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GIFT OF
Dr. FRflfin BILLING6.

ikiS^asst

GIFT OF
Dr. FR/ifiK BILUNG6.

FOCAL INFECTION

THE LANE MEDICAL LECTURES

BY
FRANK BILLINGS, Sc.D. (Haev.), M.D.

DELIVERED ON SEPTEMBER 80, 31, ie, iS AND 24, lOlS

STANFORD UNIVERSITY MEDICAL SCHOOL

SAN FRANCISCO, CALIH)RNIA

D. APPLETON AND COMPANY

NEW YORK AND LONDON

1916

d: appleton & company

• • •

» • •

• • •

" V • • •

• • • •

* • *•

• • • • • • •

• •

• * • •

Printed in the United States of America

B59
Co p. I

INTRODUCTION

The Importance of the etiologic relation of Focal Infection
to Systemic Diseases has been a subject of study in the clinical
material of Rush Medical College, in affiliation with the Uni-
versity of Chicago and the Presbyterian Hospital for the past
twelve or more years.

As the study progressed, the attention and cooperation of
clinicians and laboratory workers were aroused and developed
into a scheme of "team work." This esprit de corps eventually
embraced the nursing staff and the patients. Real clinical re-
search was made possible by this cooperative spirit. Living
morbid tissues were obtained at surgical operations and also
from other patients, who submitted voluntarily and in many
instances requested the removal, when necessary under local or
general gas anesthesia, of bits of infected tissue (muscle,
capsule of joints, lymph nodes, erythematous nodes, fibrous
nodes of tendons ) of exudates and of the blood, for experimental
purposes.

Histologic and bacteriologic studies of this material were
made. Animal inoculation was carried on and the lesions of
the experimental animals were studied and compared with the
morbid human tissues which were the source of the investi-
gation.

Eventually the Memorial Institute for Infectious Diseases,
the Otho S. A. Sprague Memorial Institute and the Pathological
and Research Department of St. Luke's Free Hospital of Chi-
cago cooperated in the work.

The conclusions based upon the research were not made until
a critical survey of the work and the results were investigated

42171

vi INTRODUCTION

by other qualified clinicians, pathologists and research workers.

I may not name, because of want of space, all who have co-
operated in the team work, which has made the research a
practical success and has opened up a broad field for a more
extended study along similar lines. To my clinical colleagues
in the college and hospital I extend my grateful thanks. Pro-
fessors L. Hektoen, E. R. LeCount and H. Gideon Wells have
been of invaluable aid to all of us, with advice always helpful
though sometimes critical. The members of the house stafF
have rendered invaluable help by a tireless and enthusiastic
bedside and clinical laboratory service. Many of these
internes have continued in the work as clinicians, patholo-
gists and clinical bacteriologists. Drs. D. J. Davis, R. T.
Woodyatt, H. K. NicoU, W. E. Post, E. E. Irons, A. M.
Moody, F. W. Gaarde, J. J. Moore, and George H. Coleman
have done notable work in bacteriology, chemistry, and in
experiments upon animals.

The broad significance of the relation of focal infection to
systemic disease has been made more definite by the brilliant
work of Edward C. Rosenow, who joined the clinic in 1904.

These lectures, therefore, represent the cooperative study of
many workers. I have made free use of the results of the
labors of all who have aided in the work and I am proud to be
their spokesman.

Frank Billings.

CONTENTS

IMCTXJBM VAQM

I. A General Consideration of Focal Infection . . 1

Site of Primary Foci — Etiology of Focal Infection —
Susceptibility to Systemic and Local Diseases from the
Focus of Infection — Greater Susceptibility to Systemic
Disease from a Focal Infection Undoubtedly Occurs —
The Diagnosis of the Focus of Infection — Mode of
Dissemination of Bacteria and Toxic Products from
the Focus of Infection — Focal Infection and Anaphy-
laxis.

II. The Streptococcus-pneumococcus Group. Trans-
mutability OF the Members Thereof. Patho-
genicity and Specific Tissue Affinity of Trans-
mutation Forms 26

Transmutation Within the Members of the Strepto-
coccus-Pneumococcus Group.

III. Acute Diseases Related to Focal Infection ... 48

Acute Rheumatic Fever — Rheumatic Endocarditis,
Myocarditis and Pericarditis — Chorea — ^Acute Sys-
temic Gonococcus Infection — Malignant Endocardi-
tis — ^Acute Nephritis — ^Acute Appendicitis — Cholecys-
titis — Acute Gastric and Duodenal Ulcer — Acute Pan-
creatitis — Erythema Nodosum Herpes — Spinal Mye-
litis — ^Adute Osteomyelitis — Thyroiditis — Iridocyclitis.

IV. Chronic Diseases Related to Focal Infection . . 107

Chronic Infectious Arthritis — Chronic Infectious Ne-
phritis — Chronic Cholecystitis — Chronic Peptic Ul-
cer — Chronic Infectious Endocarditis.

Vll

viii CONTENTS

UBCTUBB . PAOB

V. Treatment 127

Focal Infection — Treatment of Resulting Acute and
Chronic Systemic Diseases — Serum and Vaccine Ther-
apy-

Bibliography 159

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GAVE THE LANE MEDICAL LECTURE

in 1916 here at Stanford, get copy.

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under Frank Billings name
Anything published in that period

Billings: 1854-1932

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LIST OF ILLUSTRATIONS

no. PAoa

1. Strain 595 as a hemolytic streptococcus isolated from a

case of scarlet fever . 28

2. Strain 595 as streptococcus viridans 29

3. Strain 595 as a pneumococcus 29

4. Strain of streptococcus from rheumatism 30

5. The same strain as in Fig. 4 after it was transformed

into a pneumococcus 31

6. Highly virulent pneumococcus 31

7* Same strain as in Fig. 6 after transformation into hem-
olytic streptococcus 32

8. Streptococcus^ nodular^ valvular and mural endocarditis

of dog 5S

9* Vegetative and ulcerative endocarditis of aortic valves

and aorta of dog 60

10. Section through vegetations on mitral valve shown in

Fig. 9 61

11. A glomerulus containing a hyaline thrombus .... 63

12. Masses of fibrin in a glomerulus 64

13. A glomerulus in which are masses of cocci filling a group

of capillaries 65

14. Marked hemorrhage of the appendix 67

15. Hemorrhage and localized infection of mucous mem-

brane 68

16. Human appendicitis 12 hours after onset in young man 69

17. Diplococci in peritoneal coat of appendix 70

18. Hemorrhage necrosis and leukocytic infiltration ... 71

19. Streptococci in lymph follicle shown in Fig. 18 . . . 72

20. Streptococci and fusiform bacilli in human gangrenous

appendicitis 72

X LIST OF ILLUSTRATIONS

no. pAcn

21. Hemorrhage^ necrosis and leukocytic infiltration of ap-

pendix 24 hours after infection 73

22. Streptococci and fusiform bacilli of appendix of rabbit 73

28. Photomicrograph of 24-hour culture in ascites-dextrose-

broth of a streptococcus 74

24. Hemorrhagic cholecystitis in dog 75

25. Marked edema of gall-bladder in dog 76

26. Streptococci in lymph space of edematous wall of gall-

bladder shown in Fig. 25 77

27. Photomicrograph of 24-hour ascites-dextrose-broth cul-

ture of streptococcus from human ulcer . . . . • 78^

28. Marked ulceration of stomach in guinea pig .... 79

29. Photomicrograph 24-hour ascites-dextrose-broth culture

of a streptococcus from blind abscess of jaw • • . 79

86. Ulcer of stomach of dog 80

81. Capillary filled with diplococci in the apex of ulcer

shown in Fig. 80 80

82. Section of wall of stomach of rabbit 81

38, Streptococci at apex of wedge-shaped area shown in

Fig. 82 82

84^ Hemorrhagic pancreatitis in dog 88

35, Section of pancreas in dog 84

86, Photomicrograph showing diplococci in area of round

cell infiltration 85

87* Subcutaneous tissues from erythema nodosum in man . 86

88. Subcutaneous tissue from erythema nodosum in man . 87

89. Smear from single colony in ascites-dextrose-agar . . 87

40. Smear from blood of guinea pig 88

41. Photograph showing circumscribed hemorrhages of the

skin and symmetrical hemorrhages of the fascia of

the inner aspect of the legs of a rabbit 89

42. Section of skin of rabbit showing hemorrhage and leu-

kocytic and round cell infiltration of subcutaneous
tissue 90

48. A diplococcus in the area of infiltration shown in Fig. 42 91

LIST OF ILLUSTRATIONS xi

no. PAQl

44. Section of the artery, from the area of subcutaneous

hemorrhage 91

45. Diplobacilli in the wall of artery shown in Fig. 44 . . 92

46. Photomicrograph of 24-hour culture in ascites-dextrose-

broth of a streptococcus from the spinal fluid of a
rabbit 92

47. Herpes as seen on under surface of the skin over the

lower right thoracic region of a rabbit 9^

48. Diplococci in the hemorrhagic spinal ganglion • • • . 94

49. Herpes of the skin of the inner and upper aspect of

right thigh of a rabbit 95

50. Thrombosis of a vein (a) and paravascular infiltration

(b) of the posterior spinal root 96

51. Diplococci in leukocytes within a thrombosed vein . . 97

52. Diplococci in hemorrhagic and infiltrated area shown in

Fig. 53 97

53. Marked hemorrhage (a) and leukocytic infiltration (b)

surrounding the lumbar nerve 98

54. Herpes of tongue^ mucous membrane about teeth and

lips of rabbit 99

55. Herpes of skin of left side of face of rabbit . . . . 100

56. Hemorrhage (a) and round cell infiltration (b) of the

gasserian ganglion of dog 101

57. Section of iris and ciliary body of rabbit 104

58. Photomicrograph of streptococci in area of infiltration

shown in Fig. 57 105

59. Localized hemorrhages (a) in the sclera near the limbus

and at the attachment of the external rectus muscle

of rabbit 106

60. Diplococcus adjacent to area of hemorrhage in Fig. 59 . 106

61. A typical subacute focal lesion in the cortex . . . . 114

62. An interlobular vein surrounded by lymphocytes and

plasma cells 115

63. Cholecystitis and cholelithiasis in dog 117

xii LIST OF ILLUSTRATIONS

no. FA<n

64. SiEfeptococci and leukocytic infiltration in peritoneal

coat in perforating ulcer of the stomach of man . . 118

65. Streptococci in peritoneal coat of ulcer of stomach in

rabbit 119

66. Streptococci and leukocytic infiltration in chronic ulcer

of man 119

67. Chronic ulcer of duodenum of dog 13 weeks after a

single intravenous injection of streptococcus from
ulcer of the duodenum of man '. . . 120

68. Chronic ulcer of duodenum of dog 13 weeks after a

single intravenous injection of streptococcus from
human ulcer 120

FOCAL INFECTION

LECTURE I

A GENERAL CONSIDERATION OF FOCAL INFECTION

Permit me to express to you my sincere appreciation
of the honor conferred upon me, by the Trustees and
Faculty of Stanford University Medical School, to
give the fifteenth course of the Lane Medical Lectures.

