barcroft 8 upon the relation of the carbon dioxide 
content of the alveolar air t<> acidosis in cases of cardiac and 
renal dyspnoea. Their data upon this point are much less 
convincing than those of Straub and Schlayer. Lewis and 
his associates describe a tesl based upon the principle that the 



percentage of oxygen taken up by the blood under certain 

standard conditions is controlled in pari by the non-volatile 
acids in the blood. Suggestive results were obtained in certain 
special cases of dyspnoea. In the data, which they report, upon 
lactic acid in the blood uo distinction is made between lactic 
acid and the lactate-. 

Forges and Leimdorfer B have also found that the tension of 
carbon dioxide in the alveolar air is in general parallel to the 
symptoms of unvmia. However, a lowering of the carbon di- 
oxide tension in the alveolar air cannot be regarded as pathog- 
nomonic of acidosis. Forges, Leimdorfer and Markoviei* 
report a marked lowering in decompensated cardiac cases. 

Henderson and Palmer," from a study of the acidity of the 
urine, came to the conclusion that acidosis is an important 
symptom in cardiorenal cases. The method used by them con- 
sisted in the measurement of the concentration of hydrogen 
ions in the urine by a series of indicators. The average acidity 
in a group of cardiorenal cases was higher than the average 
acidity in a group of normals. The average of a group of 
nephritic eases was intermediate between the cardiorenal cases 
and the normal individuals. It is important to note, however, 
that the extreme values found in cardiorenal cases practically 
coincided with the extremes found in normal individuals. 
Expressed as negative logarithms, the extreme normal values 
van- from 4.82 to 7.4."). with an average of 6. whereas the 
cardiorenal eases range from 4.5? to 7. 48, with an average of 
5.33. 

In considering the signs by which one ordinarily recognize! 
acidosis in diabetes, it is evident that a true acidosis may exist 
in nephropathies without conforming to all of the details which 
are seen in diabetes. With the study of acidosis in various 
conditions it might be possible to determine the characteristics 
which are essential in any acidosis and those which are found 
only under special conditions. In any advanced acidosis one 
would expect, a priori, to find the following features: 

I. Examination of Clinical Symptoms: 
1. Partial or complete coma. 
■.'. Air hunger. 

3. Bright color of the mucous membranes and the 
venous blood. 
II. Diminution of the Carbon Dioxide of the Alveolar Air. 

III. Examination of the Blood: 

1. Diminution of the carbon dioxide. 

2. Diminution of the titratable alkalinity. 

3. Relatively constant behavior of the physico-chem- 

ical reaction. 

IV. Examination of the Urine: 

1. Increase in excretion of ammonium salts.* 
'.'. Increase in acidity. 
A". Deficit of the Body in Bases (conveniently determined 

by the increase in tolerance to bicarbonate). 
Of this list many features might be absent in mild, oi 
moderately severe acidoses, ami would appear only under ex- 
treme conditions. The clinical signs, though very suggestive 



* Except in those cases where alkali is lost from the bowel. 



May, 19] 1. 1 



JOHNS BOPKINS HOSPITAL BULLETIN. 



143 



are uol pathogi ionic. The data for the ana 

r air and the titratable alkalinity of the b • ■■ 
tiiR-ilv suggestive. Almost no data are available upon I 

lum dioxide contenl of the hi I. The excretion • 

in the urine is normal and there is m> Bt liking changi 
urinary acidity. In certain types of nephropatl 
in uremia, a very striking incn 

Two interpretations suggesl thema eadily: 

losis, and i 2 i retention of bicarlx 
of renal lesions. The explanation of this pheni 
might give conclusive evidence in regard to the 

in renal disease. The following poi 

• 
a ns of ai idosis usually develop Ln 
n m n 

titratable alkalinity. 
kidney continues to > ■ 
massive injections of bicarbonate. 

■ u of in acid urine from the neutral or slightly 
alkaline blood presumably represents a definite fui 
activity on the part of the kidney, and not a merely passive 
phenomenon, [f assumes that massive amounts of bicar- 
bonate are accumulating in the blood stream on account of the 
inability of the diseased kidnej to excrete it. then it wi 

• ect that the kidnej would cease 1 te acid. 

Indeed, if ai ai cumulated in thi 

. then it would be difficult to explain the sourci 
which material could be obtained for the formation 
retion of bicarbonate n 
place readily in the presence of extensive diffuse li - 

On the other hand, tin 
readily explained on tin h as : 

normal ammonia contenl of the urine. 

nting toward the : 
lively abnormal quantity 
ds in the urine. 
The normal excretion of ammonia point* 

I 

spond to tie • 

i- justified in i 

alkalies in tl 

i 
- th a resulting a< i um 

after injection inti 
rried out : 
I. Examination of ui 

I . Vcidit) In Fol i '- • 



III 

!" 

III. Kxami 

i . i 
.'. R 

d to phenolphthah 

I V. Kxaniinal ion o 

A partial reporl 
ti -i- were made has 

upon titratable alkalinity. 
examination of the urine, the titt 
and the tolerance t< 
I V of tin- former publii ation." In the present pa] 

ince t<> sodium bii arl ate is tabulal 

bicarbonate « ith the um 

factor in tl xplanati f t 

is not the sole factor. 
In the determinations 
n. intravenously, i 
ordinary severity. If no 

eated in C or 8 hour-. In t ; ■ 
initial inji i 
ployed. Thi 

•.'II mitlUte- ;lt 100 t . Ill .111 \ 

than l'\ I' 

hut merely to di ten 

or partial. In the diuresis followii 
injectio 

■ 

Ultra!. 
In i 1 



144 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 279 



centrated over the free flame until no more amnions was 
given off. The data recorded in the table, therefore, represents 
the reaction after the removal of ammonia. 

The carbon dioxide determinations of the blood are necessary 
on account of its importance as a sign of acidosis. Inasmuch 
as an advanced acidosis is required to produce significant 
changes in the carbon dioxide content, this determination was 
omitted on many of the less severe cases. Preliminary deter- 
minations were made with the Haldane-Barcroft apparatus, 
designed for the analysis of 1 cc. to '2 cc. quantities of blood. 
Inasmuch as moderate quantities of blood were available in 
the ordinary uraemic cases, there was no special advantage in 
using only minimal amounts. The determinations were carried 
out by an application of the method of Warburg" for minute 
amounts of carbon dioxide in water. The principle of this 
method is that carbon dioxide precipitates barium from a solu- 
tion of barium hydrate as the carbonate. Using a known 
amount of barium hydrate, the excess may be determined by 
titration with dilute standard acid in the presence of the 
precipitated barium carbonate. 

Certain modifications of the technique used for water were 
desirable in working with blood on account of the smaller 
volumes of material which are available and the higher con- 
tent of the blood in carbon dioxide. In the first place, certain 
precautions were necessary for the protection of the blood 
specimens during their transference from the wards to the lab- 
oratory. In order to avoid loss of carbon dioxide, the blood 
was collected under barium hydrate and the precipitated 
barium carbonate was subsequently decomposed with acid. 
Barium hydrate was chosen because of the difficulty of secur- 
ing carbonate-free specimens of the metals whose hydrates and 
carbonates are soluble. Throughout the work the standard 
barium hydrate was protected from the carbon dioxide of 
the air by a layer of toluene, both in the stock supplies and 
in the apparatus, during the absorption of carbon dioxide 
given off from the blood. A layer of toluene (about 1 cm.) 
was poured into each of the duplicate absorption cylinders. 
The barium hydroxide was transferred with an ordinary pipette 
by an open window without any appreciable error from the 
absorption of atmospheric carbon dioxide during the trans- 
ference. After the introduction of the barium hydrate under 
toluene in the absorption cylinders, the entire apparatus was 
connected up and washed with carbon dioxide free air. For 
this purpose the apparatus is arranged with a double set of 
connections, one of which leads through the barium hydrate, 
the other through the air over it. This makes it possible to 
wash the apparatus free from carbon dioxide and subsequently. 
after the evolution of the carbon dioxide from the blood, to 
wash tin' gases remaining in the flask into the barium hydrate 
wiih carbon dioxide free air. The exact details were as fol- 
lows: for the collection and measurement of the blood speci- 
men-, the neck of a 50 cc. graduated flask was cut off about 
2 to :: em. above the graduation mark; 30 cc. of y 2 % barium 
hydrate solution was measured into this flask- and then tightly 
stoppered. When the materials are handled rapidly, away 
from the neighborhood of Barnes, the error during this pro- 



cedure is negligible and it is not necessary to use a protecting 
layer of toluene. A little more than 20 ec. of blood was taken 
from a vein in the arm, in the usual way, and discharged into 
the flask of barium hydrate up to the graduation mark, and 
with the needle of the syringe dipping under the surface of 
the barium hydrate. The flask was then stoppered and the 
mixture thoroughly shaken. The flasks of barium hydrate 
were kept in the refrigerator before use in order to minimize the 
error of measuring the blood at a higher temperature than that 
for which the flask is calibrated. Under these conditions the 
blood does not clot and, if necessary, the specimen can be kept 
over long periods before analyzing. It is preferable, however, 
not to allow it to stand over night, since the precipitated bar- 
ium carbonate settles out over the bottom of the flask ami 
increases the difficulty of transferring it subsequently. 




Twenty cubic centimeters of N/10 barium hydrate were 
placed in cylinder A and 10 cc. in cylinder B. Each of these was 
diluted with freshly boiled water to about 75 cc. The water bath 
was kept at 75° to 80° C. to promote the absorption of carbon 
dioxide. With the double washing afforded by the Folin absorp- 
tion tube and with careful heating at the beginning of the evo- 
lution of carbon dioxide, complete absorption could be obtained 
without the use of a third cylinder of barium hydrate. The ac- 
companying diagram illustrates the apparatus at the beginning 
of the determination. ( is a tower, 35 cm. in height, of 
sodium hydrate sticks: /•' i> an 800 cc. short-necked Kjeldahl 
flask for the reaction mixture of blood and acid. A and B are 
the cylinders (22 x 1 cm.) for standard barium hydrate, and 
WB a hot water hath at 75° to 80° ('. With barium hydrate 
in the cylinders .1 ami /.' ami with the stopcocks in the position 
shown in the diagram ( No I closed and 1, 2, and 3 open) suc- 
tion is applied gently ami the apparatus washed for about 30 



May, I'M L] 



JOHNS BOPKINS HOSPITAL BULLETIN. 






to !■"> minutes t" free it from carbon dioxide. Then th< 
is stopped and all of the • -• •'■ Thi - 

oalyxed is washed through the separatory funnel with 
about ''ihi ec. of freshly boiled water anil followed 

thophosphoric acid. Tl uixture 

is then heated for In or 15 minutes at the boiling point. This 
can ordinarily !»• done without the use of paraffin to 
foaming. The use of paraffin makes the evolul 

gular and in of the fluid in the 

■ in cylinders t" suck hack. The long absorption tubes 
ng above the 1 3 linders wi re 
from tl - When tin' heating is finished, the - 

again opened and a current of air i> carried tl 
the apparatus for about 30 minutes. Tl harium 

hydrate is then titrated in the absorption cylinders 
hydrochloric acid against phenolphthalein. 

The calculation <>( the results under these conditions 
simple. The burette reading in cubic centimeti - 

- I and multiplied !> 
bon dioxide. Eighty-four i- the equivalent in X 28 solution 
of 30 cc. of an N 10 solution. Thi cubic centum 
solution neutralized by the carbon dioxide, when multiplied by 

cubic centu 
760 nun. in "20 cc. of blood. (One cubic centimeti 
solution for reaction with barium hydrate i> equivalei 
cc. of carbon dioxide under standard conditions. ) This 
multipl cubic cenl 

in 100 cc. of blood, or the volumes per rent of carbon 

•ids method was tested upon 30 o . quanti- 
;m carbonate containing 15 volumes 
arbon dioxi md upon normal human 

ie carbonate solutions wi 
in actual practice to within 3 to 5 volume* 

ild Ih- run a little closer. The relative 
... though tl ■ 

•'u- : 



0.0176 

Volumes • ; !"■ 






A br> 
order to 
which I 
heart lesions, all wi 

: interval ol 

■ 

• nod when I 

f carbohydr 
sufficiently I 

in all of the eases in tie I 



which or 5 
bicarboi 

which ' 

. phenolsulp 
pletely suppi 

tnparativel] small in an 

phonephthalein w, 

in the uriii. 

as high as 160 gran - 

of substances which are known to 
- : namely fluids, - 

venous blood 

cally pathognomoi sis. In four typi 

values Mined from 10 to '.' I volumi • 

a normal of 1 1 to 52 volumes . 

which occur in uremia 

by oil 

Ammonia I 
uncomplicated bj hepatii 

III the ;e illllllll.lt ;■ 
Ill tin 

III thi ■ 

moin.i 
in thi 

indn id 



146 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 279 



acid. In Case A, who received in all 160 grams of bicarbonate, 
an alkaline reaction of the faeces was not obtained after an] ol 

the injections or at section. In another patient. D. in whom 
70 -rams of bicarbonate were injeeteil, the intestinal contents 
at section were found to be slightly acid to litmus. No free 
ammonia was present in these specimens. 

Kffr, I on Glmicai Stympfoms.— Observations on the effect of 
the administration of bicarbonate were made with especial 
reference to three features, namely : coma, dyspnoea, and the 
total output of urine. Of the seven cases in uraemia, live were 
sufficiently comatose to be either practically or wholly unable 
to respond to simple questions. In one of these, B. there was 
no change in his mental condition. Of the other four, one 
came nut completely from the uraemia, though this result was 
probably not to be attributed to the bicarbonate. In the other 
three there was distinct improvement in the mental condition, 
which could be directly attributed to the injections, though 
none of these recovered completely from their stupor. The 
improvement was shown by a diminution in their restlessness 
and by their ability to answer questions, and even to carry 
on a limited conversation. In one patient, C, the improvement 
appeared within a few hours after the administration of 30 
grams of bicarbonate, whereas in another. A, no change was 
noted till 100 grams had been injected. . The air hunger which 
existed in three cases (A, C and D) was definitely relieved 
by the injections. The respiratory changes in two patients 
( II and .1 ) were especially interesting. These men had con- 
tinual dyspnoea which did not disappear even upon rest in bed. 
However, after the administration of bicarbonate, this dys 
pncea disappeared completely and did not return during the 
several weeks that they remained in the hospital. In a third 
case (L) the dyspnoea was not affected by an amount of bicar- 
bonate sufficient to render the urine alkaline. 

The effect upon the excretion of urine was not especially 
noticeable in the cases with a normal output. In the cases 
with oliguria the output improved as a rule, though exact 
measurements were often very difficult on account of the incon- 
tinence of many of these patients. In two instances ( A and D) 
a definite polyuria followed the injections, and in a third case. 
with anuria of 15 hours duration, a polyuria developed within 
8 hours after the injection. 

Si mmakv of the Data ix Table I. 
In summarizing this evidence, then, we bave a striking 
increase in the tolerance to fixed bases in many nephritics. 
The parallelism between this increase in tolerance and the im- 
poverishment of the blood in titratable alkali is crucial evidence 
of a marked deficit of the body in bases or in substances which 
readily give rise to bases. This deficit is often sufficient to give 
rise to definite clinical symptoms. In four cases of uraemia, 
the carbon dioxide content of the blood was markedlj Lowered. 
These features justify the diagnosis of an acidosis of high 

grade on the basis that the essential feature of 

impoverishment of the body in bases or in substances which 
readily give rise to bases. Such an acidosis is characterized 
by: 



1. An increase in the tolerance to bases. 

2. Decrease in the titratable alkalinity. 

3. Decrease in the carbon dioxide content of the blood. 

4. Xormal excretion of ammonia. 

5. Absence of any disturbance of carbohydrate or fat metab- 

olism. 
The question was raised as to whether the bicarbonate in- 
jected in the ura^mic cases is retained as such, or whether it 
is retained on account of an acidosis. It is seen that this 
question requires a little modification. In any case, even 
in an acidosis the bicarbonate which is injected is retained as 
such, that is for use as an alkali. The point at issue, is whether 
the bicarbonate is retained in considerable excess over the nor- 
mal content of the blood on account of the failure of the kidney 
to excrete it. or whether it is retained to replace a deficit of 
carbonates in the blood and other tissues. The latter explana- 
tion is clearly the correct one. It seems probable that after 
the urine has been rendered alkaline by bicarbonate, an insig- 
nificant amount might be retained on account of renal suppres- 
sion : but practically all of the bicarbonate is retained to restore 
the content of the tissues to normal. 

Definition of Acidosis. 

A priori, it is to be considered that an increase in the excre- 
tion of ammonia is an essential feature of acidosis. However, 
there are cases of nephritis and uncomplicated diabetes which 
show a definite change in the titratable alkalinity and a sig- 
nificant increase in their tolerance to bicarbonate without an 
increase in ammonia. Such cases justify the conclusion that 
an acidosis is not necessarily accompanied by an increase in the 
excretion of ammonia. The changes from the normal metab- 
olism to a state of acidosis are purely quantitative. It is 
evident that there is no natural division, and any such divi- 
sion in the early stages would necessarily be purely artificial. 
By definition, then, an acidosis is a general impoverishment 
of the body, from any cause, in fixed bases or in substances 
which readily give rise to fixed bases. The essential funda- 
mental features that have been established thus far which 
would he common to all acidoses are: 
1. An increase in the tolerance of the body to fixed bases. 
•.'. A diminution of the titratable alkalinity of the blood serum. 
3. A diminution of the carbon dioxide of the blood. 

These are the features which are well understood and are 
readily susceptible of demonstration. They would, of course, 
be accompanied by related changes: a low carbon dioxide coi 
tent of the blood should result in a low tension of carbon 
dioxide in the alveolar air, an analysis which is not always 
satisfactory in a. comatose patient, or in one who is, for any 
reason, unable to co-operate. Similarly, the reduction of the 
titratable alkalinity might be accompanied by a slight increase 
in the excretion of neutral salts in the urine, but it is evident 
that it might readily be well-nigh impossible to detect this 
change in excretion. The ammonia content of the urine is by 
no means an absolute criterion of the presence or absence ol 
acidosis. It may he normal even in moderate grades of dia- 



May, 19] l.j 



JOHNS HOPKINS HOSPITAL BULLETIN. 



1 1: 



lictn acidosis. On the other hand, the relative and 
amounts of ammonia may be comparatively high in certain 
toxaemias in which acidosis is absent; a toxaemia oi 
was reported in which the daily output of ammonia was as 
high as two grams and the coefficient reached 10 
ditions in which acidosis could In- excluded." Then 
condition which definitely would not come under tln> defini- 
tion of acidosis : namely, the localized accumulation of acid in 
special organs or tissues, Buch as Fischer" has described as 
occurring in the kidney. 
Two methods are available fur the detection of these features 

uf acidosis; namely, the reaction of b! 1 serum to phenol- 

phthalein and the effect of the ingestion of Bodium bicarbonate 
upon the reaction of the urine. These methods havi 
evidence of acidosis of vary ing grades in diabetes, in nephropa- 
thies, in anaemias, and in rheumatic fever. Either o 
would presumably be applicable in the de 

from any cause whatever. The details of these tests are very 

simple. Fur the first, I cc. oi serum i- added to 25 

ami the mixture shaken thoroughly. The precipitated 
proteins are filtered off ami the alcoholic filtrate, without 
g the precipitate, i- evaporated to dryness with a few 
drops of phenolphthalein >< >ln t i< m. taking care to avoid dilu- 
tion of the alcohol from an excess of -team during evaporation. 
In the earliest changes from the norma] th< filtrate 

- red, hut tie- residue after eva] apidly loses its 

color at the temperature of the water hath i '< to I"' m 
whereas the normal specimens retain their color foi 
hour-. Details of the more advanced changes are - 
erence No. l l. 

The te.-t by means of sodium bicarbonate i- equally simple. 
f sodium bicarbonate are L r i\en by mouth unless 
□testinal complications that would interfere with ab- 
sorption are present In that case intrave - injection may 

Preferably, the patient should void .i' the 
administration of the bicarbonate. Practically any normal in- 
dividual, on an ordinary mixed diet, will react, usually in 

hours, h\ excreting a urine which i- ueul ra 
to litmus. When a specimen does not react sharply to litmus 
l>a|»-r. a few cubic centimeters Bhould he thoroughly •• 
tube t.. promote the change of bicarbonate b 
■ as which are faintly acid to litmt 
slightly alkaline to litmus B • 
I h do not react the bicarhonab 

in increasing quantities Buch a- 2 30 gran 

B hour-, the reaction of the urim 
epetition. "i n some i a-. - ma--, i 

n without affecting the react f the urine, 

- in I in 2 da 
It i- possible in a general way to determim 
depletion in 
ill-licit of as much as 20 grams i an be 
tion of the blood, hut certainlj 
toms. A deficit of approximate!} ■■ 
change in the behavior of the blood, hut -i 
to any appreciable dyspnoea i 



or 80 -ram-, thn 

'h"\ '» »'hii 

in bed. It i- difficult to determim 

quantities which would cause the n mptoraa 

of stupor an- 

production of these symptoms. In two cases which were 

observed a c lition of air hunger ami parti., 

relieved temporarily by the injectioi 

respectively, h -■ emed dear that th 

the immediate cause of death ii I md one may assume 

thai Buch quantities approach the limit.- which would be 

fatal in the depletion of the body in 

ghtly lower than the highest value- obtained in diabetic 
coma in which a deficit of 200 grams has been rep 
interpretation of the figures in diabetes i- complicated by the 
rapid formation of acid ami i 

by ammonia. In fatal cases n seems probable that th< 
hau-toil suppl) of fixed bases i- only a minimal quantity ; 
therefore, it would not he surprising to find that thi 
available Bupply uf substances in the body yieldii 
is iii the neighborhood of the equivalent 
Bodium bicarbonate, or at least of that general oi 
magnitude. 

Clink \i Sionii icaxi 

aring upon the -c 
the acidosis observed in tl 

severity ■■!' the condition of the individual patient- was 
mean- proportional to the degn i I n some | 

the lack of carbonates was extreme, while in othi 

slight that no symptoms of dyspnoea devclo|)cd. In one 
1. 1 the dyspnoea was not typical I j md was 

ntly of reni 

From thesi nsiderations, it 

•or anil thai 
not the cause, of tin 
merelj a- a termit I in an appn 

Bhofl - that there n 

out any appn 

Bymptot 

- 
m part 

ii Id Im- 



148 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 279 



TABLE I. EXAMINATION OF C I 
CASES 



CLINICAL RECORD. 



Respiration 

,vith regard to 

dyspnoea. 



Well-marked 
dyspnoea. 



Hypertropliied, compen 
sating. 



Well marked hypertro 
phy. compensating. 



Well marked 
Moderate . . . 
Well marked 



Air hunger.. . . Hypertropliied, compen-jWell marked 
sating. 



No air hunger. 
Moderate 
dyspnoea. 



None 

No dyspnoea.. 



Hypertrophy. Frequent 
breaks 



Hypertropliied, compen- 
sating. 



Well marked 



Moderate 
Well marked 



Average 
blood pres- 
sure (mm. 

of Hg.). 



190 
140 
180 

220 
240 

210 
180 



Fluid balance Acidity in 

(average % of N/1 

daily output). solution. 



Polyserositis.. 500 ec . 
Well marked. . Norma 



None Anuria 1 5 

hrs. 



None Com'neing 

oliguria. 

Well marked. . Normal 



Slight. 



Polyuria. 
Oliguria.. 



3.5% 
2.3% 



3.0% 



3.5% 



1.5% 

3.8% 

2.7% 
2.5% 



5.2% 

4.0% 
3.5% 



Deficit in 
sodium bi- 
carbonate 
(grams). 



160+ 


Acid.. 


40+ 


Acid.. 


30+ 


Acid.. 


70 


Xeutr 


30 


Ampb 



Neutral 
Alkalin 



EXTREME CASES WITH AD 



Frequent at- 
tacks of dys'-j 
pnoea. 

Dyspnoea o n 
exertion. 

Constant dys- 
pntea. 



Hypertropliied, dilated. Moderate . . 
Frequent breaks. 



Constant. Well 
marked. 



Hypertropliied, compen 
sated. 



Hypertropliied, dilated. Well marked 
Frequent breaks. 



Partially compensated 
on admission. 



Dilated. Partially com- 
pensated on admission 



Slight. 



190 
200 
140 



Slight . 



In lower e x 
tremities. 



Well marked. 



Oliguria 3 . 0% 
500 ce. 



Normal 
Polyuria.. . 
Polyuria.. . 



3.1% 
2.5% 
2.0% 



Normal 2.0% 



3.7% 

4.2% 
2.6% 
8.7% 

11.6% 



so 1 ' 

70 2 
80 



Alkalir 

Alkalin 
Alkalin 
Alkalin 

Alkalin. 



OUTSPOKEN CASES WITH MORE OK 



M 


41 


Cheyne-Stokes, 
with marked 




Well marked 


170 


Well marked. . 


Polyuria . . . 


4.0% 


7.1% 


30 = 














dyspnoea. 




















N 


49 


Slight dyspnoea 


Acute mitral endocar- Moderate. . . 
ditis. 


140 


Moderate 


Normal. . . . 


1-5% 


11.8% 


30- 


Alkali"' 






O 


67 




Hvpertroph v, c o in p e n slight 

sated. 


160 


Puffiness, fail' . 


Normal .... 


2.7% 


3.0% 


20 = 


Alkalim 






P 


54 




Slight liypertrophy,com- Moderate. . . 
1 ting. 




PuffVs.eyelids 






2.2% 

4.0% 


10 = 




Q 


39 




200 






10- 


Alkaline 
































l%to3% 


2% to 5% 


5 


Alkaline 


erage. 















No color after 5 minutes. 



MlY. 



JOHNS Hnl'KINs HOSPITAL BULLETIN. 



' D1FFUS] NEPHROPATHIES. 

MIA. 



' S< ll"\ 



Blootl xrum. 



„ 



Rrhivior I 



















\ lor. 

0.9% \ ■ 



Residue a" i 

t-vapor it 



s 



I to 10 dilution 
trrmn in wat.r. 









Pink. 

llltlll- 



No color... 
0.8% Pink. 



Trace' 



0.7% No 
0.8% Pin 






'■ 



Pink. 
Red 



ri\ i: -\ mptmmv 






\.. color No 



: 

1 o 



0.8% \ loi Si i: ' 

,,!,„ ..I No F«int pink. 






\., color. . No i 



Deal 

■ 






S\ MIMi'M- 












; 






























iva before death. ' After O.onu 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 279 



readily obviated by the injection of bicarbonate though special 
precautions might be necessary in the many cases where the 
bleeding is done primarily for the relief of some mechanical 
embarrassment to the circulation. 

Diagnosis of Uraemia. — The wide variation in the degree of 
acidosis in these cases of uraemia raises the question as 1" 
whether eases may not occur in which it is absent altogether. 
No snch instances have been encountered; the readiness with 
which slight grades of acidosis can be detected, and the fre- 
quent appearance of the milder grades, even in cases of only 
ordinary severity, would indicate that chronic uraemias without 
any acidosis would be at least, comparatively rare. In the 
diagnosis of uraemia there is often an opportunity for consider- 
able variation of opinion. The similarity of the symptoms 
which may result from cardiac, renal, and cerebral lesions 
sometimes renders differentiation rather difficult ; in compli- 
cated cases where changes in all of these organs are present, 
it may be impossible to determine what features predominate, 
li seems probable that metabolic changes occur in these eases 
which can be correlated with the clinical features. The exami- 
nation of the blood and urine for such factors as the titratable 
alkalinity, rest nitrogen, and the renal function in conjunction 
with the clinical picture might enable one to differentiate more 
sharply certain types of these cases. The cases of uraemia 
reported in this paper were by no means free from cardiac and 
cerebral complications, but only those types were selected in 
which the uraemic symptoms predominated very definitely. 

Clinical Estimation of the Degree of Acidosis. — Several 
methods have been proposed for the rapid clinical estimation 
of the degree of acidosis in diabetes. A review of this subject 
by Addis ** appeared recently. They depend, for the most part, 
upon the simplified methods for estimating /?-oxybutyrie and 
acetoacetic acid or acetone. Obviously, such methods are 
particularly applicable to diabetes. In renal disease, as a 
preliminary step, the examination of the titratable alkalinity 
is desirable, since it gives information at once at to whether 
the administration of bicarbonate is urgent and also an idea of 
the amount which will be required. The determination of the 
tolerance to bicarbonate combines in one step a measure for 
therapy and a method for comparing the extent of acidosis in 
different individuals. 

Relation of the Acidosis to Salt Action and to Therapy. — 
In considering the treatment of the acidosis of nephropathies 
one may ask how much good may be expected and also what 
dangers there may be from the use of the comparatively large 
amounts of suit that are often necessary, on the basis that the 
effect of salt in the production of oedema is due to the general 
properties of salt action. In regard to this latter point it is 
importaul to remember that one is not increasing the car- 
bonates above the normal, but merely replacing a deficit of 
this salt. It is important to know the effect of bicarbonate 
upon the excretion of urine, the production of oedema, and the 
work of the heart. As regards the excretion of urine, there 
is a definite tendency of the bicarbonate to cause an increase 
in the total output. It might be expected that in the advanced 
uraemias the injection of massive doses of bicarbonate during 



a period of one to two days would tend to produce an oedema. 
However, the fluid balance was not disturbed, or else a polyuria 
resulted. In cases where there was a pre-existing oedema, there 
was no tendency for it to increase or diminish. When acidosis 
develops in the uraemia of chronic renal disease its treatment 
by massive injections of bicarbonate offers not more than re- 
lief from air hunger and temporary improvement in the mental 
condition and general comfort of the patient. The effect on 
uraemia of the early treatment of acute nephritis can best be 
studied in Asiatic cholera. In this disease acute nephritis 
occurs in all severe cases and uraemia develops with surprising 
regularity. Where treatment was instituted early in the 
course of the disease it was found that no deaths from uraemia 
occurred in a series of 76 cases, whereas in a corresponding 
control series there were 10 deaths from uraemia.* On the 
other hand, the chronic nephritides extend over such a long 
period of years that it would be extremely difficult to determine 
the effect, in regard to the subsequent development of uraemia, 
of the early administration of therapy before the signs of an 
outspoken acidosis had appeared. The treatment of the early 
grades of acidosis would be a simple and rational procedure 
and would seem to offer some possibility of exerting a favor- 
able influence upon such a slowly progressive condition as 
chronic nephritis. 

It is obviously necessary to establish the existence of acidosis 
in each individual patient in preference to the routine treat- 
ment of all cases as recommended by v. Hdsslin. 21 This is 
readily accomplished, either by the examination of the blood 
serum with phenolphthalein. or by the administration of 
increasing quantities of bicarbonate until an alkaline reaction 
of the urine is produced. The choice of carbonates for admin- 
istration is important, especially for intravenous injection. 
The normal carbonate destroys red blood corpuscles rapidly 
in vitro, causing extensive haemolysis and discoloration of 
haemoglobin, even in the presence of serum. While such action 
probably does not take place in vivo, yet it is conceivable that 
less evident injury may occur. One argument which has been 
advanced in favor of the normal carbonate is that it can take 
up additional carbon dioxide, relieving the internal respira- 
tion, whereas the bicarbonate cannot take up any additional 
carbon dioxide. However, this would not seem to be impor- 
tant, since the bicarbonate, on passage through the lungs, gi\e> 
off carbon dioxide and can then take up more from the tissues 
for transportation to the lungs. Weight for weight, sodium bi- 
carbonate neutralizes only about five-eighths as much acid as 
the carbonate. Concentrations of 4 or 5%, however, cause no 
haemolysis of washed red corpuscles in vitro, whereas, trac- 
tions of a per cent of the carbonate are very active against 
red cells producing haemolysis and discoloration of the haemo- 
globin even in the presence of serum. Accordingly, very much 
stronger solutions of bicarbonate can be used than would be 
advisable with the normal carbonate. The relatively long 
duration of the effect of bicarbonate" is a hopeful feature in 
therapy of nephritic conditions as contrasted with the short 
duration in diabetic coma. 

Treatment of acute nephritis by the injection of massive 



May, 101 ;.| 



JOHNS BOPKINS HOSPITAL BULLETIN. 



151 



mil neutral - ried out bi I 

and others at the suggestion i 

a performed on the basis thai an a< 
acote nephritidee without determining its in the 

individu - Furthermore, the quantity t" be admin- 

was determined by the clinical symptoms witho 
• .a of the urine, 
thai the reaction <>f the urine be followi 
mii'le to the quantity of carbonate t.> be administered. In 1 1 1 i ~ 
I have doI considered the relief of nephritis by the 
employ The conclusions 

i 11 obtained in regard i tlVr from I 

araely, i l i that a localized ai 
hydrogi n ions in certa e body 

□ the generally ai 
the term, and i '.' i the impoverishment in bases which 
aximum in unemia re] ind nol 

thf renal condition. 

Dsidering the etiology of this 
renal d - rident that the carbonates are deph I 

by thi eh from the body, Imt through cl 

- bility of their destruction b> 
il action is through neutralization by acids, Tl 

ce from which such acids could come, 
ppears in the literature of the presence of any ab- 
normal acids or salts of a< '\<\< in the blood i>r urine of nephritic 
' the normal functions of the Iridnej is the pro- 
duction and • From a neutral or slightly alka- 

W'ith the impairment of tl ther funi I 

the ki> unlikeh that this functional 

red, with the result that then- is a verj - 
■ id in the urine and a 

the blood i 
hich are Bup it 
m fur the long duration .,! ■ 
- in renal d - 
thy that tie 
parallel t" the si . 
: 

1 

■ 
I from an 
of ammonia, bui I rom an inl 
ammoi during thi 

available for the neutralizatii 

in the blood neutralization bj the carbonab 

which l'ii! 

i" the ki'ln- 



1. Tile - 

•.'. The effi cl ol i 

:t. Tin- i 

lack nf an} , „ ii„. 

mi which could i ■ 
On tin- basis one would expect t.. Bnd 
urine .i. 
11. ■ml. re 

titration of I 
lo imt support this vie* 
dity m a group ol 
ii was slightly higher than the norn 
so high as tin' average in a group nf d< 
' asee. Of the individual . a-.-, tin-.. 
lower limit- of normal, while the remaining 11 
higher than the normal average, hut onlj ■ 
_ r her than the normal maximum. 
It i- noteworthy that evi 
the renal tissue with a marked impairment nf prai I 
its functions, the ..rL'an -ill: " ■ 
in a remarkable degree. Patients in fatal unci 
ing in tin- .■••' • 

a urine nf distil 
that fixed bi i 

int.. the body in e .>f the kidi 

tits i- apparently one «>f tin 

|N-r-l-tr 

( ,.'. , 

I. Tl 
impoverishment of the 
readil) 

•hmeiit in b 

neutralization bj 
In eithi 

I I. The fu 

1. An 

\ 

\ 

III. i 



152 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 279 



2. The ammonia excretion may be increased even to the extent 
of 2 grams per day with an ammonia coefficient of 40%, 
in conditions in which there is no acidosis. 

IV. An acidosis of high grade occurs in certain nephropa- 
thies. The acidosis reaches its maximum in the uraemia of 
acute and of chronic diffuse nephropathy. It is not a terminal 
event, for it is often present in relatively high grade in out- 
spoken cases many months before the development of uraemia. 
It represents the effect rather than the cause of the renal 
lesions and thus constitutes a condition of only secondary 
importance. 

V. The characteristics of the chemical pathology of this 
acidosis are: 

1. Increase in tolerance to bases. 

2. Decrease in titratable alkalinity of the blood. 

3. Decrease in the carbon dioxide content of the blood. 

4. Normal excretion of ammonia. 

5. Absence of any disturbance of carbohydrate or fat metab- 

olism, and absence of the salts of any abnormal or- 
ganic acids. 

VI. The changes in the titratable alkalinity of the blood 
which can be detected by the use of phenolphthalein afford a 
ready means for the prompt diagnosis of acidosis and the 
method is particularly applicable in renal disease. In this 
condition it furnishes a definite indication of the amount of 
bicarbonate that will be required for the relief of the acidosis. 
The determination of the tolerance of the body to sodium 
bicarbonate also affords a delicate method of general applica- 
tion for the detection of acidosis. 

VII. Examination of the faeces showed that bicarbonate 
was not excreted into the intestine even in the cases in which 
massive doses were injected. 

VIII. Some of the toxic symptoms of uraemia are due, not 
to the presence of a toxin, but to the absence of a normal con- 
stituent of the blood, namely, the carbonates. Therefore, the 
therapeutic bleeding for the removal of any toxins that may 
be circulating causes at the same time a still further diminu- 
tion in a substance in which the blood is already seriously de- 
pleted. This disadvantage could be readily obviated by the 
injection of bicarbonate at the time of bleeding. 

IX. This acidosis is perhaps the result of defective function 
of the kidney in the normal separation and excretion of acid 
salts. If this supposition is correct, the acidosis would be an 
indirect expression of renal retention. In support of this it 
has been found that the acidosis is in general parallel to the 
ordinary signs of renal retention, such as the suppression of 
the excretion of dyes and sugars and the accumulation of non- 
protein nitrogen in the blood. 

Discussion. 

This evidence of acidosis offers a satisfactory explanation 
for some of the clinical symptoms which occur in uraemia. 
The coma in some eases is due to an impoverishment of the 



body in bases and can be partially relieved by the injection of 
bicarbonate. In uncomplicated cases the typical air hunger 
which sometimes develops and the accompanying bright color 
of the mucous membranes is another expression of acidosis. 

In the acute nephritis of Asiatic cholera, the early adminis- 
tration of massive injections of sodium bicarbonate results in 
permanent benefit. Chronic diffuse lesions lead eventually 
to the development of acidosis, which if not treated will pro- 
gress to such an extent as to produce the clinical picture of air 
hunger. In the stage of uraemia acidosis sometimes constitutes 
the immediate cause of death. In the selection of carbonates 
for therapy, the bicarbonate meets the essential requirements. 
The administration of the normal sodium carbonate is re- 
garded as unnecessary and inadvisable. In any acidosis the 
administration of bicarbonate may be continued until the 
urine becomes alkaline, even though extensive renal lesions 
are present. 

In the nephropathies which show an increase in tolerance to 
sodium bicarbonate this salt fails to be'excreted, not on account 
of defective elimination by the kidney, but because there is a 
deficit of carbonates in the body. When the content of the 
body has been restored to normal, excretion of bicarbonate 
takes place and the urine becomes alkaline in reaction. 

One of the principal points in this paper is that an acidosis 
of high grade may occur in the absence of any disturbance in 
the carbohydrate metabolism and without producing an in- 
crease in the excretion of ammonia. Important confirmation 
of this would be obtained if one could establish an experimen- 
tal method for the production of acidosis without increasing 
the output of ammonia. It would also be helpful to know the 
effect of general anaesthesia upon renal patients in whom 
the respiratory mechanism is already overtaxed by an acidosis. 

If one distinguishes between a disorder of metabolism and 
an. intoxication, then the spontaneous acidoses should be 
classed as a disorder of metabolism and the term " acidosis " 
is perhaps more appropriate than " acid intoxication." 

This investigation -has been conducted in the clinic of Prof. 
L. F. Barker ; it is a pleasure to express my appreciation to 
him for a stimulating interest in this work. 

REFERENCES. 

1. Walter: Arch. f. exper. Path. u. Pharmakol., 1S77, VII, 148. 

2. Benedict: Arch. f. d. ges. Physiol., 1906, CXV, 106. 

3. Naunyn: Der Diabetes Melitus. Wien, 1906. 

4. Emerson: Clinical Diagnosis. Philadelphia, 1906, 193. 

5. Palmer and Henderson: Arch. Int. Med., 1913, XII, 153. 

6. Magnus-Levy: Bull. Johns Hopkins Hosp., 1911, XXII, 40. 

7. Straub and Schlayer: Miinchen. med. Wohnschr., 1912, L1X, 
569. 

S. Lewis, Ryffel, Wolf, Cotton and Barcroft: J. Physiol.. 1918, 
XLVI; and Heart, 1913, V, 45. 

9. Porges and Leimdorfer: Ztschr. f. klin. Med., Berl., 1913, 
LXXVII, 464. 

10. Porges, Leimdorfer, and Markoviei: Ztschr. f. Klin. Med., 
Berl., 1913, LXXVII, 446. 



May, 191 l.] 