I am complimented also by the fact that the group
of workers with whom I am associated, has been en-
gaged in the clinical and laboratory investigation of a
subject about which you desire to hear.

Systemic or general disease due to a local infection is
a conception as old as medical knowledge.

Long before the development of bacteriology there
had been noted many examples of general disease aris-
ing from trivial and serious accidental and surgical
wounds. The general disease was, as a rule, character-
ized by chills, fever, and general debility and was often
fatal.

The cause was thought to be contamination of the
wound or focus with some substance which caused putre-
faction. Hence the resulting general disease was called
septic. The so-called laudable pus of an uneventful

healing wound, when contaminated with putrefactive

2 FOCAL INFECTION

poison, which changed in color, fermented, acquired a
bad odor, and, gaining entrance to the blood stream,
caused pyemia or septicopyemia. Discussion as to the
origin of the putrefactive agents brought forth many
theories until the epoch-making discovery of Semmel-
weis ( 1847) who traced the constant prevalence of child-
bed fever in the Vienna lying-in hospital to contamina-
tion of the genitalia of the woman in labor by the un-
clean hands of students and physicians fresh from the
dissecting rooms. Cadaveric poison, therefore, was
proved to be a cause of childbed sepsis. Local infection
followed by embolism, thrombosis and septicemia were
recognized as successive stages which were observed in
surgical and obstetrical sepsis. E. Klebs was probably
the first to recognize that local and general sepsis were
due to microorganisms which he termed microsporon
septicum. But no material gain in practical results oc-
curred until the deductions of Lister, based upon the
brilliant researches of Pasteur, that wound infection was
due to a virus animatum and the rational application by
Lister of measures to prevent wound infection. Lister-
ism — antiseptic surgery — ^was of rapid growth and in its
evolutional form as applied today makes general sepsis
in surgery and midwifery a criminal offense due to ig-
norance, carelessness or faulty technic.

But focal infection, which is the subject of these lec-
tures, is broader in its application than is expressed in
surgical sepsis.

During the last decade a new interest has been
aroused in the subject of focal infection as an etiologic
factor of local and of general diseases. The wider dis-

A GENERAL CONSIDERATION 3

cussion of the subject made it appear as a new prin-
ciple. The wider and broader interest in the subject
has been brought about by a better knowledge of bac-
teriology, of modes of infection, and by cooperative lab-
oratory and clinical research.

A focus of infection may be defined as a circum-
scribed area of tissue infected with pathogenic micro-
organisms. Foci of infection may be primary and sec-
ondary. Primary foci usually are located in tissues
communicating with a mucous or cutaneous surface.
Secondary foci are the direct results of infection from
other foci through contiguous tissues or at a distance
through the blood stream or lymph channels.

SITE OF PRIMARY FOCI

Primary foci of infection may be located anywhere
in the body. Infection of the teeth and jaws, with the
especial development of pyorrhea dentalis and alveolar
abscess, infection of the faucial and nasopharyngeal
tonsils and of the mastoid, the maxillary and other
accessory sinuses are the most common forms of
focal infection. Submucous and subcutaneous abscesses
including the finger and toe nails are occasional foci.
Chronic infection of the bronchi and bronchiectasis;
chronic infection of the gastro-intestinal tract and aux-
iliary organs of digestion, including cholecystitis, ap-
pendicitis, intestinal ulcers and intestinal stasis due to
morbid anatomical conditions; chronic infection of the
genito-urinary tract, including metritis, salpingitis,
vesiculitis seminalis, prostatitis, cystitis and pyelitis, are
not uncommon forms. Infected lymph nodes, which are

■^

4 FOCAL INFECTION

secondary to the primary foci named, become additional
depots of local infection. The secondary lymph node
infection may persist after the etiologic, distal, primary
focus has been removed or has spontaneously disap-
peared. Other secondary foci may appear in various
tissues as a part of the general or local disease which
results from a primary focus. As we shall seej systemic
and local disease may occur through infection from a
focal point by way of the blood stream. This mode of
infection is often embolic in character. The tissues so
infected may constitute new foci, which in part explains
the chronicity of many local and general infections.

ETIOLOGY OF FOCAL INFECTIONS

Focal infection especially of the structures of the
mouth and the upper air passages is a very prevalent
condition. The incidence of infection of the mouth
is enormous everywhere. In addition to the presence of
innumerable saprophytes in the mouth and pharynx,
one may find in the saliva and pharyngeal mucus, strep-
tococci and staphylococci, micrococcus catarrhalis, pneu-
mococci, diphtheria and pseudodiphtheria bacilli, men-
ingococci, tubercle bacilli and many other pathogenic
bacteria. C. C. Bass (1) and others state that endameba
buccalis was found in the mouths of 95 and even 100
per cent, of all adults examined. The presence of these
infectious microorganisms in the mouth and upper res-
piratory tract indicates unhealthful surroundings and
individual uncleanliness. The individual carrier infects
others by contact and by other means.

A GENERAL CONSIDERATION 5

The character of local infection in various parts of the
body is so important that separate consideration must
be given to each kind.

Pyorrhea D entails and Alveolar Abscess

Pyorrhea dentalis and alveolar abscess (Rigg's dis-
ease) is^ condition incident to all classes of adults. It
is much less prevalent in the young. It is a disease
which fundamentally involves the periosteum of the root
and neck of the tooth ( peridental membrane ) . It is the
chief cause of the loss of the permanent teeth. It may be
associated with caries of the crown, and, on the other
hand, the crown may remain normal. The infection
first attacks the edges of the gum, which may be macer-
ated by decaying food particles between the teeth, or
the gum may be injured in masticating hard substances,
by toothpicks, and other traumatic agents. Ill health
and poor general nutrition make the gums less resistant.
The endameba buccalis and various pyogenic bacteria
which gain admission to the edges of the gums cause
retraction of the soft tissues and the exposed peridental
membrane of the neck and root of the tooth become in-
volved in sequence. This periosteum injured or de-
stroyed, there follows softening and ulceration of the
soft parts with the end result of acute or chronic alveo-
lar abscess.

Endameba has been known to be a parasite of the
mouth for many years. Its relation to pyorrhea alveo-
laris was first described by F. M. Barrett, (2) in col-
laboration with Allen J. Smith in 1914. Without a
knowledge of the work of Barrett and Smith, C. C.

6 FOCAL INFECTION

Bass and F. M. Johns (1) had recognized the relation
of the parasite to pyorrhea and had begun experimental
treatdfent with emetin. The endamebas may be found
in the gum lesions and they are numerous in the deeper
abscesses where they live on the dead tissues. Bass and
other investigators believe that the endameba buccalis
is the chief etiologic factor in the development of pyor-
rhea alveolaris.

From the pus and dead material of alveolar abscess
and the infected pulp of the teeth, with a proper technic,
cultures yield streptococci, chiefly streptococcus viridans
and streptococcus hemolyticus, staphylococcus aureus
and albus, fusiform bacilli and other less important bac-
teria. Doubtless the endamebas play an important part
in the occurrence of pyorrhea alveolaris and permit in-
fection with the pyogenic bacteria. The bacteria pres-
ent in the infected areas are the important factors, how-
ever, in the causation of general infection from the
focus.

Acute and Chronic Tonsillitis and Infection of
Lymphoid Tissue in the Nasopharynx

The faucial tonsils are frequently infected through
contaminated air, infected food, especially milk, and by
direct contact with infected individuals. Many children
have large tonsils and overgrowth of other lymphoid
structures of the pharynx which make a good soil for
bacterial growth. Hypertrophy of the tonsils and ade-
noid overgrowth in the nasopharynx interfere with res-
piration, resulting in deformities of the bones of the face
and thorax. Obstruction of the upper air passages pre-

A GENERAL CONSIDERATION 7

vents proper drainage from the nasal cavities and ac-
cessory sinuses and leads to infection of the middle ear,
the sinuses of the head and the mucous membrane cover-
ing the turbinate bodies. In adult life small faucial ton-
sils may look innocent because of a smooth covering of
mucous membrane which seals over infected crypts or
an actual abscess. So, too, the stumps of tonsils, the
remains of tonsillotomy, may contain infected crypts
sealed by the operative scar.

Infected tonsils and adenoids may yield cultures of
streptococcus mucosus, streptococcus viridans, strepto-
coccus hemolysans, micrococcus catarrhalis, pneumococ-
ci, bacillus mucosus capsulatus, grippe bacillus, diph-
theria and pseudodiphtheria bacilli and other pathogenic
microorganisms. The tonsils and surrounding lymph
tissues may be a focus of tuberculosis from which lymph
nodes of the neck and mediastinum may become in-
fected. Smith and Barrett (3) found endameba buc-
calis in the tonsils of five of seventeen patients. The
presence of endamebas in the tonsils would probably
favor deep pyogenic infection.

Mastoiditis and Sinusitis of the Maanllary and Other

Accessory Sinuses

Mastoiditis as an extension of nasopharyngeal infec-
tion through the eustachian tube and middle ear is a
serious and frequent disease of the young and occasion-
ally of adults. Members of the streptococcus-pneumo-
coccus group are the usual infectious agents. Staphylo-
cocci and influenza bacilli may be the invaders. The
proximity of the mastoid cells to the venous sinuses of

8 FOCAL INFECTION

the skull makes this focus a frequent source of sinus
thrombosis, bacteriemia and meningitis.

Infection of the accessory sinuses is of frequent oc-
currence during the changeable seasons. The most fre-
quent bacterial causes are strains of streptococci, pneu-
mococci, micrococcus catarrhalis and influenza bacilli —
less frequently staphylococci. In chronic sinusitis, often
unrecognized, various pyogenic bacteria occur with the
occasional presence of colon bacilli, the bacillus welchii
and various saprophytic organisms. Sinus infection is
frequently chronic because of faulty drainage. When
chronic it may present local symptoms only when a new
"cold" is acquired.

All infectious foci of the head may be associated with
secondary infection of the lymph nodes of the neck and
mediastinum. Kretz (25) records six hundred autop-
sies with especial reference to the infection of the cer-
vical lymph nodes. In childhood, he says, the superfi-
cial nodes of the anterior triangles are involved and soft,
while in adults the deeper glands at the angle of the jaw
and the region of the internal jugular vein are more
often involved and are usually indurated. He stated
that in 90 per cent, of the bodies examined the glands
showed streptococcus infection and 10 per cent, yielded
other bacteria. Kretz believes that many children suffer
from acute glandular fever, due to angina, and that the
infectious microorganisms pass rapidly through the
cervical lymph channels and glands with resulting severe
bacteriemia and fever. Hence a fatal result obtains in
virulent types of glandular fever in children. He states
that in older people the filtration through the deeper

A GENERAL CONSIDERATION 9

cervical glands is slower. Consequently the virulence
of the bacteria and the degree of bacteriemia may be
less. The lymph node infection may disappear with
the removal of the primary focus or may persist actively
as new foci in the production of systemic disease or the
infection of the nodes may become permanently latent.

Chronic Bronchitis and Bronchiectasis

Long standing bronchitis associated with emphysema,
asthma, and bronchiectatic cavities presents a type of
localized chronic infection which msiy be an etiologic fac-
tor in systemic infection and trophometabolic changes
in bones and joints probably due to toxic products ab-
sorbed from the site of infection. The sputa in the
conditions named yield cultures of many saprophytic
bacteria as well as streptococci, staphylococci, pneumo-
cocci, influenza bacilli, micrococcus catarrhalis, fusi-
form anaerobes and other pathogenic bacteria.

Focal Infection of the Gastro-intestinal Canal, Vermi-
form Appendix, Gall-bladder and Pancreas

Auto-infection and auto-intoxication from the intes-
tinal canal as a cause of disease is a popular idea with
the medical profession. Stasis of the intestinal contents
is alleged to be an important factor in the causation
of auto-infection. Intestinal stasis may be due to habit-
ual constipation, to partial obstruction of the intestines
due to congenital defects, or to acquired morbid ana-
tomical conditions which favor the presence of patho-
genic bacteria with putrefactive changes, resulting, it is
believed by many, in toxemia and systemic disease. An-

10 FOCAL INFECTION

emia, chronic arthritis, Bright's disease, arteriosclerosis,
and even local diseases like appendicitis, cholecystitis
calculosa and peptic ulcer, are believed to be caused by
stasis and putrefactive changes in the intestinal con-
tents. This large focus of infection has been attacked
in the attempt to remove the offending bacteria by intes-
tinal antiseptics, colonic flushing, buttermilk and other
lactic acid bacilli containing fluids and tablets and ca-
thartic waters, and th^ surgeon has invaded the abdomen
to correct the intestinal stasis by removing kinks, veils
and other alleged deformities, and even by resecting the
entire colon.

There is doubtless some truth in the theory of in-
testinal infection, but the pathogenic microorganisms in
the intestinal canal, which remain there as infectious or-
ganisms, gain entrance chiefly by swallowing infectious
material from the mouth, throat and nose and also
through infected food and drink, especially milk, for
milk is very apt to contain streptococci which are viru-
lent or may become so. Streptococci and other patho-
genic bacteria probably infect the lymph tissue of the
intestine or may pass into the lymph nodes of the mes-
entery and set up active or passive infection. As we
shall see later, streptococcal infection from a focus in
the head may hematogenously cause appendicitis, chole-
cystitis, peptic ulcer and pancreatitis. In addition to
the immediate local damage, the bacteria in these tissues
may form new foci from which proximal lymph nodes
may become infected. From these new foci further ex-
tension gf the infection may take place through the
lymph channels or the blood stream or through both.

A GENERAL CONSIDERATION 11

Appendicitis is usually caused by a strain of the
streptococcus group from a mouth or throat focus. The
colon bacilli and other members of the intestinal bac-
terial flora in the appendix may take on pathogenic
qualities and cause a mixed infection. Often this mixed
infection is fulminating and severe. Chronic types of
appendicitis not only cause local distress and digestive
disturbances, but may become a cause of infection of
the mesenteric glands and through the lymph vessels
and blood stream may infect the liver, bile tracts, and
subdiaphragmatic tissues. Cholecystitis may also be
caused by a streptococcus infection from a focus of the
head. The infectious microorganism carried in the
blood stream from the focus may lodge in the terminal
blood vessels of the fundus of the gall-bladder. The
inoculated blood vessel becomes wholly or partly oc-
cluded by endothelial proKferation and leukocytic infil-
tration, and blood containing the bacteria escapes into
the wall of the bladder. Necrosis of the local tissues
and rupture of the infected material into the gall-blad-
der may occur. Acute severe cholecystitis may result.
Less severe infection may result in a chronic cholecysti-
tis and subsequent gall-stone formation. Typhoid and
colon bacilli may cause cholecystitis or may be associated
in a mixed infection of the organ. Cholecystitis may
be a focus of systemic infection.

The rectum, with its rich supply of hemorrhoidal
veins, becomes a focus of infection, through ulcers, in-
fected thrombi in veins and local abscesses. Infected
thrombi from these points may produce acute circum-
scribed hepatitis ( abscess ) , and bacteriemia.

12 FOCAL INFECTION

Foci of Infection of the Genito-urinary Tract

Immediately after childbirth, miscarriage or abortion,
the endometrium is very susceptible to infection by any
of the pyogenic microorganisms. The resulting focus
is usually serious because of the tendency to the forma-
tion of infected thrombi in the uterine sinuses. The
bacteriemia which results is severe. At other times
the endometrium is not a frequent site of focal infection.

The fallopian tubes are very susceptible to infection
with pyogenic bacteria, but most frequently the cause
is the gonococcus with resulting obliterating salpingitis
or abscess which may infect the peritoneum. Tubercu-
lous salpingitis may cause tuberculous peritonitis. Fo-
cal infection in the form of gonorrheal vaginitis is a
common disease of defective girls and of girls in hospi-
tals and public institutions. The condition is important
because of the readiness with which it is conveyed from
individual to individual by contact or through fomites.
The condition usually remains a local one with conse-
quent discomfort confined to the parts involved. Oc-
casionally the peritoneum, joints and other tissues may
become infected from the vaginal, uterine and tubal
focus.

The seminal vesicles and testes are sites of focal in-
fection with the gonococcus, tubercle bacillus and pyo-
genic bacteria.

Probably tuberculous infection of the genital ap-
paratus is secondary to a focus elsewhere. Tuberculous
infection of testes usually involves the seminal ducts and
vesicles by extension through the lymph channels, blood

A GENERAL CONSIDERATION 13

stream or vas deferens. This focus may result in gen-
eral tuberculosis or involve the urinary bladder and kid-
ney by the blood stream or lymph canals.

Gonorrheal vesiculitis may be acute or chronic and
lead to gonorrheal arthritis, acute or chronic, or to gon-
orrheal bacteriemia, and ulcerative endocarditis. Infec-
tion of the seminal vesicles may be due to streptococci
and staphylococci and cause systemic disease. The pros-
tate gland may be infected with gonococci, streptococci,
staphylococci, tubercle bacilli, colon bacilli and other
less important bacteria. When infected and enlarged it
is an important factor in infection of the bladder, ureters
and kidneys, by causing urinary obstruction and cystitis.
Cystitis may be due to pyogenic bacteria, tubercle ba-
cilli, bacillus pyocyaheus, typhoid bacilli and other bac-
teria. The colon bacillus is a very common inhabitant
of the urinary tract and usually is apparently not harm-
ful. In the presence of bladder stasis and in other types
of cystitis (tuberculous, streptococcus, staphylococcus
cystitis), the colon bacteria may take on pathogenic
qualities as a mixed infection. Acute and chronic cysti-
tis may be the source of infection of contiguous tissues
and through the lymphatic vessels and lymph nodes of
the base of the bladder and in the walls of the ureters,
infection of the pelvis and parenchyma of the kidneys
and perirenal tissues may occur as shown by S. Sugi-
mura (4) and Carl Franke (5). The kidney and its
pelvis, however, is usually infected hematogenously with
pyogenic bacteria, typhoid, colon and tubercle bacilli and
other microorganisms. Indeed cultures of the urine,
with a proper technic, will yield characteristic bacteria,

14 FOCAL INFECTION

during the incidence of many infectious general and
local diseases, as shown by George F. Dick and Gladys
R. Dick (6). The kidney and renal pelvis may be
the site of focal infection which may cause infection of
the ureters and bladder through the urine contaminated
with tubercle, colon, typhoid and pyocyaneus bacilli,
pyogenic cocci, bacillus proteus and with other bac-
teria.

Subcutaneous abscesses and abscesses about the nails
are occasionally the source of systemic infection. Fur-
uncles and carbuncles are well known sources of acute
bacteriemia, especially in patients debilitated by ex-
hausting diseases of which diabetes mellitus is an ex-
ample.

SUSCEPTIBILITY TO SYSTEMIC AND LOCAL DISEASES FROM

THE FOCUS OF INFECTION

The high percentage of incidence of localized infec-
tion, especially about the head, has already been stated.
The greater number of these individuals affected, both
young and old, do not develop acute systemic disease
therefrom. A majority of children suffer from chronic
infection of the tonsils and nasopharyngeal lymphoid
tissue with occasional acute exacerbations, while the in-
cidence of acute rheumatic fever and endocarditis is
relatively small in youth. Nevertheless, rheumatic
fever and endocarditis are unquestionably the result of
focal infection of the mouth and throat.