.JOHNS HOPKINS HOSPITAL BULLETIN. 






11. Henderson and Palmer: J. BtoL Chem., 1913-13, XII 

13. Sellards: Hull. .Johns Hopkins Hosp., 1913, XXIII, 

13. Palmer and Henderson: Arch Int. lied., 1913, XII. 

14. Sellards: Bull. Johns Hopkins Hosp.. \'.*U, XXV. 1"1 
L5. Warburg: Ztschr. f. Physiol. Chem., 1909, l.xi. 361. 

16. Weill: L'Aaotemle au ooars dea nephrltea chronlquea. Paris 

1913. See also Agnew: Arch. Int Med., 1914, Xlll. 486. 
r, Martin II Nephritis Ne* Yerk. 



IX. M.lfNI! 

XLV. 
19. Addle Call! SI \i. 440. 

- llar.ls Phllipplni i a H. 
3haklee: Ibid . 1911, vi. 

it v. HSaslll ch. t kiln Mi i 147 

jcher ir \ 

Arch, int '. 



THE WORK OF T1IK OUT-PATIENT DEPARTMENT <>1 
HENRY PIIIPPS PSYCHIATRIC (LINK ' 



HE 



The Dumber of patients in the dispensary of the 

B Phipps Psyi ib l May 1. 

• ni> presented bj mptoms of mental 
■ varying in type and degree. In \ ■ 
- a rather vague idea in the profession at large 
problems deal! with in such a dispensary, 
preliminary remarks may lie eJ 

rder mean- a disorder <>f the biolog 
individual which is shown in its higher adjusti 
such a disorder can nol he understood without taking into con- 
sideration the complex activities of tin- individual, not only the 
al, the metabolic ami physiological adjustmi i 
implex adjustments which cannot 
quately described undeT term- that .1.. do! include the 

or. The ne adjustments, however, maj be 

interfered with bj vhich act at varii 

- damage t" the brain by injury 
i -ult in very peculiar conduct, or the adjustment t" 
vironment may be interfered with by tie 
m of poison introduced from without, 

■ id, or developed witllill the orUatllMl: 

or typhoid, or the source of the disorder ma 
■ I 

nl may l»- the result of 

Of the ■ 

adjustment in which no primary 

■ ■ 

■ 

and hallucir 

: net. the difl ' mi the indi'. ii 

as a rule tie 

to him by I 
which this j. 
never I 



6. 1914. 



IIFBEL1 .M.I '.. 
Johns Hopkins Univt 

The above n 

with a ease of mei • in mind i 

of a primary distui 
activity. The phj 

mechanisms. An adequati pi 

the basis of any Bat 

aminatdon of a menl 

ignore none "f the usual clinii 

the presence of any ini 

mamled. therefore, in psychiatric « lie. In 

dispensary work time is limited, compn 

and therefore the physici 

els him to consider thi in the 

individual cast . This da - oot ind under- 

value the r61e played by tie- simpler i 
of mental disorder. It Bimpl 
pen, ■in-,, nas led ! I 

that hi 
Rcation. 

To _• 

done in 

month <>f January 

of dill 



154 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| No. 273 



3. Children with psychoneurotic symptom-. 

4. Children with pronounced speech defect. 

With regard to the children with simple intellectual defect, 
the degree has always been estimated by the Binet-Simon 
scale. The etiological factors have been gone into and an at- 
tempt made to find out how far the defect could be attributed 
to ante-natal conditions, or to some organic lesion, either at 
childbirth, or during some infectious disorder of childhood. 
The family history of some cases has been investigated in a de- 
tailed manner by a special worker. The practical question 
with regard to such children is the extent of the further possi- 
ble development in the individual case. Is the defect based 
on any remediable cause, is it only an apparent defect? Thus 
a child with a refractive error uncorrected, with headache, 
unable to maintain sustained attention, may fidget, annoy 
the others, become a source of annoyance to the teacher, get 
quite out of touch with the authorities, drift into the com- 
pany of the really bad boys and develop habits impossible later 
to eradicate. Can the child be expected to become a wage- 
earning citizen and should its training have that in view, 
that is, should its training be along the lines of teaching in 
the ordinary grades, assuming that the ordinary school cur- 
riculum is a reasonable one? Or is the child never going to be 
a self-supporting social unit, will it always have to be safe- 
guarded against exploitation, against becoming the tool of the 
unscrupulous, against becoming a disseminator of immorality ? 

Children with marked mental defect not based on remedia- 
ble conditions require special training. The aim of this train- 
ing should be correct conduct and the acquisition of mechani- 
cal ability, and not the general concepts of ordinary education. 
When the constitutional defect is not definitely recognized, the 
teacher is apt to apply misdirected energy, e. g., to 'try to teach 
a boy of S or 9 years something which, with his defective 
equipment equal to that of a boy of 4 or 5. years, he is abso- 
lutely unable to grasp. Such children waterlog a class, impede 
the teaching of the more valuable scholars without conferring 
any compensatory advantage on the defective child. It is, 
therefore, important that the child should to a certain extent be 
standardized and his education have a direct reference to his 
actual capabilities. A satisfactory training of the child is the 
best guarantee of the later happiness of the individual. Un- 
less the defect is recognized and proper measures taken, the 
child is apt to drift into bad company, develop criminal habits, 
and be a serious draw-back to the community. The danger 
of the exploitation of the female is obvious. 

In many children, the general mental defect is accompanied 
li\ ,i \ariety of neurotic symptoms, and these children present 
extremely interesting problems. The psychoneuroses in the 
adult are only intelligible in the light of the development of 
the character of the individual, and in the children with neu- 
rotic symptoms one has the opportunity of studying at a verj 
early stage developments which throw much light on the dis- 
orders of the adult. 

The children are difficult to study under dispensary condi- 
tions. At first they are shy. uncommunicative, on the defense. 
Their visits are apt to be at rather long intervals, tin \ are 
in a peculiar environment which does not elicit their character 



istic reactions. Therefore one is frequently almost altogether 
dependent on the anamnesis. Here the social service depart- 
ment is able to give invaluable aid and to furnish a good idea 
of the actual environment of the child and of the remediable 
defects which it presents. 

The following cases illustrate types of children dealt with: 
Jan. 9, 1914. E. C. D., a boy of 7, is getting along very well at 
school, but during the last year has presented evidence of unstable 
equilibrium. The boy has bad dreams, and he has recently been 
stealing. The aunt considers that these symptoms came on after 
an operation for hernia last year, but the boy already had some 
difficulty with his instinctive life even before that. He had already 
been masturbating for about one year and he wet the bed until 
the age of six. 

Remarks. — The case illustrates the frequent occurrence of 
fears and bad dreams in association with difficulties in the 
sexual life. It shows the importance of these fears as evi- 
dence of the advisability of helping the child in the sphere 
where help is apt to be refused. Scolding and punishment are 
apt merely to increase the tendency of the children to deal in 
a blind and evasive way with troubles which are almost inevi- 
table in the course of development. The relation of stealing 
to the other difficulties of the patient has not been traced, 
but it is a symptom which must not be accepted as an irreduci- 
ble defect of character, but as something which may be further 
analyzed and modified. It may be possible to help this boy 
by some educative talks and thus prevent the further develop- 
ment of an evasive way of dealing with his personal difficulties. 

Jan. 17, 1914. A. A., a boy of 8% years, had been pilfering for 
four or five months. The father dragged the boy to the clinic on 
the chance that the doctors might remove something from the 
boy's brain. At the consultation the boy was absolutely uncom- 
municative and frank relationships were not established. The 
father, disappointed at the impossibility of an operation, did not 
think it worth while to bring the boy back to the clinic. The 
social service worker made a home visit. She found that after 
each episode of pilfering, the boy was not punished physically, 
but was threatened and scolded to such purpose that for two ot 
three days he was panic-stricken and in tears. The case presents 
a problem of very great importance, and the endeavor will be 
made to try and get into friendly relationship with the boy to see 
whether the stealing can be understood more clearly. 

Jan. 9, 1914. C. E. D., a boy of 9y 2 , whose mental age is 7V 2 years. 
The mental retardation is here due not to faulty environment 
or to a poor education, but to actual disease of the nervous system. 
The boy was a seven months child, had spasms at IS months, fre- 
quent screaming spells until 5 years, and later, occasional attacks 
of a convulsive nature. 

Remarks. — This case is one of a very large group of chil- 
dren who are brought to the dispensary, with a history of con- 
vulsive phenomena at some period of childhood. In some eases 
the disorder is in relation to more or less coarse damage to the 
brain, which appears to have been caused either by prenatal 
influences, difficulties of child-birth, or infective disorders in 
infancy. In other cases the patient presents no neurological 
symptoms except the convulsions,' and the etiological factors 
are very obscure. From the point of view of treatment, these 
patients arc of course very disappointing. They form an in- 
teresting material of study, for our knowledge of convulsive 
phenomena and the underlying conditions is extremely 
meagre. 



M\v. 1914] 



JOHNS llol'KINs HOSPITAL BULLETIN. 



Jan. 12, 1HH. J. B.. a boy of 14. during the winter o( 
began to stay in the bouse and made only desultory attempts to 

play or read. He showed a marked change of disposition and was 

quarrelsome with the other children. He would sit about In the 

idgeting in his chair, smilinp without cause. 11. 
ad as to p< rsoi il cleaj II : ■ ■ Mi 
time he showed a compensatory fastidiousness with retard to 
eating. He would wash his dishes over and over befon 
He would refuse to eat things, saying that they were not clean 
easily frightened, especially at night. 

- 
symptoms have no 'louht to be partly understood in i 
to the habit of masturbation, which had b> ■ 
-oeiation wit bad boys. The father - 

to the boy about it. but as a matter of fact tb 

afraid of hi? father. 

Two '.i— maj ■ who have been coming to the 

•able time : 

May 24, 1913. M 3 i- a queer, jerky little girl of 7 who i- ei 
tremely fidgety, jumps about the room in a somewhat odd manner, 
is at times inattentiye. asks questions as if she were rather Btupid, 
and is apt to pretend that she does not know the nature of the 

illation of the doctor, etc. what Is especiall: 
acteristic of this patient is her incessant asking of questions, manj 
of which have quite obvious answers. Although the patient makes 
a superficial impression of being stupid, she is of normal In- 
tellectual level and her teacher finds her quite bright at school. 

irks. — To understand the underlying forces and the 
mechanism of such a disorder i< a difficult and I 
and i~ not made any easier by tin- infrequency of t 

sary. It is important to take this . ... 
ing of the child seriously, and e main 

questions and what is the curiosity which thus e 
so indirectly. In I 
■ 
fortun.. v frank relationship. S 

understand the r> :■■ 
in which this child has ght up and which put a 

strict taboo on many of the simple qui e child. The 

mother doubt to t 

ght in omitting to punish hi 
Id, who bad madi 

father was disturbed at the p - 
of the patiei I 
ruin her soul in ■■' 

in matters of training and in the regulat 
the chili 9 ferred with I 

child w 

21, 1913. W. S„ a difficult 
school, unruly and bad-tempered at bi 

og animals and children The environment, 
probably partly the cause of the boy's diffli ' 
punished the boy >• 

hours he was obliged to study Hebrew with his fit 1 • 
little time for amusement 'lie' mi utal agi 

of a child of 11 years In school be 
this account he disliked his tea. 

rks. — In tl - 

■ 



tained tin- inl 
out of 

3 

attitud, 
with a 
work. 

locial s.r\ i. ■ 
W. H . a bOj "I ! 1 . 

some > • • 

erratic in his behavior, fastidious In I in his 

Bleep, afraid to sleep awaj 
masturbation bj comrades and treated Impi . 
For this latter eplsi thrashing fr 

mother, which probably wi 
m t . ■ deal with on. 

mbination of thi Bymptoms In I 
common one, sleeplessness, disturbing dream 
masturbation. 

child was at fault. Thi 

ami the irregularity of his ho 

sions <<i tb.- ,'iily faulty . 

with such a situation bj 

i- absolute h Deceseary. The worker has visited t' 1 

ularly, has instructed the parents ii 

■ for the |> 
in the country, has arranged for 1 
graded nth the prii 

S 

psychoneur 

Dralidism. i 
dispensarj condil 
treatment involves tin n 
ami difficult 

by this group of 

Jan. .':•. 191 1 8 B . a young « 
complained ol 

she was quite i. ippj , In 1 

arded f"i>r 

; 



156 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 279 



only a vague nervousness with surface cheerfulness and conven- 
tional smile. In this case, too, the problem was to educate the 
patient in regard to those factors which had been dealt with very 
evasively, the semi-delirious episode itself being the disguised 
expression of factors repressed from her conscious life. 

Jan. 28, 1914. B. K. M., a clergyman of 46, several months 
previously had had an attack of quasi-unconsciousness. since when 
he had complained of excessive fatigue. Nineteen years pre- 
viously he had had a nervous attack which his physicians said 
bordered on St. Vitus' Dance. The very fact that he had become a 
clergyman was to a certain extent a compensation for difficulties 
not squarely met. He had given up another occupation to enter 
the ministry, and one year later he had the involuntary move- 
ments referred to above. In the third year of the ministry he had 
a worse break-down. Nine years later he had an attack of short- 
ness of breath, palpitation, marked anxiety, disturbing dreams of 
the nature of nightmare. 

Remarks. — Even in a single interview it was possible to see 
in outline the mechanism of the disorder, and to put this 
before the patient. The amount of insight thus acquired by 
the patient along with the reassurances given him seemed to 
be decidedly helpful. Such a case, however, requires rather 
prolonged treatment, and the patient did not live in Baltimore. 
The case was gone over with the family physician who accom- 
panied him, and the patient was recommended to go over 
with his physician in very much greater detail the main points 
which had been only partly reviewed during the consultation. 

The following cases represent a type very familiar in dis- 
pensary work, so familiar as to have lost much of its interest for 
many physicians. Although familiar with these cases, we are, 
however, far from understanding them and they present prob- 
lems of very great psychiatric interest. 

Jan. 20, 1914. H. G. is a very typical example of this group of 
patients. She is a woman of 39, very unhappily married, who says 
that she is tortured by her husband, that he makes her sick, that 
she only wishes to live for her children. The patient complains 
of a variety of somatic symptoms, pain in the head, tightness in 
the chest, pain in the abdomen, but a thorough physical examina- 
tion reveals nothing to account for her bodily symptoms. 

Remarks. — The patient's invalidism appeared to be in close 
relation to her general unhappy situation. She had, however, 
not reacted with the special symptoms of a hysteria nor an- 
other psychoneurosis. This type of invalidism is partly intel- 
ligible as a reaction to the definite situation ; to a certain ex- 
tent it affords protection from the demands of the environment 
and brings in certain immunities and privileges. It might 
best be described as a " situation-neurosis." The importance 
of the formulation in this term is that we keep before us the 
pract ir.il problem of seeing whether after all the situation may 
not In- advantageously modified, so that we do not confine our- 



selves absolutely to dealing with the patient as an isolated 
unit. At the same time it is important to encourage the 
patient to face frankly the difficulties of the situation and to 
realize the presence of internal obstacles of which she was 
previously ignorant. We thus try to improve the adjustment 
of the patient at whatever point we find available for modifica- 
tion. It is probable that in this case the patient had never 
in her life reached a satisfactory level of independent activity. 
As a child she had been wrapped up in her mother, and after 
the death of her mother she said that -she had cried a whole 
year. The analysis of the development of her character arid 
of the circumstances which led to her unsatisfactory marriage 
would probably have thrown some light on the later develop- 
ment of invalidism, which after all represented a rather child- 
ish type of reaction. 

Jan. 27, 1914. A. A., a Hebrew woman of 38, complained fluently 
and continuously of innumerable pains. She clamored for sympa- 
thy. She knew that the hospital doctors could not help her, but 
she could not stay away from them. Whenever she was taken into 
a hospital, her condition changed entirely and she was well in a 
couple of days, but she relapsed after her discharge. In this case 
the same problems are brought up as in the previous one. 

Jan. 16, 1914. J. B., a woman of 40, after some trouble with her 
neighbors, became nervous, sleepless and suffered from headaches. 
Her complaints found little sympathy with her husband who had 
been nagging her ever since her marriage 17 years ago. She had 
been in one hospital, but left after one week, as she was disgusted 
with the treatment. 

Remarks. — In this case we see how an illiterate woman, un- 
happy with her husband, in the face of additional difficulties 
in life, falls back on a variety of mild complaints which relieve 
her of some of her responsibility and throw it on society. It 
is very difficult in an illiterate patient of this type to do much 
in the way of getting her to understand the true nature of the 
trouble, as an inferior adaptation to the actual situation. It 
is difficult enough with an educated woman of the same age. 

It is interesting to notice the percentage of Russian Hebrews 
in this group. This type of disorder is probably closely related 
to the racial character and to the special difficulties in the life 
of immigrants of this class. 

The above very summary review may serve to indicate the 
actual problems dealt with in the dispensary; these problems 
are not only of great psychiatric interest, but touch many vital 
interests of the community. They raise important social and 
educational issues, and it is hoped that even where in the 
individual case little can be done, the thorough study of the 
disorder in its complete setting may contribute data of value 
iu relation to the mental hygiene of the community. 



DYSTROPHIA EPITHELIALIS CORNE.E: REPORT OF A CASE.* 

By Lloyd 11. Whitiiam, M. D., 
Assistant in Ophthalmology, The John* Hopkins University. 
The patient, a ae?ro, ">?> years of age, married, and a white- i plaining that, for several weeks prior to that date, there had been 
washer by occupa tion, came to the clinic on June 9, 1913, com- a gradual diminution in the vision of his right eye, unaccom- 

*From the clinic of Dr. Samuel Theobald, Baltimore Eye, Ear and panied by pain. There seemed to be a " shadow " before his eye, 

Throat Hospital. and for the past week it had been slightly sore. 



Mat, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



Previous medical history negative; no malaria, no trauma, do 

syphilis. Qroaa Inspection revealed a well-nourished, vigorous 

man with a rather dry. roars.' Bkln, and a coated tongue, but, on 

nng no abnormal appearand 

Minute inspection of the cornea of the right eye, with the 

binocular loupe, showed .1 small, central, superficial, herpetic, 

.1 loss, which was clear, uninflltrated, and stained faintly 

with fluorescein. Midway center ol t' 

bus a very faint, whitish crescent was Been, evidently 
tween the epithelium ami Bowman's n r in the 

anterior lamella; of the substantia propria. The corm 

thelium. itself, surrounding this ana anil extending to within 
mm. of the limbus, was diffusely clouded and 

tons, minute distinct vesicles being present There 
lj Blight congestion of tin clllarj vessels and tie 1 
normal in appearance, although the pupillary v 

■ ■■ globe was not elevated, .-•■■- 

KOpe, and \ision was limited to 
•t thought was of a rar d k. ra 

intlami: 

■ 

nutritional affection, an epithelial dystrophy, due, 

-. lew which was partial!} 
by finding din ibllity of that cornea as comp u 

normal in that n 

illowlng 

made by In 

gulable, little fibrin. Hb 

ill mononui 

Blood pressure, 1 I s mm. 

on Pirquel I, negative 

iced under an appropriate 

1 with no appro lable 1 bangc In th< 
until .In 

■■ ration ol thi 
thelium. and on Ju 

■ 

I 

much di 
stippling— giving I: 

It is 
ing and unrecorded 
with a foreign bod) lm| 

tral 

turn, in addttli 
was a ! 

iy with fluon 
was more pronoun 
■ 
sugar fn 

■ rtaklng fi 



On tin 

la] dtsturban 

■ 
ind plet< restoration did not occur for - 

time t> 

which was promptly relieved 1 

hydrochloric! solul 

the corneal 

Id, for the in ■ 
with the ophthalmoei op< 1 1 1 

ImprOVl in. nl In: 

noted that, I 111 ' 
genera] 

rated ti 
II.- .. 

■ 

still pr< 

Four 
of urim 

produi ' 

Stri. 1 

told to instil 

stimulate tin nut r ' 

The man « 
had dimlnisl 

■ 

■ 

althougl 

S 






L58 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 379 



similar cases, and added their reports to the literature upon 
the subject, a total of 17 cases. 

The slow and progressive course of this condition distin- 
guishes it clinically from any of the inflammations, for the 
latter are marked by a period of progression, followed later 
by one of regression, while anatomically the dystrophies are 
characterized by degenerative changes as opposed to the cel- 
lular invasion of inflammatory lesions. 

The majority of dystrophies are the expression, either of a 
local disturbance of nutrition, or, as Reese has pointed out. 
some general malnutrition : for example : the deposits of 
mucin in myxcedematons subjects after thyroidectomy, the 
grayish-green discoloration of the cornea occurring in dissemi- 
nated sclerosis, and. according to Weeks, disease of the Gasse- 
rian ganglion and traumatism. (A physiological parallel to 
the dystrophies is found in the familiar " arcus senilis.") But, 
to dystrophy of the corneal epithelium no definite aBtiological 
factor has been ascribed. Hence the writer feels some hesi- 
tancy in advancing his opinion that diabetes was the direct 
or remote cause in the case which has just been reported, even 
though the diet and presence or absence of sugar did so 
markedly influence the ocular condition. 

If the metabolic disease in question did bear some definite 
relation to the trophic disturbances which took place in the 
cornea, some interesting conjectures as to the modus operandi 
might be made. Was the process caused by a direct toxic 
action on the trophic apparatus, for instance, by a temporary 
flooding of the blood or lymph with diacetic acid or beta-oxy- 
btityric acid ? Or was the degeneration purely a nutritive one 
caused by a perversion of the pabulum normally carried to the 
corneal epithelium, and due to a degeneration in the walls of 



the small blood vessels? Again, might the bullous condition 
of the epithelium to analogous to the desquamative derma- 
titis so constantly observed in diabetes? 

Epithelial dystrophy is easily differentiated from Family 
Nodular Keratitis, from affections due to noxious vapors, from 
keratitis vasculosa with herpes, from post-operative sclerosis, 
and from hyaline or fatty degeneration of the cornea. 

The case just reported resembled those of Fuchs in that it 
was associated with transitory periods of hypertony, and. some- 
what one described by Eeese with a bulla in the center of the 
opaque cornea. It makes the third reported case associated 
with pericorneal injection. 

The pathology of dystrophia epithelialis cornea? is rather 
vague : Paul Knapp contends that it is due to an oedema of 
the epithelium. Fuchs has had the opportunity of making a 
microscopical examination of one case. There was gray- 
ish opacity and roughening of the surface of the cornea from 
small vacuoles in the epithelial cells, and newly formed tissue 
between Bowman's membrane and the epithelium. This tissue 
is homogeneous, and without signs of hyaline or mucoid degen- 
eration. The epithelium covering it is thinner than normal, 
but the cells are not flattened or hornified. He thinks that in 
the earlier stages the epithelium is probably thickened and 
vacuolated. 

BIBLIOGRAPHY. 

Ernst Fuchs: Areh. f. Ophth., 1910, LXXVI, 478. 
Paul Knapp: Arch. f. Ophth., 1911, LXXVIII, 331. 
Arnold Knapp: Trans. Am. Ophth. Soc, 1911, VII, 745. 
Dunbar Roy: Arch. Ophth., N. Y., 1912, XLI, 490. 
Uribe y Troncoso: Ann. Ophth., 1912, XXI, 369. 
Robert G. Reese: Ophth. Rec, 1913, XXII, 133: Arch, of Ophth., 
1914, XLIII, 57. 



LOUIS HEBERT.* 

By M. Charltox, 
Librarian of McGill Medical Library. Montreal, Canada. 



Every student of Canadian history knows that from the first 
days of the colonization of Xew France, an important role as 
colonists was played by members of the medical profession. 
If they were not remarkable for any great professional bril- ■ 
lianey, they were generally men of sterling character and 
courage. Louis Hebert, apothecary, surgeon, and agriculturist, 
is regarded, next to Champlain, as the "Father of New 
France.'* When Champlain induced his old friend of Port 
Royal to venture once more to become a colonist of Xew 
France, he knew he had accomplished a greater work in build- 
ing in. his colony than had been done since its foundation. 
For Louis Hebert had proved his worth at Port Royal, not 
only as a surgeon, but as a keen and ardent agriculturist. 

When Champlain returned to France in 1617, his mind 
filled with the wondrous future he was planning for Quebec, 
he knew it was of vital import, to obtain as colonists nun of 
the besl type, oo1 jail-birds, as Roberval had had to contend 

♦Presented by Dr. Henry M. Ilnr.l at the meeting of The Johns 
Eopkins Historical Society, March 9, 1914. 



with, nor mere adventurers, who came for the love of adven- 
ture or gain, and went away again, but men who would cul- 
tivate the land. And so the thought of his friend came to him 
— Louis Hebert, who had cultivated such beautiful gardens 
at Port Royal, until that settlement was destroyed by Samuel 
Argall, when Hebert returned to France. 

Louis Hebert had received a good education, for his father 
was a man of repute, being apothecary to Catherine de Mediuis. 
Louis followed his father's business and had a shop on the 
banks of the Seine, where he was well patronized. But in the 
summer of 1606, he suddenly announced to his friends ami 
relations that he was sailing with Poutrincourt and fifty other 
colonists for the Xew World, of which there had lately been 
so much talk. Among others who sailed in the ship was a 
Parisian lawyer, historian, and poet named Lescarbot. the 
friend and lawyer of Poutrincourt. It is to Lescarbot we are 
indebted for the vivid portrayal of how the first winter in the 
new settlement at Port Royal was passed. "'For my part," 
writes Lescarbot, " I can say that I never worked so hard in 



May, 



JOHNS HOPKINS HOSPITAL BULLETIN. 






• 
-. in making alleys, building sumnn 
rye, barley. garden plai 

them, for I to find ont, 

ility of th<- - 

rt and the 

must 
M>rk by moonlight, digging and planting 
• i>ert returned !•■ Paris in the autumn ■ 

•!. Poutrineourt's son. He • 
court in managing and taking 

then returi 

8 
on plain arrived in Prance in L611 
- _ tiled him with his marvellous 
I 
m his famil; 
M 14. ( 'hamplairj fur tradii 

make him an all' 
■ 
riving at ETonfleur, Hi ri in and 

. thai all thi 
to him In vain dii 

ep their pr 
lim one hundred crowi - two hundre 

but rather than return to 

Sen World. 

and when thej • 

J 

«i' are told in t! • 



and in connection with that it 
■ 
ml a half earlier, I I 
ih White. 



after n 

■ 

th, the 

dwelling in what \ 

I 
the 1" 

farmii - 

lie »i 

what hi 

fanner. 

i laimed that 

tin- was added !■■ I 

Of tllf fief i'f ■!'! : 

right!} 

: 






■ 



1 60 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. m 



Champlain, when Kirke captured Quebec, were the Hebert and 
Couillard families, as well as a surgeon, Adrien Duchesne and 
his wife, who came to Quebec in 1618. Duchesne was the sec- 
ond medical man to settle there. 

When Champlain returned to Quebec after the treaty of 
St. Germain-en-Laye, he was accompanied by Fathers Paul 
le Jeune and Anne de la None. They went immediately to 
Madame Hebert's house, the only one spared in that scene 



of desolation. Here Madame Hebert lived with her second 
daughter, Guillemette and her son-in-law, Guillaume Couil- 
lard. Couillard had come to Quebec in 1613 as a carpenter. 
But he had soon become, under Louis Hebert's teaching, an 
active farmer. In 1628, instead of tilling the ground by hand, 
oxen were used, and so well had Couillard managed Hebert's 
farm that it was spoken of as the one fertile spot at Quebec 
when Champlain returned. 



PROCEEDINGS OF SOCIETIES. 



THE JOHNS HOPKINS HOSPITAL MEDICAL SOCIETY. 

December 15, WIS. 
A Case of Infection with Agchylostoma duodenale Treated with 
Oil of Chenopcdium (with Demonstration of Specimens). 
Dk. Robert L. Levy. 

The patient, a Norwegian sailor, aged 23, was admitted to the 
Johns Hopkins Hospital eight weeks ago, complaining of headache, 
general bodily pains and swelling of his legs. He had always been 
strong and a hard worker, and had sailed to almost all parts of the 
civilized world. The present illness began in Mexico one month 
before admission here. There, for the first time in the course of 
his wanderings, he went about barefoot. He soon developed a 
painful sore on the dorsum of the left foot, which discharged and 
resisted all efforts made to heal it. He noticed no itching of the 
foot. Shortly afterward the feet and legs began to swell and the 
patient felt weak, irritable and incapable of work. He went to a 
hospital in Mexico and remained there three weeks; during this 
time he was given no medicine. The swelling of his legs, however, 
disappeared and he was discharged somewhat improved. Twelve 
days before admission here his legs again began to swell, he felt 
feverish and weak, and there was moderate diarrhoea, so he 
boarded a ship for this country and landed in Baltimore. 

On admission there was striking pallor, fever, tachycardia, 
brawny cedema of ankles and lower legs and a pigmented scar on 
the dorsum of the left foot. He was extremely weak and very 
irritable. The blood showed 1,660,000 red cells, 6,440 white cells 
and a haemoglobin of 25^ (Sahli). In addition, there were seen 
many hyaline and crescent forms of aestivo-autunmal malaria. An 
examination of the stools revealed the ova of Trichuris trichiura 
and of the hookworm. 

The malarial infection was soon gotten under control. The 
whip worm ova spontaneously disappeared from the stools follow- 
ing vigorous purgation, but the usual medication with thymol, as 
recommended by the Porto Rican Commission, failed to get rid 
of the uncinaria, though thrice repeated at one week intervals. 



Accordingly, our patient was given the oil of chenopodium 
according to the directions (slightly modified) of Schiiffner and 
Verwoort ( Miinchen. med. Wchnschr., 1913, LX, 129). The patient 
was starved for eight hours, at the end of which period he was 
given an ounce of Epsom salts. Two hours later, 16 drops of the 
oil of chenopodium on a teaspoonful of granulated sugar were 
administered. This dose was repeated at two-hour intervals 
until three doses had been given. Two hours after the last dose 
of chenopodium the patient was given an ounce of castor oil and 
50 minims of chloroform. On sifting the stools collected during 
the next 24 hours. 19 hookworms of the Old World type were found. 
Ova continued to be discharged in the faeces. On repeating the 
treatment five days later, seven more hookworms were expelled, 
and this time no ova could subsequently be demonstrated in the 
stools. However, another course of chenopodium was given to be 
sure that no parasites remained; none were expelled. The stools 
have since been free from ova, and I believe we may consider the 
patient cured of his intestinal parasitism. He has gained 30 
pounds in weight. The blood now shows: 

R. B. C, 4,110,000; W. B. C, 11,000; Hb. (Sahli), 70^. It is 
of interest that whereas on admission the eosinophiles formed but 
7', of the white cells, there is now an eosinophilia of 36^;. Such 
a rise in eosinophile cells the Porto Rican Commission regards as 
of good prognostic import. 

As compared with thymol as a vermifuge in uncinariasis, oil of 
chenopodium seems to offer certain very definite advantages: 

1. According to Schiiffner and Verwoort it is more efficacious. 

2. It is not unpleasant to take. 

3. Its ingestion is not accompanied by any disagreeable after- 
effects. In a recent article Stiles and Boatwright have pointed out 
that unpleasant symptoms appeared in over half of a large series 
of cases treated with thymol, and carefully observed to determine 
this very point. 

4. In therapeutic doses it is non-toxic. Thymol occasionally, 
though rarely, produces symptoms of serious intoxication. 



NOTES ON NEW 1300KS. 



la Memoriam: Dr. James Livingston Thompson, Dr. i>,< 

Thompson. (lndianapo\ . The Hollenoeck Press, 

This small volume is a collection of pleasant and fitting tributes 
to these two noteworthy practitioners of Indianapolis. They 
were both men of mark; but many fine men like them pass away, 
and their work and names are soon forgotten, for they are uneorn- 
memorated, and so such "In Memoriam'" tributes are always 
precious records in the history of the medical profession. All 
friends oi these two doctors will be grateful to see these warm 
expressions of affection and esteem thus perpetually recorded. 



Surgery o) th< i ppi Abdomen By John B. Deaver, M. D., etc., 
and Astlet Paston Coopeb Ashhtjbst, M. D. Vol. II. Illus- 
trated. $5. (Philadelphia: P. Blackiston's Sort .( Co.. 1914.) 

It is more than four years since the first volume of this excellent 
surgery appeared, but the wait is compensated for by the thorough- 
ness and completeness of the second and last volume. The authors 
have carefully studied the great amount of literature on the sub- 
jeets treated — gall bladder, liver, pancreas and spleen — and their 
work is one that all surgeons will be glad to own. Their reputa- 
tion gives weight to their words, and the lists of references make 
it easy for the reader to look up original articles. The now 



Kay, 191 l. ] 



-lollNs BOPKINS HOSPITAL BULLETIN. 



eompleted "Surgery of the Upper Abdomen" la an 
contribution by American authors to the literature ol Burgery, 
and will bring then well won repute by foreign Btudenl 
subject. 

;.s Annual I Volume xxvi 

C. Men I:. Chemi* ./I Works, I 

Pharmacologists especially, and thosi who 
will find in this volume much valuable Information 

. i> reliable, carefully prepared from I 
authorities, and is conveniently arrant 

I . can easily secure one for all 
and -> m i-i , ,ni from this list, and can use it »i' 
if be follows the directions given. 

Edui at ion: I £ 

n ■ma Educational Progreas. Edited by 
J. McKekn Cattkll. Volume II. MeSicai Retearch an 

■i. By Richabd M I'l.iini. William H. Welch, W. ii 

Mown T. PrANKI in IV Mm. LEWELLYS P. BabKEB, Chab 

Mntor, W. l'. Cannon, w. t. Councilman, Theobald Smith, 

lbt, C. B&. Jackson, B. P. Lton. James B Hi 
John II l> 3. J 

Jakes Bwnro, W. W. Km, Hknbi h Hon mi. -on. the late 
'' \. Bona and the late Henri P. Bownm h, 
and Qarrtion, s. v. 1 1 »«, /■'/.:. < 

The basis of this handsome book of 536 pages seems to be the 
Bve Hitchcock Lectures delivered at the University ol California 
in 1912 by Prof. U M. Pearce, of Philadelphia (originally pub- 
lished in Popular Science Monthly), which cover 88 pagi 
remainder of the tHHik consists wholly of papers published during 
■ twenty years In various medical an ournals. 

different strata of thought during thi 
mention! d and consequently at 1 

Into his- 
tory and have given place to new Ideas and 

■ • med subversive of prop' 
of m i ' Ion. 

Prol Pearce'a lectures r, lati to prob- 
Immunology, pr, - 
chemistry, experimental pharmacology and experimental path- 

n which he gives an admirable review ol I 
immunity which were Initiated by Behring and Kits 

phtheria antitoxin of Behring and Knorr; I 
• ■f Ehrlich • of Wright ; the pi 

immui dow best Illustrated in typhol 

tion of complement . the condll 
creased susceptibility known as anaphylaxis; the stud] 

able or ultra: 

In pr- 
ill man in 1 960 

n in 1880 « I 
i fever; of I 
n 1893 and 
which had Import 

of the I' "f malaria and y. I 

and other lue to paihogi no- proto 

is followed bj a review ol the wonderful worl 

in dei I 

toxic ag 

Ivarsan to deal 
- that "with a record of about ■ dosen i! ' ; - 

used to cure or modify disease can 

protozoa, chemotherapy offors proa:, 



s.Tuin therapy ind vaccination In bacterial disea ■ 

limit thi 

Ism of cell .•• ': . It) 

in different part- of thi 

pharmacology, experimental patholog] and 

dthough inn, ,r.- full of i • 

unusual value ami should 
tin- hands ol ail mi dli ,i tudi uta i bi ■• brli ■ 

Mods ami rrsiilts ,,| in,-,,, 

i her study 
The succeeding pap, i a all 

t, but all are valuable contribul 
branches ol medical education Occaslonallj 
" Expert 

ptlmlam, we 
cynicism T if the industrious editor o 

worthy volume 

on "University Control" may be presented u] a plane 

of high Idealism. Tin' whole situation rails tor a much ■ 
Banal attitude than has ■ ly of writers 

upon it 

/.• »/• '/i. .1/ and 8oi 
m , ,, • India l 9 i Call nil 

tendi ■ "i Prinfino, India, 191 

Btudiet on the Mouth Part* and Bucking App 

I But king H;, 
Ho i 
Mo king Mui u i mn f W Cbaoo, \l D 

For a small 
an- of real Interest and li , 
exhaustive pap- rt \n 
and are valuable contribul 

ing in 

M li IllUBl 

The aul 

■ 

■ 

do nut think 

quently fail ' * 

gllng operation ','. : 

and not r. 1> on I I ■ II 

of i 

durlnr 



ltja 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 279 



We are told that the volume for 1914 contains accurate figures 
from the audited accounts of six thousand distinct institutions 
for the year ending December 31, 1912. No person who has not 
wrestled with the intricate statistics of a single hospital can 
adequately appreciate the immense labor involved in this annual 
review of the statistics of charity and philanthropy. 

In addition to these statistical reviews of the operations of hos- 
pitals we find interesting accounts of several distinctive British 
organizations to foster and extend their work, such as " The King's 
Fund and the League of Mercy," " Hospital Sunday " and " Hos- 
pital Saturday." The apparent decline of the Hospital Sunday 
movement which seems to require each year a larger subvention 
from legacies and interest from invested funds seems difficult of 
explanation. In the United States the observance of Hospital 
Sunday was a direct importation from England, and as it did not 
grow out of any popular feeling, it is not strange that it has never 
had any adequate support, and outside of two or three large 
cities we now hear little about it. In England, however, it was 
wholly different. It is possible that " The King's Fund and 
League of Mercy " tended to draw- away its supporters among the 
upper classes; and "Hospital Saturday " its friends in the labor- 
ing classes. 

The comparative tables of the cost of nursing in the London and 
Provincial Hospitals respectively are full of interest. The cost of 
nurses, per head, to use the editor's phrase, in London in 1912 
varied from fifty-four pounds at St. Bartholomew's to thirty-nine 
pounds eight shillings at Guy's; and outside of London from 
forty-three pounds six shillings at the Glasgow Royal Infirmary to 
thirty-two pounds eight shillings at the Dundee Royal Infirmary. 
A strong plea is made for more definite systems of accounting in 
every Nurses' Training School in order to determine the exact 
cost of maintenance. It is suggested that separate accounts be 
kept of every item of support, even where the Nurses' Home does 
not possess a separate kitchen. A separate kitchen requisiton 
sheet is further suggested for each and every department of a hos- 
pital so that it may be shown what sums are expended for food, 
etc., per person upon the medical staff, the nursing staff, the em- 
ployes and the patients. The practice of lumping together such 
expenditures to secure an average daily cost of support of all per- 
sons residing in the hospital irrespective of the varying circum- 
stances and cost of maintenance is justly deprecated. 

In view of the comparatively small number of convalescent hos- 
pitals or homes in America it is of interest to note that three hun- 
dred such institutions are to be found in the United Kingdom 
alone. It is evident that we need a much larger number. 

The financial details of the expenditures of hospitals in Great 
Britain and America are thoroughly analyzed and deserve careful 
study by all hospital officers. It is to be regretted that compara- 
tively few hospitals of the United States are thus reported because 
of the lack of uniform systems of recording expenditures. The 
leading hospitals of English-speaking countries owe it to them- 
selves to agree at an early day upon a form of comparable sta- 
tistics. 

Bovine Tuberculosis and Its Control. By Verantjs Alva Moore, 
M. D., etc. $2. (Ithaca. X 7.: Carpenter d- Co.. 1913. ) 

Now that the subject of tuberculosis has gained a widespread 
attention, this hook should find a large and interested public; for 
tuberculosis in cattle has assumed an integral and important part 
in the broad plan for suppressing the disease. It touches human 
pathology and hygiene, invades sociology and encloses pressing 
economic questions. In simple form Dr. Moore gives the essentials 
about bovine tuberculosis. The information is not exhaustive, 
but it is in general accurate and it is an advantage that the book 
is perfectly intelligible to intelligent laymen. 

Disputed questions are treated with moderation and conserva- 
tively, especially for instance, the chapter on the value of tuber- 



culin in diagnosis. The methods of eliminating tuberculosis from 
herds are given full consideration. Those interested in the estab- 
lishment and maintenance of sanitary dairies should find the book 
invaluable. 

Modern Problems in Psychiatry.. By Ernesto Lugaro. Trans- 
lated by David Obr, M. D., and R. G. Rows, M. D. With a fore- 
word by Sir T. S. Clouston, M. D., LL.D. $2.50. (Manchester 
University Press. 1913.) 

The first edition of this work was published in 1909. No 
radical alteration has been made in this edition. The book is one 
which enjoys a well-deserved popularity owing to the clearness 
with which some of the more general problems in psychiatry are 
discussed, but on the other hand some of the more modern prob- 
lems are practically not touched upon. According to Clouston, 
however, who writes a foreword to the book, Lugaro has pointed 
out future lines of research more clearly and fully than almost 
any of the modern authors. 

In the general introduction the relation of psychiatry to general 
medicine is discussed, and the importance of welding it with 
general clinical medicine is strongly emphasized. Chapters are 
devoted to the psychological problems, the anatomical problems, 
pathogenesis, etiological problems, nosological problems, and prac- 
tical problems. 

Throughout his work Lugaro discounts the importance of 
psychic causes in the etiology of mental disorders, and his some- 
what formal point of view may be seen from the fact that of all 
factors he regards them as being the most insignificant. 

Ophthalmic Diagnosis. By Dr. C. Adam, Berlin. Translated by 
M. L. Foster, M. D. Illustrated. (New York: Rebman Com- 
pany, v.ii.;.) 

This is probably one of the best, if not the best, atlas of the 
internal diseases of the eye which has ever appeared. Not only 
are the pictures well nigh perfect, exhibiting the minutest changes 
in practically every disease, and altered condition of the fundus 
oculi met with, but the descriptions accompanying the same not 
only describe the plates, but furnish a wealth of accurate clinical 
and pathological information. The cases shown have been so 
carefully worked up and described that we regret that the author 
has not inserted the possible vision which each case had in every 
instance, while suffering with the pictured eye lesion. This 
would have made this work incomparable as a work of reference 
in medical-legal and court questions, as far as the internal lesions 
of the eye are concerned. This book deserves to be held in the 
highest esteem by all medical men. 

Surgery of the Eye: A Hand-book for Students and Practitioners. 
By Eisviv TbsoK, M.D., and Gerald H. Grout, M. D. Illus- 
trated. $4.50. (Philadelphia and New York: Lea & Febiger, 

Publishers. /.'</.:> 

There is nothing particularly new or novel in this work, nor are 
the operations described more accurately or better than in many 
text-books on the eye, which do not aim to be devoted exclusively 
to eye surgery. The work, externally, is of good size, but this is 
found to be due to large print, and large pictures, many of which 
are entirely unnecessary, rather than to an abundance of valuable 
subject-matter. Surely no one capable of doing eye surgery need 
be shown, by means of a full-page photograph, how to illuminate 
the eye-field with a hand lens, nor need he be shown how to apply 
ointment to the conjunctival cul-de-sac. What's the need of show- 
ing an eye surgeon how to apply lid retractors, giving two full 
pages to illustrate this simple procedure? Even in the text a large 
amount of the subject-matter is devoted to the unnecessary descrip- 
tion of commonplace steps. To recapitulate, the beginner Will not 
need this work, and the eye surgeon will likely have at his finger's 



May. 191 |.| 



.Johns uoi'kins hospital bulletin 






Ii tails mentioned >o laboriously, long bi 
likely to want a book of this title We oonBldi 

mall, and have been disappointed In its penu 

Ophtlfi Bj i'n uu i - II 

M n Qlostrated. $■). [Philadelphia: P. 

mosi unsatlBfactor] books which .> i 

led " International 
of Ophthalmic Practice," but w< think that facl should no( 

iltory puttini r, as found In this volumi 

'. n whim, and U t 
I, or more Importance. He dors not limit 
■ 
ophthah -:• and small, dealing with 

must Import 

■ 

tory in it- present mam tat Ion. Probably if 

d more clearl 
rk worth while, but In its present arrai 

this book has tmt a limit 

I Gl I S^ 

Edinburgh. Illustrated ' Thi MacmiVan 

Is a very satisfactory small work on the eye, and unlike a 
large number of others, is not an abbreviated edition ol 
the larger textbooks, but is distinctly the author's own work, and 
m it, at times, bis own opinion, sometlmi 

with tl 

author ntative, but be is simply positive in Irs 

well for the student. 
. Instruction from a well-informed 
author skilfully Introduces the required amount ol 
pathol". rlology along wit 

ordinary daily work of the student In 
il be found to be helpful and \ 
• nt may have to refer U 
■ l the rarer i 
with thi 'ii of clinical ophthalmolo 

writer this work will afford additional lnt< 
• Ileal little work, well . 

U ' I 

i ' 
practical pi 

■ 

;. length tl ■ 



form w It 

obstetrii 

Tin- l 
draw II 

trat. d $8.60 

In this small hand 

■ ■ r 
The 
from thi id t> \t book 

let with in norma] pregi 
and then conslderlni 
during the sai 

■ 
ovum, with the formation ■ .ia. are from 

standpoint particularly good, am - dim 

cult Bub orl but compi 

llent, no di • 

an- rather brl< i and the h 

•'. r 1 1 • ■ r . In hi 

of the child's 

.Ii; 
In thi 

-uflir ' 



164 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| No. 279 



functional entities grouped together. The chapter on respiration 
is especially pleasing and satisfactory, and may well serve as a> 
model. Those upon degenerations, temperature, hepatic disease, 
carbohydrate metabolism, and gout, contain stores of useful and 
suggestive information for the student, presented fully in a clear 
and good style. 

On the other hand, a few chapters, as those concerning digestion, 
and circulation, fall below the general standard, while the kidney 
is much slighted. A little tendency is observed here and there to_ 
state opinions in such a way that they may possibly be mistaken 
for accepted facts. 

Throughout this book a working knowledge by the reader of 
chemistry, physiology, and laboratory procedure is assumed. 
In this and in its general aim it is to be commended as a step in the 
proper direction. 

A Clinical Manual of Mental Diseases. By Francis X. Deri i \i. 
M. D., Ph. D. $3. (Philadelphia and London: W. B. Saunders 
Company, 19X3.) 

This book is based upon the annual course of lectures delivered 
by the author at the Jefferson Medical College. The classification 
adopted is exceedingly cumbersome, and unfortunately leads to a 
great deal of very unnecessary recapitulation. 

The symptomotology of the various clinical entities is faith- 
fully described, but it is all presented in such a formal way, with- 
out any case histories, and with practically no attention paid to 
more recent teachings in psychiatry that it is exceedingly unsatis- 
fying. Particularly is this the case when one comes across such 
statements as: "Manic-depressive insanity is probably due to a 
toxin, the recoveries from the individual attacks suggest the 
formation of an antitoxin." 

Then again it is rather surprising in this age to find hysteria 
considered in a chapter where mental diseases related to somatic 
affections are discussed. 

In considering the eye-signs of general paralysis it is stated 
that in addition to the light reflex being lost that the reaction of 
accommodation is sooner or later involved, and then not content 
with this it is further emphasized that " the more advanced the 
case the more likely is there to be loss of accommodation, and in 
almost all cases the loss is present in both eyes simultaneously." 

To allow him to make such statements the author's experience 
must surely be unique. 

There are so many questionable statements made throughout the 
book that one could not conscientiously recommend it as a safe 
guide either for the physician or student. 

Clinical Pathology. By P. N. Panton, M. A., M. B. 446 pages. 
$4. {Philadelphia: P. Blakiston Son & Co.. 1913.) 

The author's attempt to produce a book intermediate in size 
between the larger and smaller works on " Clinical Pathology," 
which would meet the demands of the student and practitioner, 
has been unsuccessful, and for obvious reasons. Medical litera- 
ture of the day has no legitimate place for this type of compend 
which sacrifices scientific accuracy and scope of statement to the 
ambition of including within one volume the subjects of blood- 
bacteriology, puncture fluids, urine, the alimentary system, the 
eye, skin, respiratory tract and histology. Of necessity, brevity 
of statement and the lack of detailed discussion, combined with the 
absence of any references to the literature, tend to foster the all 
too prevalent habit of drawing sweeping conclusions from insuffi- 
cient data and for this reason especially the book is unsuited to 
the student. For the practitioner there exists a vast amount of 



indefinite disjointed statements, tests with scanty interpreta- 
tions and a general arrangement of subject-matter calculated 
to discourage further reference to the book. Errors of omis- 
sion are not uncommon — such as the absence of the polariscopic 
determination of sugar, newer methods of blood counting, or the 
estimation of the degree of pleocytosis in the cerebrospinal fluid. 
One and a half pages suffice to describe all forms of malaria. Such 
statements as are made with respect to the differentiation of 
amoeba?, the constancy of the amount of complement in guinea 
pig's serum, and the taking of 10 cc. of spinal fluid with impunity 
are a few of many questionable statements; while the six lines 
devoted to the Calmette reaction leave one with the feeling that 
the author is not aware of the real truth of the matter. 

Illustrations, though few in number, are, for the most part good, 
and the text is quite free from typographical errors. 

The Elements of Bacteriological Technique. By J. W. H. Eyre, 
M. D., etc. $3. (Philadelphia and London: W. B. Saunders 
Company, 191$.) 

The second edition of Eyre's Bacteriological Technique re- 
written and enlarged has just been published by Saunders. It 
consists of over five hundred pages, devoted entirely to the tech- 
nique of bacteriology, divided into twenty-one sections. 

These sections deal with such subjects as: Common glass appa- 
ratus, methods of sterilization, the microscope, staining methods, 
methods of identification and study, experimental animal inocu- 
lations and bacteriological analyses. 

The material is presented in logical sequence, each subject being 
well described, and special attention being paid to all essential 
details. The illustrations are numerous and of considernble merit, 
each one having its own intrinsic value in being accurate, and 
suggestive. 

Several chapters deserve special note, as for instance, the open- 
ing chapter which gives a complete list of the glass apparatus 
commonly used in bacteriological work, and is followed by a use- 
ful consideration of the various methods of sterilization. The 
section entitled " The Microscope " affords a brief but compre- 
hensive description of this instrument, and includes a discussion 
of the various accessories necessary for microscopical work. The 
section on " staining methods " is especially useful in giving a 
detailed description of the composition of the various dyes and 
all the latest methods of differential staining. A brief description 
with the classification of fungi preceding a short disussion on the 
life cycle of bacteria affords a splendid comparison between the 
two classes of microscopic life. Thus the relationship from the 
evolutionary standpoint is made clear. The chapter on " Meth- 
ods of Identification and Study " is especially worthy of note. By 
a detailed study of the macroscopical, microscopical, biochemical 
and physical properties of various organisms a thorough and com- 
plete method for identifying them is given. The discussion on 
technique in relation to experimental animal work in bacteriology, 
though somewhat detailed, is worthy of considerable attention. 

The treatise is concluded by a consideration of the technique of 
both quantitative and qualitative bacteriological analyses of water, 
milk, sewage and foodstuffs, which are highly important from the 
standpoint of practical or applied bacteriology. The methods 
outlined are the ordinary methods universally employed without 
any additional new ones. 

This text-book is primarily intended as a laboratory guide for 
beginners. It may be highly recommended for the purpose for 
which it was primarily intended, as it is exceedingly thorough and 
gives all of our important modern methods. 



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BULLETIN 



OF 



THE JOHNS HOPKINS HOSPITAL 



Entered u Second-CUa Matter it lite Baltimore. VUrvUnd. PoitorScc. 



Vol. XXV.-No. 280.] 



BALTIMORE. JUNE. 19 14. 



[Price, 25 Cents 



CONTENTS. 



Continuous Propagation of Amoebic Dysentery in Animals, 
i Illustrated. i 
Itv \V vi rn: Aimitr IS u i.nu. M.D., and A \ nisi w \\ I 

uin-. M.I) 

' tore in Bodgkin'a Disetv* . -• • ond Paper. 

B] I . II. Bl MIN... M.I) 

Bodgkin'a Die 

Bj i . II. Bt mini.. M. I) 177 



A Clin 

Bj J. I.. Yirta M D 



!->'• 



shed W .!!• ■ 
with ■ ' 

i:. i 0B8O.X, M.I) 

I'"' 

Hooks Rei eived ... 



CONTINUOUS PROPAGATION OF 

Bj fl 

Am'|;i:w W 

I CllnU 

OUTLINE 

I introduction and literature 

pagation of ontamoba- in animals is limited, 
or four passu t 

~i ruin nt' enl u 
beca 

• loss of rirnli 
II. Method of transmission: 

1. Method of inoculation. 

• rial. 

i.il r> t.ir.l i 

of suitable temperatun and dilnl 
handling of the li rial 

III Behavior of a strain of dj 
anit: 
: Effect on the clinical i 

• ria. 
IV Relation of the etna ral laws of tl 

zoan and bacterial Infe. 
V Correlation ol U ese data with ; 
■ of strain b] 
1. Failure of Infection "ti account ol n i 
lilure of Infection on u • out t of 
VI Conclusions that passage In animals If 

The infection of lower animal- with ami 
sente some exceptional and complical 



AMCEBIC DYSENTER1 IN AMM \l S. 

B 

LED8. 

/7i> Johns H 

rariation in indi 
of tip 

with tl 
qnentl) beei 

Will' • 

nnali • 



166 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. m 



observers. There was no evidence of any diminution in viru- 
lence and the strain was lost through accident. Wenyon con- 
cludes that it should be possible to propagate a strain of 
entamoeba? indefinitely in animals. Darling 4 has confirmed 
and extended Hartmann's observations. He concludes that the 
pathogenic entamoebas not only become avirulent on passage, 
but that they undergo definite changes in their morphology 
and life cycle: the trophozoites diminish in size corresponding 
to Entamaiba minuta and the tendency to encystment in- 
creases. 

These authors, with the exception of Wenyon, distinguish 
carefully between two pathogenic strains: Namely, Entamoeba 
histolytica (Schaudinn) and Entamaiba tetragena (Viereck). 
Werner investigated several strains of entamoeba? and dis- 
tinguished between histolytica and tetragena on the basis of 
morphological differences. As regards their biology, Werner 
could discover no constant differences either as regards their 
virulence, the number of passages that could be obtained in 
animals, the course of the disease in animals, and the path- 
ological effects that could be produced. Hartmann's state- 
ments apply to E. tetragena. Darling, on the basis of Wer- 
ner's results and his own experience, has emphasized more 
the difference in infecting power between the two types. Re- 
cording to him the histolytica-like strain can be carried as 
high as six passages, while the tetragena type rarely infects 
beyond two generations and often dies out in the first series of 
animals inoculated. The loss in virulence and infecting power 
in both types are, according to Darling, associated with definite 
morphological changes in the organisms, notably in the trans- 
formation which he has described as the " small generation," 
a form assumed by the organism in the generation before 
encystment occurs. Apparently there has been no attempt to 
propagate the parasitic but non-pathogenic Entamaiba eoli, and 
it i- evident that the pathogenic entamoebas have not been pro- 
pagated except for a limited number of passages in lower 
animals. If one accepts that there are two species which are 
pathogenic for man, this statement applies equally well to 
either species. In 1911, however. Walker 5 reported observa- 
tions which led him to conclude that two distinct species have 
not yet been established and that E. histolytica and E. tetra- 
gena are identical. He concludes that the morphological 
differences in the vegetative state in E. histolytica and E. tet- 
ragena which were originally described by Viereck 10 and Hart- 
ma.irn are extremely inconstant and that both of these types 
form their propagative stage in the same manner, i. e., by the 
production of a four nucleated cyst. The reproduction by the 
process of budding, which, according to Sehaudinn's descrip- 
tion, occurs in histolytica, was not observed by Walker.. The 
identity of these two species has since been accepted by Craig," 
Wenyon,^ and in its essentials by Hartmann : and by other 
observers. It seems to us that the evidence for the establish- 
ment of E. tetragena as a distinct species is wholly insufficient. 
Accordingly, we shall tentatively use the term E. histolytica 
of Schaudinn to include the four nucleated propagative stages 
discovered by Viereck until the nomenclature is definitely 
established. Hartmann ' has recently suggested that the ter- 



minology should properly revert to that suggested by Council- 
man and Lafleur.* In case strains of E. histolytica with 
characteristically distinct propagative stages should be estab- 
lished, it might be desirable to retain the term "tetragena" 
to indicate a variety of E. histolytica but not as a distinct 
species of entamoeba 3 . 

The determination of whether the propagation of amoebic 
infection in lower animals is self-limited becomes of interest 
from several standpoints. It is naturally of importance in the 
determination of the laws of protozoan infection and immu- 
nity. Moreover, in the absence of any methods for cultivating 
either the pathogenic or parasitic entamoeba?, the infection of 
animals is extremely desirable in order to obtain a suitable 
supply of material for study. This applies not only to the 
localities where acute cases are rare, but also to the endemic 
.iivns in the tropics. The infection of animals is so uncertain 
that only a minimum of experimental work has been done 
upon morphology, pathogenesis, and experimental therapy. 

Methods of Transmission. — In attempting the propagation 
of a strain of dysentery in animals, the literature indicates 
that the routine of various workers has been fairly uniform. 
Accordingly, we have followed the usual technique as closely 
as feasible. < !ats or kittens were selected. In the choice of 
the various routes of infection, we did not have occasion in 
this series to make use of feeding experiments. The majority 
of animals were inoculated by rectal injection. However, in 
order to secure the first transfers from man to lower animals. 
the infective material was injected directly into the ca?cum. 
A small incision was made in the abdominal wall, the syringe 
needle was inserted through the wall of the caecum, and the 
injection was made directly into the lumen. This procedure 
gave distinctly better results than were obtained, even under 
the most favorable conditions, by other methods of injection. 
The explanation for the high percentage of infections which 
was obtained probably depends upon a number of minor fac- 
tors. Other strains of entamoeba? are under investigation at 
present and the discussion of this procedure will be reserved 
for a subsequent communication. 

The first strain of dysentery with which we worked occurred 
as an initial attack in a negro, who had contracted dysentery 
in Xorth Carolina with a history of three months duration. 
Duplicate injections of about 3 cc. each of a bloody mucous 
stool rich in trophozoites were made into the caecum by lapa- 
rotomy, in an adult eat and a half-grown kitten. After an 
incubation period of seven days, both animals became acutely 
infected. The adult cat developed a mucous diarrhoea with 
very large amoeba? and death resulted after sixteen days. The 
kitten showed a bloody dysentery with smaller organisms, and 
lived for nineteen days. Subinoculations were made from 
both animals immediately after death by injections into the 
caecum in four animals. In all four death occurred promptly 
in one to five days from peritonitis, accompanied usually by 
septicaemia. 

A little later a second case of dysentery was admitted to the 
hospital. This was an acute relapse, the original infection 
having been contracted in the Philippines a year and a half 



L914.] 



JOHNS HOPKINS OSPITAL BULLETIN. 






sly. I ► 1 1 r i 1 1 lt the first fourteen months of the 
then had been several acute relapses with compli 
of symptoms to the interim. He was then treated with 
tine and temporarily relieved. After four months he returned 
to tho hospital in another acute attack. Emetine treatment 

. and the patient bad been 
grain, hypodermically, daily for three days before th< 

itained from which the first animals were 

In commencing the propagation of this strain especial 
timi was given to the following features: 

1. Subinoculation from animal to animal at the first ap 
pearance of clinical symptoms in preference to waiting for the 
death of the animal or lill the later stages of the in 

- lection of suitable temperature and diluting agents in 
the handling of the infective material. 

lion of kittens (half -grown or younger) 
than adult animals. 

I. The injection of tin 1 infective material directly tl 
the lumen of the bowel into the caecum in addition to the 
injections by rectal tube. 

letaila of this routine wen- comparatively simple. \- 
the transfers were made at the first appearance 
_■■- in an infected individual. 
fresh material was used for injection. r.-ually not mi 
one hour elapsed from the timi btained 

till the injection of all animals was completed. When the 
not made at the beginning of the infection the 
animals were usua I in preference to wail 

ortem material. The contents of the lumen 
bowel when faecal or purulent were discarded ami 

itained by scraping the mucosa of the intestine. In 
injected material consist) 
exclusively either of blood ami mucus with little or no 
illation with fasces ami w ith relal i 
opic examination. Trop 
illy in large numbers in all the material which was 
: aid were not infrequently accompanied b) m 
the intracsecal inj© tions il wa 

inn. us ami blood i ould be 
of moderate bore, pn>\ ided thai 

ded without emulsifying in tap water or in 
ition in tap wa: 
win- di ' mi 

left intact, for it was found on micr pi< al examii at 

preserved hitter in the fluid in 
ody than in any 
i .\ hich were tried were tap wab r i 

■ ! teclvnically pure sodium chloride in tap wafa r 
I, ii. I ami il..*. per cent dilut • 

specimens of hi | ami mucus from the 

• ■! w ithout tin- addition of ai 
diluting fluii 

ami 0.5 p. 
optimum con. .nt rat ion 
narrow limits according to the naturi 



the amoeba) were found. Furtl and that, in 

ance w ith t on of other I 

though I.-- eil their vitality i riM.m 

temperati 20 C. than at in< ubator t. i 

Young an 
than a. |ult-. The younj out 100 

grams ani itibility 

varied directly with tlic age and 
optimum susceptibility occurred in 

half-grow n as ha- b I into the 

caecum were used more particularly for the injection of a. lull 
animals an. I in the early transfi 

injection by high rectal tube proved to he more suitable than 
the mt ra caeca I inoculat ii 

The following observations were kept as a rout 

1. Examination of the material which was injii ted b" 
an.! stained preparatio 

".'. Determinati i the incubation period. 

; ions upon the course of the infection in animals 
and when possible stain. '.1 preparations ..t amc 
late in the i infection 

I. Determination of the occurrence of !■ 
with especia ' i he cause of death in fatal infi 

For the Btained preparations the mat. rial wa- fixed by the 
w.-t method, and carried wet throughout the entire pn 
staining and mounting. The technique was essentially that 
used by Walker. 1 - ■ re made b out the 

material on cover Blips 
the specimens wen read in this mam.' 

were fin it in a little tap wat. r or iu 

-alt solution in tap water. Thi 

. t's fluid fo d then 

over ni 

t.-n-.-h in Delafield's ha?matoxylin for ten to thirty minutes 

and washed 

nation. Ti- 
nt and absolute i tl" n 
mounted ii 

. uh. in. 
. linical 
blood . 



168 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



oculation, the infection appeared as an acute outbreak charac- 
terized sometimes by a day in which one or more soft stools 
were passed, followed within a day by the discharge of both 
blood and mucus, and the presence of numerous active amoebae. 
Whenever possible, this first discharge of blood and mucus was 
used for inoculation. 

Blood cultures were made by aspiration from the heart 
according to the usual routine when the animals appeared ill, 
when they were sacrificed, or at the time of death. Septi- 
caemia was encountered just before death in the majority of 
instances. In the early inoculations by laparotomy into the 
caecum there was no difficulty whatever from peritonitis after 
the puncture of the caecum even when a large syringe needle 
was used and the injected material was rich in faecal matter. 
Subsequently, peritonitis became extremely difficult to avoid 
although the injected matter consisted macroscopically of 
blood and mucus and a small needle was used followed by 
careful cautery of the puncture wound. 

Effect on the Clinical Course. — The general results which 
we obtained with this strain were somewhat unexpected. The 
entamoeba?, instead of losing their pathogenicity after several 


stained preparations provided these are made from suitable 
characteristic specimens. This strain after passage through 
kittens showed no deterioration in the organisms in regard to 
size, motility, staining reactions, and structure of the nucleus. 
Encystment frequently occurred with the four nucleated cyst 
predominating, but the vegetative forms were always present 
in excess of the cysts. On the other hand, however, there were 
numerous opportunities for obtaining degenerated types cor- 
responding to those described by Hartmann '• e - and by Dar- 
ling. 1 - c - The organisms often became much less typical in 
chronic cases of long standing and in acute cases when bacterial 
complications developed such as a bacteriaemia or a purulent 
bacterial enteritis. Moreover, degenerative forms were fre- 
quently found in stools which, though freshly obtained, had 
often remained for some hours in the lumen of the intestine 
where the entamoeba? were extensively contaminated with 
faeces and were subject to bacterial fermentation and various 
deleterious influences. When such animals were sacrificed, 
typical entamoeba? were found higher up in the intestine or in 
the scrapings from the mucosa. In this connection it may be 


passages, increased remarkably in virulence. The incubation 


|io 

? 9 
o 8 

a. 7 
§6 
< 5 

3 i 

I'" 

° 2 

> 1 


























period in the four animals used for the first three passages 


























was almost exactly six days with a duration of the disease 






















/ 




lasting as long as six and a half weeks. These periods were 


















/ z 




/ 




shortened until in the sixth passage an incubation period of 


















tig 








two and three-quarter days was obtained, with death occurring 


















Is? 

s| 








one day later. Not only did the virulence increase, but the 


















oil 








trophozoites, instead of diminishing in size to the minute 


















=il 








race which has been described, remained active and vigorous 


























without any suggestion of degenerative changes. The strain 


















Us. 








became so active that it was not a simple matter to insure its 
continuation. A comparatively large number of animals were 
required to avoid absolutely the possibility of the loss of the 
strain through accident. On some occasions as many as six 
or seven animals were required to insure a single passage. 

It soon became apparent that the changes in virulence and 
morphology which had been described as occurring constantly 
upon subinoculation of entamoeba? did not apply to this strain. 
When this was well established the number of animals used 
for any one passage was reduced to two or three. After eleven 
successive passages had been secured the strain was allowed to 
die out. All of the infected animals reacted typically — both 
clinically and pathologically; the morphology of the entamoeba- 
found in them was characteristic. Tin' incubation period in 
the ninth, tenth and eleventh passages in a total of five animals 
ranged from five to nine days. This return to the longer incuba- 
tion period was perhaps due in part to the continued passage of 
the strain by rectal injections rather than by direct inoculation 
into the caecum, but also to the use of material taken several 
hours post mortem. The accompanying diagram (No. 1) 
shows some of the essential features of the successful inocu- 
lations. 

Effect on the Entamoeba. — Morphologically, the typical or- 
ganisms show no degenerative changes either in fresh or 


PASSAGE I lr IIr TV V VI VH Vm IX X XI 

Diagram 1. 

This diagram includes the average incubation period of all ani- 
mals used in each generation except two adult cats. These were 
not included because adults are known to be unfavorable subjects 
with longer incubation periods and do not offer fair comparison 
with the incubation period of younger and more susceptible ani- 
mals which were used in the other inoculations. 

noted that some of the degenerations described by Darling 
occurred in specimens which were obtained post mortem. The 
accompanying plate illustrates typical specimens of organisms 
obtained from the patient, and from the eleventh passage in 
cats. Small degenerative forms occurring in the second pas- 
sage are also included. Biologically, there was a definite 
increase in the virulence of this strain which was shown 
principally by the progressive shortening of the incubation 
period in the successive passages. 

There were two conditions which were especially difficult to 
control; namely, (1) bacterial infection, and (2) in a few 
animals, the failure of the amoeba? to infect even under opti- 
mum conditions. The accompanying diagram (No. II) shows 
the total number of animals used in the individual passages 
with the general result in each case. Table I gives the details 
of the animals which became infected and Table II those which 
did not become infected. More complete protocols are given at 
the end of the paper. 



Ji sk. 1914.] 



JOHNS BOPKINS HOSPITAL BULLETIN. 






1>1 LGBAM II. SHOWING Till: NUMBER 0» VMM aid I SI D AND Till 

PlTIENT. 

I 

Incubation Pi 



Second Passage 
Incu.ba.tloi 



Thirl i'ililiv 

in Period « Days 



.11 Cat VIII 

iri'iE the incu- 
batioti ; ■ 

.Vey.: ' 






Oat IV 

Stpaltrt. (General pel 



Fourth 
Incubation Per. 



I'll VI 



Fifth Passage 

■•.ciih.it ion Perio 

■ ..t \II 
I 



Birth I'jiwbc 

I I I 

\MII I.IWII 






Passage 

I 
Cat win 



1 ik'h'h Passage 
Average lncuh.it I 



Ninth Passage 






Pi— ft 
I 







nth Passage 
Incubation Period a Para. 

I Wll 
(Inoculatrd with Tery small amount of material.) 
The eight animals which failed to o. ■ ■ - . 
are connected by the broken line. 






Iitlon. 









Kirtal tub) 









• • .11 .!«-. 






■ 

Killed Iftl 



Killed lit. 



I \l!l 1 II. 

Mti - M liti it inn • 











■ ,1 Ml 


Adult. 














j grown. 






■ it \M 

CM \l\ 

















will) thi 
rfaicb 



170 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



of some of the animals resulted in a general septicaemia. 
Frequently this septicaemia was fatal before the incubation 
period of the entamoeba? had expired. This behavior was rare, 
however. In the majority of animals no septicaemia occurred 
until after the development of lesions in the intestine. In no 
case, however, did an animal die of an uncomplicated amoebic 
infection, but in all fatal cases there was a secondary septi- 
caemia. This invasion was not only secondary, as a rule, to 
the amoebic infection, hut it often came on very late; the 
blood culture was sterile in one instance only when taken in 
an advanced stage of the dysentery. The bacteremia, there- 
lure, though a secondary factor, is important in its bearing 
upon the cause of death in this series of animals. 

It was also noted repeatedly that the development of septi- 
caemia, or of extensive peritonitis, resulted in a failure of the 
entamoeba? to cause infection. This is mentioned on account 
of its direct bearing upon the possible explanation of the loss 
of the strain reported by Wenyon. In one of his animals the 
protocol records the development, not only of septicaemia, but 
of pyaemia. We have, therefore, in this strain reported by 
Wenyon and in the two strains reported in this paper, examples 
of the frequency and importance of the secondary invasion by 
bacteria. The records of the strains propagated by Werner 
and Darling do not give any information in regard to the 
influence of the accompanying bacteria. 

On account of the importance of this secondary invasion, 
the various bacteria obtained at blood culture were studied to 
determine whether one or several species were carried over into 
the blood in any given individual and whether a single strain 
was carried through all the animals or whether several species 
were involved. An examination of all the cultures, exce] 
from the second to the ninth passage, inclusive, showed a pure 
culture of a single organism. This was a small streptococcus 
forming short chains and producing identical culture reactions 
on ordinary media. In one animal of both the third and 
fourth passages, the cultures contained a bacillus in addition 
to the usual streptococcus. 

As regards the second source of difficulty it. has been an 
almost universal experience that not infrequently infection 
fails to take place even under the most favorable conditions. 
Thus, when a series of young kittens are inoculated with fresh 
blood and mucus rich in trophozoites and cysts, a certain 
number of them will frequently escape infection. The ex- 
planation of this has not been investigated rigidly, but it is 
apparently due to a variety of self-evident accidental eircum- 
rather than to a natural insusceptibility of these 
individuals. 

Relation to the General Laws Governing Infectious Pro- 
cesses. — This strain of entamoebas, instead of constitul 

ion, conforms to the general laws governing infectious 
processes. It serves to illustrate very well certain features of 
infectious diseases which are especially characteristic of the 
protozoa. Tlu onset of the disease was acute. The course ter- 
minated fatally in the first attack or became chronic. It did 
not run an acute self-limited course, ending in death or com- 
plete recovery, such as occurs in some bacterial diseases and 



certain conditions of unknown etiology; e. g., Asiatic cholera 
and yellow fever. There was no evidence from the clinical 
symptoms that one attack of dysentery conferred any immu- 
nity. When the condition of a carrier was developed, the in- 
fected individual did not enjoy freedom from symptoms, but 
was subject to acute relapses. As with many bacterial and 
protozoan parasites, the rapid passage of this strain through 
a series of individual- produced an increase in its virulence. 
The original incubation period of six days, which was required 
for the production of bloody mucous stools containing motile 
amoeba?, was shortened to two and three-fourths days by five 
passages. The total course of the disease from the time of 
inoculation was shortened in this instance to four days. This 
shortening was due, in part, to the early development of bac- 
teremia and an increase in the virulence of the accompanying 
bacteria. There was nothing which suggested in any way 
that the early appearance of amoebae in the bloody mucous 
discharges could be connected with changes in the bacterial 
flora of the intestine. It is to be assumed that the exact de- 
tails of behavior would vary with the individual strain. Thus. 
if a less virulent strain from a chronic case were injected into 
adult animals, there would surely be a smaller percentage of 
infections with less severe symptoms, and some strains might 
be comparatively difficult to propagate. Nevertheless, we feel 
thai, under favorable conditions, the general rule will be that 
tlic passage of a strain will not be self-limited. Indeed, it 
would In: ill' considerable interest, epidemiologically, if amoebic 
infection in susceptible animals died out after a few passages 
from one individual to another. If this were proved to be 
true, then amoebic dysentery, upon introduction in a suscepti- 
ble species in an uninfected zone, would almost necessarily die 
out of itself, instead of becoming endemic. 

Correlation with Previous Results. — The increase in viru- 
lence in this strain after a comparatively short number of 
passages does not exclude tlic possibility that a long continued 
passage through a great many animals might attenuate the 
virulence, as sometimes happens in the case of trypanosomes 
for example. The conclusion, however, is definitely refuted m 
this instance, that the entire strain necessarily undergoes 
morphological degenerations in that the virulence is lost, and 
that a strain dies out after at most from four to six pas 
The question arises as to whether this strain constitutes an 
exceptional ease or whether it represents the typical behavior 
of the pathogenic entamoeba?. An examination of the condi- 
tions governing the infection suggests that it is possible to 
correlate these apparently contradictory results. The conclu- 
sion that the passage of dysentery is self-limited is based upon 
two considerations: namely, that the parasites lose their viru- 
lence -inee the animals fail to become infected, and that the 
morphology of the amcebae shows degenerative changes, in 
regard to the failure to infect, it must he remembered that 
several explanations as well as loss of virulence suggest them- 
selvi s. In the first place the infection by feeding or by inocu- 
lation per rectum is extremely uncertain. The most unfavor- 
able results are reported by Walker." in Manila ; with optimum 
infective material, no symptoms and no parasitization occurred 



J INK, 1914.] 



JOHNS BOPKINS HOSPITAL BULLETIN. 



171 



in thirteen animals representing ' ie un- 

certainty of feeding experiments and of injections per rectum 
as compared with the din through the wall of the 

cecum may account for Bome of the failui 

The effect of the bacteria which happen to aco 
entamoeba is striking. In both of the .-trains reported in tin- 
paper and in that reported by Wenyon it lias proven a trouble- 
some factor. An examination of diagram No. II wil 
how easily tin- .-train might have been lost purely ' 
the effect of the accompanying bacteria. In two i 
crucial stages, it- | tided on the results in 

animal, although considerable precaution had beeu ta 
secure a Dumbei ected animals. It i- not Lm 

that the selection of material at the onset of Bymptoms is 
advantageous both on account of active 

amoeba? that are obtained and also because the bacteria are 
somewhat less abundant. 

In r>. - which havi 

emphasized particularly by Darling, it is ootewortl 
these n - in part, upon whether the entamo 

studied at tl • late in the course 

disease after the infection has become subacute or < 
It is. quite possible thai nued growth in oi 

with the possibility of specific reaction on the part of tl 
may produce changes in the infecting organisms, whei 
rapid passage from tible animal to another 

not am pportunity for tin- developmi 

ehanges. Thus, in some anin 
were perfectly typical at the ■ mptoms, but 

tively amoeboid. M 
frequently hi 

■ 
small d< forms, li was evident that tin- . 

the stool in the lumen of the bowel undei 

could usual! d. Thus, there are man; 

in an animal which may result in thi 
It mu-t be 
that the occurreni 

■. typical forms at tie 

n .. 
I 
typical 

rtmann that tin- natui - 

must be taken into account in 

3ome of the strain- may i 
vinilencc of the accompanying bai •■ 



V. Tl • 
re-inoculatmi: int. in I 
individual ral 
■' ' 

of the 
cecum into the lui 

material which « 

In vii 
previous faihi 
to any inherent chai 
of the Bubini 

SUMMARY. 

1. 'I 

the object of securing continu 

tion through a I in the 

second passs 

through eleven so 

2. 'Tin- straii it 

changes appeared in the morphology of tin- 1 

at the -;!■■ ■ 

course and patholo ml the 

eleven | 

3. The props i | 
by the virulence of th( 

1. T 
passages in animal 
. 
in confoi iNii;, n itii thi 

D18I 

We 
amcebii 

that /■.'-■' 

virulem 

■ 
virulem 

: 
accomt i 

individ 






172 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| tfo.280 



3. Eectal injections of trophozoites have proven definitely 
less effective than direct inoculation through the wall of the 
caecum into the lumen. 

4. The degenerative changes in morphology of entamoeba 
which have been described can be explained in part by the 
(a) long period which the specimens may have remained in 
the bowel before they were examined and by (b) the com- 
paratively late stages of infection at which the specimens were 
selected. In view of these considerations, we feel that the 
previous failures were due to accident, and not to any inherent 
changes occurring in the entamoebas upon subinoculation. 

PROTOCOLS OF ANIMALS USED. 

> ikst Passage. 

Oct. 6. Cat I. % grown. Intracaecal injection with stools from 
patient. Oct. 11: Typical dysentery with many amoebae. Oct. 15: 
Sick: continued bloody stools. Sacrificed: Gut normal except the 
rectum which was filled with bloody mucus; no gross ulceration 
present. 

Second Passage. 

Oct. 15. Cat II. Vz grown. Intracaecal injection from Cat V. 
Oct. 21: Typical dysentery with many amoebae. From Oct. 21 to 
Nov. 7 stools soft, no mucus, blood or amoebae. Nov. T: Typical 
bloody mucous stools with many amoebae. Nov. 29: Coma; death. 
Autopsy: Large intestine showed diffuse inflammation with many 
motile amoeba?. Large liver abscess. 

Oct. 15. Cat III. % grown. Intracaecal injection from Cat V. 
Oct. 21: Bloody and mucous stool. Oct. 21 to Nov. 7: Stools soft; 
no mucus, blood nor amoebae. Nov. 7: Bloody mucous stools with 
amoebae. Nov. 16: Death. Autopsy: Slight subcutaneous infec- 
tion. Circumscribed ulceration with blood in lower 2 inches of 
large intestine. Blood culture from heart positive. 

Third Passage. 

Oct. 21. Cat IV. Yz grown. Intracaecal injection from Cats 
II and III. Oct. 27: Typical dysenteric stools with many 
amoebae: continued until death. Oct. 31: Died. Autopsy: Ulcera- 
tion of lower end of colon with mucus and blood containing active 
amoebae. Blood culture positive. 

Fourth Passage. 

Oct. 27. Cat V. % grown. Intracaecal injection from Cat IV. 
Nov. 1: Died suddenly. Autopsy: Entirely negative. Blood 
culture (heart) positive. 

Oct. 27. Cat VI. % grown. Intracaecal injection from Cat IV. 
Oct. 31: Died. Autopsy: Negative except for few amoebae found in 
stained preparation of rectal contents. Blood culture (heart) 
positive. 

Oct. 2S. Cat. VII. Adult. Intracaecal injection from Cat. IV. 
Nov. 5: Died. Autopsy: General peritonitis. 

Oct. 31. Cat VIII. Intracaecal injection from Cat IV. Nov. 7: 
Died. Autopsy: General peritonitis. 