A majority of civilized mankind, who are city dwell-
ers, carry a latent tuberculous focus, usually infected
lymph nodes of the mediastinimi, mesentery or else-

A GENERAL CONSIDERATION 15

where in the body. A comparatively small nimaber de-
velop clinically recognizable tuberculosis.

The marked prevalence of alveolar abscess is not
associated with the frequent incidence of acute systemic
infection. Probably the frequent relation of pyorrhea
to rheumatic fever, heart disease, nephritis and other
acute local and general infections has not been given
the etiologic importance it deserves. Granting this fact
one must still recognize the comparatively small inci-
dence of acute systemic disease arising from alveolar
abscess.

The incidence of chronic gonorrheal infection of the
prostate gland, seminal vesicles, vagina and fallopian
tubes is very large as compared with the occurrence of
gonorrheal arthritis, tenovaginitis, gonococcemia, and
ulcerative endocarditis.

The escape of a great majority of persons who harbor
foci of infection from manifest clinical systemic disease,
is the reason given by many thoughtful physicians for
disbelief in the etiologic relation of foci of infection to
systemic and local infection, especially of the chronic
types.

Based upon the present knowledge obtained by clini-
cal and laboratory research and experiments upon the
lower animals, there can be no doubt now of the etio-
logic relation of localized infection to both acute and
chronic systemic diseases. Many of the systemic chronic
processes are sequential to primary acute diseases, etio-
logically related to focal infection. Other chronic sys-
temic diseases are primarily due to infection derived
from focal infection.

16 FOCAL INFECTION

The relatively rare incidence of systemic disease as
compared with the marked prevalence of focal infection
may be answered, partially, at any rate, by well known
facts concerning immunity both natural and acquired.

The natural defenses of the body, due to the bacteri-
cidal and antitoxic powers of the tissues, blood plasma
and cells, especially the phagocytes, protect the major-
ity of us from the acute infectious diseases. All individ-
uals do not possess an equal degree of natural immunity ;
some more readily succumb to the invading infectious
agents. When the animal body is invaded with patho-
genic bacteria the natural defenses are increased by
their presence in the tissues and blood. The processes
are : first, the phenomenon of positive chemotaxis with
resulting leukocytosis and the acciunulation of leu-
kocytes in the areas of infection of the tissues by the
formation of local exudates, liquid (purulent) and fi-
brinopla»tic, which may serve as walls of protection
against further direct invasion; second, leukocytic
phagocytosis with destruction of the invading bacteria ;
and third, the formation of protective antibodies in the
blood and tissues.

Similar protective processes may be induced in the
body by the injection of non-lethal amounts of living
or of dead pathogenic bacteria into a healthy man or
animal.

It is not improbable that the bacteria of a focal infec-
tion may excite the development of additional defenses
in the host and prevent the evolution of a sequential
systemic disease.

Bacteria may diminish in virulency and pathogenicity

A GENERAL CONSIDERATION 17

and exist as harmless parasites of the skin, mucous
membranes and probably also as foci in the tissues
(KoUe and Wassermann (7)), for it is known that
the reaction of the tissues is influenced by the virulence
of the bacteria. A non- virulent streptococcus would be
disposed of by the tissues with but little local or gen-
eral reaction.

GREATER SUSCEPTIBILITY TO SYSTEMIC DISEASE FROM A
FOCAL INFECTION UNDOUBTEDLY OCCURS

Immunity both natural and acquired as described is
not absolute. Pasteur found that the marked immu-
nity of the chicken to anthrax could be overcome by
lowering the body temperature by immersion of the
fowl in cold water. It is known that physical and men-
tal exhaustion, starvation, exposure to cold, debility
from alcoholic dissipation, the misuse of narcotic drugs
and exhausting general disease may reduce the natural
resistance.

Inniunerable instances of the incidence of the sud-
den onset of pneumonia, rheumatic fever, tonsillitis,
sinusitis, nephritis, septicemia and other infectious proc-
esses have been recorded after exposure to extreme cold.
Undoubtedly the latent pathogenic bacteria usually
present in the nose and throat may acquire coincidently
with the exposure specific pathogenicity, and are able
to invade the host because of the lowered resistance and
because of added virulency. The acquisition of specific
pathogenicity and tissue affinity by the members of the
streptococcus-pneumococcus group will be fully con-
sidered.

18 FOCAL INFECTION J

Exhaustion and debility from physical and mental
overwork, starvation, chronic disease and other condi-
tions are important etiologic factors in the occurrence
of acute and chronic systemic disease from focal in-
fection. This is notably true of the chronic infectious
arthritis and myositis.

Many of the lesser ills of the body in the form of
subjective soreness of the tissues, joints, muscles and
nerves are possibly the result of slight infection from a
focus in the mouth or throat or some other region of
the body, especially in individuals with a lessened re-
sistance. This is perhaps a vague hypothesis, but in-
stances of the disappearance of these clinical phenomena
with the institution of individual hygiene and removal
of an existing focus of infection is suggestive of the
truth of the statement.

THE DIAGNOSIS OF THE FOCUS OF INFECTION

Usually a focus of infection is disregarded by the
patient and physician unless it cause local discomfort.
When a systemic disease occurs which present-day
knowledge associates with a primary infectious focus,
the site of the focus must be located. The character
of the systemic disease may point to the most likely lo-
cation of the primary portal of infection. The primary
focus of acute rheumatic fever, endocarditis, chorea,
myositis, glomerulonephritis, peptic ulcer, appendicitis -
and chronic deforming arthritis, as examples, is usually
located in the head and usually in the form of alveolar
abscesses, acute or chronic tonsillitis and sinusitis. One
would look for the focus of gonorrheal arthritis in the

A GENERAL CONSIDERATION 19

genito-urinary tract. The failure to find a focus in the
expected situation should indicate an extension of the
field of examination until the primary infection shall
have been found. In a superficial and hasty examina-
tion the site of the focus of infection may escape detec-
tion or the focus may be assumed to be in uninfected
tissues and organs. Every patient should be carefully
interrogated as to the past and present condition; a
general examination should be made, including, if neces-
sary, the services of specialists in diseases of the ear,
nose and throat, the pelvic organs and the gastro-in-
testinal tract, and in all patients with evidence of pyor-
rhea and sinusitis the service of the rontgenologist is
demanded. Bacterial cultures made from the surface
of the gums and tonsils, which will usually yield patho-
logic types of bacteria, are not an index of focal infec-
tion located in the dental alveoli or tonsils. In alveolar
abscess, by scraping the accumulated "tartar" and exu-
date from the exposed neck of the tooth and by penetrat-
ing as deeply as possible into the infected alveolus, one
may readily obtain material for microscopic examination
which usually yields endameba buccalis and bacteria.
Cultures of the feces may yield strains of streptococci
and other bacteria not usually found in the intestinal
flora. These bacteria may not be specifically pathogenic
in the intestinal habitat and if free in the intestinal con-
tents and not infecting the intestinal structures are
quite likely not to be harmful to the host. Bacterio-
logical examination including cultures should always
be made of the sputa, urine, uterine, vaginal and
urethral discharges and exudates obtained by massage

20 FOCAL INFECTION

of the prostate gland and seminal vesicles, for they
often yield results of diagnostic importance. The na-
ture of the general disease and its relation to a sup-
posed focus may be made more evident by the coincident
histologic and bacteriologic studies, both miscroscopic
and cultural, of exudates of synovial cavities, and of
excised lymph nodes proximal to the infected regions;
bits of infected muscles; fibrous nodes on tendons and
aponeuroses ; the blood, and also of the exudate of the fo-
cus; and by the inoculation of animals with strains of
the dominant pathogenic bacteria so obtained, while the
cultures are young. The discovery of the similarity of
the pathogenic organisms in cultural characteristics, in
the focus of infection and in the infected tissues, and the
production of a similar infectious process in the inocu-
lated animal from the tissues of which the infectious bac-
teria are afterwards recovered^ constitute reasonable
proof of the etiologic relation of the focus of infection to
the existing systemic infection. Many successful clinical
and laboratory studies of this kind have been made with
patients suffering with rheumatic fever, subacute or
chronic infectious endocarditis, chronic infectious arth-
ritis, appendicitis, peptic ulcer, cholecystitis, glomerulo-
nephritis and other diseases.

MODE OF DISSEMINATION OF BACTERIA AND TOXIC
PRODUCTS FROM THE FOCUS OF INFECTION

Hematogenous

Systemic infection and intoxication from a primary
focus is usually hematogenous. The bacteria may be
compared with emboli loosened from the place of origin

A GENERAL CONSIDERATION 21

and carried in the blood stream to the smallest and
often terminal blood vessels. If virulent and endowed
with specific elective pathogenic affinity for the tissues
in which they will lodge, and if in sufjficient number, the
invading bacteria will excite characteristic reactions in
the infected tissues and a sequential train of morbid
anatomical lesions. The evolution of the anatomical
lesions and the clinical phenomena aroused thereby are
dependent on the type and virulence of the bacteria,
the character of the tissue and the function of the organ
involved. The specific tissue reaction consists of a local
inflammation with endothelial proliferation of the lining
of the blood vessel with or without thrombosis ; blocking
of the blood vessels ; hemorrhage into the immediate tis-
sue ; positive chemotaxis with resulting multiplication of
the leukocytes and plasma cells in the infected area, or
fifcrinoplastic exudate with local connective tissue over-
growth.

Lymphogenous

The infectious microorganisms may also pass from
the focus to other tissues through the lymph channels
and lymph nodes. This may occur from the primary fo-
cus coincidentally with hematogenous systemic infection.
Primary focal infection of the tonsils, nasopharyngeal
tissue, the accessory sinuses and the mastoid cells is not
infrequently associated with secondary infection of the
lymphatic vessels and lymph nodes of the neck, some-
times extending to the mediastinal lymph nodes. The
lymph nodes which drain areas of tissues which have
been infected hematogenously from a primary focus
may become infected and enlarged from the systemi-

22 FOCAL INFECTION

cally infected areas as in infected joints, cholecystitis,
appendicitis and infection about the pelvic organs.

The tissue reaction which occurs in infected lymph
nodes varies in intensity with the virulency and char-
acter of the invading bacteria. Thus a varying degree
of inflammation results in proliferation of the lymphoid
cells with swelling and tenderness of the nodes. These
secondary foci may continue as active depots of supply
of bacterial infection to other tissues. If the invading
bacteria of the lymph node are pyogenic and virulent,
positive chemotaxis will result in the invasion of the
infected gland with leukocytes and a circumscribed ab-
scess may result. Lymph node infection with necrotic
changes may rupture into or may cause infectious
thrombophlebitis in a contiguous vessel and bacteriemia
may result. In other instances the infection in the
lymph node may be a protection by holding the invad-
ing organisms in a tissue environment which renders
them latent and for the time harmless to the patient.

SYSTEMIC INTOXICATION

Systematic intoxication from a focus of infection is
characteristic of the exotoxic bacteria. Diphtheria and
tetanus are two examples of infectious disease in which
the morbid tissue reactions are caused by soluble toxins
excreted by the specific microorganisms in a focal area*

It has been assumed that focal infection due to micro-
organisms which produce endotoxins may cause sys-
temic disturbances by dissemination of toxic substances
from the focus. It is suggested that the toxic material
may be formed by biochemical reactions excited by the

A GENERAL CONSIDERATION 23

microorganisms and the tissues and cellular exudate of
the focus; also that autolysis of the dead microorgan-
isms of the focus sets free the endotoxin. Hence it is
said that morbid processes of a degenerative and meta-
bolic character which may occur in many organs and in
varying degrees of severity, are caused by toxins and
toxic substances elaborated in a focus of infection.

Semmelweis, Klebs, Virchow, Pasteur, Lister and
others proved long ago that virulent microorganisms
are the cause of infectious disease. Modern bacteriology
and clinical research are adding day by day incontestable
proof that bacterial invasion and infection of tissue is
the fundamental cause of many of the systemic diseases,
which have been classed as toxic, metabolic or nutri-
tional. A sequence of the fundamental and primary
infection of tissue may create a morbid anatomy, dis-
turbed function, malnutrition and in consequence sec-
ondary metabolic and degenerative changes. The endo-
toxin of the invading bacteria is set free in the blood and
tissues and is a factor in the cellular reaction expressed
in general infection by chill, fever, disturbed functions
and altered metabolism and in local infection by cellular
reaction and symptoms varying with the character of
the invading bacteria, the anatomical lesions and dis-
turbance of function of the tissue and organ involved.

FOCAL INFECTION AND ANAPHYLAXIS

Focal infection may be the cause of the condition
known as anaphylaxis. The bacterial protein of the
pathogenic microorganism of the focus may sensitize
the body cells.

24 FOCAL INFECTION

If a foreign protein gains entrance to the body par-
enterally, via the blood stream or the lymphatics, the
animal body always responds to the parenteral intro-.
duction of the foreign protein by the production of
specific antibodies to that foreign albumen. The forma-
tion of the specific antibodies requires a certain period
of time. After this interval a second introduction of
the same protein, again by a parenteral route, results
in a union of the newly formed antibody with the anti-
gen (foreign protein), which may excite physical phe-
nomena of an explosive character. These phenom-
ena, the so-called anaphylactic shock, differ materially
with various species of animals and with man. In man
the typical phenomena may consist of bronchial spasm,
urticaria, vasodilatation and fall of blood pressure, eosin-
ophilia, physical weakness and arthropathy. In some
individuals, urticaria or bronchial asthma may be the
only expression of anaphylaxis.

Anaphylaxis has been studied as serum disease by
Rosenau and Anderson (44), Park (47) and others.
Von Pirquet (43), Weil (42), Meltzer (52) and
Vaughan (45) have shown the relation of anaphylaxis
to the symptom expression of infectious disease and to
bronchial asthma. Theobald Smith (39), Auer and
Lewis (46), Jobling, Petersen and Eggstein (53) and
many others have reported the result of extensive re-
search upon laboratory animals in the production of
immunity and of anaphylaxis.

The relation of anaphylaxis to bronchial asthma,
many dermatological lesions, gastro-intestinal symp-
toms, cardiovascular disturbance, especially arterial

A GENERAL CONSIDERATION 25

hypotension and other morbid conditions, of man, has
not received the attention which its importance de-
mands. Definite clinical evidence has been established
of the etiologic relation of confined focal infection to
anaphylaxis, in the form of bronchial asthma and other
morbid conditions. The subject is not well understood,
but is so important that it demands the cooperative re-
search of the immunologist and clinician.

LECTURE II

THE STREPTOCOCCUS-PNEUMOCOCCUS GROUP.

TRANSMUTABILITY OF THE MEMBERS THEREOF.
PATHOGENICITY AND SPECIFIC TISSUE AF-
FINITY OF TRANSMUTATION FORMS

TRANSMUTATION WITHIN THE MEMBERS OF THE STREPTO-
COCCUS-PNEUMOCOCCUS GROUP

Recent coordinate research in clinical medicine and
bacteriology, fortified by animal experimentation, has
made more evident the etiologic relation of focal infec-
tion to systemic disease.

The main and fundamental principles which have
been proved are :

1. The apparent confirmation of the transmutability
of the members of the streptococcus-pneumococcus
group in variations of morphology, cultural character-
istics, biological reactions and also of general and spe-
cial pathogenicity.

2. The acquisition of pathogenic elective tissue af-
finity by bacteria in foci of infection in culture media
and serial animal passage.

In a clinical and bacteriological study of chronic in-
fectious endocarditis Rosenow (8) and Billings (9)
confirmed the report of Schottmiiller (10) in the isola-
tion from the blood during life of the patient of a pure

culture of streptococcus viridans. Schottmiiller (10)

STREPTOCOCCUS-PNEUMOCOCCUS 27

isolated a streptococcus from patients with chronic in-
fectious endocarditis, which grew fine colonies on blood
agar plates, was non-hemolyzing, but produced a
greenish halo around the colonies. In consequence it
was named streptococcus viridans and because of its low
pathogenicity for animals it was also called strepto-
coccus mitior. The streptococcus viridans, isolated from
the blood of our eleven patients, was cultivated in vari-
ous media and animals were inoculated with successive
strains. The behavior of the strains obtained from all
patients was the same. The end result was a pneumo-
coccus of specific pathogenicity for animals in the pro-
duction of pneumococcemia and pneumonia.

In consequence of these results the bacteriological
diagnosis of our series of observed patients was chronic
pneumococcus endocarditis. Rosenow soon recognized
the fact that the bacteria studied were typical pneumo-
cocci and that transmutation of the original pure cul-
ture of streptococcus viridans had occurred in form,
culture characteristics and in general and special patho-
genic virulence for animals.

Since that time Rosenow (8) has apparently eon-
firmed the transmutability of the members of the strep-
tococcus group and that the property of trans-
mutation is reversible within the members of this fam-
ily. He says: "From this study the apparent po-
sition of the various members of the streptococcus
group may be illustrated by the position of the fingers
in a partially flexed hand, in which the hemolytic
streptococcus occupies the position of the little finger,
the pneumococcus the place of the index finger (the op-

28 FOCAL INFECTION

posite extreme), streptococcus viridans (representing
the group of more or less saprophytic, noii-hemolyzing
streptococci) the middle finger, the streptococci from
rheumatism the ring finger, and streptococcus mucosus,
having some of the properties of both pneumococci and
streptococci, the thumb. In this grouping there is in
general an increase in parasitism and virulence as we

B. 1. — Stuain 595 as a

OF SCABLET FeVEB,

broth. Gram stain.

approach the thumb {streptococcus mucosus)." Rose-
now has arrived at this conclusion by working with
strains of streptococci and pneumococci obtained from
various sources: Strains of hemolytic streptococci iso-
lated from patients suffering from erysipelas, puerperal
sepsis, scarlatina, acute tonsiUitis and acute polyar-
thritis; from cow's milk and other sources; strains of
streptococcus viridans isolated from tonsils, alveolar
abscesses, the blood, from other tissues and cow's milk;
streptococcus mucosus from sputa, tonsils and else-

STREPTOCOCCUS-PNEUMOCOCCUS 29

Fro. 2. — S»«Ain fiSS AS Stbeptococcps Vbidans. Smear from 34 hour cul-
ture in ascites-dextroae-broth. Grain stain.

where and pneiimococci isolated from sputa, the blood
during life and post mortem, the exudate of empyema,
from hepatized lung and also Cole's (11) strains I and

Fio. 3.— S™ain 59S A8 A PuEUMococcce. Smear from 24 hour culture
in ascites-dext rose-broth. Capsule stain.

80 FOCAL INFECTION

II. These have been successfully made to assume the
varying types as to form, cultural characteristics, bio-
logic reactions and special and general pathogenic viru-
lence of the group.

The technic which Rosenow pursues consists of the
use of the ordinary solid and liquid culture media iri
which the oxygen content is increased and decreased,

Fm. 4, — Strain of Stseptococcus fbom Rheumatism Which Piodcced
SuOHT He.molvsis oh Blood Aoab and Myositis in Ahimau. Smear
from blood agar slant. Capsule stain.

the use of hypotonic and hypertonic media, cultures
made in symbiosis with bacillus subtilis as the occasion
may indicate and of serial animal inoculation. Haessli
(12) produced transmutation of a non-color-forming
strain of streptococcus fecalis, by passing it several times
through horse serum, when it finally became strongly
hemolytic and had acquired all the pathogenic charac-
teristics of streptococcus erysipelas. By the same
method streptococcus viridans first lost its greenish

'■ ■"■ ■■'^-*

'w 4

► .^,

» o :>»

*t ^ < V

•

^^^^H

^^M Pig. fi.— The Same Stbain j.s in Fig. 4 Afteb It Was Transfokmeo Isto ^M

^^^H A Pheumococcvs. Smear from blood agar slant. Capsule stuin. ^|

^^^ '*

'■""i^"^. ' \

%^M^,

■

"^tt^.*

■

^^H FlO, 6. HlOHtT VlHCLENT PjJEUMOCOCCUB. TyPE 1. OlHGINALLV IboLAITD ■

^^H BT Neufeld. Smear from surface and water of condensation of blood g

^^H agar slant. Capsule stain.