Oct. 31. Cat IX. Rectal tube injection from Cat IV. Nov. 6: 
Typical dysentery with blood and mucous stools and many amoebae. 
Nov. 7: Sacrificed. Autopsy: Lower colon and rectum filled with 
bloody mucus containing many amoebae. Blood culture (heart) 
positive. 

Oct. 31. Cat X. Rectal tube injection from Cat IV. Nov. 7: 
Blood and mucous stool. This cleared up and animal remained 
perfectly well until sacrificed in February. Feb. 2: Sacrificed. 
Autopsy: Entirely negative. 



Fifth Passage. 

Nov. 7. Cat XI. Adult Intracaecal injection from Cat IX. 
Nov. 10: Sacrificed. General peritonitis. 

Oct. 7. Cat XII. Vi grown. Intracaecal injection from Cat 
IX. Nov. 12: Typical dysentery with blood, mucus and numer- 
ous amoebae in stools; continued until death. Nov. 16: Died. 
Autopsy: Marked swelling, thickening and ulceration of lower 
3 in. of large bowel. Contents consist of blood and mucus with 
innumerable amoebae. Blood culture (heart) positive. 

Nov. 7. Cat XIII. Vz grown. Rectal tube injection from Cat 
IX. Nov. 11: Typical dysentery with many amoebae. Nov. 12: 
Died. Autopsy: No gross lesions in bowel. Contents consisted 
of blood and mucus with many amoebae. 

Sixth Passage, 

Nov. 12. Cat XIV. J / 2 grown. Intracaecal injection from Cat 
XII. Nov. 17: Typical stools with few amoebae. No further symp- 
toms noted. Jan. IS: Died. No autopsy. 

Nov. 12. Cat XV. % grown. Intracaecal injection from Cat 
XII. Nov. 16: Died. Autopsy: Extensive subcutaneous abscess: 
general peritonitis. 

Nov. 12. Cat XVI. % grown. Rectal tube injection from Cat 
XII. Similar injection repeated on Nov. 13. No symptoms noted, 
no amoebae found. Died in January. Autopsy negative. 

Nov. 16. Cat XVII. % grown. Rectal tube injection from Cat 
XII. Nov. 19: Typical dysenteric stools with many amoebae: con- 
tinued until Nov. 25. Dec. 12: Autopsy: Colon negative; purulent 
pericarditis and empyema. 

Nov. 16. Cat XVIII. ti grown. Rectal tube injection from Cat 
XII. Nov. 19: Typical dysentery with many amoebae. Nov. 20: 
Died. Autopsy: Thickening and ulceration in rectum. Blood 
culture (heart) positive. 

Nov. 16. Cat XIX. % grown. Intracaecal injection from Cat 
XII. Nov. 17: Died. Autopsy: General peritonitis. 

Nov. 16. Cat XX. % grown. Intracaecal injection from Cat 
XII. Nov. 17: Died. Autopsy: General peritonitis; colon con- 
tains mucus and slight amount of blood with many amoebae. 

Seventh Passage. 

Nov. 17. Cat XXI. y s grown. Rectal tube injection from Cat 
XX. Nov. 20: Typical dysentery with amoebae. Died in late 
afternoon. Autopsy negative. Blood culture positive. 

Nov. 19. Cat XXII. y s grown. Rectal tube injection from Cat 
XVIII. Dec. S: No dysentery nor amoebae. Died. Autopsy 
negative. 

Nov. 19. Cat XXIII. i s grown. Rectal tube injection from Cat 
XVII. Nov. 22: Typical dysentery with many amoebae. Nov. 
23: Killed. Superficial ulceration over rectal mucosa with many 
amoebae. Blood culture negative. 

Nov. 19. Cat XXIV. Adult. Rectal tube injection from Cat 
XVII. Dec. 8: Typical dysentery with many amoebae. Jan. 14: 
Died. Autopsy negative. 

Eighth Passage. 

Nov. 23. Cat XXV. ;£ grown. Rectal tube injection from Cat 
XXIII. Nov. 26: Typical dysentery with active amoebae. Amoebae 
very large size. Nov. 27: Died. Autopsy: Rectal ampulla in- 
jected and filled with bloody mucus containing many amoebae. 

Nov. 23. Cat XXVI. y s grown. Rectal tube injection from Cat 
XXIII. Nov. 26: Dysentery with amoebae. Dec. 2: Died. Au- 
topsy: Rectum hyperaemic with ulceration. Contents showed very 
numerous amoebae. 

Nov. 23. Cat XXVII. % grown. Rectal tube injection from Cat 
XXIII. Nov. 26: Animal is distinctly sick — no stool examination 
recorded. Dec. 1 : Died. Autopsy: Marked injection with swollen 
granulomatous ulceration of mucosa in region of sigmoid and 



THE JOHNS HOPKINS HOSPITAL BULLETIN, JUNE, 1914. 



S V. - S, 



Jt*f '^Bf 



M 











G 



.Irvr. 1914.] 



.HHINS HOl'KlNs HOSPITAL BULLETIN. 






especially over the rectum. 
Blood culture positive. 



Contents shoved many t> i 



Ni\ in Pass 

t XXVIII. ] i grown. Rectal tube injection from 
Cat XXV. Pec. 6: Animal sick: stools contain n 

- rificed. Colon com 
tained much pus and active amcebse. Mucosa of rectum 
and swollen, no ulceration; contents here contain blood and mucus 
with numerous amiebs. Blood cultures positive. 

Dec. 1. Cat XXIX. :; i grown. Rectal tube Injection fx< 

XXVII. Dec. 16: Bloody stools Dec. 26: Distinct] 
numerous bloody stools Dec. 28: Died. Auti i 
hyperemia of rectal mucosa: contents of bowel here an 
No microscopic examination for amoebte di I 

Dec. 6. Cat XXX. •» grown. Rectal tube injection tro 

XXVIII. Dec. 14: Found dead. Autopsy: Colon hyperemic with 
swollen granulomatous appearance over !• ctai mucosa. Numerous 
dead am 

Dec. 6. Cat XXXI. 'i grown. Rectal tube injection it 
XXVIII. Dec. 26: Typical dysenteric stools. Dec. 28: Died. An 
f rectum: no ulceration. 

El i VI M it PA88 \'.i . 

Dec. 11. Cat XXXII. ' K grown. Rectal tube injection fr 
XXX Dec. 19: hysenteric stools containing many ainn t 



22: Typical stools contaii kutopay: 

Hyperemia and B« I gut at 

this point showed mucus and blood »it 
motile an 



4. 
Bull 



BIBLIOGRAPHY. 

Werner: alfla. U. 'Prop Hyg., 1908, XII, 426. 

Hartmann: Arch. I 

Darling: Ann. Trop. Med. and 1 I 
Soc. pal 

Craig: J. Am. Med Ass . 1913, i.x 

J. Infect. I>is.. 1913, XII 

Hartmann: H VII. S. 






8. Councilman & Lafleur: Johns Hopkins H II, II. 



395. 

9. 

10. 



Walker: 
Viereck: 



Philip 

iffs. u. Tr..| 



EXPLANATION OF TROPHOZOITES IN PLA1 

t Magnification, ■ 

Fio. 1. — From the stool of the pal 

i -From the eleventh passage In anln 

.ting forms from I 
from a fresh stool, obtained on the third da 

symptoms. 



THE BLOOD-PICTURE IN HODGKIN'S DISEASE. 

SE< <>M> PAPER. 

.11. l'.l NTIXG, M.D. 

i Prow the PoM - of the Onivt rtity of 



In an ear' • - disease, I >■•■ 

hire which - 
to war: ii thai the diagnosis of thi 

rui^'ht ■ ■ m blood smears with a 

;racy. The earlier paper was based on a 
d all but one of whi b 

Dorii it lias been 

blood of 1 1 .: which the 

It has thus • 
ftndi: 
The 

mewhat higher ['• 
is usually given. It is further rather -•: 



1 This work has been aided by a grant from the Roi 
Institute of Medical Research. New York. 

ns Hopkins Hosp. Bull.. 1911. XXII. 



majoril ler the thirty-third year, while 

• r i t \ of the 

The -tui]\ 

the normal ' there 

is not a 

includu 

l 
narilv 



174 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 280 



GROUP ONE. 



Case 

No. 


Sex. 


Age. 


Appai. 
dura- 
tion. 


Leuko- 
cyte 
count. 


N. 


E. 


B. 


S.L. 


L.L. 


L.M. 


Tr. 


I 
II 


M. 
M. 

F. 
M. 
F. 
M. 
M. 
M. 
M. 
M. 
M. 


21 
10 
40 

8 
64 

5 
31 
33 
33 
37 
17 


4 mos. 
1 yr. 

mos. 

5 mos. 
3 mos. 

5 mos. 
14 mos. 

6 mos. 
5 mos. 

18 mos. 
? 


7,500 
9,500 


51.2 

56.2 

36. 

59.4 

54.8 

54.4 

44.8 

64.2 

16.S 

70.4* 

60.4 


3.2 
8.6 
0.6 
4.6 
4.2 
2.4 
4.6 
0.4 
0.6 
1.8 
2 


1.6 
6.4 

0.2 

0.4 
0.4 
0.2 
0.4 
0.0 
1.4 
o.l 
0.6 


25.4 

16.4 

39.2 

21.8 

2(1 

22.6 

19.4 

16.4 

33.4 

10.6 

20.8 


10 
7.4 

10.6 
3.6 
9.8 
8.6 

13.4 
9.2 
3.8 
3.6 
6.2 


2.« 

1.6 
2.4 
2.4 
0.6 
0.4 
0.0 
0.2 


8.6 
11 
10.6 


V 

VII 

IX 

XIII 


9,900 
4,480 

4,200 
6,000 


10.2 
9.2 
9.4 

15.0 
9.2 






13.6 


XXI 

XXIII 


low 
10,000 


13.2 
9.8 



'Count taken with recent surgical incision still unhealed. 
GROUP TWO. 



XXII 
XXIV 

XXVI 



M. 


30 


. 


10,000 


79.4 


0.2 


0.4 


5.8 




3.4 


M. 


16 




18,000 


81.6 


0.6 


0.4 


4.2 


3. 


1.0 


M. 

M. 


33 






76.2 
84. 


1.4 
0.0 


0.6 
0.0 


7.6 
3.8 


1.0 


6. 

1.0 




14,300 


M. 
F. 


22 
33 


1 yr. 
1 yr. 




81.8 
85.4 


0.2 
2.8 


0.6 
0.0 


2.6 
3.2 


2.6 
0.4 


1.0 

0.2 


19,000 


F. 


52 


2 yrs. 


100,000 


89.2 


0.0 


0.0 


2.4 


1.0 


0.6 


F. 


20 


1 yr. 


9,000 


84.4 


1.2 


o.o 


2.2 


4.2 


0.4 


F. 


34 


t 


12,400 


85.8 


0.2 


0.4 


4.4 


3.2 


0.6 


F. 


38 


2 vrs. 


22,000 


82.6 


2. 


0.0 


6.2 


2.4 


0.0 


F. 


24 


1 yr. 


20,000 


90.4 


0.4- 


0.0 


2.1 


1.4 


0.0 


F. 


22 




6,200 


78. 


2.6 


1.2 


4.4 


0.2 


0.0 


M. 


27 


7 mos. 


41, hi HI 


84. 


1.6 


0.0 


8.8 


0.4 


11.2 


K 


IV 


4 mos. 




72.0 


0.9 


0.4 


15.3 


3.0 


n. 1 



* Over 1 year. t 10 months. ( ?) 

N. = Neutrophile, E. = Eosinophil, B. = Basophile, S. L.= Small Lymphocyte, 
L. h.— Large Lymphocyte, L. M. = Large Mononuclear, Tr.=Transitional. 

t Case XXV was apparently counted in a transition from the early to the late 
blood-picture. Later counts show an increase in neutrophiles to 78. 47c and a decrease 
in lymphocytes to 7.6%. 

tirely clear. While the primary blood-picture is usually found 
in cases of relatively short duration, and with comparatively 
localized lesions, there are enough exceptions in the series to 
indicate that these are not the sole factors. If it were pos- 
sible to examine every gland in every case one might find a 
pathological explanation for the change. Glands from two 
of the cases with the sharpest leukocytosis indicated that in 
these the disease was progressing more intensely. There was 
more necrosis and a marked infiltration of the gland and sur- 
rounding tissue with neutrophile leukocytes. As a result of 
the bacteriological investigations of Dr. Yates and myself, 3 I 
was on the point of accepting the possibility that complicat- 
ing infection with staphylococci might be responsible for this 
increased intensity of reaction when cultures from several 
glands in a very recent case with such a picture gave only 
the diphtheroid organism. Inoculation of monkeys with the 
diphtheroid organism has produced the primary blood-picture, 
with a slight tendency toward the secondary picture in one 
monkey, inoculated with an organism of increased virulence. 
Pathological study of these experimental lesions indicates 
strongly that while necrosis of lymphocytes leads to 
taxis for eosinophiles, the necrosis of the proliferated en- 
dothelioid cells and fibroblasts leads to positive chemotaxis 
for neutrophiles. Thus, in the eases with greater intensity 
of the process, we have the neutrophile leukocytosis. ' 

Turning to the other changes in the differential count, the 
most striking feature, as indicated in the earlier paper, is the 
increase in the so-called transitional leukocyte — the large 



Arch. Int. Med., 1913, XII, 236. 



mononuclear cell with indented or lobed nucleus, abundant 
protoplasm and fine azurophile granulation with Wrighfs 
stain. These cells are absolutely increased in all cases, and 
relatively increased in all except those with well marked 
leukocytosis; and even in these latter cases the transitionals 
are the most numerous cells except the neutrophiles. Thus, 
in the group of cases with the primary picture, one finds 
the percentage varying from 8.6 to 15, as opposed to a nor- 
mal of 7.5; while in the secondary group, the percentage 
is above normal excepting in four cases with a relatively sharp 
leukocytosis, and in these it varies from 4 to 5.4. There 
seems every evidence from blood counts and gland sections 
in a variety of conditions that these cells are derived from the 
cells of the germinal centers of lymphoid tissue, and from 
cells lying upon the reticulum of the lymph cords, and not 
from the endothelial lining of the lymph sinuses. 

The lymphocytes, except for a moderate increase during 
the first few months of the disease (35.4, 37.2, 49.8 per cent), 
show a gradual percentage diminution, until in the later cases 
they vary from 7.6 to 3.4. Apparently the toxin active in 
the disease, in small doses, leads to a stimulation of lympho- 
cyte production, but in large doses leads to their destruction. 

The circulating eosinophile cells show quite a variation in 
number in the different cases. This seems to depend chiefly 
upon the reactive power of the marrow. The chemotactic 
substance which attracts the eosinophile to the glands ap- 
pears to be some product resulting from the destruction of 
lymphocytes. Even in the early phase, when this destruc- 
tion is relatively slight, and there is chiefly proliferation 
of lymphocytes, the normal marrow does not seem able to 
compensate and there is a circulatory deficiency. Later, in 
the well established cases, even with greater demands', marrow 
compensation is usually excessive, and there is a moderate 
eosinophilia. In exceptional cases there may be an extreme 
eosinophilia as shown by a blood smear sent me from the 
medical laboratory of the Johns Hopkins Hospital, in which 
there was 68 per cent of eosinophiles in a count of 20,000, 
and as seen in Case XII of this series, in whom on one 
occasion there was 33 per cent of eosinophiles in a count of 
30,000 leukocytes. In the latter case a rather marked skin 
reaction to the X-ray may have accounted for the increase. 

The basophiles are increased in very early cases, but later 
almost disappear from the circulation. Basophiles, as well 
as eosinophiles, may be found in smears from the lymph 
glands in Hodgkin's disease. This, taken with the blood 
counts in monkeys inoculated with the diphtheroid organism, 
suggests that the basophile reaction is specific. However, 
basophiles appear to be constantly increased in chronic naso- 
pharyngeal and nasal sinus infections, and it may be that 
such infections in conjunction with the primary lesion of the 
disease, lead to the early increase in Hodgkin's disease. 

In all cases the great increase in blood platelets, noted in 
the earlier paper, has been found, and with the increase there 
are always abnormally large platelet masses and pseudopodia. 

One may summarize the blood finding then as follows : 
throughout the disease there are two constant features, an 



.h \i.. 19] L] 



.loiixs HOPKINS [OSPITAL BULLETIN. 






'• an absolute incn aa in the 
■nal leukocytes. In regard to the other elem 
early cases there is a transitory increase in lymp 

ind a deficiency in eosinophiles, with a normal 
or low neutrophile count, followed by a gradual 
lymphocytes and a moderate eosinophilia. In lal 
is a marked neutrophile leukocytosis, and a diminution 
of all other elemi the transitional li 

All • 

ii reproduced in the monkey following 
th the diphtheroid organism isolated from 
own by the counl • 
here given, the prompt increase in tl 

ncy in eosinophiles follow 
eosinophilia. and the early stimulation of the lymphocj 
gradual reduction. The counts 






i 



Inoculation 

I 



31.4 

».8 
60.0 






many mitoses in el 
marked eosinophil] 

Dg it may be seen thai ' 

naturally ar value in din 

lar fill.. 

■ 
the din_ 

what more difficult, but, in m 

majorn 
ally lie- 
are apparently two 
glands — that 
format 

aired. The prin 
the secondar; 
but the clin: 

The blood counts which i 
of the glands are 






Curs. 


i 






H 






1. 




















Ml 

n 




VI 






Mil 












I 
II 






III 




































































with a 
low tra 
cases is in : 
ease. In ad 

tubern. 

kin's (li- asi . and : 

my exi" I ith the 

ejcercis. 

from tl 

nosing 

so-called malignant lyn 

rbital tumoi 
ular ai 

: from that "f Hoi 

• 
explain 



■ 






176 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



Gradual improvement under treatment. Increase in size of one 
gland left at first operation in March, 1913. Removed. Appar- 
ently well— 1914. 

BLOOD COUNTS. 

Date. R.b.c. W.b.e. N. E. B. S.L. L.L. L.M. Tr. 

I\ I '09 4,712, i !l,50() 56.2 8.6 0.4 16.4 7.4 11.0 

I. 22, '10 ■'.'>". ''.MO 63.6 3.6 0.0 12.0 12.0 2.0 6.8 

III. 12 ,'10 53.1 6.2 1.0 13. 16. 1.6 9.8 

\. 8, 'in 1,960, ''.Slid 53.2 5.2 0.4 27.8 4. 1.4 8.0 

II. 13, '12 8,000 57. 4.4 0.2 27.4 I. 0.2 6.8 

VI. 3, '12 5,51)11,(1110 7,000 64. 4. 0.2 19.8 3.2 0.2 8.4 

III 10, '13 39.6 10.4 0.6 25. 10.4 1.0 13.0 

[X. IS. '13 64.2 3.6 0.6 22. 1.8 0.0 7.8 

Note.— Recurrence found after paper was in press, associated with return of blood 
picture to that noted earlier during; active stage of the disease. 

Case III. — April 1, 1909. Male, white, 30. Seen 2 weeks after 
second operation for glands of neck. First operation 6 months 
previous at Rochester. Diagnosis, Hodgkin's disease. 

BLOOD COUNTS. 
Date. R.b.c. W.b.c. N. E. B. S.L. L.L. L.M. Tr. 

IV. 1, '09 4,560,000 10,000 79.4 0.2 0.4 5.8 3.4 10.8 

Case IV (Dr. Tupper, Eau Claire, Wis.). — February 5, 1910. 
Female, white, 40. Onset, — months previous in right inguinal 
glands. Subsequent involvement of left inguinal, left axillary, 
left and right cervical glands. Test gland shows well-marked 
active Hodgkin's picture. Death in October, 1910. 

BLOOD COUNTS. 
Date. N. E. B. S.L. L.L. L.M. Tr. 

II. 5, '10 36. 0.6 0.2 39.2 10.6 2.8 in. 6 

Case V (Dr. Yates). — November 9, 1909. Male, white, 8 years. 
Enlargement of cervical glands began 5 months previous to date. 
Left inguinal glands also enlarged. Test gland, November 30, 
1909, shows hyperplastic stage of lesion. January, 1910, cervical 
glands removed. October, 1910, von Pirquet test negative. April, 

1911, mucous membrane haemorrhages, anaemia. Died January 10, 

1912. Involvement of mesenteric glands, chylous ascites, wasting. 

BLOOD COUNTS. 

Date. R.b.c. W.b.c. N. E. B. S.L. L.L. L.M. Tr. 

XI. 9, '09 9,900 59.4 4.6 0.4 21.8 3.6 10.2 

X!. 30, '09 50.8 5.8 0.6 20.8 7.2 8.§ 

II. 26, '10 5,000,000 5,000 55.2 1.4 0.4 22.4 9.2 2.0 9. 4 

IX. 7, '10 5,16(1,000 8,700 59.4 1. 1.2 16.4 6.6 5. 10. 4 

IV. 21, '11 3,456,000 4,800 63.2 1.8 1. 10.2 4.6 1.4 17. g 

Transfused. 

IV. 24, '11 3,176,000 3,800 54. 6.8 0.2 17.8 4.8 1.8 14.6 

V. 2, '12 2,024,000 S.300 67.6 1.4 1.4 6.8 9.6 0.6 12.6 

Transfused. 

V. 5, '11 2,760,000 4,500 54.6 2.6 2. 18.8 7.6 0.6 13.8 

V. 9, '11 3,200,000 4,000 50.8 4. 1.6 25.8 6.4 0.6 10.8 

Transfused. 

V. 10, '11 60. 9.8 0.6 8.2 6.8 0.4 14.2 

V. 13, '11 3,400,000 3,500 56.2 4.8 0.8 17.6 6.4 0.4 13.8 

V. 22, '11 3,712,000 3,400 55.8 3.2 0.0 19.8 3.6 1.2 16.4 

V. 29, '11 3,080,000 3,600 56.4 3.4 1.6 18. 8.1 0.6 11.8 

VI (Dr. Sullivan, Madison, Wis.). — March 1, 1910. Male, 
white, 16. Left cervical glands much enlarged. Marked indura- 
tion of neck. Enlargement noted for only 1 month, but the 
amount of sclerosis in test gland suggests greater duration. March 
10, wound resulting from removal of gland for diagnosis still un- 
healed. May 13, wound healed but induration of neck marked. 
Death during 1911. 

BLOOD COUNTS. 

Date. W.b.c. N. E. B. S.L. L.L. L.M. Tr. 

III. 10, '10 18, I "i 6 0.6 0.4 4.2 3. 1.6 S.6 

V. 13, '10 27,(101) 80.6 1.0 o.i) 7.5 2.S 0.8 0.4 

Case VII (Dr. Bennett, Oregon, Wis.). — January 5, 1910. Fe- 
male, white, 64. In October, 1909, general glandular enlargement 
with clinical diagnosis of Hodgkin's disease. Death June 30, 1910. 

BLOOD COUNTS. 
Date. R.b.c. W.b.c. N. E. B. S.L. L.L. L.M. Tr. 

X. 24, '09 3,200,000 4, 4S0 

I. 5, '10 64.8 4.2 0.4 20.0 9.8 1.6 9.2 

Case VIII (Dr. Yates). — Male, white, 33. Onset in March, 1907, 
with supraclavicular glandular enlargement. In September, 1908, 
supraclavicular and left axillary glands most enlarged. Some 



enlargement of right cervical, axillary and inguinal glands. Octo- 
ber 30, 1908, excised gland shows typical and advanced Hodgkin's 
disease. Death occurred May 20, 1909. 



BLOOD COUNT. 



B. S.L. L.L. 



1.4 0.6 7.6 



L.M. 



Tr. 
8.2 



Case IX (Dr. Yates).— October 3, 1910. Male, white, 5. Marked 
enlargement of left cervical glands of 5 months duration. Test 
gland shows well marked Hodgkin's changes. Death from shock 
at operation. 

BLOOD COUNT, 
i.e. N. E. B. S.L. L.L. L.M. Tr. 



54.4 



2.4 



0.2 



Case X (Dr. Yates). — Male, white, cervical Hodgkin's. 
made 2 months previous to death of patient. 



9.4 



Count 






N. 
84. 



0.0 0.0 3.; 



S.L. L.L. L.M. 



1.0 1. 



Case XI (Dr. Baird, Eau Claire, Wis.). — December 8, 1910. 
Male, white, 22. Enlargement of supraclavicular gland noted one 
year previous. Axillary glands enlarged at date. Test gland shows 
definite Hodgkin's picture. 



BLOOD COUNT. 



S.L. L.L. L.M. 



.81.8 0.2 0.6 



Tr. 



Case XII (Dr. Yates). — Female, white, 33. October, 1911. En- 
largement of the right cervical and axillary glands of one year's 
duration. Test gland showed a picture of advanced typical Hodg- 
kin's disease. Cervical glands removed February 13, 1912. Subse- 
quent X-ray treatment. Removal of recurrences in right axilla 
and left sub-clavicular region January, 1913; March, 1913; July, 
1913. Clinically well 1914. 

BLOOD COUNTS. 



Date. 


W. b. c. 


N. 


E. 


B. 


S.L. 


L.L. 


I.. M. 


Tr. 


IX. 


27, '11.... 


19,000 


So. 4 


2.8 


0.0 


3.2 


0.4 


0.2 


8.0 


X. 


3, '11.... 


21,000 


72.4 


11.0 


0.2 


5.6 


2.2 


0.2 


8.4 


\. 


31, '11.... 




73.8 


6.2 


0.8 


7.6 


2.5 


0.6 


8.2 


Nil. 


1, '11 


35,000 


84. 


2.9 


1.1 


4.7 


0.9 


0.1 


6.3 


Ml 




21,000 


72. 


11.0 


0.4 


9.2 


0.9 


0.0 


5.5 


II 


13, '12 




74.2 


9.2 


0.2 


9.2 


1.2 


0.0 


6.0 


III 


15, '12.... 


30,000 


48.0 


36. 


1.4 


9.0 


1.2 


0.0 


4.4 


IV 


10, '12 .. 


17,000 


73.2 


10. 


0.6 


7.2 


0.6 


O.O 


8.4 


V 


3. '12.... 


17,000 


74.2 


9.6 


0.2 


10.8 


1.4 


0.0 


3.6 


VI. 


1, '12.... 


12,500 


77.8 


7.4 


0.8 


8.8 


0.0 


0.2 


6.0 


\ 


8, '12.... 


16,000 


70. 


12.6 


0.0 


8.6 


1.8 


0.2 


7.0 


VI 


27, '12.... 


15,000 


72.6 


8.6 


0.4 


7.4 


3.4 


0.0 


7.6 


1 


11, '13.... 


16,000 


80.3 


5.0 


0.1 


4.2 


2.6 


0.2 


7.6 


II. 


14, ■]::..... 


13,000 


71.8 


12.2 


1.0 


7.4 


1.4 


0.0 


6.2 


Ill 


3, '13.... 


15,500 


64. S 


13.2 


0.6 


12.4 


3.2 


0.0 


5.8 


IV 


12, '13. . . . 


15,01111 


74. 


6.8 


1.0 


10.0 


0.8 


0.0 


7.4 


VII 


14, '13 


15,000 


71. 


8.8 


l.S 


10.6 


1.6 


0.0 


6.2 


\ III 




7,000 


51.0 


10.0 


0.0 


27.0 


0.8 


0.2 


11.0 


1. 


22, '14.... 


11,000 


66.0 


9.6 


0.8 


15.0 


1.4 


0.6 


6.6 



Case XIII (Dr. L. F. Barker, Baltimore). — Male, white, 31. 
Enlargement of cervical glands, right side, of fourteen months 
duration. Test gland positive. 

BLOOD COUNT. 
W.b.c. N. E. B. S.L. L.L. L.M. Tr. 



Case XIV (Dr. S. T. Reeves, Albany, Wis.).— Female, white, 50. 
The glandular swelling had first appeared in the left cervical 
region two months previous to the patient's death. At the post 
mortem examination January 15, 1913, there was found rather 
general glandular involvement, but especial enlargement of the 
mesenteric and retroperitoneal nodes and of the lymphoid ele- 
ments of the spleen. There was also a chylous ascites, well 
marked anemia and emaciation. Leukocyte count estimated from 
ratio of 1 white cell to 29 red cells. 



Jim. 191 1. 1 



JOHNS HOPKINS HOSPITAL BULLETIN. 






HI. ' "1 ST. 



XII 



I), 









XV i Cook County Hospital, Chicago). — Female, u 
Marked enlargement of cervical glands; moderate of axil] 
inguinal glands. Spleen palpable. Duration fourteen months. 

ind positive 

BLOOD cm NT. 

B.L. I. I.. 1..M. Tr. 

li. -. :- 9,000 - 

XVI iDrs. Mayo. Rochester!.— Female, white. 34 
years previously she noticed a swelling on the right side of her 
neck, followed by the appearance of other small tunun 
months before date enlarged lymph-nodes appeared on ■ 

side of the neck and in the right axilla. Six weeks pr 
. in tin- left axilla. Physical examination r 
in addition to these nodules, a mediastinal mass, and a six months' 
pregnancy, over which were felt discrete firm noduli - 
slipped under the examining hand. Test gland positive. 



hi. 



I..L. I..M. 



■ ■ 

XVII i I irs. Mayo. Rochester).— Female, white, 28. Marked 
( the cervical nodes and rather general glandular 
tineas began with involvement of the i 
glands two years previous to date. Test gland showed ■ 
many giant cells and eosinophils in the m> 

BLOOD ' "I NT. 

v i . B --ill I '■ 
(2,00 - 

XVIII (Drs. Mayo. Rochester).— Male, whit 
patient had had an abscess of a tooth six months previously. 
About t before coming to the hospital patient bad 

noticed a painless Bwollen node in the left supraclavicnli r 
This had increased in size during the time of observation. The 
large node removed was of a uniform medullary appear 
gross section, and microscopically showed lymphoid ai 
tlielial hyperplasia, with the presence of giant cells, beginning 
diffuse 1 eosinophilic infiltration. The architecture 

of the node was destroyed. 





BLOOl NT, 








Date. 




I..I.. 

















XIX (Dr Frank Billings, Chicago).— Male, wl 
Loss of weight since January 1, 1913. Glandular 
noted In February, 1913 On examination, in April, i 
enlargement of cervical, axillary and inguinal glands, ' 
spleen. Abscess of right upper molar found. Gland ahowi 



■ 



- 



XX i Hr C. P II 

January, 
Pebraar 

• num. Cla: 



Ml 8, 






- 



XXI ' ,lr ' cal glandular 

enlargi 

various times. Ton-ill., i 
group of glands In 









XXII iHr. c. B. Pfahler, Pblladelphi white, 

rvlcal glands noted In N 
volvement of mediastinal, ad retroperil 

in ■ 

Dite. 

\II. 

Case XXIII (Dr. H. L. llrich, Mini. 
Operation for glands ol the neck at 
Rochester. Novi mbi r, 1911 

Gland removed in 1913 i f Kin- 

laboratory as Bodgktn 
enlarged glands In both and in right axill 

gland shows unmistakable, typical well-devi 
ease lesion. 



- 






XXIV i I >r i 
ment first noted in May, 1913. Uarki 
axillary and mi dia ittnal i land M 
mation. Test gland show 
but typical Hodgkil 









n. 






Ml. 20, ' :-: 

XXV I Dr. J ' 

rical and axillar] 
marked perlglandu 

r duration 



i 












BODGKIN'S DISE \-l 

!•.■. i : I'. 



My Lnten -' is 
experiments performed in the laboi 
the Onivers I jrlvania in 

the intraperitoneal u 



1 Paper read at a meeting of The Johns Ho] 
cal Society, Feb. 2, 1914. The work fornn 

report has been aided by a grant from the Rockefeller Institute 
of Medical Research. 



somm i' 



178 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



the glands, led to the development of a working theory as 
to the pathogenesis of Hodgkin's disease which I still hold, 
though in a modified form. This conception of the disease 
was, that the changes in the lymph glands were due to the 
filtration through them of a toxin elaborated at some primary 
focus of infection, and were in consequence entirely of a 
secondary nature — an end-result. For the explanation of the 
progress of the disease, I must introduce a subsidiary theory 
which seems borne out by pathological and experimental ex- 
perience, that lymphadenoid tissue affords not only a mechani- 
cal, but also a chemical, filter for peripheral lymph, protecting 
the body cells generally and the red blood cells in parti, alar, 
from a variety of toxins, at the expense of its lymphocytes. 
So in Hodgkin's disease, the primary group of glands, for a 
considerable length of time, protects the body from the toxin 
elaborated by the infectious agent. The removal of that 
group of glands by its ultimate sclerosis or by the hand of the 
surgeon, while the primary focus remains intact, exposes the 
body to an extension of the process to further glandular 
groups and, eventually, to an anasmia and a cachexia. 

This theory slumbered until 1908, when, on my return to 
Wisconsin, I found that Dr. Yates was deeply interested in 
the disease, and we decided to join forces in an attempt to 
unravel its difficulties and to further its treatment. We have 
been handicapped throughout by the distance between us, and 
more by our inability to control a sufficient material for 
study. We have, however, through the kindness of friends 
in the medical profession, come in contact in one way or 
another with 28 cases. 

Prom the standpoint of general etiology, the most striking 
feature of this series is that 13 of the cases were females and 
15 males; and further, that while the males were, with but a 
single exception, under 34 years of age (and the exception but 
35 at onset), the ages of 8 of the females ranged from 33 to 
fi4 years. Both of these features are in contrast to Ziegler's 2 
statistics derived from 210 cases gathered from literature. 
While it is dangerous to draw conclusions from a small series 
of cases, it would appear equally dangerous to follow Ziegler's 
method, if I may judge from a single case of which I have 
knowledge, 3 included in his series. 

The study of these cases from a pathological standpoint 
has but strengthened the conviction that the lesion of Hodg- 
kin's disease is essentially of inflammatory nature. The work 
of Eeed and of Longcope leaves practically nothing of impor- 
tance to be added to the description of the changes within the 
glands themselves, unless one emphasizes the fact that there 
are cases in which the disease runs so intense a course that 
the necrosis and the inflammatory reaction in the glands 
almost overshadow the more usually accepted chronic Hodg- 
kin's disease picture. This appears to occur without sec- 
ondary infection as far as cultures can determine. 



: Die Hodgkinsche Krankheit, Jena, 1911. 

3 Among his cases of Hodgkin's disease of the spleen is in- 
cluded a metastasizing sarcoma of the spleen-pulp, published by 
me some years ago. In this case there was no involvement of 
the lymphoid tissue in the spleen or elsewhere 



Aside from the gland lesions there are, however, two points 
in the pathology of the disease which deserve mention. Care- 
ful search will, in the majority of cases, reveal a primary 
inflammatory lesion which was present before the enlargement 
of the glands occurred. In primary cervical Hodgkin's dis- 
ease, this is most apt to be in the tonsils, teeth or nasal 
sinuses. In one primary cervical case, an otitis media of some 
duration proved the source of the infection. In a primary 
inguinal case the physician gave a history of a sharp attack 
of cystitis preceding the glandular enlargement. However, 
infection through the gastrointestinal mucous membrane is 
possible, as shown in cases in which the lesions are confined 
to the lymphoid tissue of the tract and the mesenteric glands. 

The second point I wish to emphasize is that, while the 
glands in Hodgkin's disease remain discrete, they are, never- 
theless, bound together in chronic cases by a mass of sclerotic 
tissue. In other words, there is in the disease an extraglandu- 
lar inflammatory process which is of a relatively acute nature 
in early cases, showing a marked inflammatory oedema and a 
moderate and diffuse infiltration with polymorphonuclears, 
as well as with large and small mononuclears. There is an 
early stimulation of fibroblasts leading to the marked sclerosis 
of chronic cases. 

That there is a general systemic reaction in Hodgkin's dis- 
ease and not simply a process within a gland or group of 
glands is indicated by the changes in the blood picture, to 
which I have given considerable study, but to which I shall 
refer only briefly here, as I have considered them in detail in 
another paper. 

A study of 25 cases shows that they may be divided into 
two groups according to their blood picture. The first of 
these groups includes roughly those cases of less than a year's 
duration, and the second, those of over a year's duration, al- 
though duration does not appear to be the chief factor in 
determining the blood picture. The blood in both groups 
shows a marked increase in blood platelets, with the presence 
of large platelet masses and megalokaryocyte pseudopodia. 
The only other constant feature is an absolute and usually a 
relative increase. in the so-called transitional cell — the large 
mononuclear with indented or lobed nucleus and abundant 
protoplasm with azurophile granulation. This is Mallory's 
endothelial leukocyte, but I believe it is derived from the cells 
of the reticulum of lymphoid tissue rather than from the 
lining of the sinuses. 

Except in these two points, the two groups of cases van' 
in blood picture. The first group shows little, if any, increase 
in the total leukocyte count ; the second, usually a pronounced 
leukocytosis, even up to 100,000 cells per cmm. In the very 
early cases of the first group, there is a deficiency in eosino- 
philes, a slight increase in basophiles, and a fairly well marked 
lymphocytosis. This is followed after compensation by a 
slight cosinophilia. and by a gradual decrease in lymphocytes. 

In the second group of cases, we have a neutrophile leuko- 
cytosis, the percentage of these cells ranging from 76 to 90 
in the series. Lymphocytes are exceeded in number by the 
transitionals in 10 out of 13 cases falling in this group. 



1914.] 



JOHNS BOPKINS HOSPITAL BULLETIN. 






three may !><■ 1 1 1«- only varieties of cells found 
blood picture appears to be of diagnostic value ii 

Hilar enlargement; at least, the differ* 
from tuberculosis of the glam - 
able, however, to differ© I 

- i-called malignant lymphoma by tin- blood 
te of the failure of others t" obtain organisms in cul- 
. I ':. Yates and I made 
wherever opportunity i altural 

method the agent producing the disease, <>ur earrj 

ration and post mortem examination were failures. 
Our bui ganism, which we are i onvinced 

is the cause of the disease, was, 1 believe, the resull 
following factors: i suitable medium, the implanta- 

md tissue with interglandular tissue, 
and incubat ifficiently long period. Th< » 

pted purely by accident. We felt that the or- 
ganism was one of the Bo-called l 

ted cultural material suitable 
f..r the growth of the tubercle bacillus; i. >■.. I 
medium and glycerine-phosphate-agar. We further concluded 
that the organisms were few in Dumber in the glands and were 
■ gland ib large as the diameter 
of the • uld permit were implanted, with tl 

that in this way we should stand mi of implanting 

ms, and also with the thought of furnishing si 
human a ism a start at growth. Finally 

• tubes and ini ubated them indefinitely. 
(>ur -:'ul implantation was made in February, 

owth of a diphtheroid organism in 
and on lycerine-phosphate agai 

■ 1 1 -in in an] 

whicb 
■ i cultures. 1 1 found 

usually in pure culture, in cervical, azillai 

r. not infrequentl) 
iwth of a u would !"■ fo 

•i from 
the patient operated upon. 

may appear in but 

eblj fr<>m r 

. ' Dursing u 
growth upon 1 1 i « - medium indi 

ritures, howi ery luxuriantly fron 

and on> A for our • 

liruvrth of this i ulturt . 

human cases. 
The organism \t I 

able that about ri 

■ 



different 

granuls 

involution form-, short, plump bai illi a 

■ 

predon 

•: guitable n 
bacilli. 

While < in: _■: 

not j.r< ..liii e death in but highly 

virulent to Is 

disapp 

most innocuous to 

was had to the n 

with. B .n the 

lymph glands simihu to those found in • 

would 

n a foothold, apparently, ai 
nieiit and the periglandular induration would su 
ever, that difficult 

;m in pure cultun 
developing at the Bite of an inoi ulat i 

used for injection of the other n.- 
From one of these monkeys an enlarged gland 
one week after inoculation in its vicinity, and « 
Bubcutaneously into another monkey. Tl 
10 weeks with marked invol 
The organism was pun' cultun 

to the original culture. I tin 10 

. and with most n 
throughout. 

tare ami has show n pro 
the last inji 
Btrated the 

■ 
'I'll. • 

cells, with endothi I 
a prolifi 

idowed '■■• I 
polymor] 



180 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



find that some obscure infections in man resulting in extensive 
subcutaneous inflammatory reaction without pus formation, 
and in intense glandular reaction, will be proved, upon bac- 
teriological investigation, to be cases of acute Hodgkin's dis- 
ease. 