32 FOCAL, INFECTION

color producing quality, finally became heniol>i:ic and
a strain of streptococcus mucosas became hemolytic.
Haessli finally states that his experiments confirm the
clinical differentiation of streptococci as demonstrated
by Schottmiiller, SchottmuUer (10) probably recog-
nized the transmutability of members of the streptococ-
cus group pathogenic for man which he classified as

Fio. T. — Tmk Same Sthain as iv Kig. 6 Afteh Transformation' Into Hemo-
lytic Stheptococcl's. Smear from surface and water of coDdensation
of blood ugur slant. Capsule stain.

streptococcus longus ( hemolysans ) , streptococcus mitior
(viridans) and streptococcus mucosus. Schottmiiller
(10) also described strains of streptococcus mucosus,
which possessed all the characteristics of strains first iso-
lated from patients with parametritis in 1896, obtained
in pure culture from the blood and hepatized lung of five
patients with clinical lobar pneumonia. The strains de-
scribed occurred as diplococci with capsule in chains of
ten to fourteen pairs. Evidently he did not recognize
the pneumococcus as a member of the group and espe-

STREPTOCOCCUS-PNEUMOCOCCUS 33

cially its close relation to the streptococcus mucosus.
Transmutation within the members of other groups of
pathogenic bacteria probably occurs. The members of
the colon-typhoid group shade into one another in
form, motility, cultural characteristics and in degrees of
pathogenicity from nil to exalted virulence.

Virulence and Elective Pathogenic Tissue Affinity

The varying virulence of facultative pathogenic bac-
teria has been long recognized. Environment seems to
play an important role. This seems especially true of
living tissue environment. Not only may there be a
variation in general virulence, but apparently a special
pathogenic virulence for certain tissues may be acquired.
In this connection we may note the recent epidemics of
septic tonsillitis, frequently associated with fatal bac-
teriemia, due to milk infected with streptococci from
human carriers. The acquirement of a selective specific
tissue affinity by a strain of streptococci has been noted
by Forssner (13). By culture in kidney and kidney
extract the ordinary streptococcus pyogenes (hemoly-
sans ) , which had no pathogenic elective affinity for the
kidney, was converted into a strain, which injected in-
travenously into animals constantly produced outspoken
anatomical lesions of the kidney. This Forssner be-
lieves is positive proof that the bacteria of a local in-
fection may attain a specific pathogenic and elective
tissue affinity.

By making continued cultures in bouillon, for a long
time these specific kidney strains assumed a general
virulence. Again grown on kidney and kidney extract,

34 FOCAL INFECTION

the specific kidney pathogenicity was regained and
maintained through numberless generations. This spe-
cific kidney pathogenicity was lost after a few genera-
tions in continued bouillon cultures. The general viru-
lence was also finally lost.

Poynton and Paine (14) in a discussion of the re- {

lation of malignant to rheumatic endocarditis state that i

the diplococcus isolated from patients with acute rheu-
matism caused acute non-suppurative arthritis and sim-
ple rheumatic endocarditis in rabbits. In culture after
a few months the same strain of diplococci caused ma-
lignant endocarditis in the inoculated animal. They
could not recover the diplococcus from the nodular vege-
tations in rheumatic endocarditis, but succeeded in ob-
taining pure cultures of a smaller diplococcus from the
large vegetations and contained thrombi of malignant
endocarditis. They concluded that the diplococcus
rheumaticus was capable of producing not only arthritis
and rheumatic endocarditis but also malignant endo-
carditis. Rationally we may interpret their observa-
tions and results as a transmutation of the diplococcus
rheumaticus in virulency and in specific pathogenicity.
Our clinical observations and Rosenow's experiments
seem to show that the members of the streptococcus-
pneimaococcus group may acquire specific pathogenic
elective affinity for certain tissues in the primary focus
and also in the tissues.

Clinical examples have been observed of acute ap-
pendicitis; cholecystitis; acute gastric and duodenal
ulcer; acute and subacute glomerulonephritis; rheimiat-
ic fever; erythema nodosum; herpes zoster; malignant

STREPTOCOCCUS-PNEUMOCOCCUS 35

endocarditis ; simple endocarditis ; myocarditis and other
acute and chronic systemic diseases, associated with co-
incident focal infection of the tonsils, accessory sinuses,
dental alveoli, the skin and its appendages, the fallopian
tubes, the prostate and seminal vesicles and other foci.
Dominant pathogenic bacteria have been isolated from
tissues and exudates of patients at surgical operation;
by blood culture; from the urine; from joint exudates
and pieces of tissue (muscular, lymphoid, joint capsules
and fibrous nodes ) , removed with the consent and often
at the request of patients. These cultures have been
intravenously injected into laboratory animals and at
the same time cultures of bacteria isolated from the
primary foci of the patients have been likewise used
to inoculate other animals.

The evidences of the specific elective tissue affmity of
the pathogenic streptococci from the various tissues and
likewise of the primary foci is very marked. This is
significantly expressed in the following table prepared
by Rosenow (8) from an enormous number of animal
experiments.

The principles of localized infection in man and ani-
mals are so important that the technic of the experi-
ments and the interpretation of the table by Rosenow
are quoted very fully here.

Techvic

The streptococci were usually grown from sixteen to twenty-
four hours at 37° C. in tall columns of ascites (10 per cent.)
dextrose (O.S per cent.) broth (0.6+ to 0.8 -|-) to which
sterile tissue (guinea-pig kidney or heart muscle) was often
added; the sterility of the ascites fluid and broth containing

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STREPTOCOCCUS-PNEUMOCOCCUS 37

the tissue was always proved beforehand. After incubation
smears were made, the cultures were centrifuged in the con-
tainers in which they were cultivated,^ the supernatant fluid
was decanted and the sediment suspended in sodium chlorid
solution so that 1 c.c. of the suspension contained the growth
from 15 c.c. of broth. The doses for rabbits (ear vein) were
usually from 0.5 to 3 c.c, and for dogs (leg vein) from 1 to
5 c.c. of this suspension. The injections were made quite
rapidly through a rather fine needle (22 g^^g^)9 usually within
an hour after the suspension was made. Blood agar plate cul-
tures were made at the time the suspensions were injected to
study the character of the organisms, to test their viability and
to save them for further study. This is an important precau-
tion because negative results have at times proved to be due to
early death of the recently isolated organisms in the broth
cultures. In the accompanying table, "when isolated" indi-
cates the first or second and, occasionally, the third or fourth
cultures, or the first culture after one animal passage. "Later"
indicates that the strains were cultivated for a week or longer.
"After animal passage" indicates usually from the second to
the sixth animal passage.

The strains tested from appendicitis, ulcer of the stomach,
cholecystitis, rheumatic fever, erythema nodosum, myositis and
endocarditis include strains isolated from the characteristic
lesions as well as from the apparent atrium of infection. Those
from herpes zoster were from the tonsils and spinal fluid, and
those from epidemic parotitis were obtained by catheterizing
Steno's duct and from the tonsils. The strains from miscel-
laneous sources were usually from tonsils approaching the
normal condition ; and the laboratory strains were streptococci
or pneumococci cultivated on artificial mediums for a long time
and had lost all apparent virulence. The figures in the lowest
line of the table represent the average percentage incidence

^ The common 8-ounce nursing bottle is used both as a culture
flask and centrifugal tube, and serves the purpose admirably.

38 FOCAL INFECTION

of lesions In individual organs following injection of various
strains of streptococci except those from the specific disease.
Thus the first figure indicates that 5 per cent, of the animals,
injected with the various strains except those from appendi-
citis, showed lesions in the appendix.

Care was exercised to obtain growths from the depths of the
supposed primary focus with as little contamination from the
surface as possible, the cultures being made from the material
expressed from the tonsils or from emulsion of extirpated
tonsils after thorough washing in sodium chlorid solution. The
material from the depths of pyorrheal pockets was obtained
by means of a pipet.

For the study of pathogenicity of the cultures, dogs and rab-
bits were chiefly used, being killed with chloroform at the de-
sired time, usually in from twenty-four to forty-eight hours.
Post mortem examinations were always made as soon after
death as possible. A thorough inspection in a bright light with
the unaided eye or with the aid of a hand lens was made for
focal lesions. The exact character of the lesions and the pres-
ence of the streptococci in each of the various diseases have
been determined by microscopic study of sections. Cloudy
swelling is not included in the results given in the table. Hemor-
rhage, localized necrosis, exudation and infiltration were the
usual lesions. Thus, in case of the joints, hemorrhage about the
joint or turbidity of fluid, as determined with a pipet, or both,
were considered as evidence of arthritis. Hemorrhages in the
pericardium and turbidity of pericardial fluid, due to leu-
kocytes, were considered as evidence of pericarditis. The post
mortem study of animals often symptomless is essential to o\>-
tain accurate knowledge of the pathogenicity of a culture, and
must supplant the older method of merely finding out whether
a culture produces death or not, a method still too much in
vogue. The table includes data only from those animals in
which the post mortem was comprehensive, and does not in-
clude some of the earlier experiments, especially on endocardi-

STREPTOCOCCUS-PNEUMOCOCCUS 89

tis. Increase in mortality rate, earlier death and greater de-
gree and distribution of lesions following standard dosage were
considered as proof of high virulence. Changes in the spleen
and liver were so rare following injection of the strains as
isolated, except those from cholecystitis, that they are not
included in the table. Acute splenitis and such changes in the
liver as focal necrosis, parenchymatous and bile duct hemor-
rhages and acute degeneration with marked acidity occurred,
however, after the strains had acquired greater virulence from
animal passage. In the earlier experiments not sufficient at-
tention was paid to the occurrence of lesions in the thyroid,
thymus, suprarenals and lymphatic glands. Later a closer
search for lesions in these structures was made, especially after
it was found that lesions in the thyroid followed intravenous
injection of bacteria isolated from goiter. It must be said, too,
that strains of streptococci from rheumatic fever, myositis and
cholecystitis produce hemorrhages in the thyroid quite com-
monly, while those from other sources rarely produce them.