There is one other relationship of Hodgkin's disease that 
needs mention. Morphologically there is great difficulty in diag- 
nosing between various types of so-called malignant lymph 
gland lesions. As I have mentioned earlier, in a case of malig- 
nant lymphoma, with a primary, slightly greenish tumor in the 
orbit, aud with general glandular and splenic enlargement, 
the blood picture was identical with that in Hodgkin's dis- 
ease. Furthermore, a culture was obtained from the glands 
in this case of an organism quite similar to, if not identical 
with, that obtained from cases of Hodgkin's disease. Billings 
and Rosenow have also reported the cultivation of a diph- 
theroid organism from a case diagnosed histologically as lym- 
phosarcoma. In the chloroma case there was noted at opera- 
tion, also, the same marked interglandular sclerosis seen in 
Hodgkin's disease. These findings practically force the sug- 
gestion, open to further proof or disproof, that these diseases 
differ but quantitatively and not qualitatively. 



To summarize our picture and revise our theory, Hodgkin's 
disease is an infectious disease due to a diphtheroid organism, 
the Bacterium Hodgkini. There may often be found a pri- 
mary lesion at the portal of entry. While in some cases the 
organisms may remain for a long time localized in the vicinity 
of the portal of entry, in other cases they early gain en- 
trance into the general circulation, and may be widely dis- 
tributed. The organism and its toxin show a special affinity 
for lymphoid tissue, and produce in this the characteristic 
changes of Hodgkin's disease, changes varying somewhat ac- 
cording to the intensity of the toxin, but resulting ultimately 
in the sclerosis of the glands. There is at the same time an 
interglandular inflammatory process, at times very acute, but 
resulting finally in a dense sclerotic tissue. There are also 
characteristic blood changes in the disease. 

The glandular changes can then be considered only as the 
result of a toxic action, and contribute to the patient's death 
merely incidentally, when certain gland groups are extensively 
enlarged. The cells of the enlarged glands, though atypical, 
show none of the antagonism to the other body cells charac- 
teristic of malignant neoplasms. 



A CLINICAL CONSIDERATION OF HODGKIN'S DISEASE. 

By J. L. Yates, M. I)., P. A. C. S., Milwaukee. 



This work has been aided by a grant from the Rockefeller 
Institute for Medical Research. 

Grateful acknowledgment is made to the directors of Columbia 
Hospital for encouragement and assistance. We desire also to 
thank other medical friends for their aid; especially are we 
indebted for the hospitality and help from the Mayo Clinic. 

Read at a meeting of The .Johns Hopkins Hospital Medical 
Society, February 2, 1914. 



This communication is based upon studies made during the 
last six years in conjunction with Dr. ('. H. Bunting, of Madi- 
son, Wis., and is to be regarded as both elementary and pre- 
liminary in nature. 

Definition. — Temporarily Hodgkin's disease may be con- 
sidered an infectious, non-contagious affection due to the B. 
Hodgkini. It is characterized by a somewhat variable, though 
definite, reaction in the lymphatic and perilymphatic struc- 
tures, specific changes in the blood picture and by the manifes- 
tation of little or no tendency to spontaneous recovery. 

Diagnosis. — Heredity and contagion have little, if any, sig- 
nificance in the history. The sexes are equally represented (16 
males, 15 females) between five and sixty-four years with an 
apparent tendency to appear comparatively earlier in males 
and later in females. As a rule there is disclosed nothing suffi- 
ciently definite symptomatieally to indicate the time of info 
tion or the portal of entry. Enlargement of the cervical 
glands is commonly noted as the first evidence of the disease, 
and is usually discovered by chance during a period of well 
being. Infrequently this glandular enlargement is preceded 
by a sense of lassitude, or there may have been a well-defined, 



if not severe, irritation in the throat, nose, eye or ear. Glands 
in the lower posterior cervical triangle are more commonly 
noted primarily than those higher up, further extension taking 
place, in order of frequency, to the axilla on the same side, 
to the opposite cervical region, the mediastinum, the opposite 
axilla, to the groins and the peritoneum, the spleen and liver; 
Primary involvement in the inguinal glands has been noted 
as following cystitis and leucorrhcea or has appeared with- 
out the least evidence of any exciting cause ( lymphosar- 
coma?). In acute cases the enlargement of glands first 
affected, and the subsequent extension to other members of 
the same group and to other groups of glands may be rapid 
and rather steadily progressive. Perhaps more often there 
are alternating periods of enlargement and regression e\en 
in the acute type. During the periods of enlargement (this 
is noticed by the more observing patients) the individual 
glands seem partially to lose their identity, the whole group 
becoming fused into a nodular mass. This may lead to boggi- 
ness in the subcutaneous tissue or even to redness and edema- 
tous induration in the skin. Excision of tissue and subsequent 
microscopic study by Dr. Bunting has demonstrated that 
these changes are due to waves in the acuteness of the peri- 
adenitis, rather than to increased adenitis and may ha\e 
an important bearing upon the question of treatment. Early 
bad effect upon the general health is attributable to tox- 
aemia which is always sufficient to affect the blood picture. 
During intervals of regression in the glandular enlargement 
there is apt to be a sense of greater well being, with a corre- 



1914.] 



.IOUNS HOPKINS [OSPITAL BULLETIN. 






spondii.. issitude when there is an incn a 

inont. Thus it ma ted that there a in the 

toxin prodai I 

appears the secondary anaemia duo pro i 
anism, and racelj . 
- 

exhaustion of the bone marrow. T] 

late in thi 
any intercurrent infection and has thus far indicate 

•: may resu 

thoracic duct wit] 

immonly su 
■ 1^ with in 
inevil i 

made without lal 
. ical and ba 
3 
explanation. 

oitis £0 
iricular glai 
clinically they may be indifferentiable. Lymphatic leukemia, 

d by Cohnheim and Wnnderlich to 
pseudoleukemia or Hodgkin'a d 

-.■ of one cat 
extremely significant observation, particularly if thi 
from a lymph gland in that 
Bhould hini. In 01 

and t« ma i clinical and : 

Buntinp ha- 

• 

cally diagnosed lympho 

'-. Bunting's 
Bull., L911, XXII, 11 ; 

■ 
Buntin . 
that, in his hands 

I 

maladies with and with 



M. & S J . 1914, I'l.XX. i. 
•.! An. 



complii 

cal pii hi 
and th< I 
picture is establish 

kcmia. lympl 

warrai | 
harmful in n 

individ 

■ 



182 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



tioD with intraperitoneal involvement. Mediastinal infection 
is almost, and intraperitoneal extension is certainly, of hope- 
less prognosis and must so remain until more efficacious meth- 
ods of treatment are developed. 

The following treatment which has been and still is being 
developed is based upon this philosophy : fostering localization 
of the infection with earliest possible elimination of the same. 
The therapeutic procedures are regarded as primary and 
supplementary and have been applied as will be indicated to 
favorable and unfavorable cases. 

Primary Procedures. — Portals of entry in so great a major- 
ity of individuals are to be found in the mouth, throat, nose 
and ear, that routine radical tonsillectomy, competent investi- 
gation and treatment of teeth, accessory nasal sinuses and 
ears are prerequisites and should often include skiagraphy. 

The demonstration by Dr. Bunting of lesions of Hodgkin's 
disease,of the unmistakable Dorothy Eeed type, in tonsils man- 
ifesting little, if any. abnormality, in situ, has confirmed the 
propriety of this attitude. In addition the likelihood of dis- 
semination from these foci through the circulation, especially 
the lymphatic, is notoriously great. Organisms resembling 
B. Hodgkini morphologically have been observed in abscesses 
about the roots of teeth and in the discharges from nasal 
sinuses. The danger of gastrointestinal and even peribron- 
chial infection from such sources is real if slight. Any real 
danger in this disease, be it however slight, is a grave danger 
and neglected may determine a fatal issue otherwise avoidable. 

Surgical removal of the greatest portion of the disease thai 
can be accomplished with safety, gentleness and thoroughness 
as advocated by Halsted in extirpating cancer, appears to do 
most to throw the balance of power in favor of the individual. 
This is always to be done after recovery from tonsillectomy 
which is best accomplished, when possible, under local anes- 
thesia. Virtually as complete an excision as that advocated 
by Crile in cancer of the cervical glands should be made for 
involvement is always wider than appears externally and has 
often extended to all the regionary glands. When excision is 
incomplete, recurrences are generally prompt and these early 
recurrences usually manifest decidedly increased virulence. 
Since the microorganisms are probably present in the peri- 
glandular tissue, it is impossible to overestimate the impor- 
tance of thoroughness, gentleness and the sharpest possible 
dissection and of not operating during a period of acute peri- 
adenitis. It is, moreover, inconceivable under any condition 
that the field of ' operation could remain uncontaminated . 
This, therefore, should be thoroughly treated with tincture of 
iodine and drained. The immediate reaction is greater and 
the healing not so smooth but the tendency to recurrence is 
definitely reduced. Incidentally scar tissue is notoriously poor 
soil for the persistence of infection. A patient's resistance 
is not long or materially reduced by this type of intervention 
and there is a deal of comfort in the realization that many 
bacteria and their toxins, together with degenerate tissue the 
result thereof, are truly innocuous in vitro. 

One emaciated child of five succumbed to an ill-advised 
operation. One woman died from an anesthetic before an 
operation to decompress her mediastinum could be begun. 



With these exceptions, not even many repeated interven- 
tions on the same individual have been followed by more 
than temporary distress, and not to our knowledge has the 
course of the disease been unfavorably affected by surgical 
work when done, according to the principles enumerated above. 
On the other hand excisions and re-excisions are commonly 
followed by improvement other methods have failed to achieve. 

Supplementary Procedures. — The whole area of operation 
should be subjected to X-rays, in measured doses, begun the 
same or the first or second day after excision and repeated 
thereafter as frequently and for as long a time as safety per- 
mits. Wherever else the disease is present or suspected, 
should be also thoroughly treated. Dr. Foerster and Dr. 
Baer have spared neither time nor pains in cooperating in 
this work and it is quite impossible to estimate how greatly 
these patients, nearly all of them indigent, have benefited 
by their generous attention. 

Control observations from the same individual indicate 
that it is impossible to obtain cultures from glands after 
they have been thoroughly X-rayed, that such glands and 
periglandular tissue show increased sclerosis with the appear- 
ance of more giant cells and hyaline degeneration within the 
glands. Moreover, individual glands, and those in chains 
and groups, that have been shown histologically to have been 
the seat of definite Hodgkin's disease have disappeared more 
or less completely and remained stationary for two, three and 
the years after X-ray treatment given subsequent to the 
removal of exciting foci. No such result is unfortunately as 
yet to be recorded in retrosternal involvement. 

Vaccine. — Our experience is too limited to make possible 
any statement as to curative results from this treatment. 
Each case receiving vaccine treatment is being followed with 
repeated blood studies by Dr. Bunting, who is kept in igno- 
rance of the source of the specimen and the nature of the 
treatment. Unquestionably there may be temporary sub- 
jective and apparently objective improvement attributable to 
the vaccine. Certainly there may be actual harm done even 
with small doses. We believe that until more is known of 
the late and permanent results of vaccination it is essential 
to regard this as a part of a method of treatment, be it cura- 
tive or prophylactic against recurrence, which is as yet of in- 
sufficiently demonstrated value. 

Serum. — A startling similarity, noted by Bunting in the 
lesions of the experimental disease in monkeys, in very acute 
human disease and in those occurring in fatal diphtheria, 
together with the diphtheroid type of organism, suggested a 
possibility of benefit to be obtained from administration of 
diphtheria antitoxin. This has been given adequate trial. 
Some subjective and possibly some objective improvement 
followed its use. This questionable improvement was tran- 
sient at best and nothing to warrant its routine administra- 
tion was noted. The serum was assumed to be without any 
specific action. 

Comparison of three varieties of antitoxic serum and one 
normal horse serum as to bacterial agglutinins and lysins for 
different strains of B. Hodgkini and B. diphtheria disclosed 
no regularity in action. 



Jixe. 1914.] 



JOHNS EOPKINS HOSPITAL BULLETIN. 






Transfusion has not been found to 1 E any lasting value, 

-•nee of spontaneous hemorrhag 

transfusions, to restore the p 
■ irculation. 
Drugs. Pi al superstitii 

with a temporary suspicion that the disease was due to a fun- 
to the administration of salvarsan intra-muscularrj 
ami intravenously. In febrile cases it may redm 
perature t" normal for a daj or two. and even cause 
and hepatic enlargements to diminish materially but only 
temporarily. It was without appreciable effect nj 
mate outcome. T 
Benic no more thai ol has not been g 

Eygit much importance cannot be attached to 

maintaining these individual- upon the hig le level 

ncy. Recurrei our to 

ipon the wa onsiderable or even slight phase 

Mental depression over a short perio 
•o indui i- a recrn 
ands have been repeatedly < ■ ■ 
- and axilla i. previously operated upon, which 
haw finally reman ■ any evidei 

for apwards of three years. In one individual, with a late 
return I I, glands excised showed but an ordinary 

chronic adenitis, indicating strongly the probability o 
cure, after two previous operations when tissue i 
i. ally that of Eodgkin's di 

Line Blightly f < ■ l > r i 1 < • with 
of only an axillary gland or two in < .:■ 
perature returned to Qormal promptly after thi 

a tendency, if thi 
. criterion, to exhibit an increasing chronic- 
ler in the pn 

a hat any recurrenl gland will 
do undi favorable conditions and und< 

tion. It 
gland under lex 
which ■ lj and with trifl 

again to be instituted as if it were a primarj op 
ode that th 

mpting to b I 
supplemi 

cation of more definite! primary pn 

Je. 

That : B 

tnav be liket w of childn i 

apse! null nee l>e broke: I 

will fall. CTnfortunately, in tl 

sequence may avail little a- any bial 

• d. if in addition. 
Probably no part of the chain • i 
lesion which should therefore l>e elim 
mit. T~:-ually this is demanded it' ai yi 
in the line of curative therapy. 



or all meth 
turd tii' 

comfortable and I 

Thi- niu. ! 
the future po 

stimulating ■ 
iy timl comforl in the 
rate i 

hibiting the i 

A CM 

an individual show 
blood picture, four to 6 

Bed by the knowledge thai recrudi 

shorter pen. 

ill : 

[.—June, IS 
year. Seen two days before death. Very extensive Invol 

most intense distress which was uncontrollable by opium 
due to anesthetic given in an attempt i 
Which was filled with a mo 
itself. 

ii.- October 8, 1908. W. i; . i 

year. Left side of neck from mastoid to I" kffl 

from midline in front to behind anterior margin ot tl 

u. cupli 'i bj mass ol 

October 10, 
ease histologically. Cultui 
healing. X-ray treatment begun and i 

.tunc 24, L909 
region ol submaxillary gland 

august 16, 
kins di 

October 22, 1910. G< neral cond 
glands at Up ol byold pn 
toid. i !he i and 

Julj i. 1913 Hillary. 

i and inn hum • 
..ll\ 
Januai j 27, 1914 
tion. Bl 

in a gland i 

Mar. 

polyvali 

In left 

April 
goal irrll I 

U ri- o • 

Nov ■ • 

kins .1 

eicnl. : 



18-4 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



December, 1912. Few glands smaller than peas in left posterior 
triangle, one gland smaller than pea in right posterior triangle. 
Axilla? similar. Groins and abdomen negative. 

January, 1914. Reported to Dr. Bunting. Health excellent. 
Blood picture normal. It was from the study of this blood pre- 
viously that the characteristic blood changes were recognized. 

Case V.— September, 1909. G. R., male, set. 8. Enlarged glands 
noted by public school nurse eight months before. No effect on 
general health. History unimportant. Large mass of glands be- 
low angle of left jaw. No general glandular enlargement. Chest 
and abdomen negative. 

September 30, 1909. Gland removed for diagnosis. Positive. 

November 15, 1909. Cervical mass excised. Marked periglandu- 
lar sclerosis. Incomplete operation. Tonsillectomy. X-ray and 
hygienic treatment. 

September 7, 1910. Recurrence noted beneath angle of jaw. Ex- 
cised. Positive Hodgkin's disease. 

October 8, 1910. von Pirquet test negative. 

November 25, 1910. General condition excellent. No recurrence. 
Mediastinum free. 

February 9, 1911. General condition good. Small glands in 
both sides of neck and both axilla?. 

March 7, 1911. Readmitted to hospital because of profuse nose- 
bleeds. Coagulation time six to seven minutes. Subsided under 
rest and administration of horse serum (?). 

April 20, 1911. Again admitted to hospital. Bleeding from nose 
and gums. Anaemic. Febrile. Spleen enlarged. Abdomen dis- 
tended. Transfused — mother. 

May 1, 1911. Again transfused— mother. 

May 9, 1911. Again transfused— brother. 

May 17, 1911. Onset of first marked attack of continued fever. 

May 22, 1911. 0.3 gm. " 606 " in buttocks. Some effect on tem- 
perature. 

June 15, 1911. Recurrence of febrile state. Given 0.3 gm. " 606 " 
intravenously. Reduction of temperature but for two days only. 
Decrease noted in size of spleen and liver which had lately become 
enlarged. 

July 22, 1911. Another attack of Pel-Ebstein fever with epis- 
taxis. Liver smaller, spleen same size. 

August 21, 1911. Recurrence of fever. Spleen large, liver 
smaller. 

September 1, 1911. Only evidence of disease in glands in group 
about submaxillary. Excised. Positive Hodgkin's disease. Emul- 
sified and injected into guinea pigs. No effect. Cultures: White 
coccus and B. subtilis. 

September 20, 1911. First recurrence of fever since operation. 
Bleeding from nose and gums. 

October 16, 1911. Fever continued. Rapid local recurrence of 
gland under ear. 0.2 gm. " 606 " intravenously without effect. 

January 23, 1912. Gradually failed. Increasing emaciation and 
abdominal distension. Death from starvation. Necropsy— chylous 
ascites. Advanced retroperitoneal lymph gland involvement. Gen- 
eral wasting. Anaemia. Cultures— contaminated. 

Case VI.— December 2, 1909. F. v. S., male, a?t. 10. Under nour- 
ished. Slightly enlarged glands both sides of neck, both axilla? 
and both groins. Abdomen negative. Harsh and prolonged ex- 
piration at left apex. Blood positive Hodgkin's disease. 

January 10, 1910. Tonsillectomy. Glands for diagnosis from 
groin, neck and axillae. Cervical glands positive Hodgkin's dis- 
ease. X-ray and hygienic treatment. 

April 26, 1910. Slight glandular enlargement persists. Growing 
rapidly and gaining in weight. 

October 5, 1910. Still gaining, von Pirquet test positive. Glands 
remain the same. 

September 10, 1913. Glandular condition about same. Harsh 
breathing at left upper, von Pirquet test positive. Few slightly 
enlarged glands palpable. 



January 6, 1914. General condition excellent. Blood picture 
normal. Glands quiescent. 

Obviously so small a number of cases is of little value, save 
in the lessons to be learned from mistakes. 

Case I was virtually dying. Intervention was prompted 
only by desire to relieve a degree of distress too great to admit 
of description. Treated early in the disease, the outlook 
would have been excellent. 

Case III, almost certainly hopelessly involved when first 
seen, possibly illustrates the impotence of the X-ray to control 
the progress of the disease so long as the primary focus and 
the major portion of the disease remains. Prognosis was 
probably bad from the outset because of early extension of the 
disease to the mediastinum. 

Case V illustrates the harmful results of incomplete surgi- 
cal intervention. This boy was of the puny type and a con- 
genital pessimist. Had better judgment prevailed and the 
slightly added risk of a complete radical excision been ac- 
cepted primarily, it is conceivable that this life might have 
been saved. 

Case II, apparently more unfavorable than Case Y pri- 
marily, was treated the more radically because of supposed 
hopelessness otherwise. This child was discouragingly puny, 
but an aggressive optimist. First recurrence (9 months) 
accompanied evident deterioration in general health with 
prompt improvement following excision. Suspected recur- 
rence three years after the first was unaccompanied by any 
effect upon general health. Microscopic examination proved 
these glands to be free of changes due to Hodgkin's disease. 
Finally four and one-half years after last positive evidence of 
the disease was found, while feeling perfectly well and after 
repeated physical examinations with special attention directed 
to the mediastinum had failed to disclose any evidence of 
disease, a routine blood examination 'indicated a recrudes- 
cence. Stereoscopic skiagrams revealed glandular enlarge- 
ment behind the left sterno-clavicular articulation. The pri- 
mary operation had extended down to the region of the 
thoracic duct, indeed it was probably injured and ligated. 

Cases IV and VI, both nephews of physicians were given 
every benefit of early and late treatment and serve as proof 
that the disease is curable without the aid of any specific 
therapy. 

In conclusion even these few cases indicate that primarily 
Hodgkin's disease is a localized process, susceptible of cure 
when properly treated as a malign, though chronic infection. 
It may persist for years without manifesting itself save in the 
' blood picture so that cures may not be assumed until after 
an uninterrupted duration of years of persistently normal 
conditions. 

A sovereign remedy for all cases is not now conceivable. 
At present the greatest need is some therapeutic agency to 
control glands not directly accessible; for once extension, 
which may occur early, has reached either the thorax or ab- 
domen the prognosis becomes relatively, if not absolutely 
hopeless. 



. 1914.] 



•loHNX HOl'KI -1MTA1. BULLETIN. 






some qnpublished wate1 
bell; with observations i 



OR SKET( III - OF SIR I II MM ES 
\ HIS ^RTISTH Ql 4LITIES. 

if, i» . - 



I bring these unpublishi 

•. with tlii' hope, thai it ma\ ■ 
publish otl 
both di 

rhaps, whose : 
■ 
:' the true dd BtimoJati 

aerally. At 
ondly, Sir i 

will at- 
■ 

may improve our methods in the n 
anatomy itself. 

. which I 

for his 

rk i >n tin- ari 

• thej did si 
• tii. in my mind, 
S 
emplify certain prim-ii' 
worth 

I am doing my sketches in wal 

[nation ho« 

qually well to them. V 



• These sketches « 

see British Medical Journal, !-• 
-Ibrary oft] 

for 1 
Its librarian 

.ire most of them 
water-color, showing the lilcti coloring mid b 

drawn andoubl 
or aboi;- rles was still h 

g with his el hn, for with I 

Ipt of the pi 
edition of his Eng 

1 
especially in the third, which !>■ 
head an ited a* draw i 

the picture more I 
compliment ;i favorite pu| 
tnterpi 
t Paper presented at the XVIIth Intarnatloi 

.ne. 



Charli - 

It is tru. thai I 

figures are'ral 

than Btn 

(lUent labour And 

been m 

palntii.. 

without \ it'or. and in whl 

a bad foundation for ■ good plctui 

in thi.- ' 

oniy should !•• strong!} i 

' 

should be graduall 

outllie 
position 

■walling - • 
ant. 1 

Plat 

■ 



with U 



1SG 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



Figures 1 and 2 were drawn from dissections done in the early 
Edinburgh days, while Figure 3 is later London work, and 
indicates that he considered the dissection better adapted for 
his etching. It all shows his careful selection. 

In Plate V, Figure 2 is reproduced, while Figure 1, which 
appears in the first and second editions, is replaced by another 
drawing to show the arteries of the face. 

With these changes, the drawings have been reproduced by 
engraving or etching, and done by himself, with the exception 
of Plates II, III and X, which were etched by J. Stewart. 

The accompanying script which is his own handwriting, 
in my judgment, is the script of a copy-book, written with 
great care and deliberation, when time seemed no object, but 
only the wish to produce an accurate and beautiful " copy " 
for the printer. It is like the delicate, precise handwriting 
of the Latin races. Throughout his life his handwriting 
changed but little; even when it shows rapidity, it is a beau- 
tiful flowing script, quite Spencerian in its curves and hair 
lines. 

Examination of these sketches with a magnifier shows 
rapid work, with much of the drawing done with the brush 
itself. I see no pencil marks showing any drawing before 
taking up the brush. Even the coursing of the vessels is 
largely, if not wholly, rapid brush work, especially the smaller 
ramifications. The general outline of a head will be drawn 
with the brush, rapidly, and with a bold and free sweep. 
There is no hesitation anywhere, and he is sure of his drawing. 
He is not making any pictures, to be reproduced as such, but 
simply feeling his way to the more careful and accurate etch- 
ing; and I cannot but believe, too, that the etching itself is 
made with the dissected j>art before him. John Bell ever in- 
sisted upon a careful copying of the dissection, and he taught 
this lesson to his younger brother with his wonted insistence 
and emphasis, and that Sir Charles learned his lesson well we 
have good evidence. Alluding to these very plates, he wrote : 
" I have etched most of the plates with my own hand, prefer- 
ring accuracy to elegance." 

While it was very evident from his published drawings 
how prolific his artistic work was, and how great his industry, 
these sketches give even better evidence of his rapidity and 
facility. In his first published work, A System of Dissections, 
there are many beautiful plates on a larger scale, which could 
have been easily reduced for the smaller, work ; but, no, his 
artistic sense and energy demanded new drawings and fresh 
dissections, and so we have a series of entirely different illus- 
trations, additions, and improvements in the third edition 
which make it almost a new work. This in itself shows the 
artist and the man of science. 

A comparison of the sketches with the etchings show 
some interesting and suggestive differences. Generally speak- 
ing, it may be said that as illustrations of dissections there is 
deterioration in the etchings. In the first place, five of the 
plates are much reduced in size. Size is an important 
in artistic conception, and in the grasp of the architectonic 
plan of any structure. Reduce Michael Angelo's David or 
the Venus of Milo to a one-foot figure, and no matter how 



perfect the reduction, how much is lost! Great as the draw- 
ings of Vesalius are as faithful copies from nature, and 
especially so when compared with the work of his predeces- 
sors, much of the effectiveness of the faithful copy is lost 
in the small size. Even his imitators, who simply enlarged 
these drawings, took a great step forward. We turn the pages 
of the De Humanis Corporis Fabrica more quickly than the 
pages of the Tabulce of Albinus. Compare Sir Charles's 
small etchings of the arteries with Maclise's life-size drawings 
in Quain's splendid work. The etchings are more finished 
and delicate, but much less effective than the drawings of 
the less gifted artist, and almost entirely on account of the 
"size. Of course the two works had different objects in view. 

The trend of anatomical illustration is towards . larger 
figures. Where the etching is the same size as the original 
sketch we can see the improvement from more careful draw- 
ing, and the greater distinctness of black and sharp lines. 
He was undoubtedly influenced in the small size of the other 
sketches by the subsequent etching. In the reproduction of 
Plate V Sir Charles himself, still influenced by the size of the 
prospective volume, has committed the error, rare with him, 
of overlooking the value of relationships in anatomical deline- 
ation, for in etching the arteries of the face, he has omitted 
the great trunk in the neck, well shown in the original sketch, 
and has etched for us a head cut off close to the base of the 
skull. A lack of proper relationships is worse than poor draw- 
ing. Sir Charles, of course, takes no liberties with his 
"copy"; he is always the faithful copyist. But J. Stewart, 
who etched Plate III, instead of faithfully copying the right 
iliac crest, as drawn for him, has seen fit, while Sir Charles's 
back was turned, to take every liberty with it, and he has 
given us a strangely scolloped bone. He also omitted the os 
pubis and ischium, which are in the original, and which give 
us the relationships of the iliac and beginning femoral arte- 
ries. He has, however, introduced the skull, omitted in the 
sketch, which shows he had the anatomical preparation be- 
fore him. 

While in a few instances the etched artery is better defined 
than the vessel drawn with the brush, it usually suffers in 
comparison, for the painted vessel is well accentuated, and 
even exaggerated. Exaggeration, when properly applied — 
for only the real artist can use it correctly — is a true principle 
of art. The Greeks had the audacity to increase the facial 
angle, and with what marvelous effect ! The genius of M ichael 
Angelo put its own limits on bony prominences and swelling 
muscles, and his drawings and plastic art are good anatomical 
models to-day. 

The sketches, as well as the etchings, show an ever present 
sense of the third dimension. His drawings are never flat. 
Even in his descriptions of the ligations of the arteries, he is 
ever mindful of their depth. On this point examine Plate II 
(Third Edition), showng the femoral with its profunda 
branches; the drawing is almost stereoscopic. Many bean? 
tiful examples could be given to show this quality. 

In a general way, it can be seen that Sir Charles has fol- 
lowed the principle which he sets forth in the essay from 



1914.] 



JOHNS BOPKINS I OSPITAL BULLETIN. 






vrhicfa 1 have quoted, namely, that the anatomj 
strontrly marked in the sketch, and in the finis 
"should be gradually softened into the modest) 
While tli is was probably tin' prevailing 

im sure the day would i 

•rikc.-; the n - • of all anal 

delineation when he writes: ••The chara 

t and life." Art is ; life, and the 

tic. If 
the artist paints the dead body, it must suggest the lifi 
ra. I f he paints til'' d ly, the more 

irts in their true relationships wil 
their funci 
■ 

oeral ; never yel 
I 
lightly touched without son 
Sir Chi art in general, and this 

a way more appl than in anal 

But in all his writings and in 1; 
Irawings, his aim ever was to raise anal 
and elinieal drawings to a h . Hi 

in one of his letters to his brother I 3 times 1 

think of finishing my anatomy of the muscles in painting in 

This was a great idea and we should • i 
to carry it out to its fullest extent : and if ot of anat- 

omy i- to grow b ■ atimate 

growth, di and functioi 

ith it. 
1 well when a youi 

innd, of Sir I 
Bell's " S " displayed in a shop 

plates, and 
v ith the two-volume edition 

And now after m u 
I • !f looking at tl ■ 

sure, and an added appreciation. What 
charm? In what 

II know that with every trui 

d. which i It 
■ ■ 

apply in our 

order, hut when the - 

ment. it requires a higher ordi 
bring it within thi 

the dead to life: that in the dead body, M 
the life which has flown ; that in the 

the muscles and hi 1 

alive and function i 
great deceptii 



many 

and plasl 

■ 

of it sot land, 

rding to a i 

elling in •'■ 
hitherto attempted. Many of them, I 
are now. aloi 
the Colli 

1 

In the M idd 

could publish tl 

me. 

and in many ways full;, 

of the 

subject, the point of view from at nt, the 

relationships 

skillful drawing of the d 
is no hesitation in I 
form : and v 
■ 

color and gum U : " the 

ition. 
Iii Plate I. for example, in d 
not only shown 
which come into n 

• 

and iii. 

tanly. ' 

urti-t will al 



188 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



shoulder girdle by John Flaxman to an anatomist recently, 
and he remarked "I never quite saw the clavicles before." 
It was all the point of view. 

Plate XV, showing the femoral and its branches with the 
nerves on the anterior face of the thigh, is quite the perfection 
of anatomical drawing — certainly for showing the course 
of an artery and its deep branches — with the rest of the limb 
in outline, drawn with faint precision, without one unnec- 
essary line. With consummate skill he shows us the relation- 
ship between the anterior crural nerve and the branches of the 
femoral, and the obturator nerve picked up by a tenaculum. 
When Sir Charles dissected this thigh, he not only made a 
skillful dissection, but he saw the true significance of the 
parts and gave them an artistic expression. This was his 
genius. To him the dead body was always alive and the 
impulse to draw it, whole or dissected, was as strong as the 
impulse to " frisk it " when he heard lively music. The 
drawing pencil was constantly in his hand and his drawings 
are legion ; and I doubt not many a fine one worthy of repro- 
duction lies hidden away somewhere in this great little island. 

This work, begun in 1799, was completed in 1803, and at 
the same time he was making dissections and drawings for 
his three works on the anatomy of the brain, of the nerves, 
and of the arteries — work done well before he was thirty. Of 
his work on the arteries I have already spoken; of the plates 
on the nerves, we have good evidence of his skillful dissection 
and faithful copying from his subject, for he has drawn the 
courses of the nerves in delicate lines to their finer ramifica- 
tions, with the flaccid and widely separated muscles conse- 
quent on nerve dissection. 

With the modern anatomies before me, and the great ad- 
vancement in the minute anatomy of the brain, I must 
confess to the charm and fascination of his plates. Though 
more than a century has passed, their delicate coloring still 
holds. But more than that, you see his comprehensive grasp 
of structure and how skillfully he brought it out. He repro- 
duces but one plate from an outside source, one of the base 
of the brain, with the twelve cerebral nerves, from Vic d' Azyr, 
a bit of anatomy he was afterwards to work out so carefully 
and to draw for us in his own inimitable way. 

And this prompts the observation how wholly his own his 
illustrations are, and entirely uninfluenced by outside sources. 
If he copies an old plate it is for its historical value. His 
treatment, his point of view, is his own always ; and like his 
brother John, he never published a work which was not all 
himself. 

When Sir Charles went to London in 1804, he carried with 
him the manuscript of his " Essays on the Anatomy of Ex- 
pression," the illustrations for which were to show his ability 
to give expression to the emotions in portraiture. In the first 
edition, we find a number of little sketches, showing great 
facility in drawing as well as a keen sense of the delicate 
shades of facial expression ; but quite aside from the merits 
of the illustrations, both the drawings and the text bring us 
face to face with the man. However excellent anatomical 
drawings may be, and individual too, in a way, they i annot 



reflect the personality of the artist like a work dealing with 
the emotions and passions described as well as drawn. This 
work Sir Charles labored many years to perfect in the succeed- 
ing editions; he eliminated much that appeared in the first 
edition of 1806, and added more, and labored long to make his 
drawings what he wished them to be; and in doing all this, 
he laid bare his own nature with an unconscious abandon. 
In no other of his works, with the exception of his published 
letters, do we have revealed to us the man himself — his 
enthusiasm, his deep insight into structure and function, his 
general artistic sense and love of the beautiful, his sensibility 
to the moral and religious in life and art, and finally, a deli- 
cate and refined sentiment which pervades all his writings 
and all his drawings which can give an expression of this 
feeling. Mere intellectual brightness and smartness seem 
common enough, but real sentiment, in its best sense, is much 
less common. It draws a halo around the seeming common- 
place ; it gives an added push to enthusiasm ; it gives a charm 
even to the drawings of the dissected body. With all our hard 
facts, let us cultivate sentiment and let us rejoice when we 
find it in a man of science. Only an artist of a fine and deli- 
cate sentiment would have drawn for us the face of the 
laughing child which closes the introduction to this work. 
After Sir Charles went to London, though he carried on 
with equal assiduity his anatomical researches and his lec- 
tures on anatomy, his published drawings were chiefly to illus- 
trate pathology and surgery and the incidents of the clinic. 
Many figure drawings of patients in the hospital are full of 
expression and sentiment, and you feel at once they are true 
to the life, and veritable portraits. He made many of these 
sketches at Portsmouth, after the battle of Corunna, and in 
Brussels, after the battle of Waterloo, and Baron Larrey, years 
later, recognized many of them on a visit to London. He con- 
ceived the idea of elaborate paintings and portraits, showing 
the patient and the disease. This seems to me a great idea. 
We may well take it up, for I see ahead the time when the ad- 
vanced stages of malignant disease will be a rarity indeed, 
will pass away, in fact, and the medical historian will have 
to search past records to find the clinical features of inoper- 
able cancer. They will be prized like the portraits of an ex- 
tinct race. Many of his figure drawings, though mere 
outlines, showing malignant tumors, are of greatest value. 
His brother John had this gift of rapid sketching; but he 
was more inclined to complete the picture. One of his 
sketches, however, seems to me to surpass anything of Sir 
Charles's as evidence of deep feeling. It is his sketch of the 
case of Alexander Macdonald, evidently sarcoma of the arm.* 
Quite aside from its scientific value, he has made its pathos 
beautiful, a classic face of long suffering, and the disheveled 
hair almost like a wreath of laurel for the heroic fight of a 
brave spirit with death. The young man was dying when he 
made this sketch. He has brought a malignant tumor within 
the confines of Art, and no amount of mere skill in drawing 
can do this alone. 



*The Principles of Surgery, by John Bell. London, 1S0S. Vol. 3, 
p. 82. 



THE JOHMS HOPKINS HOSPITAL BULLETIN. JUNE, 1914. 






THE JOHNS HOPKINS HCSFITAL BULLETIN, JUNE, 1914 



PLATE VII 





tqp r 



3 







\ > 






« 










' Pi \n: VI. 



.h KB, 1 IM l.| 



JOHNS HOPKINS OSPITAL VI I.I.KTI N. 






I cannot emphasize t"" strongly the value of th< -• clinical 
Entering the hospital one morning he 
of dislocation <>f the head of the femur and i 
fracture of its aeck; ami he draws for us mosl 
fully the clinical features; shortening, rigidity, and u 

of the foot in tli le; evereion, shortening, and preternatural 

•■- in tlic other; we have nothing In modern llu 
quite so good. 

He conceived the idea of elaborate and artisti 

ations, and carried it out beautifully, drawing ins t ru- 
in situ and the operative hand at work, or ind 
the objective point of the operation. In his " Sui 
cially, are many of these little sketches in outline, always 
with an expressive hand holding an instrument, and showing 
lance what it would take a page to describe. 
Though sir Charles did so much for artistic delineal 
anatomy and medicine, and wrote so much on the value of 
anatomy to the art i~t. it i- only in passing reference and hints 
in his letters that he has anything to Bay of the applicatioi 

of Art to anatomy and medicine, to us at least, a : 

important subject. He did think anatomy of great use to 
the artist, both in painting and Btatuary, and he ha 
u- strong reasons for his belief. In this he went furth 

lu- brother John, who. while admitting it- value, 3ideml 

it rather limited and sharply defined; mile-- controlled l>> 
genius, the anatomy wa- apt I a pail 

in the conception and execution. Bui a greal book is 
written on the value of Art to anatomy and medicine. Choulanl 
* * * in his admirable work on the hist 

■ion down to L850, has done much in an histoi 
bibliographical wax to -how the advances from i 

fr ature; hut the real 

lion of the principle- of Art to anatomy, and nil it will mean 

in the future development of that 

pounder. Certainly if we are to attract artists I 

anatom) itself should he treati 
standpoint. We must 'nrniLr Art to anatom} befi 
it to the artist; the;, can be made re< iprocal. Bui 
influen applied to anatomy will 

\ stud 
form or structure without its life is tie i 



lie who :u without the lift 

thing; and the mo the form gi 

life, the re truh an 

The time ini,-i i ome when t! n ill offer not 

only the dead bod) for diswi tion, hut will help show h 
way. the life of it- part-. the mils, le- of an arm. 

the student will have by him the well developed arm of the 
athlete to -how the muscles alive.* 

Sir t h irli - 

delineati ale. hut only partially attempted to 

carry it out. 1 1 we , an gel an \ • for as the 

Holy ( !ra I. lei us ha re i |ual] I for u- 

the dissected body, that v. 1 1 would 

real stimulus to anatomical study. Onl) then will our 
anatomy become truly significant; onlj then -hall w. 
real artistic anatomy; and then wl 
will becomi and even beautiful. 

The genius of Sir Charles Bell was toward- this 

mi the function hack of the form, and with 
a Confident and ready hand to draw for US what he -aw. He 

bad thi Hon. of relationship, of relative 

values, of the point of \ ien ; and with it all that deli< at 
beautiful sentiment which colored his life as well a- l 
It was indeed Goethe's mildc Macht and the > 

Light of Matthew Arnold. 

A. John Bell's sketch oi | Uexander Macdonali 

ing the artistic drawing of a malignant tumor, evidi 

Plate 4. I >raw Ini ■ Ing the 

external carotid and its branch) b work. 

In the etching we m ireful working up of detail 

t» tter drawing of the arterj . Reduced about one third. 

I'l.x ii .". I 'raw Ing and .tcliin; 

The draw Ing 

a different sketch. Redut 

Plate 6 I 'raw ing and 
ti-riial carotid, and VI rtt ln.il ai I 

show many different es; thi dra 
duced about one third. 



bichte and Bibliographic der anatt i 
nach Hirer Bezlehui nachaft und 

Knnst, von t>r Ludwig Choulant Leipzig, : 



•Sir Charles had ' 
his let i m by i >r \\ \v K< • ii iii ti ■ 

of the 7th in' 

r ii work w I 

which tn 



JOHNS IIOI'KI >SPITAL BULLETIN. 

The Hospital Bulletin i I tails of hospi isary pi 

of thi M - . of the Hospital, 

of the Hospital. It i . . 

(For 

A complete index to Vol. I-XVI of thi 



190 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



NOTES ON NEW BOOKS. 



Social Work in Hospitals: A Contribution to Progressive Medicine. 
By Ida M. Cannon, R. N. $1.50. (Survey Associates, Inc., 
Publishers for the Russel Sage Foundation.) 

There is no one so well qualified as Miss Cannon to interpret the 
uses of hospital social service, not only by reason of the study she 
has made of the subject, but because she has put so much of her- 
self into the movement and has been so live an influence in its 
development. 

Miss Cannon's is the first text-book on social work in hospitals 
that lias been published, and though she feels that notwithstand- 
ing the widespread interest in the movement it is of too recent date 
and the experience gained of too experimental a nature to justify 
the laying down of dogmatic rules, either as to the function of the 
social worker or the proper organization of the work; still she 
points to certain ideals that have developed and fundamental prin- 
ciples that have been evolved. 

She follows the history of hospital social service from the 
beginnings, referring to the social work of the medical students 
at The Johns Hopkins Hospital, under Dr. C. P. Emmerson, as one 
of the four important contributions towards the development of 
the movement, through its various phases and problems to the 
future ideals and possibilities. The book is full of helpful sug- 
gestions, dwelling upon the importance of thorough social train- 
ing and efficiency and pointing out the dangers and pitfalls con- 
sequent upon poor standards. She puts before us, in a convincing 
manner, the interdependence of medical and social diagnosis and 
treatment. 

Miss Cannon's book is a constructive piece of work that should 
be read by those interested in hospital management as well as by 
physicians, nurses and social workers. 

Lectures on Tuberculosis to Nurses. Olliver Bruce, M. R. C. S., 
L. R. C. P. $1. (New York: Paul B. Hoeber, 1913.) 

This book is "based on a course of lectures" delivered to the 
Queen Victoria Jubilee Nurses. The value to nurses of a descrip- 
tion in detail of opsonic index technic, also of methods of 
physical examination of patients is questionable. The opsonic 
index is mentioned too often throughout the work, considering 
the present views of any value it may have in tuberculosis work. 

Such a course of lectures would be of benefit to a junior medical 
student, but can hardly be useful as a standard for nurses. 

Diseases of the Digestive Canal. By Dr. Paul Cohnheim. Edited 
and translated by Dudley Fulton, M. D. Illustrated. Third 
edition. $4. (Philadelphia and London: J. B. Lippincott 
Company, 1914.) 

■That the profession have recognized the value of Cohnheim's 
work is indicated by the fact that the publishers have brought out 
a new edition, which varies but slightly from its predecessor. It 
is a well written, helpful book for students and general practi- 
tioners. 

The American Illustrated Medical Dictionary. By W. A. Newman 
Dorland, M. D. Seventh edition. Revised and enlarged. 
$4.50. (Philadelphia and London: W. B. Saunders Company, 
1918.) 

The author has added five thousand terms to his previous 
edition, and his work continues to grow in value, and with each 
new issue its popularity will become greater. With the active 
growth in medical and allied sciences such a dictionary becomes 
absolutely essential to all students, and Dr. Dorland's can be 
recommended most heartily. 



The Surgical Clinics of John B. Murphy, M.D. (December, 1913.) 
Published Bi-Monthly. (Philadelphia and London: W. B. 

Saunders Company. ) 

The majority of the papers in this number deal with bone 
lesions, and are well illustrated by X-ray photographs. Those 
anxious to learn how Dr. Murphy conducts a students' clinic will 
secure a good impression of his manner and style by reading the 
concluding paper in this issue of the " Clinics." 

Oxford Medical Publications: Manual of Surgery. By Alexis 
Thomson and Alexander Miles. Vol. III. Operative Surgery. 
Second edition. Illustrated. $3.50. (London: Henry Frowde 
and Hoddcr & Stoughton, 1913.) 

This Edinburgh surgery is one that must appeal to many 
students and operators. The text is concise, simple, and practical, 
and the illustrations clear and well chosen. The authors are 
acquainted fully with the work done in foreign clinics, and their 
manual is, to put it simply, excellent. 

A Text-Book of Physiology for Medical Students and Physicians. 
By William H. Howell, M. D., etc. Fifth edition. Thor- 
oughly revised. $4. (Philadelphia and London: W. B. 
Saunders Company. 1918.) 

No fresh word of commendation is needed for this famous 
classic. To every real student a new edition of this book is a true 
pleasure; and it is a source of infinite satisfaction to him to have 
Dr. Howell's views on the latest work along physiological lines. 

Practitioners' Visiting List. $1.25. (Philadelphia and New York: 
Lea & Febiger, 191 ' h ) 

The publishers have issued an attractive book, well suited to 
the needs of many practitioners. It is furnished with a large 
variety of tables to which reference is frequently useful. The 
"List" is practically arranged, convenient, and neat in appear- 
ance. 

Progressive Medicine. Edited by Hobart Amory Hare, M. D. 
Assisted by Leigiiton F. Appleman, M. D. Vol. IV. Decem- 
ber, 1913. 

This volume contains reviews of diseases and surgical conditions 
of many of the abdominal organs, and of the surgery of the ex- 
tremities and tumors, and of such problems as anaesthesia, shock 
and infections. The need of "Progressive Medicine" is distinct, 
and the publication is prepared with ability and thoroughness, so 
that it is of real value to the majority of the medical profession. 

Pyorrhea Alveolaris. By Friedrich Hecker, M.D. .$2. (St. 
Louis: C. V. Mosby Company, 1918.) 

The author is a dentist as well as a physician, so that he has 
had ample opportunity to become acquainted with this disease, 
but it is to be feared that he is on the wrong track in attempting 
to distinguish eleven different varieties of this affection. Further 
study will probably show that this classification can be much 
simplified when the causative organism is finally distinguished. 
The pathological illustrations are marred by the lettering, and 
the book adds nothing to what is already known about this disease. 

Chloride of Lime in Sanitation. By Albert H. Hooker. ( New 
York: John Wiley <& Sons, 1913.) 

This little book of some 200 pages contains an excellent his- 
torical account of the development of our knowledge of the 
chemistry of the chloride of lime of which calcium hypochlorite, 






JlNE, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



191 



CaOCl , is the active disinfecting agent, together with I 
directions for its practical use. The extent to which this disin- 
fectant is being employed is well illustrated by the rather volumi- 
nous literature cited. It should prove of great value to pi 
sanitarians. 

ind Cure* of Crime. By Thomas Speed "Mossy. [81 
O. V. Mosby Company, 1 
Mr. Mosby is a lawyer anil a former pardon attorney of t 
of Missouri. He has seen many criminals, ami read widely, 
judging from numerous extracts in this volume, on penology, bin 
he has compiled a work <|iiiti- elementary in character and one 
which offers no new suggestions to the real stud' nt of this subject 
The photographs of criminals inserted here and there III 
ume are not helpful to the reader, for there is no reference to them 
in the text. 

London Medical Publication*: The Principles and Pro 

Medical Hydrology. By H. FoBTKSCus Pox, Ml' (London). 
[London: Untventty of London Press > 
Medical hydrology or hydrotherapy is a subject not so well 
understood, either by doctors or nur^. s, as il should be, and here 
is a book on this method of treatment which is distinctly helpful 
It is not a profound treatise on hydrotherapy, but a clearly written 
guide book covering the essentials in a simple and satisfactory 
manner. It is divided into four parts: 1, The Physiology of Bath- 
ing; 2, Hydrotherapy; ::. Medicinal Springs and Baths; and 4, 
Indications for Hydrologies! Treatment 

■ uses of Children. By Hkvby Eros n nv. M D 
revised edition. (St Louit: 0. V. Mosby Company, 1913.) 
This book now appears in its second edition and ci 
pages. Many chapters have been rewritten, and a few Illustrations 
have been added. In the appendix, the Standards and Methods for 
the production of Certified Milk as adopted by The American 
Association of Medical Milk Commissions are given. These 
standards are chiefly of interest to the producer of milk and 
from the point of view of the reviewer add but little to i 
of the book for students and practitioners. The present da] 
tendency is toward simpler methods in the feeding of infants. The 
complicated formulte for the modification of milk found in tie' 
appendix are not only of questionable value but are confusing to 
one desirous of obtaining practical information along this line. 
Tlu'ir use should not !»• advis.-d. The text is written with a dis- 
regard for the proper English construction of the sent 
many instances authenticity for the statement of facts is lacking 
By way of illustration, on page 276, the author says, "In 

- does a complete climatic change ha 
action as in children convalescing from enterocolitis Fro? 

soutli of Mason and DlXOn'S Line, no Other I I 

flclal than removal to points In Michigan. The large amount of 

water through Hii- - 1 : . r • Imparts a lite giving something ' 

which works wonders in these eases." Many of t! 

are poor and unnecessary Some of them (pages 101, 

may be of lnt< agriculturalist and to t!.- pi 

milk, but scarcely to students ot medicine The I K m\ 

tended for the stud, ni and the general practitioner dot 
its purpose satisfactorily. 

Treatmi nt of 1 r, M. D. Tr 

by L 

pony, 1919.') 

This work of 600 pages Is the first English edition tr 
from the French by Dr. Leon Blanc 

The author deals with the subject from two main 
the soil and the germ, and emphasises greatl] 



soil. His contention .ill in all in tuben i 

Is made unneoessarU] emi r ..i is a 

<nized by the pro; 

It i s dail ' reliance should bo placed on drug 

medication in I 
generally held, and the author Calls to prove his claim. 

Tuberculin is gis> 
greater the gravity of tub. ren. 

initial dose," is mystifying, and even if true would requll 
explanation of proof. 

Altogether the book is only fair. It is written f 
practitioner and some of the matter could !'•• taken out without 
lessening the value of tin- work. 

The translation is very good the English b 
readable. 

International Clinic*. Vol. iv jl'. [Philadelphia 

and London: J. II. Lippincott Company, 191 

Medicine, surgery and neurology are well In the 

"Clinics." Some of these are too long, but thi rarthin, 

Sewall, and Proescher are among the best In the volume. B 
the more modern views in neurology an- presented In on.- or two 
papers, and • ugi ni< - Is abused by having two articles attributed 
to it, which would be bett< r classified under • sdlng 

The term eugenics is generally misunderstood and misapplied by 
American writers. 

Cunningham's Text-Book of Ami/mm/. Edited by Abthui Roam- 
Bon, M. i>., F. R. c. S., Ed. Fourth edition. Enlarged ami re 
written. Illustrated. 16.60 

Co., mis.) 

From the title one would naturally Infer that this work was 
like Gray's, that is, the writing of one anaton ntrary, 

it is the reverse, there being (or I ntrlbu 

tors, all Englishmen, and there is. what i 

chapter by Cunningham. Hut i inator of this 

compilation it still partly bears hi- > 

chief competitors in the medical 0OC? in 

■ ■■ anatomj b i 
in English as the work of a single author. Cunningham 
Book in its n< undoubtedly a book that will appeal t" 

itudenb toi It I rerj liberally 111 

clature, hs an admirable Index, irefullj 

dern 

By John II Mt bskb, m l> . 
It. vi-. d bj Joan H Mi - i a, Js . U 1' lllu ill I 
d< iphla 

Bo many addition ol varii i 
methods of n 
edition of Mn 
work sri 

This ha 
largely hi- I I 

hlch all wl 

I ftfOMMl! Of 

Con 

i B 

I 
rially t 
merit i> 



192 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 280 



Aside from this the reader will gain little, as the methods of 
interpretation and diagnosis are too brief and hardly abreast of 
the times. Roentgentherapy is not discussed. 

Disease and Its Causes. By W. T. Councilman, A. M., M. D., LL. D. 
(New York: Henry Holt & Co., litis.) 

This little volume published in a series known as the Home 
University Library of Modern Knowledge, should serve the useful 
purpose of giving the laity reliable information concerning the 
topic with which it deals. In about 250 pages Dr. Councilman 
defines disease and describes its extrinsic and intrinsic causes. A 
large portion of the book is devoted to a discussion of the infec- 
tious diseases, though other organic diseases, especially diseases 
of the heart, are briefly dealt with. The subject of insanity is also 
discussed and the relations of degeneracy and criminality to states 
of the nervous system touched upon. In the last chapter of the 
book the relation of modern conditions of life to the extension of 
disease is taken up. 

We do not know of any other small volume in which the layman 
can find such a mass of information so clearly and attractively 
presented concerning the matters with which modern medicine 
has to deal. 

Oxford Medical Manuals: The Elements of Bandaging, Fractures 
and Dislocations. By William Rankin, M. B. $1.50. (Lon- 
don: Henry Frowde and Hodder <£ Stoughton, 1913.) 

It is a small volume of 115 pages, with numerous illustrations 
and large type, so that the volume could be read easily in an hour. 
The three subjects discussed cannot be satisfactorily covered in 
such small compass, and it is to be regretted if the information 
contained is sufficient to prepare men " for the practical portion 
of their final examination." 

Oxford Medical Publications: The Practitioner's Practical Pre- 
server. By D. M. Macdonald, M. D. $1.50. 

Practical Presenting with Clinical Notes. By Arthur H. Prjchard, 
M. R. C. S., etc. $2. (London: Henry Frowde and Hodder & 
Stoughton, WIS.) 

The first of these works is nothing more than a small pocket for- 
mulary to which is appended a table of dosage, brief directions 
for common emergencies, a pregnancy table, etc. The work is 
similar to many others, and will be useful to those who like this 
class of work. 

Prichard's book is novel in its mode of presentation. He sup- 
plies a number of prescriptions, explains them by " giving, by way 
of explanatory notes, reasons for employing the various con- 
stituents, their particular actions, and any special points concern- 



ing them to illustrate the effects of the various drugs in 

combination a number of illustrative cases have been epitomized. 
The results of treatment in these are indicated in short notes, 
while the main features of each case are briefly summed up by 
way of comment." The author arranges his remarks and clinical 
notes in parallel columns, and in this small volume he can only 
cover a limited field, but the method is one with distinct advan- 
tages, as it makes more vivid than usual the effect of drugs on 
patients. Though it is more adapted to the bedside than to book 
form, yet a good student will gain much from a careful reading 
of " Practical Presenting." 

A Text-Book of Histology. By Dr. Frederic T. Lewis and Dr. 
Phillpi> Stohk. Second edition. Illustrated. $3. (Philadel- 
phia: P. Blakiston's Son <£• Co., 1914.) 

A Text-Book of Histology. By Frederick R. Bailey, M. D. Fourth 
revised edition. Illustrated. $3.50. (New York: William 
Wood <t Co., 1013.) 

Stohr's famous and most widely read work appears completely 
revised and much rewritten by Lewis, and it remains to be seen 
whether in its new form it will be as popular in the future as in 
the past. It is arranged upon an embryological basis, and as em- 
bryology now plays a much more important role in the medical 
curriculum than a few years ago, Lewis' book will be helpful for 
the student in association with his general anatomy. 

The other histology, by Bailey, familiar to and liked by many 
students, will appeal readily to many more just beginning their 
study of medicine to whom it is well adapted by its clear style 
and simplicity. 

The Practice of Medicine. By James Tyson, M. D., etc., and M. 
Howard Fussell, M. D. Sixth edition. Revised and re- 
written. Illustrated. (Philadelphia: P. Blackiston's Son <k 
Co., 1914.) 
The new edition has been abridged in parts and enlarged in 
others, causing imperfections as well as perfections. It is a pity 
that all the historical part of the subject had to be omitted, and 
also that the section on parasites, which are becoming more and 
more important in the study of medicine, had to be shortened. 
The work is more complete in having fuller accounts of some old 
diseases, and by the introduction of some diseases which are rare 
and not always included in all text-books of medicine. Otherwise 
this standard work remains unaltered, and noteworthy as the 
production of one of Philadelphia's eminent practitioners. The 
index is unfortunately incomplete; there is no reference, at least 
we could not find it, to phenosulphonephthalein, and yet this is 
mentioned as one of the important new subjects in the preface. 



BOOKS RECEIVED. 



Radium. As Employed in the Treatment of Cancer, Angiomata, 
Keloids, Local Tuberculosis and Other Affections. By Louis 
Wickham, M. V. O., and Paul Degrais. Translated by A. and 
A. G. Bateman, M. B., C. M. With fifty-three illustrations. 
1913. 12°. Ill pages. Paul B. Hoeber, New York. 

Modern Problems of Biology. Lectures delivered at the Uni- 
versity of Jena, December, 1912. By Charles Sedgwick Minot. 
With fifty-three illustrations. 1913. 8". 124 pages. P. Blak- 
iston's Son & Co., Philadelphia. 

Caticer of the Breast. An Experience of a Series of Operations 
and Their Results. By Charles Barrett Lockwood, F. R. C. S. 
(Eng. ). 1913. Svo. 234 pages. Henry Frowde, London; 
Hodder & Stoughton, London. 



Treatment of Tuberculosis. Ordinary Therapeutics of Medical 
Men. By Albert Robin. Translated by Dr. Leon Blanc, with 
the assistance of H. de Meric. 1913. Svo. GIG pages. The 
Macmillan Company, New York. 

.1 Manual of Surgical Treatment. By Sir W. Watson Cheyne, 
Bart, C. B., D. Sc, LL. D., F. R. C. S., F. R. S., and F. F. Burg- 
hard, M.S. (Lond.), F. R. C. S. New edition, entirely revised 
and largely rewritten with the assistance of T. P. Legg, 
M. S. (Lond.), F. R. C. S., and Arthur Edmunds, M. S. (Lond.), 
F. R. C. S. Volume V. The Treatment of the surgical Affec- 
tions of the Pancreas, Liver and Spleen, the Neck, the Breast 
and Thorax, anil the Qcnito-l'i inary Organs. 1913. Svo. 619 
pages. Lea & Febiger, Philadelphia and New York. 



L914.] 



JOHNS HOPKINS HOSPITAL Bl I I.KilV 






ition. By Jacqui 
Originally translated from the Qerman t>y \v. 0. R 
King. U. A. Supplemented and revised by the author 
The University of Chicago Pn 

7 h- /•/• ■ miration of 

I! Hurry, m \ .. m i>. WIS. 8°. 51 pages. J. * A. Churchill, 

London. 

in.-. Its Theory and Practice. In Original Contribu- 
tions by American and Foreign Authors. Edited 
William Osier, Bart, II D., F. R a, and Thomas McCrae, M. D. 
Volume i Second edition, thoroughly revised, tllu I 
l,ea & Feblger, Philadelphia and 
York. 

y Sir Almroth 
H Wright, M H. F. U.S. [1913.] .ail 1! 

Hoeber, New York. 

.1 Manu'il 0/ I!y \rthur C. Chri>ti.'. Willi 1: 

illustration.-, [1913.] s. 104 pages J. B Lippincott Com 
pany, Philadelphia and London. 

of Volumes for tin' Promotion of 

h and Educational rr.-ur. u Edited by J 
IfcKeen CattelL Volume II. Medical Research •/»•; • 
Uon. By Richard M. Pearce land S 

pages. Tin- Science Press, New York ami c.irrlson. 

! i. Being the 
Treatment by Waters an. I Baths By K. 1"' 
Fox, M i>. I Land I F. R Mel Boa 
rsity of London Press, London. 

• i Publications. Henry Frowde, London; Hi 
ighton, London. 

lonald, M. l> 

It of Bandaging and the 1 

William Rankin, M. \ 
B With sixty-eight original illustr.,t 

ir H. 
M R.C.a, I. i; C. I'. K N 'KM 

I. 1 nts mi'/ Tn* 

• i m i.amioit i Par ranslai 

M. i: Brewerton, F u C 8 191 

. 
Kim.-ii.-. m pages. Oxf ot 

I merit an Branch, New York 

Idles Volume third. 

With 265 illuMr • 

T'nL- • • i ork 

7. /' 

m 1 1 . r K a P., B B . r R I - 

I M S 

Mainly a Clinical Study of the Nature and 
Produced by Bullets of Small Calibn 
kins. C. B., F. K. a s. Second -dm. 

Progn*- Quarterly I 

coverles and Improvements In tin- Medical .. 

cea Edited by Mobart Amory Hare, M D 
Leighton F. Appleman, M. I'. Volume 1 \ 
111 pai ' • I 



■ 
tlon 

Pyorrh. 

Ml> IllUSl 

puny. St I 

1913. 13 

M. D. Illn 

pany, Neu York 

Spitzy Mit I'M Textabblld 

Urban a.- Schwarsenberg, Berlin and ■• 

by David orr. M. D., and K Q Ron -. M D 

by Sir T S ClOUSt Ml'. LI. I' 

Annual Ml 

Vol VI! 
Brooklin.-. 

ffaitdb* 

Vi. rt. r Bai ■■ 

ungen 19 

in Dr. Willi. : 
Textabbildui | 

1!. rlln. 

Von Dr. Julius Tandler and Dr. Siegfried i 
T. itngun 

York \\ 111 

c, R. N. Pre| 

di Iphla. 
Dititt ii). In 

rlln. 

Handb 
andi 
Paul 
Prof. It Friedri 

Rflmmel Dritl 
Kflmmel Ml) i 

and r : 
W. Catl 

dolphin Bl 



194 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[ No. U 



Meningococcus Meningitis. By Henry Heiman, M. D., and Samuel 
Feldstein, M. D. With Introduction by Henry Koplik, M. D. 
1913. 8°. 313 pages. J. B. Lippincott Company. 

Cunningham's Text-Booh of Anatomy. Edited by Arthur Robin- 
son, M. D., F. R. C. S. Fourth edition, enlarged and rewritten. 
Illustrated by 1124 figures from original drawings, 637 of 
which are printed in colors, and two plates. 1913. 8°. 1596 
pages. William Wood and Company, New York. 

In Memory of Dr. James Livingstone Thompson 1882-1913 and His 
Son, Dr. Daniel A. Thompson 1862-1904. By The Indianapolis 
Literary Club, The Indianapolis Medical Society, The Loyal 
Legion of Indiana, The Medical College of Indiana, The 
Family of Dr. Thompson, and Other Friends and Lovers of 
Many Years. 1913. 12°. 98 pages. Indianapolis, Ind. 

A Text-Book of Histology. By Frederick R. Bailey, A. M., M. D. 
Fourth revised edition, profusely illustrated. 1913. Svo. 
644 pages. William Wood and Company, New York. 

Cancer, Its Cause and Treatment without Operation. By Robert 
Bell, M. D., F. R. F. P. S., etc. Second edition, revised. 1913. 
12°. 324 pages. G. Bell and Sons, Ltd., London. The Mac- 
Millan Company, New York. 

Surgery of the Upper Abdomen. In two volumes. By John B. 
Deaver, M. D., Sc. D., LL. D., and Astley Paston Cooper Ash- 
hurst, A. B., M. D. Volume II. Surgery of the Gall-Bladder, 
Liver, Pancreas and Spleen. With 52 illustrations. 1914. 8°. 
499 pages. P. Blakiston's Son & Co., Philadelphia. 

A Text-Book of Histology. Arranged upon an Embryological 
Basis. By Frederic T. Lewis and Dr. Philipp Stbhr. Second 
edition, with 495 illustrations. Being the seventh American 
edition of Stbhr's Histology. From the fifteenth German 
edition, edited by Dr. 0. Schultze. 1914. 8°. 539 pages. P. 
Blakiston's Son & Co., Philadelphia. 

The Practice of Medicine. A Text-Book for Practitioners and 
Students with Special Reference to Diagnosis and Treatment. 
By James Tyson, M. D., LL. D., and M. Howard Fussell, M. D. 
Sixth edition, revised and rewritten. With six plates and 179 
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Scientific Memoirs. {Neiv Series.) No. GO. By Officers of the 
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CONT ENTS. 

PAOI 

The Involution of the I t.-m~ and it^ Bffeol 1 pon the Nitrogen ["be Normal I >;:i-.t i-. I ontenl ol the i 

Output of the Urine. (Illustrated.) By Im..m\- R. Bbown, \l l> and C. Whai 

l'.\ J, MtiKiti- Siniu\s ^\imi. .lit 

■ rmal Amount ol Diastatic Ferment in the Feces and its Notes on New Books . .... 

Variation in (Yrtain Diseases ol the Pancreas and in Books B ived 

tahyl Th>- Quarter Centennial Anniversarj 

:.n>\i\» K. Bbowx, m. 1) Johns Hopkins Boepital and the [Vent) tir-t innivi 

ripheral Origin of Surgical S erf the Opening of The Medical 8c I 

By Fbaxk i. Man 5, M. D The Herter Lectures for IBM 



THE INVOLUTION OF THE UTE 
NITROGEN OUT 

|; ; , .i. Moi 

I had the opportunity to study thi 
enous metabolism "f pregnanl women who had been placed 
mtaining aboul the same amount ol 
ilorinc value as i 
a, .man would select. Similar observations were made 
labor and continued for three weeks in the puerp 
curve of the urine, thus obfc 
main features. During the latter pai 
lower tluiii in non-pregnanl women; al tl 
it fell even 

■ perium it rose t" »uch 
than that generall; 

for abouM • 

■- were published theii ■ 
could be onlj a matl ; retention ol 

I, must be in the inti 
• 
promoti : of the uterus, the p 

.m. I other organs which function mi 
The nutritional rei 
inntrri 

rable; and Landsberg estimau 
of nitn 

than i- necessary ftw fetal growth alone. 'I 
retention of nitrogen during pn j 



IMS AND ITS EFFECT UPON THE 
LIT OF THE URINE. 

KONS, 

/ ' 

all who have iuvestigati il the subjei I 

- :.-.-. II . I: , M Baili jr. H 

an. I Si-it/. Inn as 
which such a retention 
The low ui 

unexplai I. It ma) n 

circulation, for whi< h I 

unknown mi 

the uterus t nl 

bination ol tin -■ 

The 
which i- regulai 

that tl 
elimin I 
While 

througl 



196 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 281 



though the woman does not suckle her baby. Furthermore, 
when lactation continues undisturbed, the nitrogen output 
diminishes about the end of the second week after labor. Like- 
wise, the suggestion which holds that too sparse a diet is re- 
sponsible for the phenomenon is equally untenable, as puer- 
peral women who receive an amount of nourishment quite 
sufficient for their weight still excrete an unusually large 
quantity of nitrogen during the first two weeks of the lying-in 
period. 

The correct explanation is very simple. Purely upon clini- 
cal grounds it would seem probable that the phenomenon is 
associated with the involution of the uterus — a proi 
which the organ is reduced within a few weeks from the size 
of a newborn baby's head to that of its fist, while its weight 
becomes diminished from 1000 to 50 or 60 grammes. The pro- 
cess is now regarded as due to autolysis which breaks the 
muscle-protein down into simpler substances. These pass 
into the circulation, are eliminated through the kidneys, and 
thus increase the amount of nitrogen in the urine. 

Fortunately, this hypothesis can be tested experimentally. 
and requires two series of observations. In the first we 
ascertain whether the increased nitrogenous output observed 
after normal labor is in any way affected by the performance of 
Cesarean section ; while in the second we determine whether 
it is influenced by the removal of the uterus at the time 
Csesarean section is performed. If there is a marked decrease 
in the amount of nitrogen excreted after the removal of the 
uterus, it would appear justifiable to attribute it to the artifi- 
cial interference with involution. The opportunity to investi- 
gate this problem was given me by Doctor J. Whitridge 
Williams while 1 was a member of the staff of The Johns 
Hopkins Hospital, and the records of two cases in which the 
observations were most complete form the basis of this report. 

Case I. Conservative Cesarean Section. 

A. W., negress, II para, 31 years old, generally contracted rha- 
chitic pelvis, pregnancy normal, expected date of confinement, Feb- 
ruary S. 

Labor began February 12 and lasted 46% hours, when a clas- 
sical Cesarean section was performed. Ether anesthesia lasted 
one hour. The puerperium was normal until the 23d day, when 
a small superficial breast abscess developed, which was promptly 
incised and healed within a week. 

Metabolic observations were begun 32 days before delivery. At 
that time the patient's weight was 119% lbs., and ten days later 
122% lbs. During this period the average daily nitrogenous con- 
tent of the food was 15.6 gm., of the urine 10.23 gni., of the feces 
1.6S gm. The average daily storage of nitrogen was 3.66 gm. 

On the day of delivery the fluid intake was 730 cc. and the urine 
measured 890 cc. The nitrogen of the food was 4.38 gm., of the 
urine 5.04 gm. The patient weighed 110 lbs. at the conclusion of 
the operation. 

Liquid nourishment alone was permitted for three days after 
operation and the diet used during pregnancy was not again em- 
ployed until the end of a week. During the first 20 days of the 
puerperium the average daily nitrogen of the food was 12.88 gin.. 
of the urine 12.15 gm. The additional loss through the milk, lochia, 
and feces resulted in a negative nitrogen balance, so that the av- 
erage daily loss of nitrogen was 3.56 gm. At the end of this period 
the patient weighed 105 lbs. 



From clinical observation of the size of the uterus, as well as 
from the character of the urinary nitrogen curve, it seemed that 
the acute involution of the uterus ended about the 17th day. Ob- 
servations, however, were continued until the 21st day, when the 
patient complained of pain in the breast. The temperature was then 
100.5° F., and two days later rose to 104.5° F. It fell to normal 
shortly after the abscess was opened. Although the urine was col- 
lected and analysed during the existence of this complication, the 
results are not included here, for the high nitrogen values ob- 
tained were due to the fever, and bear no relation to the problem 
under investigation. 

Observations were resumed after the patient had entirely re- 
covered, namely, from the 41st to the 45th day postpartum. The 
diet was then the same as had been employed during pregnancy. 
The urine nitrogen averaged 10.25 gm. per day. During this 
period the patient was practically in nitrogenous equilibrium. She 
weighed 107 lbs. at the beginning and 107% lbs. at the end of this, 
the final series of observations. 

Case II. Cesarean Section with Supravaginal Hystekei huiy. 

S. C, negress, I para, 21 years old, pregnancy normal, expected 
date of confinement, July 29. 

Labor began July 27, and shortly after its onset a Porro Cesa- 
rean section was performed. Ether anaesthesia lasted an hour and 
a quarter. The puerperium was normal, but the patient was un- 
able to nurse the baby satisfactorily on account of an inadequate 
supply of milk. 

Metabolic observations were made uninterruptedly from the 14th 
day before delivery until the 20th day postpartum. Since the de- 
cision to perform Cesarean section had been reached in advance, it 
was possible to do the operation at the close of one of the 24-hour 
periods of observation. On this account the data designated the 
day before delivery actually includes several hours. after labor had 
begun. 

At the beginning of the observations the patient weighed 96 
lbs., and at the onset of labor 99V 2 lbs. Unusually satisfactory data 
were obtained during the 11 days of pregnancy while the patient 
was taking a mixed diet. At the end of that time observations 
were desired relating to a liquid diet such as would probably be 
used for some days after the operation. These were in progress 
when labor started. 

During the last two weeks of pregnancy the average daily nitrog- 
enous content of the food was 15.02 gm., of the urine 8.70 gm., and 
of the feces 1.8 gm. The average daily storage of nitrogen was 
4.52 gm. 

Although the diet for two days following the operation consisted 
of liquids in restricted amounts, the output of nitrogen through 
the urine rose immediately and reached its maximum on the 3d 
day postpartum. An attempt was made to return to the diet which 
had been used during pregnancy, but the patient was unable to 
take so much, and was not able to do so until the end of two weeks. 

During the puerperium the average daily amount of nitrogen in 
the food was 12.50 gm., in the urine 9.10 gm., and in the feces 0.95 
gm. The patient did not suckle her baby and there was no lochia. 
The nitrogen balance was negative four days after operation, but 
subsequently was positive. The average daily retention was 2.45 
gm. nitrogen. The patient weighed 79% lbs. just after the opera- 
tion, and S4% lbs. at the conclusion of the postpartum observa- 
tions. 

The body of the uterus removed at the Cesarean section weighed 
850 gm. A small portion of the fresh tissue was dried to con- 
stant weight and showed that 70 per cent moisture was present. 
Consequently the amount of water-free substance in the entire 
uterus was 255 gm. Analysis by the Kjeldahl method showed that 
the uterus contained 38.75 gm. of nitrogen. 



Jl LY, I'M I. | 



JOHNS BOPKINS HOSPITAL BI 1. 1 I TIN. 






■ place tlnii afti i 
itpul of urinary nitrogen is high. 1 '• i i 

I I rose <'ii the •'!'! day and n i 
ibout two weeks. During this period the involu- 
tion "f the uterus was in progress; it was probably completed 
on the ltih day, certainly not later than the 80th <];i\. The 

- lion for this period was 1.9 grams i 
than during the postpuerperal period. In other words, 

irinary nitrogen excreted during the lir>t 80 days 
< >f t lie puerperium must be accounted fur. and iliis i- also the 
i presented in the case of women who have 1" 
naturally. 
With regard toa few minor points, tin 1 puerperal metabolism 
of this patienl did nut follow tin' rule. Thus, the im n 

tput of nitrogen ; • 1 i;i t later and continued 

in usual, ami also reached a greater maxi 

muni elevation than we are accustoi I t" see in the normal 

puerperium. Suchdeviati cplained by the 

influence of the amrsthetic am! by tlie fad thai the patienl was 



' ■ 










































Chai urine during pregnancy and 

i perium in Caae n In « hli !> i orro < 

.;. before or after delivery, i/m lathi 

aparotomy . The latter influi 
■ other puerperal complii 

, 

In bi ■ml 1 1 the mosl conspii 

following i • 

attributable ti» eondil 

\ 

■ 

in and of ether ana 

ll -tmlu >1 bi ' I 

v. Thus Vidal found 
« iih i hloroform thai the urine contn ined I 
much nitrogen as normal. Similar c 

; . 



marked im n 

immedi 

be obscured in tin 2 I hoi 

anaesthesia lias b» a di si ribed by Kappeler, Leppmann, 
and oil 

dogs by Hawk show that after etlier narcosis the u 
an increase in nitrogen amoui : 
Prom i i r sufficient 

the duration of an i 

nitrogen lost, and l»-ln-\.> that • indi- 

vidual must account for bui h dim 

exceptional on, but 

as a rule » ithin I* hours after ethi 
nitrogen rose and remained high foi 
for a~ long as five or six ■ 

rvations which 1 have made ii|mn gy 
show t ' 
experin 
not invariably, an increase in the urinary i 



vo// 




z , 


\ 


f \ 


o . t A 


TV i 1 


■ 

- 



Ch mm ii i bi total alti 
-. or the uteru 

th<- phenomenon ic 
of the absorption 

than in Ion 

■ I ' 



108 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| No. -.'si 



the influence of the anaesthetic, for the dietary conditions were 
identical before and after operation and there was practically 
mi loss of blood. 

In view of the experimental and clinical evidence here ad- 
duced there can be no douht that the rise in the urinary nitro- 
gen immediately following the Porro Caesarean section is refer- 
able to the influence of anaesthesia. In Case I. as well, there 
was a similar effect, but the presence of the involuting uterus 
makes it impossible to estimate exactly the influence of the 
anaesthetic. Certain other facts, however, are of interest. 
Thus, the effect of anaesthesia became evident more promptly 
in the case from which the uterus had been removed. On the 
other hand, both the maximum daily excretion and the average 
excretion were greater in the case of conservative section, which 
must have been due to the fact that the uterus was in process 
of involution. 

In further comparing our cases, however, the effect of anaes- 
thesia may be disregarded, since both were subject to its influ- 



JO 

11 
n 
n 
/t 


■ • « '■ 


■■-.—,-: ■:■ . - ; '- ;— i Chart No m 


! :.•": !/ \ 


i i ' : ! 1 ! i j i '■ ' ': i ; i : '. •■ 


i" ' '/ i\ 


. {j;! - 


1 ! ! j ! 1 ! i i i 


'■°\ '•/ |\ 


Mill!! 


1 


i ! ! i i i i i i i 




J ' ' -1 ' ' 


1 i 1 i U| ! 


:* 


1 i 1 ! i ! !• 1 j 1 




i | ; A i 


\! ' ■ /V ■ 


/ \ 1 ! j» \ 


n 




|Vr"S»-Ki \ L 


t\ ^Ti \T%A '■■ 




ijj'll i :V 


i i \ / i 


10 

1 

>' 
7 


■«:/:: 


! Vi ' i-s___^ 


-' : J ■ !\i i i i«I : 


■' i / 1 i«j i \ J • 1 ": 1 "P ! ! 1" 1 t i 






■'; i /i : ho-f"°i ' ' ■ ' rs;r~"7 • " :™r ?-- 


,i 


•J A i 1 ' 1 


t 


-i i i_ i 1 ' ' ■ : : : ' : ; : 


,i 




1 


: : ! ! 


i 














VI \2 \3\4 \S 


(, 17 ■■$■.1 '/Oi//\/2VS 


M\IS 


/6\'7i/g\/?W #r?l4\>f44S 



Chart III. — Contrasting the total nitrogen of the urine after con- 
servative Cesarean section and after the Porro operation. Solid 
line represents the excretion in Case I, in which the uterus was not 
removed: broken line that of Case II. in which it was removed. 
Figures at the side and bottom have same significance as in other 
charts. 

encc. The period chosen as the basis of comparison, naturally . 
would be determined by the duration of the involution process 
in the case in which the uterus was no! removed, ami in order 
to be sure that the records covered this period, observations 
were continued for the firs! 20 day- of the puerperium. During 
this tune there was a difference of 6] grams between the aggre- 
gate amounts of nitrogen eliminated by the two patients, an 

average daily difference of 3 grams, and it is upon the li c 

figure that stress should chiefly be laid. Furthermore, I feel 
that emphasis should be laid not so much upon the actual 
amount of difference, which might well vary when other indi- 
viduals were subjected to similar observations, but upon the 
fact that a tangible difference existed and that a larger excre- 
tion occurred when the uterus was not removed. 

A significant result of my observations is that the excessive 
excretion in Case 1. amounting to 61 grams, counterbalances 



the nitrogenous content of the uterus of the other patient. 
In fact, it more than does so. for the organ contained only 38.3| 
grains of nitrogen. This disparity of 22 grams, however, is 
within the limit of experimental error, when conditions must 
be met such as are encountered in the study of this problem. 
It is perhaps unnecessary to point out that ideal experiments 
would require that one should have pregnant women of equal 
weight, with similar appetites, with identical powers of recu- 
peration after operation, and with the fortitude to remain on 
the same diet for a period of a month. In such circumstances 
mathematical precision might be hoped for, and probably 
would be more nearly attained ; but such a favorable oppor- 
tunity is not likely to present itself. And the disparity is not 
a large one. for it amounts roundly to 1 gram of nitrogen pel 
day ; or, in other words, to a half gram per day for each patient. 
Furthermore, observations upon other women whose uteri were 
removed at the time of Caesarean section confirm the results 
presented by Case IT. The data given in the following table 
indicate that when the uterus is removed the subsequent ex- 
cretion of urinary nitrogen is regularly less than when the 
uterus is preserved. 