Results

A study of the table shows that streptococci from the various
diseases often have a most striking affinity or tropism for the
organs or tissues from which they are isolated. Thus, fourteen
strains from appendicitis produced lesions in the appendix in
68 per cent, of the sixty-eight rabbits injected, which is in
marked contrast to an average of only 5 per cent, (given in
lowest line of table) of lesions in the appendix in the animals
injected with the strains as isolated from sources other than
appendicitis. Eighteen strains from ulcer of the stomach or
duodenum produced hemorrhages in 60 per cent, and ulcer of
the stomach or duodenum in 60 per cent., a combined total of
74 per cent, of the 103 animals injected, in contrast to an aver-
age of 20 per cent, hemorrhages and 9 per cent, ulcer following
injection of other strains. Twelve strains from cholecystitis
produced lesions in the gall-bladder in 80 per cent, of the forty-

40 FOCAL INFECTION

one animals injected, in contrast to an average incidence of le-
sions here of only 11 per cent, with the other strains. Twenty-
four strains from rheumatic fever produced arthritis in 66 per
cent., endocarditis in 46 per cent., pericarditis in 27 per cent.,
and myocarditis in 44 per cent, of the seventy-one animals in-
jected, in contrast to an average of arthritis in £7 per cent.,
endocardial lesions in 14 per cent., pericarditis in 2 per cent,
and myocarditis in 10 per cent, of the animals injected with
strains from sources other than rheumatic fever. Six strains
from erythema nodosum produced lesions of the skin in 90 per
cent, of twenty animals injected, in contrast to an average of
£ per cent, in the animals injected with the strains from sources
other than erythema nodosum and herpes zoster. Eleven strains
from herpes zoster produced herpetiform lesions of the skin,
lips, tongue or conjunctivae in 77 per cent, of the sixty-one
animals injected, in contrast to the average of only 1 per
cent, of what seemed to be herpes of the skin with the other
strains. Nine strains of streptococcal organisms from epidemic
parotitis produced lesions in one or both parotid glands in 73
per cent, of the nineteen animals injected intravenously, in con-
trast to no instance of lesions here with the other strains. Three
strains from cases of true myositis produced myositis in 75 per
cent, and myocarditis (chiefly of the right ventricle) in 35 per
cent, of the forty animals injected, in contrast to an average
of myositis of 12 per cent, and myocarditis of 10 per cent,
following injection of strains from sources other than myositis
or rheumatic fever and eight strains of streptococcus viridans
from chronic septic endocarditis produced lesions in the endo-
cardium in 84 per cent, of the forty-four animals injected, in
contrast to an average of 15 per cent, with the strains other
than those from endocarditis. The results following injection
of the miscellaneous strains (usually the first culture from ton-
sils) and the laboratory strains serve as a basis of comparison
with those following injection of the strains from the various
diseases, and correspond roughly with the total average inci-

STREPTOCOCCUS-PNEUMOCOCCUS 41

dence of lesions in the various organs as given in the lowest line
of the table.

While the incidence of lesions in the organs following injec-
tion of the strains isolated from such organs is high, as shown
by these figures, the appearances at the necropsy are even more
significant. In many instances in which the animals survive the
injection for some time, no other focal lesions could be found
except those in the organ in question; and when the animal
died early, these lesions were the marked feature and the asso-
ciated ones were relatively insignificant. Frequently the injec-
tion of a very small dose was sufficient to prove the elective
localization. This elective property was shown not only by
the cultures from tissues and foci but also by the bacteria con-
tained in the foci, directly injected in other animals.

In many cases of both acute and chronic diseases the ap-
parent atrium of infection was found to harbor streptococci
having elective affinity; in the former usually only at the time
of the attack, in the latter in some instances for months. The
elective affinity, however, was less marked in the strains isolated
from the supposed focus than in the strains isolated from the
lesions in the various organs. The rather wide range of lesions,
as indicated in the table, following the injection of the strains
from herpes zoster and parotitis is due to the fact that often
primary mixed cultures from tonsils and pyorrheal pockets
were injected.

Attempts to find a method which would preserve the original
tropic property, while only partially successful, have shown
that it may be preserved for some weeks in the deeper colonies
of the original shake cultures and for as long as seven months by
keeping the suspensions containing sterile tissue in the ice chest,
thus maintaining the bacteria in a condition of latent life.

The localization of the strains from appendicitis, ulcer of
the stomach and cholecystitis as isolated, after cultivation and
after animal passage, is of particular interest. It should be
stated here, however, that these strains resemble one another

42 FOCAL INFECTION

very closely indeed in cultural and other respects. Those from
appendicitis are the least virulent, those from ulcer occupy
a middle position and those from cholecystitis are the most
virulent. The virulence seems to be one of the factors that
determine their place of survival after intravenous injection.
Now if the localization is dependent to a certain extent on
virulence, then the occurrence of ulcer and cholecystitis should
become greater as the strains from the appendix are passed
through animals, and appendicitis should occur oftener after
the strains from ulcer and cholecystitis lose virulence from
cultivation on artificial mediums. This is found actually to
be the case (see figures in table). In this connection other
facts should be mentioned. None of the strains from appen-
dicitis produced pancreatitis. The strains from ulcer and
cholecystitis as isolated (mostly those from acute cases) pro-
duced pancreatitis in S per cent, and 5 per cent., respectively,
of the animals injected. After animal passage, pancreatitis
occurred in 15 and 19 per cent, respectively, while after culti-
vation on artificial mediums pancreatitis in no case was ob-
tained.

Lesions in the intestines, exclusive of the duodenum, were
more common with the strains from cholecystitis and rheuma-
tism than with those from appendicitis, and all the strains pro-
duced intestinal lesions (chiefly of the mucous membrane and
lymphoid structures) quite commonly after they had been
passed through animals, whereas, after cultivation for a time,
no noteworthy lesions were found in the intestinal tract.

The streptococci studied from parotitis resemble the organ-
ism described by Herb^ and, like hers, produced the char-
acteristic picture of mumps in dogs when injected into Steno's
duct. Intravenous injection of these organisms produced
marked edema and hemorrhage in and surrounding the parotid.
The afiinity was so great that the streptococci were found in

^ Herb, Isabella C. : Experimental Parotitis, Arch. Int. Med.,
September, 1909, p. 201,

STREPTOCOCCUS-PNEUMOCOCCUS 43

pure culture in the enlarged parotid in three of five full-time
puppies removed from the uterus of a dog which was chloro-
formed during a marked parotitis following injection into
Steno's duct. Antigens prepared from a number of these strains
were found to bind specifically complement in serum from paro-
titis (Howell).

Lesions in the skeletal muscles occurred in 75 per cent, of
the animals injected. The number of lesions in the muscles and
myocardium in the animals injected with strains from myositis
was often in proportion to the quantity injected, and occurred
mostly in the tendinous portion and in the right ventricle.

Lesions in the kidney were especially common after injec-
tions of streptococci from rheumatic fever (39 per cent.) and
from endocarditis (20 per cent.). These occurred chiefly in the
medullary portion in the former and in the glomeruli in the
latter.

Lesions in the lung, consisting usually of hemorrhages and
edema, were rare following injection of the strains when iso-
lated and after they were cultivated on artificial mediums but,
just as was found previously, they occurred oftener after the
virulence was increased by animal passage.

That the streptococci are the underlying cause of the dis-
eases from the lesions of which they were isolated is indicated
further by the fact that they have elective aflinity for the
corresponding structures in animals. Moreover, the fact that
the same streptococcus may be made to localize in different or-
gans is in consonance with the knowledge that streptococci may
cause diseases with different symptomatology. The possibility,
however, that they are secondary invaders to some ultramicro-
scopic, filterable organism has to be considered. Filtrates of
the streptococcal cultures from various diseases were injected
in the organs from which the strains were isolated; the lesions,
however, were not due to living organisms because the broth
which was inoculated and incubated with the tissues failed to
produce any lesions. The results, while inconclusive, may be

44 FOCAL INFECTION

said to indicate that streptococci produce .substances which
cause injury specifically in the tissues from which the strains
are isolated.

Although the circulation is an important factor in determin-
ing localization, the tissues themselves play an even more im-
portant role. The question whether the lesions in the organ
for which a particular strain appears to have elective affinity
are due to the lodgment of a larger number of bacteria here
than in the other organs, or whether the bacteria lodged in
equal numbers in the various organs but survive only in the
one showing lesions, is now under study. The evidence already
obtained, however, points strongly to the former mechanism.
It appears that the cells of the tissues for which a given strain
shows elective affinity take the bacteria out of the circula-
tion as if by a magnet — adsorption.

This remarkable tropic condition tends to disappear quite
promptly both on cultivating the streptococci on artificial me-
diums and on passing them successively through animals, and
this may occur without demonstrable changes in morphology,
grouping or character of chain formation. I have previously
shown that the ability of streptococcus viridans and staphylo-
cocci to produce lesions in the endocardium is due partly to
physical clumping. A careful study of smears of the suspensions
injected in these experiments revealed no constant relation
between localization and clumping or size of the bacteria.

Individual variations in resistance to infection were found
in the injected animals. The effects of these conditions in the
host as determining factors in localization are important ; they
are probably expressions of differences in metabolism, oxidation
rates, etc., which influence the soil for bacteria. The tendency
of virulent bacteria, temporarily or permanently, to render this
soil less favorable for their growth is well established. There
is some evidence, on the other hand, which goes to show that
certain bacteria of very low virulence (commonly found in

STREPTOCOCCUS-PNEUMOCOCCUS 45

chronic foci of infection) tend actually to make this soil more
favorable. But it must be considered that differences in the
host may afford the peculiar type of reaction, on that the
individual harbors a particular form of focus of infection which
is favorable for bacteria to acquire elective properties. The
following facts support the latter view: (1) the common occur-
rence of certain non-contagious diseases, such as herpes
zoster, ulcer of the stomach, etc., during definite age periods;
(2) the fact that foci of infection afford opportunity for
bacteria to grow under varying grades of oxygen pressure and
in mixed culture, both of which have been shown to cause
changes in virulence and other properties of bacteria, in-
cluding the streptococcus group; (3) the occurrence of sys-
temic infections such as rheumatic fever, appendicitis, ulcer of
the stomach, etc., usually after the acute symptoms in follicu-
lar tonsillitis (hemolytic streptococci) have subsided, and (4)
the finding in the focus and involved tissues at the time of the
systemic infection, streptococci having elective affinity for these
structures in animals.

Since different bacteria may acquire simultaneously affinity
for the same tissue, diseases which resemble each other more or
less closely, such as the different forms of arthritis, may be due
to bacteria of different species each having elective affinity for
the particular structures involved.