Daily Avebage Nitbouex ok the Ubine 

(1) After Porro Ctrsarean Section: 

S. C. (observed 20 days) 9.10 gm. 

J. J. ( observed 16 days ) 10.92 gm. 

A. J. (observed 10 days) 8.92 gm. 

(2) After Conservative Cwsarean Section: 

A. W. (observed 20 days) 12.15 gm. 

In the normal puerperium the involution of the uterus 
begins immediately after delivery and occupies about six weeks, 
but the acute period is practically completed by the end 
of the second week. The latter estimate would seem correct 
when judged from several points of view. For example, clini- 
cal observation of the decrease in the size of the organ indicates 
that the major part of the process is effected during this period, 
while the mensuration of the individual muscle-fibres by 
Sanger on consecutive days throughout the process justify a 
similar conclusion. Furthermore, metabolic observations upon 
normal puerperal women indicate that the excretion of the 
nitrogenous products of involution is practically completed 
during the first two weeks of the puerperium. Consequently, 
if this be the period of acute involution, and if the amount ot 
nitrogen lost from the body in consequence of the process coi- 
responds to the nitrogenous content of the uterus removed at 
the time of delivery and before the commencement of invohv 
lionarv changes, it must follow that the theoretical loss of 
nitrogen per day should be from 2 to :'> grams. Upon com- 
parison of tins estimate with the average daily difference (3.0a 
grams) actually found to exist in Cases I and II, one must 
conclude that the excessive excretion after the conservative 
Caesarean section is due to the involution of the uterus. To M 
sure, in the case in which the uterus was removed the nitrogen 
output was greater for three days, but this is readily explained 
as a result of the anaesthesia. After this period, however, the 
output was greater in the case in which the uterus was under- 
going involution. 



July, 19] I.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






COMPARISON OF TOTAL NITROGEN OF I KINK AFT] 
SERA \ll\ i: \\l> PORRO I i SARI kN. 





I. 


3. 


i 

1" IS 
11.90 


5. 


6. ; 


1 

i Me II..... 


i 7" 5.49 
10.50 l."..7:i 


10.90 
17.84 


15.19 
9.P0 


13 i- 12 .7 12 79 

: • 


m .■ . . 


- 1-10.24 


+6.74 
11. 


— 7.25L5.29 






,0. 


ij. 


14. 

11.80 11 16 
8.10 0.30 


Cue I 

Cut II 


12.35 12.64 14.26 
7.02 B 64 g 1" 


11.34 12.08 
8. 10 


Differ* 


— 1. 00 




—2.94—3.48 


— :i.T" - 





17. 


- 


ToUl. 

243 "i 
182 03 




Cue 1 

1 Me 1 1 


10.28 

- 31 


12.9] \2.M 13.32 
56 6. 13 


12.15 
9.10 






— :i.;i — .>.7i> — 7. Hi 


—61.01 


— :i.n.-. 



\- esull of my investigations, 11 is apparent that Hie 

• of involution causes ;i rise in the urinary nitrogen 
iinil ilnit the amount 1 of excessive elimination corresponds to 
the nitrogenous content « »f the non-involuted uterus. My 
observations offer confirmatory evidence of t!ii< fad from 
three points of \ i> •%% : First, by the comparison of the puer 
(M-r.il and postpuerperal periods when the uterus has m 
removed; secondly, from the comparison of the :i_- 
ezcretion in cases in which the uterus was removed and in 
which it was not; and, thirdly, from the comparison 
actual daily difference in bu 

amount "f nitrogen which would be expeel suit of 

the involutionary process. We may, there! 

-I tin- involuting uterus pass into th< 
lation, kidneys, and in some mi a£ 

additional work ii|»>n it 1 during the • 

the puerperium. 

It does not follow, however, thai the diel should 
uerium. On 1 1 1 « ■ contrary, oui 
■ 

quire sin h restriction, pro* ided the 
is normal. If any therapeutic inference may be draw 
in the nature of a justification of the presi 
allow .1 generou* tlj delivered womi 

* * 1 1 il ther hand, in patients Buffering from h 1 

icy, the additional work which the kidneyc 
form in the puerperium d a matter of pi 

portancc. In such circun 
tin- fullesl opportunity t<> recover from thi 
they have been subjected, and, with this end in 
should be limited. Such precaution 1- n< 

the renal cells have been damaged, bul 
an excretory capacity somewhat greater than no 
girabii . 



■ iat in the days immed 
the kidneys 

1 1 1 1 > > 1 1 l; 1 1 the 1 onsumptii 
Formerly , tli Inrjri 

attributed to the eliminat ial which hi 

viously been retained, ;m<l « 
toxaemia. Such n \ iew 1- .'\ ident I) 
tions show that the large 1 \< retion 
w <•! I as in normal cases, 1- due to the involution 1 

TABULATION OF DATA 

(' v^i 1 I \ \\ '. I CoNMKRVATIM l'l-nn\ S 

1 Uterua not ren 



Hi; before Klni.1 bj 



1755 
1755 

17.V. 
I7.V. 



000 

1150 



Dailj 





1325 


163(1 




1630 




1440 


1000 


1440 


limn 


1 tin 




llil!' 





urn. 
II »1 

I 

15 00 
17. :m 
15 7" 
15.70 



7 II 
13 10 

I 



' 



1 '•- 

1 68 

1 • a 

1 68 

1 68 

I 68 

I 68 






15 7" 13 60 I 68 



- 











r 1 














mouth. 


























1 






1 7m 








110 


■J 


160 


LOO 












3 


1665 





1 




1 7 






1 

































.. 


1070 


1070 












. 


1850 








1 1 






- 




1100 


1 . 10 










■' 
















In 


J t NU 




1 . 10 










II 






15 Id 




1 1 






12 
















1 : 


1000 




1 . in 










11 






15 1" II H(l 
















1 1 III 










ie 
















17 
















i> 






15 I- 










19 






















15 III 










































11 








































11 

























2(H) 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 281 



[. (S. C.) PORRO CESAREAN Sic DION. 

(Uterus removed.) 

OBSERVATIONS WRING PREGNANCY. 





Fluid by 


CJuanl it\ 


Nitrogen 


Nitrogen 


Nitrogen 


Nitrogen 


Weight 


delivery. 


mouth. 


of urine. 


of food. 


of urine. 


of feces. 


balance. 










„. 


qm. 


n m 




H>*. 


14 


L550 


L150 


15.70 


7.60 


1.8 


+6.30 


90 


13 


1580 


1150 


15 . 70 


S.2S 


1.8 


+ .-..02 




12 


1580 


800 


15.7(1 


8.78 


1.8 


+5.12 




11 


1580 


625 


15.70 


8.31 


1.8 


+5.59 




in 


1580 


700 


15.70 


S.S2 


1.8 


+ 5. OS 




9 


1580 


600 


15.70 


T.ss 


1.8 


+6.02 




s 


1580 


(100 


15.70 


10.33 


1.8 


+3.57 




7 


1580 


950 


15.70 


■ 8.65 


1.8 


+ 5.25 







1580 


1100 


15.70 


8 . 96 


1.8 


+ 4.94 




5 


1580 


1500 


15.70 


11.24 


1.8 


+ 2.00 




4 


1580 


1350 


15.70 


9.45 


1..8 


+4.45 




3 


2880 


2250 


13.89 


9.00 


1.8 


+ 3.11(1 




2 


2880 


1800 


13.89 


8.46 


l.S 


+3.63 




1 


1760 


1200 


9.90 


6.05 


1.8 


+ 2.(15 


(191 


Daily 
















average. 


1770 


114S 


15.02 


8.70 


l.S 


+ 4.52 





OBSERVATIONS DURING l'l ERPEBTUM. 



1 


725 


000 


4.41 


10.50 


0.95 


—7.03 




2 


1510 


725 


9.14 


15.73 


0.95 


— 7.54 


791 


3 


2480 


900 


12.00 


17.01 


0.(15 


—6.59 




4 


2480 


850 


12.00 


11.90 


0.95 


—0.85 




5 


2480 


1650 


12.00 


9.90 


0.95 


+ 1.15 







2480 


1800 


12.00 


8.28 


0.95 


+2.77 




7 


2480 


1850 


12.00 


7.40 


0.95 


+3.65 




8 


24S0 


1150 


12 00 


6.67 


0.95 


+4.:;s 




9 


2480 


1350 


12.00 


7.02 


0.95 


+4.03 




10 


24SO 


1200 


12.00 


8.64 


0.(15 


+2.41 




11 


24S0 


1450 


12.00 


9.10 


0.95 


+ 1.95 




12 


24S0 


100O 


12.00 


S.40 


0.(15 


+2.05 




13 


24SII 


1750 


12.00 


8.60 


0.95 


+ 2 45 




14 


2480 


1050 


12.00 


8.10 


0.95 


+ 2.95 




15 ' 


1580 


850 


15.70 


6.30 


0.95 


+ 0.05 




16 


1580 


950 


15.70 


7.65 


0.95 


+7.10 




17 


1580 


1250 


15.70 


8.31 


0.95 


+ 0.44 




IS 


1580 


1150 


15.70 


9.20 


0.95 


+5.55 




19 


1580 


1250 


15.70 


0.50 


0.95 


+ S.19 




20 


1580 


1250 


15.70 


0.13 


0.95 


+8.62 


S4i 


Daily 
















average. 


2074 


1126 


12.59 


9.10 


0.95 


+ 2.45 





BIBLIOGRAPHY. 
Bar: Legons de Pathologie Obstetricale. II. Paris, 1907. 
Dittrich: Ueber das Verhalten der Muskulatur des puerperalen 
Uterus. Centrbl. f. Gyn., 1889, XIII, 213. 



Drapier: Influences des Ansesthesiques sur la Nutrition. Quoted 
by Hawk. 

Goodall: The Involution of the Puerperal Uterus with Special 
Reference to the Involution of its Circulatory System. Am. Jour. 
Obst., 1909, LX, 921-985. 

Grammatikati: Ueber die Schwankungen des Stickstoffgehaltes 
des Harnes im Wochenbette. Centrbl. f. Gyn., 1884, VIII, 353-357. 

Hahl: Beitrag zur Kenntuiss des Stoffwechsels wahrend 
Schwangerschaft. Arch. f. Gyn., 1905, LXXV, 31-4S. 

Hawk: The Influence of Ether Anaesthesia upon the Excretion 
of Nitrogen. Jour. Biol. Chem., 1908, IV, 321-352. 

Hoffstrom: Eine Stoffwechseluntersuchung wahrend der 
Schwangerschaft. Skandin. Arch. f. Physiol., 1910, XXIII, 327- 
420. 

Kappeler: Ana?sthesica, 1880. Quoted by Hawk. 

Landsberg: Untersuchungen iiber den Stoffwechsel von Sticks- 
toff, Phosphor, und Schwefel bei Schwangeren. Ztschr. f. Geb. 
u. Gyn., 1912, LXXI, 163-211. 

Leppmann: Ether Anaesthesia. Quoted by Hawk. Mitteil. a. d. 
Grenzgeb. d. Med. u. Chir., 1899, IV, 21. 

Murlin and Bailey: Protein Metabolism in Late Pregnancy and 
the Puerperium. Jour. Am. Med. Ass., 1912, LIX, 1522. 

Ibid: Further Observations on the Protein Metabolism of Nor- 
mal Pregnancy. Arch, of Int. Med., 1913, XII, 28S-314. 

Murlin: Some Observations of the Protein Metabolism of Nor- 
mal Pregnancy and the Normal Puerperium. Surg. Gyn. & Obst., 
1913, XVI, 43-53. 

Sanger: Die Riickbildung der Muscularis des puerperalen 
Uterus. Quoted by Kuapp. von Winckel's Handbuch d. Geburtsh. 
II. I, 198. 

Schrader: Einige abgrenzende Ergebnisse physiologisch-chem- 

ischen Untersuchungen iiber den Stoffwechsel wahrend der 

Schwangerschaft u. im Wochenbette. Arch. f. Gyn., 1900, LX, 534. 

Seitz: Innere Sekretion u. Schwangerschaft. Leipzig, 1913. 

Sillevis: Ueber den Stoffwechsel der Gravida. Centrbl. f. Gyn., 

1904, XXVIII, 1471. 

Slemons: Metabolism during Pregnancy, Labor and the Puer- 
perium. Johns Hopkins Hosp. Rep., 1905, XIII, 111-144. 

Strassmann: Chloroform Anaesthesia. Quoted by Hawk. Vir- 
chow's Arch., 1S89, p. 339. 

Vidal: Chloroform Anaesthesia. Quoted by Hawk. Compt. rend. 
Soc. de biol., 1897, XLVIII, 474-470. 

Zacherjewsky: Ueber den Stickstoffwechsel wahrend den letz- 
ten Tage der Schwangerschaft u. den ersten Tagen des Wochen- 
bettes. Ztschr. f. Biol., 1894, N. F. XII, 368. 



THE NORMAL AMOUNT OF DIASTATIC FERMENT IN THE FECES 

AND ITS VARIATION IN CERTAIN DISEASES OF THE 

PANCREAS AND IN ACHYLIA GASTRIC A. 



We have studied quantitatively the diastase in the feci 
the hope that by establishing the normal limit, especially the 
low normal, we might have criteria of value in the diagnosis 
of organic or functional diseases of the pancreas, determining 
whether or no in such diseases a definite variation from the nor- 
mal is constantly found. We have chosen the diastase in 
preference to the trypsin or lipase because of its greater sta- 



By Thomas E. Brown, M. D., Baltimore, Md. 

(From the Chemical Laboratory of the Medical clinic.) 

bility, because the trypsin digestion may be simulated by the 
action of erepsin, because of the marked proteolytic action of 
the bacteria, much more striking than their diastatie action, 
because practically all the diastase that is secreted into the 
intestinal tract arises from the pancreas, the amount from 
Brunners glands and gall-bladder, the only other sources, in 
all probability being so small in amount as to be practically 



July, 191 ».] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






negligible, unci be preformed ferment, ai 

. lire an activator. 
We haVe attempted t<> devise a method which i- - 
al and exact, and based on physiological princip 
by applying the same method to normal and pathologic 
• to draw comparisons of value in diagnosis. I 
tically all the diseased conditions the diagnosis was 
ration. 
Of course a greal many methods havi 
qualitative and a few as quantitative tests of the pai 
function— Sahli's ^lutoid <-a j>sul<-. Miiller unci Schlechf 
dure t capsule, tin- study of the stool for large amounts of 

ml fat — creatorrhoea and stercorrhcea — aft 
Schmidt diet, the Volhard method of obtaining the du 
contents from the stomach by administering olive oil by 
month and the examination of tin- fluid for the pai 
fernn nt. Ehrmann's palmitin test, Einhom's intubation 
duodenum, A. Schmidt's nuclei test, the Cammidge reaction, 
ami the alimentary glycosuria test being among thos 

- definitely quantitative, however, and 
for this j>ur|««>.' the estimation of the pancreatic fermi 

Of these ferments the trypsin and 
re more easily destroyed by bacteria, the former is 
almost similar in action to erepsin, each requires activation 
to show their maximum efficiency, the former by enterokinasc, 
the latter by bile, and the proteolytic action <>f the int< 
i may complicate the findings very markedly. 
We have, therefore, chosen diastase as the fermi i I to be 
estimated, and the fact thai it is more Btable, that : 
preformed and does not require an activator, and thai 

minimal amount supplied by the -• 
from Brunner's glands and the Kil« 
to the • -. makes it the log 

in all such estimations the Balivarj dia 
with that from the pancreas 
eliminated, but this is easily done by administering 
in liquid form in which I tewing i- not 

■ ferments found in the' -mall inti 
. peptolytic ferment, nuclease, lipase, fibrin fc 
■ ■ ing ferment, 
tion of tin- diastase. This action, o 

the intermediary i 

i. erythrodextrin, achr lextrin, a. 

■ 

lion f<>r an attempt to quantil 
mate the pancreatic ferments is the- fad that mai 
and a few human experiments (patients with a pai 
fistula) have shown that there i- definite quantitative 
a- qnalitati n the jm» rt of the pai 

quantity and character of the food ingested. Evei 
af studied the action of the : 
itic fistula in a dog, a method Buba 
ide Bernard, who demonstrated tl 
of ether on the gland's Becretion, hut it was, 
low who demonstrated the fad that there 
titative relationship between amount am 



and am.. ui;: 

on dogs Inn ing I by numbei ■ 

II - ■ 
milk a i -• hour, 

7 cc. in the -• in the third. :• cc. in the fourth, and 

fill, and that the ' 
tjonship between amount of milk <_ r i\eii and amount of juice 

ild Im' mentioned in thi 
mechanism of this ind >till is a 

considerable diffen that it 

ua- :i nervous reflex through the cortex, Popielski thai 
ius reflex through I 

5 trling, *' the formation of nor- 

and their circulation thi 

suffices to account for the whole activity ■ 
and it is doubtful whether in this activity 
plays any pari whatsoever." According t< 
ling, this hormone, secretin, i- produced by I 
the hydrochloric acid of the stomach upon thi 
found in the duodenal mucous membrane; other 
lactic, 'ii.. however, have a similar effi 
Cohnheim, the action of acids upon tin- duodenum, p 
stimuli, as the smell, taste or sight of food, and fats, fatty 

ind -cap-, all act a- stimulants to pa 
According to Wohlgemuth ' the action of thi 
and humoral, while he and other observers havi 
activating . i r . . ? . i various other substances upo 
atie -.•■ nil. n, - ii h as peptoi 
lipoids, lecithin, etc. Of special interest is the activating influ- 

I bile ii|Hin the pancreatic juii e. ^ • 
the various views held as to the 

in, as n i- "i -!•• • ial inti n -; in I 
certain of our findings, notably those in achylia 

is to the method- d< scribed f..r studying the diastase in the 

-tool to det. I 

acts win. ii ■■■ 

iodine, or tin ■•> ''"* 

Stra-i.L 
mi. h methodt 
.1-111 be 
laxatives, and tl 

1 

■ 






Bar) Uli 

XXI. 447 

•711, 

uralbl t. Im 






202 



JOHNS HOPKINS HOSPITAL BULLETIN. 



| No. -si 



Enriquez, Ambard. and Binet" and Durand' reported a num- 
ber of cases in which the digestion of starch was measured 
by the quantitative estimation of the sugar formed and by 
gi\ing the same diet, milk, the same laxative, sulphate of 
soda, ami by diluting the stool to the same extent minimized 
the errors inherent in any method not taking these factors 
into account. We, however, regard the Wohlgemuth test for 
diastase as far nmre practical than the quantitative esti- 
mation of the sugar formed, and quite as free from criticism 
on theoretical grounds. As for the results of these quantita- 
tive studies, Wynhausen* found that in most cases it varied 
between 500 and 80,000 units; Arnold 9 between 312 and 
2000. Rotky "' thought that the study of the desiccated stool 
was the only satisfactory method, and that by this method 
there is not a very great deviation in normal eases. Durand 
found by the method of Enriquez a variation between 14.3 
and 48 units of diastase in the normal stool, the units, of 
course, being different here from those mentioned above. Xo 
discussion of the ferment content of the stool would be com- 
plete without a reference to the very extensive and interest- 
ing studies of Crohn' 1 in this connection. Although devot- 
ing the major portion of his investigations to the study of 
the duodenal fluid, he has also studied the ferments in the 
stool. He did not employ cathartics and used either a fresh 
night in- early morning specimen. In the case of both duode- 
nal fluid ami stool he gives a table of normal variations for 
the three ferments, lipase, trypsin, and diastase, and of these 
three he believes trypsin is the most constant. He believes 
that the method lends itslf to prognosticating qualitative and 
quantitative variations in the strength of the pancreatic exter- 
nal secretion. 

In the methods employed by us in determining the normal 
amount of diastase in the stool we have tried to eliminate as 
far as possible all sources of error, and to so standardize the 
different steps that mistakes would be reduced to a minimum. 
The patient was given a high enema the night before, the 
evening meal being a very light one. At T a. m. the next 
day 750 re. of milk were given, at 7.30 a. m.. ami again at 
S a m.. I an ounce of Epsom salts (Mg SO.), and at 8.30 
a. m. a glass of water containing 4/ of a teaspoonful of bicar- 
bonate of soda. All the stool up to 2 p. m. was saved in a 
vessel containing two ounees of toluol, and kept on the ice or 
in a cool room. If less than 400 grammes or cubic centi- 
meters nl' stool were obtained an enema of a pint of water 
was given, as in our experience between 400 and 1100 cc. of 
stool was the amount to be expected in the individual case. 

Barring the inevitable possible mistakes always associated 
with the gathering nl' specimens, the possible sources of error 
are psychic variations in the different patients, differences in 



'La Semaine raed., 1909, II, 13. 

; Les Precedes d'Examen des Fonctions du Pancreas, These, 
Paris, 1910. 
s Berl. klin. Wchnsehr., 1909, XLVI, 14m;. 
'Zentralbl. f. inn. Med., 191?,, XXXIV, 1. 

10 Munch, med. Wchnsehr., 1913, LX, 2158. 

11 Am. J. Med. Sc, 1913, CXLV, 393, 



their intestinal bacterial flora, and variations in the motor 
functions of their stomach and intestines, but we believe these 
inevitable sources of error are reduced to a minimum by the 
method employed. 

The stool was examined as soon as possible, diluted up to 
3000 cc. with normal salt solution, stirred until absolutely 
homogeneous, a portion centrifugalized for 5 minutes and the 
supernatant fairly clear fluid used for the tests. 

Diminishing amounts of this fluid were put into a series 
of tubes, 1.8 cc. in the first, l.G cc. in the second, 1.4 cc. in 
the third, 1.2 cc. in the fourth, 1 cc. in the fifth. 0.8 ce. in the 
sixth. 0.6 cc. in the seventh, 0.4 cc. in the eighth. 0.2 cc. in 
the ninth, 0.1 cc. in the tenth, 0.0.5 cc. in the eleventh, and 
0.025 in the twelfth, and the fluid in each of the tubes brought 
up to 2 cc. with normal salt solution. If the test showed 
a negative result in the first tube, or if we suspected very low 
readings, we used a supplementary series of tubes containing 
respectively 2 cc, 3 cc, 4 cc. and 5 cc. of the centrifugalized 
mixture. To each of the tubes were added 2 cc. of 1 per cent 
solution of soluble starch (Kahlbaum). the tubes were then 
incubated at 38° C. in a water bath for i an hour, cooled 
by the addition of tap water, and by placing them under the 
cool tap, and tested quickly with a few drops of 1/10 norma] 
iodine solution, the limit being that tube before the one in 
which the first definite blue color appears. As in the case 
of the urine, slight variations in the temperature of the water 
bath and in the reaction of the medium had very little influ- 
ence upon the readings, and we, therefore, did not regard it 
as necessary to reduce all the specimens to the same degree 
of reaction to litmus. In a few of our earlier eases the stool? 
fluid in the tubes was reduced in geometrical instead of arith- 
metical progression. The results obtained in 15 normal adult 
cases, men and women being about equally represented (oui 
unit being the digestion of 1 cc. of 1 per cent starch solution 
at 38° C. in i hour), were as follows: In three cases G0,000 
units: in two, 80,000; in one, 100,000: in seven. 120,000; in 
one. 140.(100. and in two. 240,000. Of course, this means that 
there was no starch left in the tube corresponding to thes 
unit.-, and the exact figures, of course, would be somewhere 
between this and the next succeeding tube. The low normal 
reading in our series, therefore, was tube 10 or 60,000 units. 
Expressed in the units used by some others, that is the total 
amount of starch which would be digested by the whole stool 
(in -^ an hour in the water bath at 38° C), this would make 
the limits of our normal readings 600 units to 2400 units, al- 
though it is possible that higher figures for the high normal 
would l»e obtained if we carried our series of tubes to greatei 
dilutions, but we were especially interested in obtaining a low 
normal, and this, if one can judge from 15 cases, we have ob- 
tained. 

Using the same method we have studied a small group of 
eases of carcinoma of the pancreas and chronic pancreatitis, 
in most of which the diagnosis was verified by subsequent sur- 
gical operation, and also a i'\\ eases of achylia gastrica and 
aehloilivdiia. some associated with diarrhoea, and some not. 



I 



Jolt, 191 1.| 



•JOHNS HOPKINS HOSPITAL BULLETIN 






• studied, three verified l>y operation an 
tensive, the head of the par 

rth presented the typical picture of the 
fatty stools of the most marked typ . 
the stool (as all the other cas noma Bhowi 

method employed being the Ful.l casein method), di 

81 hmidt nuclei tost and positive I i 
reaction, but this patient «as not operated upon, and 
death an autopsy could not be obtained, while the fifth case 

alive, and presents a typical picture of the i 
Ail the cases were advani a four jaun- 

dice had been present for a long time, in one there 
jaundii ^all-stones were also found. 

In all five cases the firsl our series Bhowed 

starch digestion, and we. therefore, employed sup- 
tary tubes « itfa lower dilutioi 

ng put in each of these tubes 
tively, and 2 cc. of the 1 per cent Btarch solution added to 
each. In each case there was still no eviden 

ii in the n dilution (5 cc. of • 

responding to 1200 of our u] 
12 of the Btarch gramme units employed by Bome i 
we did not study lower dilution- a- we believe that the limit 
of error had been reached. Thus in each of ; 
can gay that there is practically no diastase in the -tool. Wyn- 

f tumor of the pan- 
creas; Enriq u !, \mhard and Binel found no diastase in the 
- of the head of the paner. . 
and found no diastase in one 
probable carcinoma of i ! 

idern views, based on the experin i 
Wynhausen," Wohlgemuth" and other-, almosl all thi 

ind it- ah- ! 

Listi 
of that organ, probably organ 

improbably, functional. Completi 

. weak diasi 

I!. Miiller." and with no 

1 1 trand, and if this 
■ 
in_r to Wohlgemuth. 

nail. hard, definite 
long duration and in thi -■ - mmon d 

■ 

mil gall-bla 
marked on; in only i 



tent- : 

of the cases had 

8000; I 

in other won tninu- 

tion it. 
norma! 

with hardening of the head of the organ, with much dimin- 
ished diasta-e m the Btool, and Durand reports : '. similai 
It would seem, I 

•I. hut in markedly dim 
amount. Tl 

and those without jaund 
that while jaundice of >li<>rt duration pn 
amount ivating influence of the 

shown by Wohlgemuth," nevertheless, the 
bile upon the pan, i ., n- functii 

activity , ted by certain ex] 

upon dogs. 

. 1 rh .. 

ind achlorhydria lx 
physiological interest attached ditiong. If. 

ing t>> Starling, it is the action upon the duo. . 
membrane of the free HC1, which alone call 
of the | converting prosecretin into * 

in the cases of absence of free hydroi 
he a marked diminution of pancreatic Becretioi 
i- a vicariously increased production in thi 

ment. 1 a the case of I 

■ the minimal amount found in the bile 
-mall amount in I 
sent the only other available sources in I 

■ iinuln- 
tioii i- <alled forth, and in I 
that a nervous refl 

In ". i a (plant itfll 

the st( I 
diarrho 

1 [I 
was 12 or less; in thn 
found. • 

three. 120,00 

■ 



•Berlin, klin. Wdmachr., 1910. xi.vu. mt 



• 



■20 1 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 281 



is of Immoral or nervous origin in these rases, or whether both 
play a part it is difficult to say— the fact that peptone, salt. 
lipoids, lecithin, and fats can activate the pancreas must be 
remembered, and in some of these cases, at least, both modes 
of pancreatic stimulation have been demonstrated. Our results 
in this connection agree with those of Ehrman" who studied 
a similar group of cases by aspirating the stomach after the 
administration of the Volhard oil meal and testing the fluid 
obtained for trypsin by the Fuld casein method. His con- 
elusions were that in achylia gastrica and gastric anacidity 
the function of the pancreas is not banned but is sometimes 
even better than normal, and that, therefore, to stimulate the 
pancreas Hl'l is not necessary, in fact, is not the ne< 
activator of the pancreas as he has shown on dogs with pan- 
creatic fistula. His method is to be regarded more as a 
qualitative than a quantitative one. 

As to the etiology of the achylia in our series of cases, 
carcinoma could probably be excluded in all : in all but one — a 
young man — the patients were past middle age. and had either 
defective teeth or pyorrhoea alveolaris or both; in three of 
the cases a marked splanchnoptosis was present; in two a 
long alcoholic history, and in only one. a young man, was 
there a history of prolonged overwork and worry. Xo ease 
showed that stool suggestive of pancreatic disease — stercor- 
rhcea, and it has been our experience that this finding is 
extremely rare in achylia gastrica. 

Our series of normal and pathological cases is a compara- 
tively small one, but the results are very suggestive and war- 
rant further study. In addition to continuing our studies 
along the lines mentioned in this paper, we are also investi- 
gating by this same method the diastase content of the stool 
in obstructive and catarrhal jaundice, in diabetes and in 
hyperchlorhydria and hypersecretion, and if the opportunity 
arises we shall make similar studies in diseases of the adrenal 
and thyroid glands, the close relationship between these glands 
and the pancreas being, of course, well-known. 

Before concluding this article we wish to again call atten- 
tion to the absolute necessity for the most rigorous technique 
in regard to the diastase test in the stool. As regards prelimi- 
nary preparation we must remember that the stool obtained 
may represent one that has remained in the colon a consider- 
able period of time unless especial precautions have been taken. 
For that reason in all cases we suggest a light supper the 
evening before, and a thorough emptying of the large bowel 
by means of a high enema, while if there has been any history 
of constipation we give in addition a saline laxative on the 
morning preceding the examination. By these means we be- 
lieve we can practically always obtain a stool by our method 
which represent- the response of the pancreas to the food and 
laxatives given, and also one in which the deleterious effect 
of the bacteria upon this ferment is reduced to a minimum. 
It might be well, however, to give with the milk some coloring 
matter, such as carmine, so that we might have visual evi- 
dence of this fact. Of course, the condition of the salts in the 
stool has also a distinct effect in activating or depressing the 



diastatic action, but we do not believe that if our technique 
is followed out rigorously it is necessary to dialyze the stool 
and make our studies from the desiccated specimen. 

In regard to the diet, we have insisted upon, first, a liquid 
food, milk, which does not stimulate salivary secretion, and, 
secondly, a measured amount because there is unquestion- 
ably a definite quantitative response on the part of the pan- 
creas to the quantity as well as to the character of the food. 
The preservation of the specimen in a very cold place or on the 
ice and the immediate examination of it after the entire 
specimen has been obtained is absolutely essential because of 
the marked effect of temperature upon the action of the dias- 
tatic ferment, and also because if we allowed the specimen to 
remain long we are introducing two variable factors, one the 
influence of longer or shorter periods of time upon the dias- 
tatic ferment, the other the effect of varying bacterial flora 
upon this ferment. 

We believe that the wide variation in figures obtained in 
certain of the investigations is dependent upon the lack of 
insistence upon certain of these points, and that if the tech- 
nique is carried out as rigorously as outlined above the figures 
as to normal limits should be of real value. We have chosen 
the stool in preference to the duodenal contents obtained by 
aspiration in this group of cases because we believe thereby 
we can better measure the total output of the pancreas. 

Conclusions. — From our study on diastase content of feces 
in normal and in certain pathological conditions the following 
conclusions seem warranted in being drawn : 

1. The stool, if a rigorously exact method is carried out as 
to food, purgative employed, preservation of specimen, esti- 
mation of ferment, etc., furnishes a diastase content within 
definite limits. We cannot insist too strongly upon the pro- 
cedure being exactly the same in all- cases. The effect of 
w-aiting too long after the stool has been obtained before mak- 
ing the examination, the influence of variations in temperature 
in the place where it is kept, and of different laxatives and 
different foods is so great as to render results, obtained by 
methods in which insistence upon such a rigorous technique 
has not been made, of much less value. 

2. Extensive carcinoma of the pancreas showed no diastase 
in the tube of lowest dilution in our method, and this ab- 
sence of ferment should prove of great help in the diagnosis 
of this condition. 

3. In chronic pancreatitis diastase was present in the stool, 
but in markedly diminished amounts. 

4. In achylia gastrica the diastase content of the stool was 
practically normal in all the cases examined. This, in the 
first place, suggests that in the absence of hydrochloric acid 
some other method of pancreas activation is called into play, 
and. in the second place, that the diarrhoea met with in certain 
of these cases of achylia gastrica — the so-called gastrog 
diarrhoea — is not of pancreatic origin. 

5. If all the controllable factors arc standardized, the results 
obtained by the study of the diastase content of the stool 
should be of real value in the diagnosis of pancreatic dis- 
eases and in the studv of functional disturbances of this gland. 



Jl 1.1. l'.'l 1. 1 



•JOHNS llol'KINs oKIMTAI. BULLETIN. 






THE PERIPHERAL ORIGIN OF SURGICAL SHOCK. 



By l'i: l.\E I 
[f'rom th'- l.iiboratory of >.' 

te the enormous amount of work which has been done 
on BurgicaJ shock, there is still among recent writi 
general agreement as to the causes and nature of this condi- 
\ critical review of the literature reveals an astounding 
amount of contradictory experimental data, and a great number 
of diverse conclusions based thereon. This condition of the 
subject was our reason for undertaking the present Lnvi 
tion. ( >nr plan of attack may be summarized as follow s : 
i l i To determine definitely what is and what is not shock. 
i'.') To settle as nearly as possible, and one by one. the 
chief questions in dispute. These, so considered, are not of 
overwhelming difficulty. Most of them have already been 
worked out by the pathologists and physiologists. When 
. we have resorted to animal experimentation, taking 
in each case to devise experiments the results of 
which can lx> readily verified. 

(3) Either to correlate and harmonize the separate 
elusions arrived at by the methods just described into a 
comprehensive theory of shock, or else to define as nearly as 
]» .~-i liU' the limits of our present knowledge. 

/inn. - -The wop! "shock" is used in a very I 

vague way ill medical literature. Some writer- speak of 
" hemorrhagic Bhock," " psychic shock," " toxsemic Bhock," etc. 
This use of the term makes it Bynonymoue with injury. A 
study of the clinical rejh.rts of the patients supposed to have 
suffered or died from Bhock -hows how frequently this 

ir ignorance of what is really the cause of a patient's 
trouble, and also makes evident the necessity of excluding 
hysteria, cerebral injury, toxaemia, concealed hemorrhage, the 
or cold, and many other conditions befi 
-iinek is justifiable. The use of the •■■■ 
i- comparable to that of the word rheumatism. Thi 
formerly included every disease of the joints, and many 
other d des, but has been restricted gradus 

very narrow limits. 

As Meltzer.' Porter,' and others have emphasized, w 
only a clinical definition of Bhock. N 

■ - the presence of which will account for all thi 

nomciia of Bhock have ever I n conclusively di 

The signs of Bhock arc thus given by Meltzer: " \ 
general apathy, reduced sensibility, extreme motor w< i 
pallor, very ra|>i<l small pulse, thres 

»ping respirat - and subnormal temp 

insists that the presence of the circulate n phi 
ii no! absolutely necessary to the diagnosis, I 
is perhaps the best which can be given lor thi* 
with it we believe that most clinicians will be sat d. M 
has the great merit of not involving any more or 
able theory of etiology. Such a conditioi 
course of various diseases, or of surg 
result from accidents or intoxication-. The wot 
often u~>-<\ "here accidental or operative trauma 



M v\v \l. D. 
it^l Surgery of Indiana ' 

nothing to do with producing the condition 

however, for the sake of definiteness, limited our use of the 

won! to conditions associated with trauma. 

Historica /.' «. The history of the development o 
ent-day ideas ol shock has been so carefully reviewed in re- 
cent years in several easily accessible articles (see i. 
that it i- unnecessary for us to go into tins phas* 
subject in an exhaustive manner. We give the followii 
historical review, not to evaluate or harmonize the various 
theories of Bhock at present in vogue, but to -how the un- 
settled condition of the wh.de subject, and how this - 
affairs has come about 

In very early times it was observed that patients who had 
ojnred might fall into a depressed lethai 
which death might occur. Such cases were noted in which 
autopsy revealed no lesion adequate to account for deat 
word "shock '" was probably first used in the early part of the 
eighteenth century to describe an occasional effect oi gunshot 
wounds, for it was believed that the impact of a bulli I 
a " commotion of the element- of the nervous system " which 
accounted for the sj mptoms observed. Prom this period t>> the 

ry writer on surgical Bubjecfa 
shock. The idea- id' the older « rita 
though tney foreshadowed nearly all the n 
this condition. 

Thus 'i'ra\.r- (1826) states that "shock is 
functional concussion l>\ which the influeno 
the organ of circulation is deranged or suspended." And 

Savoy ' ( I860) write- that " death Iron, - 

sudden and violent impressions in some portions of the 

nervous system acting upon the heart." Thus writer- have 

anticipated the modern theories of vaso m 

cardiac failun . 

I >• asse ' (1834) defined -hock as " an at 
without which all organs pas 
the old way of Btating Mi - inhibition thi 

■ (1872 ) poetii 
tion of a rude unl 

worthy expcrimei 

of -hock in his well km 
tion foi 
many that 

till- tie I 

a long time, Crili 

ami for n HI 
of -upl- 
and Porter i- tl 

■ .- ■ 



206 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 281 



as its cause solely the exhaustion of the vaso-motor center. The 
cardiac and respiratory failures and their phenomena are only 
secondary consequences or subsidiary factors to the primary 

cause, the exhaustion of the vaso-motor center " 

The vaso-motor studies of W. T. Porter alone and with his 
pupils led him to results and views entirely antagonistic to those 
brought forward by Crile. In the first place, in disagreement 
with Crile, he states that in his numerous experiments he failed 
to find an instance in which stimulation of the afferent nerve 
caused a sufficient fall of blood pressure, except, of course, on 
stimulation of a depressor nerve. In his experiments crushing 
or electrical stimulation of the testis always gave a rise and not 
a fall of blood pressure. Continuous stimulation of the central 
ends of the sciatic, brachial or other afferent nerves for many 
hours gave uniformly the same rise of pressure as at the begin- 
ning. An analysis of 765 blood pressure records from stimulation 
of the sciatic and brachial (and depressor) nerves of rabbits, cats 
and dogs brought out the result that the " percentage change in 
blood pressure, which is the true index of the condition of the 
vaso-motor cells, increased as the blood pressure falls." Even in 
experiments where all the clinical signs of shock were present, the 
blood pressure very low, the temperature subnormal, the heart 
beat weak and often irregular, and the irritability of the nervous 
system apparently much reduced, stimulation of the depressor 
nerve lowered the blood pressure by 45 per cent. All these data, 
says Porter, are wholly opposed to the hypothesis that exhaustion 
of the vaso-motor center, brought on by over-stimulation, can be 
the cause of shock, but he is very emphatic in his assertion that 
the vaso-motor cells in shock are neither exhausted, depressed 
nor inhibited. Porter contradicts Crile's facts and disagrees with 
his exhaustion theory; but apparently he also disagrees with 
Howell's view, that inhibition of the vaso-motor and cardiac cen- 
ters is at the bottom of the phenomena of shock. 

The disturbance of pulse, rate that is so often noted in 
shock has led some observers to look to a disturbance of heart 
action as a primary cause of shock. Thus Howell " thinks 
that one of the causes of shock is inhibition of the cardio- 
inhibitory center. Boise" states that the essential cause of 
shock is excessive sympathetic irritation manifested mainly 
by a tonic contraction of the heart and arteries. " Shock is 
therefore due to cardiac spasm ; an incomplete ventricular re- 
laxation, mainly of the right side." This reflex stimulation 
he supposes to pass through the accelerator nerves by way of 
the stellate ganglion. 

Almost the exact antithesis to the vaso-motor failure theory 
is the theory of Malcolm. 16 His view is that the arteries, more 
especially the peripheral arteries, are contracted during shock 
and that as a result of this the blood is " forced into the 
splanchnic area." This, he thinks, leads to important changes 
in the composition of the blood and tissues. 

The idea that inhibition is a cause of shock is a very old 
one anil is the basis of many theories. The terms vital de- 
pression, inhibition of innervation, inhibition of the vaso- 
motor center, inhibition of the cardio-inhibitory center 
(Howell), all testify to the wide prevalence of this thought. 
Meltzer 1 has formulated the inhibition theory in the broadest 
and must satisfactory manner. He presents as evidence for 
his conclusions some observations upon the caecum of the 
rabbit. The movements of this organ can be observed in the 
intact animal through the abdominal wall. They cease when 
the skin of the abdomen is incised. He has shown that this 



is due to a definite inhibitory reflex. He thinks that perhaps 
other functions can be inhibited in a similar manner. He 
deserves special credit for emphasizing the fact that low blood 
pressure and an accelerated pulse rate are not always present 
in shock. 

Leonard Hill 1T states that in Ms opinion shock is due to a 
depression of the sensory synapses, producing a decrease in 
tone of the central nervous system. 

The most recent and at the same time the most radical 
departure from the other theories of shock is that of Hender- 
son, 18 who believes that shock may be caused by a loss of 
carbon dioxide by the tissues; the loss being brought about 
by excessive pulmonary ventilation or by exhalation of car- 
bon dioxide from exposed viscera. He denies that vaso- 
motor failure is present in shock and claims that the develop- 
ment of shock may be prevented by safeguarding the body 
from loss of carbon dioxide. 

Various other possibilities have been suggested as a cause of 
shock. Among these might be mentioned the hypothesis that 
it is a derangement of the thermogenic mechanism :"'° that it 
is a condition of perverted metabolism due to trophic im- 
pulses ; 3 that it is due to a pathological change in the chro- 
maffin tissue. 30 Little or no evidence has been produced to 
support these hypotheses. 

A great amount of work upon special phenomena of shock 
has been done, for example, upon the state of the arteries, the 
condition of the various vital centers, the specific gravity, 
gaseous and cellular content of the blood, etc. To much of 
this work we shall have occasion to refer later. 

Method of Experimentation. — The experiments described in 
this article were performed upon animals which were under 
full surgical anesthesia. Ether was the anesthetic used. No 
animal was allowed to feel pain at any time, and all the 
animals were killed before they regained consciousness. 

Scope of the Present Investigation. — We wish to emphasize 
here at the beginning that the scope of the present experi- 
ments includes the phenomena which occur in the anesthetized 
animal. Our results, while strictly comparable to what may 
be observed on human patients during operation, do not apply 
to cases of so-called "pure" shock which may be met with 
under the conditions of ordinary life. Shock of this kind may 
be due to much more complex causes than the type we have 
studied. 

Original Investigation — the Standard of Shod-. — We found 
it very difficult to determine when an animal had passed 
into a state of shock. In the protocols of some observers a 
markedly low-ered blood pressure is taken as the sole indica- 
tion of the presence of shock. Other workers note, in addition 
to the blood pressure the pulse and respiration. It can be 
demonstrated all too easily that low blood pressure, rapid 
pulse and irregular respiration may be produced by the action 
of the anesthetic alone. It seems to have been thought suffi- 
cient to state : " after reducing the animal to a state of shock " 
without giving either the method of its production or any crite- 
ria by which it is possible to judge whether the animal really 
was or was not in a condition of shock. This lack of definite- 



.It ly, L914.] 



JOHNS BOPKINS HOSPITAL BULLETIN. 



damental matters makes o 
arches "ti shock of Bomewhat qui si 
value. 

_ .1 r- « i . • • I no animal as being in a condition • 
sent : 
1. !/>-- of sensibility as shown by the lai 
administering an anesthetic when the eye refl* J 
•.'. Pallor of the mucous membnu 

Small weak pulse. 
I. Irregular, rapid, shallow or gasping respiration. 
Markedly lowered blood pressure. 

fundamental importance of these criteria merits b 
• "ii of them. When all the above Bigns are ; 
and when there has been no hemorrhage, we believe that it 
will be generally admitted that shock in the full clinii 
term i- pn 
We r ■ .1 by the fact that in many cases an animal 

might Bhow all the signs given above except a n 

ssure. Many times we observed dogs which 
mucous membranes and impaired •■ 
tinii. and which required but little anesthetic for 

■lit in which the Ii1>»h] pressure was but 20 t" 10 mm. 
lower than at the beginning of the experiment In order, 
r, t" mak«- our results absolutely beyond criticism we 
nued our manipulations until the blood | 

-third t le-fourth it- original level before we 

ed the annual as in si 

- icfc.— Our lir-t endeavor was 
the quickest ami most certain method of producing 

■ fill to avoid even the slightest hem- 

fnr tin- special purpose, and in a large number 

dentally made, we at! 
ition without opei 

i c lition which 

In all the others the blood pressure wa* 
i millimeters lower than 
ami ju-t as much [ministered 

I 

• 5 hours i. 

rve trunks. 

Ins -. I- 

id nut produ ition. Int. 

stretching of a mixed nerve I 
fluctuation in bJa but intermittent and 

both brachial plexus* - for a period "f four hours 

U - true that blood :■'■ 
piration and 

m n<. ■ ted, providii 

that t 

Blightly, rarely over 10 mm.; in boi 
curred. 



turn di 
In t 1 

must be us< d to i 

Our 
many other ■ in which a 

observe tin ■ 
are bo 

state that it i- in,- 
in I to 
thf abdomen, without inducing hemoi 

medullar} i • 
i 1 1 ir~ of Hill ay." 

- 
1 1 tors who hi 

to Btimulati 

ClIllillL- 

than the etimulal 

experiments. Perhaps the moat important of 
increase in the temperature of the anim 
eliminates heal chiefly by way of the lungt 
greatly increased in rate and depth. Tl 

lily be 
shown by applying cold to the part- of thi 
not Bubjei h d lo thi h< at I' I 
not ...cur. Furthi 
heating tin M<h-I , auses im] 
ti— in- of the body. 

We have found that hi 
surfai • 

■ 

of heating only tin blood of 

[ili-!,. 

which wen 
which ' 

■ 

Third 



308 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 281 



its normal size. On incising it clear fluid poured freely from 
the cute. In all the animals the blood at autopsy was found 
to be dark and thick and all the veins, both splanchnic and 
peripheral, were dilated. 

The condition produced in these experiments fulfilled all 
the requirements of the clinical definition of shock. Death 
seemed to result from primary cardiac failure. We can state 
most emphatically that the condition did not result from 
traumatic stimuli, or loss of carbon dioxide, but was wholly 
due to over-heating of the blood. We positively demonstrated 
that the vase-motor center was active, because it constantly 
responded to the tests which we shall discuss later. 

The effect of excessive cold was observed upon an animal 
which was subjected to a continuous rectal injection of ice 
water. In an hour and a half the animal was reduced to a 
condition resembling shock. The only noticeable difference 
between the condition of the animal in this experiment and 
that of those which had been subjected to heat was the charac- 
ter of the pulse. The rate of the heart beat was greatly de- 
creased and the amplitude of the beats increased. Section 
of the vagi only slightly modified the cardiac action. The 
animal died from primary cardiac failure. 

The Production of Shock by Forced Ventilation of the 
Lungs.— We attempted to produce shock by Henderson's" 
method of forced lung ventilation. In a limited number of 
experiments of this character we were able to produce the 
condition in only one case. Our trouble was probably the 
same as Henderson records in regard to his first experiments 
— an inefficient pump. But we are quite certain that the 
artificial ventilation was greater than it would be possible for 
the animals themselves to have produced by the greatest pos- 
sible forced respiratory movements. In the one case in which 
the signs of shock did appear autopsy revealed the fact that 
both lungs, with the exception of a small part of the upper 
left lobe, were consolidated. We could not determine whether 
tli is condition had existed before the beginning of the experi- 
ment, but as the dog was apparently a perfectly healthy 
animal, it is extremely probable that its lungs were normal. 

The Production of Short by Opening the Abdomen and 
Exposing the Viscera. — Our next method was to open the 
abdomen and expose and traumatize the viscera. This in 
every instance produced shock. Sometimes the condition 
came on quite rapidly ; in other instances the process was 
delayed. Upon opening the abdomen the blood pressure 
usually fell, due to lowered intra-abdominal pressure. While 
the viscera were being exposed the blood pressure showed 
marked fluctuations, due to the mechanical manipulations. 
If the intestines were squeezed the pressure might tempo- 
rarily become greater than normal, because of the better 
tilling of tlie right side of the heart. But gradually blood 
pressure fell and usually within an hour shock was present. 
In many cast's it was not necessary to administer ether after 
the abdomen was opened, even when the experiment extended 
over a period of several hours. 

In reviewing the protocols of various observers it is inter- 
esting to note their use of visceral traumatization to produce 



shock. It is surprising how few experiments are on record in 
which, if the method of producing shock is stated at all, this 
was not the means employed. The observer may begin an 
experiment by crushing a foot or burning a part, and may 
obtain some fluctuation in blood pressure by such means, but 
sooner or later, as if discouraged by the progress made, he 
invariably adds, " and the intestines were manipulated." The 
protocols are few which do not record directly or indirectly 
a complicating hemorrhage or a section of the abdomen. 

In all our experiments, unless otherwise stated, shock was 
produced by exposing and traumatizing the abdominal viscera 
of an etherized animal. The condition was never called shock 
unless the clinical signs as previously stated were present, 
except in special experiments, e. g., in the use of curare, 
section of the cord, etc.. which made it impossible to note 
some of the signs. 

The Condition of Various Tissues and Systems in Shock. — 
An endeavor has been made to study individually each system 
which might be affected in shock, the attempt being to de- 
termine what part it played in the production of shock, and 
how it was affected by the resulting condition. 

The Vaso-Motor Mechanism in Shock. — The Vaso-Motoi 
Center: Our work corroborates Porter's 13 conclusions in 
regard to the condition of the vaso-motor center in shock. 
Stimulation of mixed nerves produced a marked rise of 
blood pressure, even in extreme degrees of shock, and stimula- 
tion of the depressor nerve produced a comparable fall in the 
same condition. We were able to corroborate Seelig and 
Lyon's !3 results in regard to the effect upon the blood pres- 
sure of stimulating the central end of the vagus. In every 
case this yielded a rise of blood pressure in shock. In some 
instances the rise was actually greater in the shocked animal 
than in the normal one. 

The reaction of the center to the concentrated hydrogen 
ion content of the blood is as marked after the production of 
shock as before. The production of a wide pneumothorax in 
a shocked animal gives a blood pressure tracing not influenced 
by the respiratory movements. Under these conditions an 
asphyxia! rise in the blood pressure takes place. In some 
cases the pressure of an animal in marked shock was more 
than doubled ; in other instances but a moderate, and rarely 
but a slight rise occurred. The same result was obtained if 
the animal were made to inhale high percentages of carbon 
dioxide. The injection of lactic acid does not produce a con- 
stant result even in the normal animal. However, we have 
records which show a marked increase in blood pressure in 
the shocked animal produced by this supposedly normal 
chemical stimulant. An increase of intra-cranial pressure pro- 
duced the same relative increase of blood pressure in the 
shocked animal as in the normal one. 

The Condition of the Arteries in shuck. — The Peripheral 
Arteries: The pallor which occurs in shock might be due 
to one of two causes: (1) The constriction of the peripheral 
vessels, which prevents a flow of the blood to the skin : or ( 2 | 
to a dilatation of the splanchnic vessels, which causes the 
blood to be drained out of the skin. Seelis and Lyon M have 



July, 1914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 






. investigated the condition of the peripheral arteries 
in shock and have concluded that these vessels are constricted. 
Bartlett," who has investigated 1 1 1 * - same question, reai 
. contrary conclusion. 
Neither of the methods used by these investigators 

- re results in our hands. For this reason we employed 
older and simpler physiological methods. During the pro- 
duction of shock, peripheral venous pressure, as taken from 
the femoral vein, de< rcases. This U usually very mark 

may take place before blood pressure has greatly decreased. 
If the Bciatic i- cut in the shocked animal there is an im- 
mediate and decided increase in the pressure of the femora! 
vein. This i- evidence that the arteries of the limb a 
strictod during the production of shock and that there 
siderable vaso-motor tone, even when the blood press 
very low. 

Tin tongue of the dog is an organ which is liberally sup- 
plied with vaso-motor tihers. Fortunately these run in scpar- 

rve trunk-. The major part of the dilators 
through the lingual nerve." while the constrictors are carried 
in the ; This furnishes an ideal arrangement for 

the study of this particular phenomenon. If one hypo 

anlated in a curarized dog the tongue becomes 
slightly paler on the side innervated by this nerve; if the 
lingual nerve i- stimulated the tongue becomes very red and 
tie- \( ins stand out very prominently upon the corresponding 
I ■ the animal is reduced to shock the phenomenon, upon 
stimulating the lingual, is even more marked. The reddened 

- ami bulging veins of the corresponding -el.' con- 
itrikingry with the pallor of the opposite Bide of the 

and the mucous membrane "f the oral cavity. The 

<>f the tongue are evidently in tone which is di 

stimulation of the dilator fibers. This tone might !»■ 

onstrictor impulses from the vaso-motor center 

or the arterial muscles themselves. That at least a pan of 

!•• to the former cause is proved by the 1 
hut quite noticeable dilatation which occurs after section of 
the hj erve which contains the vaso-constrictor 

In animals which normally have enlarged ves 

• is result ■ an !>•• better observed if a slight as- 
roduced in the shocked animal. Tracing* 

Og in shock -how that it 

cidedly increased upon stimulate f the lingual nerv< 

experiment proves that the arteries of the tongue an 

' fiction in -: 

ge number of the vaso-constrictor fibers of tie 

car run in the cervical sympathetic nerve 1 * which fi 

■■ trunk in that animal. The blood 
of the albino rabbit show vaso-motoi 

ill, more or lees faint, lines. That tin- ■ 
in caliber i- not a wi by tie I i 

lowerii ir below the level of the spla 

of the cerv ieal -v u 



tation of them. They are. therefore, under vaso-motor tone 
in shock. 

The unpigmented paw of a kitten or puppy is well Buited 
for the study of vascular changes in the limbs. The vaso- 
motor fibers of the paw run in the sciatic nerve." If the 
sciatic on the one side i> cut in the normal animal the cor- 
ssumes a brighter tint than it- fellow. In 
the beginning of shock the difference becomes more marked, 
because the paw with the intact nerve becomes paler. It i- 
only when the blood pressure is very low in marked -hock 
that the paw- look alike. Even then a difference can he 
observed bj lowering both paw- below the level of the splanch- 
nic area, when the paw with the intact nerve becomes paler. 
If the sciatic of the intact leg he now severed a faint but 
distinct flush appear- on this paw. Thi- experiment -hows 
that the blood vessels of the paw are under vaso-motor tone 
in shock. 

Untraumatii Arteries in Shock.- The ar- 

teries of the kidneys wen- taken a- the most accessible of the 
untraumatized visceral arteries to study. The vaso-motor 
changes were recorded by mean- of an oncometer. This can 
he applied through a lumbar incision without entering the 
abdominal cavity and without disturbing blood pressure. 
Tracings of the volume of the kidneys were taken before, 
during and after the production of shock. 

During the production of shock there was usually an im- 
mediate kidney shrinkage, although thi- did not invariably 
occur, for at times an initial expansion occurred, while in 
other instances the volume of the kidney passively followed 
the changes in the general blood pressure. 

Roy and Bradford' have shown that stimulation of the 
central end of the sciatic nerve produces a decrease in kidney 
volume, while it increases the general I>1inm| pressure. <>ur 
re-ults show that when the blood pressure i- very high in the 
normal animal, stimulation of the sciatic nerve does not 
always produce a shrinkage of the kidney. A slight expan- 
sion may occur, hut this increase in kidney volume is always 
-o -mall a- to -h,.w that some vaso-constrictioi 
although not quite enough to offset the rise in general I>Iimk1 
pressure. 

Stimulation ot the sciatic nerve in rnoderat 
shock always produces a marked decrease in kidney volume, 
although tin- ri-e m general blood pressure might he be 
a- in the normal animal. In somi 

kidney volume following stimulation of tl :iatic could he 

obtained with a blood pressure of only 20 mm. Adi 
evidence of the vaso-constrictor ton.- of the rem 

-tin red by recording the increase in volun f the kidney 

follow ii • ion of the s with carboli 

which destroys thi 

It i- evident from these experiments that tin- ton. 

mstrictor mechanism of the d in a 

rnoderat . ami that 

even wh< n the bli od pn 
I 

hi the 



210 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo.281 



thoracic duct. A caimla was inserted into tin' duct extra- 
pleurally without producing any disturbance in blood pressure 
(ir respiration. The rate of now was determined by counting 
the dn.li> '"' accurately measuring the amount of flow per unit 
df time, (are was taken during the reading to exclude the 
effect of irregular respiration or manipulation of the intes- 
tines. A norma! rate was always determined before shock 
was produced. Tin following result- were obtained: At the 
onset of shock the lymph flow through the thoracic duct was 
slightly increased. As shock developed it might, decrease 
slightly below normal. In character the lymph changed from 
a color more or less milky to a pale reddish color. Microscopic 
examination showed many red cells present. The coagulation 
time was markedly decreased, so much, in fact, that toward 
the end of an experiment it was almost impossible to maintain 
a flow from the cauula. At this time the lymph resembled an 
exudate. 

The Cardio-Inhibitory Center in Shock. — This center is 
thought by some investigators to be inhibited in shock, while 
others claim that it loses tone. The following facts throw- 
light upon this point : 

1. An animal which has had the vagi cut does not seem to 
develop shock any more quickly than one in which they are 
intact. 

2. It is well known that if one vagus is severed while the 
other is left intact and the central end of the divided one 
stimulated, a rise in blood pressure occurs. However, by 
carefully graduating the current in some animals a reflex 
inhibition of the heart can be produced. In each dog in which 
it was possible to obtain this reflex it remained positive, 
even in the most extreme degrees of shock. That this inhibi- 
tion of the heart was a definite reflex, involving the inhibi- 
tory center, was shown by section of the intact vagus in the 
deeply shocked animal ; after this it could not be again 
obtained. 

3. In the normal adrenalin curve, after the initial rise in 
blood pressure, inhibitor}- beats occur which have been proved 
to be due chiefly to a reflex involving the inhibitory center, 
although increased filling of the heart may be a factor. In the 
tracing obtained by the injection of adrenalin in the shocked 
animal the same characteristic beats occur, after blood pres- 
sure has slightly increased. We observed their disappearance 
in shock after section of the vagi and an increase of blood 
pressure to six times the height present before the drug was 
injected. 

-i. An increase in intra-crauial pressure produces character- 
istic inhibitory beats of the heart, clue in all probability to 
bulbar anemia. These occur when the intra-cranial pressure 
is increased in the shocked animal, and cease when the vagi 
are cut. The blood pressure then increases enormously, for 
the vaso-motor center also reacts to the increased intra-cranial 
pressure. 

These experiments would seem to prove conclusively that 
the cardiac inhibitory mechanism is intact, even in the deeply 
shocked animal. 



The Heart in Shuck. — In all the experiments in which the 
animal was allowed to die from uncomplicated shock the heart 
was beating, although sometimes quite feebly, when respira- 
tion had ceased and blood pressure was practically zero. In 
many cases, upon opening the thorax when all signs of life 
had disappeared, the heart was observed to be contracting still. 
In the production of shock the pulse usually, but not in- 
variably, increased in rate. The individual beats always 
became weaker, as measured by palpation and the manometric 
tracing, but the cardiac function remained until the very last. 

Seelig and Lyon " have shown that typical shock can be 
produced after evulsion of the stellate ganglion. This cer- 
tainly removes almost entirely the possibility of the heart 
being affected through the sympathetic system. 

That the heart is capable of performing its function effi- 
ciently in shock, if only enough blood is returned to it. was 
pointed out by Hill. 3 " He increased the venous return to the 
heart by visceral compression and noted that the heart was 
able to handle the increased amount of blood effectually. We 
have been able to corroborate Hill's results. 

A more severe test of the efficiency of the heart in shock 
is afforded by the injection of large doses of adrenalin in the 
shocked animal after section of the vagi. This produces an 
enormous rise of blood pressure, often increasing the pressure 
to a level six times higher than that in shock. In every in- 
stance in which this was done the heart was able to pump 
against the enormous pressure effectually and in no instance 
was there an indication of cardiac failure. A similar test 
was made by increasing the intra-cranial pressure of a shocked 
animal in which the vagi had been cut. The vaso-motor 
center was stimulated and the blood pressure increased 
enormously, but although this was maintained for several 
minutes, the heart remained competent to perform its function. 

In view of these facts it is impossible to believe that the 
heart is the primary factor in the production of shock. These 
experiments prove that the heart is as efficient a pump in 
shock as in any other condition in which it has been sub- 
jected to a poor blood supply during a long period. 

The Respiratory Mechanism in Shock. — As shock develops, 
respiration becomes more shallow and may increase in rate, 
but quite often decreases. The most characteristic respiratory 
phenomenon of shock is the intermittent gasping type of 
respiration. All our tracings obtained from animals which 
died of uncomplicated shock show that the respiration failed 
before the circulation. However, the respiratory center of 
a shocked animal responds quite actively to afferent stimula- 
tion, to rebreathing, to inhalation of carbon dioxide and to 
the injection of lactic acid. Stimulation of the vagus pro- 
duces the usual inhibition of respiration in the shocked 
animal. 

These facts show that the respiratory mechanism is not 
primarily at fault in the production of shock, but that it is 
probably the most seriously damaged and the most easily 
injured of the medullary centers by the resulting condition. 

The Study of the Mesenteric Circulation in Shock. — In 
many experiments a microscopical study of the circulation of 



July, 191 !.] 



.JOHNS HOPKINS HOSPITAL BULLETIN. 



Ill 



the mesentery and omentum was made. The phenomena 

<i were those described by the pathologists in thi 
eal descriptions of acute inflammation. These are: I 
rid veins; congestion and Blowing 
flow, whicb later results in a more or less m I 
margination and later emigration of the leue 
late in the condition rupture of many of the small vessels and 
lular elements into the tissue spaces or to the 
- 

Histological - - ' the omentum, mesentery and intes- 

the normal and shocked animal were made ai 

red all the above phenomena in a static 
form and emphasized many of the facts which will I 
iter. 

Blood in Shock. — Specific Gravity: 
There has tw oversy in regard i<> the 

gravity of the blood in slunk. The prepond 
of the evidence is in favor of an increase of specific gravity 
in this condition. We observed that if the blood wen 
from the peripheral vessels it showed but a slight increase in 
pravity, but it' taken from the splanchnic 
marked in. i 

i, Shock. — Crile," in a series of four 
experiments upon shocked dogs and dogs suffering froi 
orrhage, comes to the following conclusions: In shi 

■ increased while the white cells are decreased; 
in hemorrhage red cells are decreased while white cells are 

ondition "f the l>l<><.d in hemorrhage need not 
or investigated here, especially as this has been done 
pletely by many observers. In the series of experiments 
in which blood counts were made before and after the produo- 
shock it was found that there was an enormo 

■ Us in the Bhocked animal, while the red 
slightly, if at all. increased. 

■ /,• by Intru-Abdbminal Trim 
Brposurt of the Viscera to the Air. In 
an incision into the abdomen jusl 
rait the hand was made. Through t li i - a gloved 
and the abdominal wall clamped 
around the wrist Intra-abdominal traumatization for a 

re minute- would lower blood pressun 
aiderably, but if the traumatization were now stop] 

on return almost to normal. However, il 

iniatization were continued for a much longer n 

tin' animal would develop the ock. That this was 

not due to an exhalation of carbon dioxide was 

ominal cavity. If the lm- were admitted slow 
intra-abdominal pressure it did i ■ 

-ilCH k. 

of the rorci in an animal in the horizontal pos 
lower cervical or upper dorsal region produces 
fall of blood pressure, due t" section of the vat 
That such an animal is 



Bhock can be shown by withdrawing the anesthetic, when the 
animal will n iousness and respond to stimuli ap- 
plied around the head. Upon opening the abdomen of an 
animal iii this condition the vessels of the splanchnic area 
en to be dilated and the viscera congested. But the 
exposure of the viscera produces a marked and imi liate in- 
crease in the congestion in the same manni r as in an annual 
which has no! been subjected to section of the cord. The 
fall of blood pressure following section of the cord is not any 
greater than the decrease which follows immediately upon 
section of the abdomen and exposure of the viscera. Evi- 
dently typical shock can be produced after section of th rd. 

Vaso-motor reflexes are no1 very easy to obtain or very 
marked in an animal with the cord severed. However, stimu- 
lation of the sciatic does produce a slighl rise in bl I pres- 
sure, A proportionate rise occurs even when blood pressure 
is very low, due to abdominal traumatization. A Blight 

asphyxia] rise of bl I pressure occurs in a dog with the cord 

sectioned. A proportionate ris icurs when Bhock has de- 
veloped. 

The Effeci of Hemorrhagt I pon th Production <>; ■ 

During the course of some experiments accidental hem- 
orrhages occurred. It was noted that Bhock developed very 
quickly in these cases. This observation agrees with the re- 
ports of a large number i order to study this 
condition more completely a series of experiments wi 
formed in which the animal was subjected to varying i 
of arterial or venous hemorrhage and the same testa applied 
as in the experiments upon the oimal. 

The mosl noticeable effect of a slight hemorrhage upon an 
anesthetized animal is the resulting depression ol -< 
A dog of ten pounds weight could be subjected to 
venous hemorrhage of 50 to 75 cc. without producing a fall 

in blood pressure of ov< r 15 mm. Bui the I E sensibility 

li that in ino-i cases only a very little, if any. anes- 
thetic was tessary, even in long-continued experiments. If 

the bleeding were done from an arterj of large size, as the 

femoral. 1.1 1 pressure fell quickly during the hemorrhage, 

but if the loss of blood were slight, vaso-motor compensation 
would restore the pressure almost bo normal. As the amount 

of hi : i power of vaso-motor 1 1 

sation decreased until I > I < » « | pressure remained \. 
Furthermore, we found that the animals which had been bled 
responded to the Bame tests for the activitj of the various 
■ ner as the animal- « hich hi 
d to shock. The condition of an animal after hem- 
orrhage could not U' differentiated from the condition of 
i.t perhaps int. 

data »'■ I: , 

justify the following conclusii 

1. It is im] ible to redui i 

orj stimulation, m 
all hemorrhage is prevei abdomen if 

.'. We have been unable to -leu U 
factor m the production of shock. 

Shock i- nol due to disturbam ■ on, hut 



51".' 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[No. 281 



the respiratory center is more quickly injured than any other 
vital center by shock. 

4. The vaso-motor center is not depressed nor fatigued in 
shock. It is the most resistant of all the vital centers. The 
peripheral and untraumatized visceral arteries are constricted 
in shock. 

5. Shuck is not due to primary failure of the heart nor to 
involvement of the cardio-inhibitory or cardio-accelerator 
mechanism. 

C. It is possible to produce the signs of shock by the use 
of excessive heat or cold. 

7. The easiest and most certain method of producing shock 
is by exposure and traumatization of the abdominal viscera. 
This, judging from the literature, has been the method used 
by nearly all investigators of shock. 

8. Shock produced by exposure and trauma of the abdom- 
inal viscera is not due alone to a paralysis of the vaso- 
motor mechanism of the splanchnic area. This has been 
shown by two crucial experiments. (1) Section of the curd 
or splanchnic nerves does not produce shock. (5) When all 
the abdominal and thoracic organs are taken from the animal 
(Carrel) this ''visceral organism" can still be kept alive for 
many hours and it can digest food, excrete urine, etc.*'' There- 
fore, some other cause than vaso-motor paralysis or inhibition 
is involved. 

It. The cause of shock is the tremendous loss of red cells 
and fluid from the blood, due to the reaction of the great 
delicate vascular splanchnic area to irritation — an acute in- 
flammation of the peritoneum-, due to trauma and exposure 
to the air and changes of temperature. The great amount of 
this loss is apparent when it is taken into consideration that 
tin' peritoneum has an extent as great as the entire cutaneous 
surface of the body. The factors involved in this reaction to 
irritation are the same as those involved in any other local 
inflammatory process, anil certainly do not involve the nerv- 
ous system to any greater extent. The profound general 
effect is due to the, actual loss of red cells and fluid from the 
circulating blood through stasis, diapedesis, exudate, endo- 
thelial changes, etc. It is to be noted that some of the 
classical descriptions of inflammation were made from obser- 
vations on the exposed omentum and mesentery. 33 In the 
course of operations in which the abdomen has not been 
opened, a loss of fluid and cells from the blood occurs. But 
the loss is, except when great areas of subcutaneous tissue 
have been exposed, comparatively unimportant, 

10. Certain accessory factors which help to produce the 
condition of shock should be mentioned. These are muscular 
relaxation, decrease in intra-abdominal pressure ami impaired 
respirations, all of which tend to decrease the amount of 
blood returned to the heart. The effect of chilling ami the 
use of hot applications should be considered. 

1 1. Degenerative changes in the cells of the central nervous 
system are the result and not the cause of shock. Policy 3 * 
states that identical changes in the nerve cells are pri 

by hemorrhage and shock. 

12. General anesthesia of moderate depth prevents painful 



impulses from affecting the nerve cells of the central nervous 
system. Nerve blocking under such conditions is useless, so 
far as the prevention of shock is concerned. 

13. A relatively slight decrease in blood supply may be 
sufficient to depress markedly the cells of the cerebral cortex. 
Care should, therefore, be taken to exclude this factor before 
ascribing such depression to inhibition. 

14. The use of the word " shock " should be avoided, and 
instead an accurate and detailed description of the patient's 
condition should be given. If the term be used at all it should 
be applied to the condition in which, without any grossly 
discernable hemorrhage having occurred, the amount of cir- 
culatory fluid is greatly diminished on account of stagnation 
of the blood in the smaller veins and capillaries or by exuda- 
tion of the fluid and cellular elements of the blood from the 
same. 

This work has been carried out under the direction of Dr. 
W. D. Catch, whom we desire to thank for his help and en- 
couragement. We are also indebted to Mr. George Boesinger 
for his assistance in the experiments. 

REFERENCES. 

1. Meltzer: Arch. Int. Med., 190S, 1, 571. 

2. Porter: Harvey Lectures, 1906-07, 98. Loc. cit., 112. 

3. Vale: Med. Rec, 1904, 66, 325. 

4. Risley: Boston Med. and Surg. Jour., 1913, 168, 112. 

5. Seelig: Int. Jour. Surg., Feb., 1914, 114. 

6. Travers: An Inquiry Concerning Irritation. London, 1826. 

7. Savoy: Holmes System of Surg., 1860. 

8. Delcasse: La Commotion, 1S34. 

9. Gross: System of Surg., 1850. 

10. Goltz: After Vale. 

11. Crile: An Experimental Inquiry into Surg. Shock. Phila., 
1899. Bood Pressure in Surg. Phila., 1903. 

12. Mummery: Lancet, 1905, 1, 696, 776, 846. 

13. Porter: Am. Jour. Physiol., 1907-08, XX, 399, 444, 500. 

14. Howell: Contributions to Med. Research, Dedicated to 
Victor C. Vaughan, 1903. 

15. Boise: Am. Jour. Obstet., 1907, V. 1. Trans. Am. Gyn. Soc, 
190S, XXXIII, 390. 

16. Malcolm: Lancet, 1905, 11, 573, 618, 737, 922; 1907, 1, 497. 

17. Hill: Brit. Med. Jour., 1910, 11, 761. 

IS. Henderson: Am. Jour. Physiol., 1908, XXI, 126; ibid, 1909, 
XXIII, 345; ibid, 1909, XXIV, 66; ibid, 1910, XXV, 385; ibid, 1910, 
XXVI, 260. 

19. Kinneman: Ann. of Surg., 1903, XXXVIII, 8, 4, 3. Int. Jour. 
Surg., 1904, 378. 

20. Bainbridge and Parkinson: Lancet, 1907, 1, 126. 

21. Hill: Further Advances in Physiology. London, 1909, 176. 

22. Janeway: Ann. of Surg., 1914, 59, 158. 

23. Seelig and Lyon: Jour. Am. Med. Assn., 1909, "L*. 15. 

24. Seelig and Lyon: Surg. Gyn. and Obstet., 1910, 11, 146. 

25. Bartlett: Jour, of Exp. Med., April 1, 1912, 414. 

26. Morat: Physiol, of Nervous Syst., 337. 

27. Meltzer: Am. Jour, of Physiol., 1903. 

28. Bayliss: Jour, of Physiol., 1S99, 16, 10. 

29. Bradford: Jour, of Physiol., 1S99, 10, 358. 

30. Hill: Further Advances in Physiology. London, 1909. lis 

31. Crile: Hemorrhage and Transfusion, N. Y., 1909, 75. 

32. Carrel: Jour. Exp. Med., Aug., 1913. 

33. Thoma: Path, and Path. Anat., London, 1S96, Cha. 11. 

34. Dolley: Jour. Med. Research, July, 1909, 95; ibid, April. 
1910, 331. 



.hi v L914.] 



JOHNS HOPKINS HOSPITAL BULLETIN. 



213 



THE NORMAL DIASTASE-CONTENT OF THE CTRINE. 

By Tiiomas R. Bb&wn, M. I».. 

\NI) 

('. Wii vino . Siti in. Jr. 



[From tlf i 

We have studied, in a series of cases, the amount ol 
diastatic ferment presenl in the urine of norma] adults in 
the hope, in tin- first place, thai bj establishing a normal tin.' 
quantitative estimation of this ferment in the urine might in' 
of value in the diagnosis of pancreatic disease, and, in the 
second place, to furnish criteria of some value in estimating 
the importance of this procedure a- a test of renal function, 
Wohlgemuth suggested this a- a satisfactory method of 
estimating tin.- secretory activity of the kidney, and Rowntree 
reported later a Dumber of cases in this connection; a- we 
shall see, probably it- greatesl value is a- a tesl of renal func- 

I'hc individuals in our series were normal mei 
women, with no demonstrable lesions of the kidneys or diges- 
tive apparatus, living on a mixed dietary. 

In studying the urine we used a slight modification of the 
•]r>t described by Wohlgemuth in the " Biochemische 
ft," based "ti the conversion by diastasi 
starch ( Ejahlbamn) into, successively, erythrodextrin, achroo 
dextrin, iso-maltose, ami maltose, the limit being determined 
by that tnbe in which the addition of an iodine solution pro- 
ration, ''. '.. when all thr soluble starch has 
averted into lower products. 

etermining the quantity of diastase in the urine, the 
four-hour specimen was carefully collected, kepi under 
toluol iii the ice-box, or in a cold place. This was diluted 
with distilled watei to 3000 cc., ami decreasing amou 
tin- diluted urine wit.' added to a series of tub 

In our first group of cases we u-.-il the thod of geometri- 

! cc. in tin- lir-t IiiIm'. 1 cc. in the 
the third, [ cc in the fourth, j cc. in the fifth, etc., 
the variation between contiguous tubes 
tin- method, we Inter, in our much largi i • 
the method of mathematical progression I 8 
in the lir-t tul««\ 1.6 in the second, 1.1 in the third, 1.'.' in the 
fourth, 1 in the fifth, 0.8 in the sixth, 0.6 in the seventh, ".I 
n the ninth. 0.1 in the tenth, 0.05 in tin' 
. and 0.025 m the twelfth, tin' last 3 rub • 
•metrical progression. 

led « ith distilled wateT to 2 . . . 
0.1 |ht c.-nt solution of soluble starch added to each tul>o. 
■• 'I for half an hour m the water hath at 38 < .. rapidly 
off at the end of that time by nearly filling tin 
with cool water, and by holding the tubes under the 
and then quickly tested by the addition o rops ■■' 

ormal iodine solution, the limit being the tul 
the tir-t tube in which blu< 
g the brown color which erythrodextrin givi 



atory of tin Medical anm . i 

In the 10 cases studied by the former method the variations 

were comparative!} small and in all cases more than l 

units, the unit chosen beinj i centimeter of 1 per 

cent Boluble starch solution completely converted into lower 
products m one-half an hour in the water hath at 38 I 

As the variation- between the contiguous tubes seem too 

greal by this method the findings by the sec 1 method are 

of more value in furnishing exact figures (see Table I ). Of 





TABLE I. 






Amount in 24 hours. 




1 


1000 cc 




■> 


1125 " 


10 + 11- 


3 


760 ■' 


8+9- 


4 


1 " 


1" . ii 




1820 " 


10 + 11- 


6 


1730 " 


10 • 11 


- 


500 " 




8 


1520 - 


10 |-11- 


9 


1460 ■■ 


9 + 10- 


10 


1070 '■ 


■, . lo 


11 


380 '• 


11 + 12- 


12 


370 " 




13 


1450 " 


11+12- 


14 


620 " 


9 + 10- 


15 


320 '• 


8 ■ 9 


L6 


1900 " 


11 + 12 


17 


1250 •• 


10 H n 


IS 


1440 " 


9 + 10- 



the 18 cases in this series in 3 the limit was tube s (1500 

units), in 5 tube 9 (3000 units) in 3 tube l" (6 

and in 3 tube 11 ( 12,000 uni 

While the variations are considerable, as woul 

from differences in the diet, as Bome E Is an more stimulat- 

pancreatic and salivar) secretion than others, and as 

the diastasi is widely distributed in the body (being furnished 

ferment by the salivary glands, pancreas, and, 

to a \,t\ Blighl extent, bj Brenner's -land-, and being presenl 

as an autolytic fermenl in the liver, muscles, blood, in fact, i'i 

practically all tl rgane and tissues of the body), 

would seem that the diasta ntenl of the urine falls within 

definite, if rather wide, limits, and anj figures -mailer than 
the low normal found (tube 8, in our second method 
sponding to L500 units) would speak cither for a 

ulating dia-ta-e or diminished renal permeability due 
to changes in the kidni 

:ie diluted urine was in 
other cases neutral, m others slightly alka idled in 

a new group of i as< ? thi i ffe I of this va 

11 J m > 1 1 the BCtil if- I 

that while a Blightlj ■ n • dii 



214 



JOHNS HOPKINS HOSPITAL BULLETIN. 



[Xo. 281 



TABLE II. 

Reaction , t l - ri "f, Limit-tui 
i\e.it_Livn. Amount in 24 hours. 

Case 1 Acid 1400 cc. 10 + 11 

Alkaline 1460 " 9 + 10 

•' 2 Ac. 1550 " 10 + 11 

Alk. 1550 " 10 + 11 

" 3 Ac. 720 " 10 + 11 

Alk. 720 " 9 + 10 

" 4 Neutral 1220" 9 + 10 

Ac. 1220 " 9 + 10 

Alk. 1220 " 9 + 10 

" 5 Neut. 1690 " 11 + 12 

Ac. 1690 " 11 + 12 

Alk. 1690 " 11 + 12 

" 6 Neut. 1020" 10 + 11 

Ac. 1020 " 9 + 10 

Alk. 1020 " 10 + 11 

" 7 Neut. 460 " 8+9 

Ac. 460 " 10 + 11 

Alk. 460 " 9 + 10 

" S Neut. 1310 " 10 + 11 

Ac. 1310 " 10 + 11 

Alk. 1310 " 10 + 11 



of the ferment, nevertheless, the variations were so slight 
as not to necessitate the bringing of all the specimens to a 
condition of neutrality, or to the same degree of acidity or 
alkalinity. Slight variations in the temperature of the water 
(from 37° to 40° C.) also showed a very slight influence on 
the activation of the ferment, as Wohlgemuth and others have 
shown, although obviously it is important to keep the bath 
at as constant a temperature (38° C.) as possible, for wide 
temperature variations have a marked effect. 

In studying the diastase contents of the urine in pathologi- 
cal conditions, we found in a case of diarrhoea with fatty stool 
the limit was tube 9 (3000 units) ; in a case of post-operative 
gall-bladder fistula with normal pancreas also 9 (3000 units) ; 
in 2 cases of chronic pancreatitis with persistent jaundice, 
the common duct going through the head of the pancreas and 
being obstructed thereby, the limits were tubes 4 (500 units') 
and i:i (750 units) respectively; in a case of advanced carci- 
noma of the pancreas with jaundice, tube 1 (333 units) ; in a 
case of pancreatic cyst, still draining, tube 7 (1000 units) ; in 
one no longer draining, tube 10 (G000 units) ; in a carcinoma 
of the oesophagus with marked asthenia and emaciation, but a 



normal pancreas, tube 7 (1000 units) ; in an early carcinoma of 
the gall-bladder with normal pancreas, tube 9 (3000 units ) ; in 
a case of chronic pancreatitis without jaundice, tube 8 (1500 
units). All these diagnoses excepit the first were verified by 
operation. Thus it will be seen that i