The figures in the lowest line of the table represent the results
of numerous experiments (833) with streptococci (220) from
a wide range of sources, and may therefore be regarded as an
index of the liability of the various organs to infection. Thus,
joint lesions occurred more often (27 per cent.) than lesions in
other organs, corresponding to the frequent occurrence of spon-
taneous arthritis in man and animals. The occurrence of le-
sions in the stomach (20 per cent.), valves of the heart (14 per
per cent.), myocardium (12 per cent.) and skeletal muscles (12
per cent.) correspond in a general way to the occurrence of
infection in these organs in man. The very infrequent involve-

46 FOCAL INFECTION

ment of the skin, tongue and the parotid in the animals is in
keeping with the rarity of embolic infections in these struc-
tures. The character of the lesions and their occurrence simul-
taneously in the joints, heart, muscles and kidneys, and the
development of chorea (7 per cent, mostly in young rabbits)
following injection of the streptococci from rheumatic fever,
parallels quite closely the phenomena of rheumatic infection
as observed in man. The strains from erythema nodosum re-
semble those from rheumatic fever, producing a relatively high
incidence of arthritis, pericarditis and myositis, a fact which
supports the view held by clinical observers, that the causative
agents of rheumatic fever and erythema nodosum must be
similar.

The tendency to localize electively within a limited range,
"monotropism," is most highly developed in the relatively non-
virulent strains isolated from chronic lesions. In the more
virulent strains from acute lesions and after animal passage, this
tendency is less highly developed, the lesions occurring over a
wider range, "polytropism." Since the bacteria which have
grown in a given tissue acquire greater affinity for this tissue,
the likelihood of these bacteria to involve other structures is rel-
atively slight; hence the secondary focus, a cholecystitis, for
example, would appear to be less important as a distributer of
bacteria than the primary focus; if, however, the secondary
focus happens to be in a joint, of which there are many, it may
play an important role in causing extension to uninvolved joints
and in preventing recovery.

The great importance of the enormous and pains-
taking experiments and the rational deductions made
by Rosenow must be apparent to clinicians, bacteriolo-
gists and pathologists.

The practical application of the principles involved
may serve to lessen the incidence of and the recru-

STREPTOCOCCUS-PNEUMOCOCCUS 47

descence of many local inflammatory organic diseases,
notably appendicitis, ulcer of the stomach and duo-
denimi, cholecystitis, glomerulonephritis, acute and
chronic arthritis and other abnormal conditions, by the
removal of the primary focal cause.

LECTURE III

ACUTE DISEASES RELATED TO FOCAL INFECTION

We have considered the causes, character and diag-
nosis of focal infection; the mode of systemic infec-
tion from the focus; the important fact of transmuta-
tion within the members of the streptococcus-pneumo-
coccus group, with coincident variations of specific path-
ogenicity and virulency and the acquirement of
pathogenic elective tissue affinity by bacteria in culture
media, in serial animal passage and in the foci of in-
fection.

We may now understandingly consider some of the
systemic infections which are etiologically related to
focal infection.

ACUTE RHEUMATIC FEVER

It is not necessary to consider the controversies which
have taken place concerning the bacterial cause of rheu-
matic fever. There is now no doubt that the diplococcus
also called by other observers micrococcus rheumaticus
and streptococcus rheumaticus, isolated from the blood
and joint fluids, throat and endocardial nodes of patients
suffering from rheumatic fever by Poynton and Paine
(14) confirmed by Beattie (15), Walker and Ryff^el
(16) and finally and conclusively by Rosenow (8), is
the true infectious cause of the disease.

ACUTE DISEASES 49

With a knowledge of the possibility of transmutation
in form, cultural characteristics and coincident varia-
tion in specific pathogenicity, virulency and tissue af-
finity, we may now understand the conflicting results
of animal inoculation with undifferentiated strains of
streptococci as reported by many workers. It is a well
known fact that virulent strains of streptococci, when
injected intravenously into animals, may produce acute
arthritis, usually with such violent tissue reaction that
suppuration occurs. But the streptococcus rheumati-
cus never produces suppuration. Doubt of its etiologic
relation to acute rheumatism also arose from the fact
that it was not usually found by cultural methods in
the joint exudate and circulating blood of patients.
But Rosenow (8) has found that with an improved
technic it may be always found, at the proper stage
of the disease, in the joint exudate, joint capsule, cir-
culating blood, tonsil, alveolar abscess or other focus.

Rosenow's studies of cultures from the joint exudate
of patients with acute rheumatism yielded three strains.
From five patients without muscular involvement, on
blood agar the colonies were green and grew in long
chains, longer than streptococcus viridans. Injected
intravenously into animals they developed acute non-
destructive arthritis, myositis, marked myocarditis with
endocarditis and occasionally pericarditis. From six
patients with acute rheumatic fever involving the joints
and muscles the isolated microorganisms produced slight
hazy hemolysis on blood agar, and grew as diplococci in
the short chains. Injected intravenously the inoculated
animals developed non-destructive, acute arthritis.

J J
^ •*•*

« • # •

<•

« •

• «

50 FOCAL INFECTION

myositis, severe myocarditis, endocarditis and occasion-
ally pericarditis. From three patients with acute rheu-
matism the joint exudate yielded small gray colonies
on blood agar. They grew in clumps of small micro-
cocci and diplococci and occasionally in short chains.
Animals injected intravenously developed a character-
istic arthritis with endocarditis and pericarditis, but no
myositis or myocarditis.

The three types of cocci found by Rosenow explains
the variations in name given by Poynton, Paine, Walker
and Beattie, i. e. : diplococcus, streptococcus and micro-
coccus rheumaticus.

The virulence of all the strains is low. All are very
sensitive to oxygen pressure in culture and all multiply
at low temperature. The three strains are transmut-
able. All produce excessive acidity in dextrose broth.
Walker and Ryffel (16) found foririic acid in the cul-
tures of the strains with which they worked.

Exposure of the inoculated animal to low tempera-
ture intensifies the disease, presumably by lowering
phagocytosis and by vasocontraction. Rosenow also
noted in some injected animals the development of iritis
by hematogenous infection. Some inoculated animals
also developed appendicitis, colitis, mesenteric lympha-
denitis and diarrhea. Poynton and Paine (14) also
have noted the occurrence of obscure infection of intes-
tines and appendix of animals intravenously inoculated
with the diplococcus rheumaticus. The intestinal lesions
produced in animals and the fact that the stool of a pa-
tient with rheumatic fever may yield cultures of strepto-
coccus rheumaticus indicate that the intestinal tract and

ACUTE DISEASES 51

mesenteric lymph nodes may be a secondary and pos-
sibly a primary focus of rhemnatic fever.

Rosenow has shown that cultures kept for one to
eight months lose the power to grow at a low tempera-
ture, the sensitiveness to oxygen tension, the production
of excessive acid in dextrose broth and at the same time
lose the specific pathogenic affinity for joint, muscle,
myocardium, endocardium and pericardium. By serial
animal passage the streptococcus rheumaticus and espe-
cially the diplococcus type, may assume an affinity for
the appendix, stomach and gall-bladder.

The clinical and bacteriological research of Poynton
and Paine, the use of blood agar media by Schottmiiller
to differentiate members of the streptococcus group
which are pathogenic for man, and the confirmatory
work of Rosenow have proven conclusively the charac-
ter of the infectious microorganism which causes rheu-
matic fever with arthritis, myositis, endocarditis, myo-
carditis, pericarditis and pleuritis.

Rheumatic fever occurs most frequently in the tem-
perate zone, among people who live under conditions
which are unhealthful and which especially induce focal
infection. It is most prevalent in the young and in
the more exposed^ male of all ages. The excess of
lymphoid tissue in the pharynx and nose of the young
explains the frequency of the incidence of the focal
infection and the subsequent rheumatism. The fre-
quent association of the onset of rheumatic fever with
lowering of the body temperature by exposure to cold
and a wetting is explained by the increased specific
virulency of the bacterial cause acquired by a low tem-

52 FOCAL INFECTION

perature and the coincident lessened resistance of the
patient due to the exposure. The frequent absence of
evidence of acute focal infection at the onset of the
systemic disease is not an evidence that no focus exists.
The latent chronic streptococcus infection of tonsillitis,
pyorrhea alveolaris, sinusitis, etc., may suddenly acquire
increased virulence and specific pathogenic affinity with
varying degrees of focal tissue reaction. This transmu-
tation of type and pathogenicity certainly occurs in the
focus of infection. The removal of the tonsils and other
sites of focal infection has been foljowed by complete
recovery of prolonged, subacute and chronic types
of arthritis and has unquestionably prevented recurrent
attacks of rheumatic fever to which the susceptibility
is increased by one or more attacks. The occurrence of
rheumatic fever after the removal of an apparent focus
may be due to secondary systemic latent foci in lymph
nodes proximal to joints, in the neck or elsewhere. The
streptococci of these secondary foci may take on new
virulence and specific pathogenicity, from the same
causes which induced like changes in the pathogenic
bacteria of the primary focus.

RHEUMATIC ENDOCARDITIS, MYOCARDITIS AnD

PERICARDITIS

Endocarditis

We have noted the fact that certain strains of the
streptococcus rheumaticus have a greater afiinity for
the endocardium than others. Endocarditis of the rheu-
matic type may be the only recognizable clinical entity,
especially in children, and may be so mild that it escapes

ACUTE DISEASES

notice. Later a valvular scar defect may be manifest.
In rheumatic fever endocarditis occurs most frequently
in children. After twenty years it occurs less frequently

during the first attack. The incidence of endocarditis
increases with the number of attacks, and always in
larger percentage in children.

As stated the virulence of the streptococcus rheu-

54 FOCAL INFECTION

maticus is low, compared with other pathogenic strains
of streptococci. Although this relatively low virulence
may vary in degree and may become high, the morbid
changes in joints and muscles consist at most of hyper-
emia and edematous swelling of the infected tis-
sues. The changes in the endocardium are also char-
acteristic of the usually mild virulence of the infectious
bacteria as evinced by the mild tissue reaction in the
form of small warty nodes of the endocardium and
valve segments. Rarely is the endocarditis so severe
as to be called ulcerative or malignant. When that con-
dition occurs a change in type or in specific patho-
genicity of the invading streptococci has probably oc-
curred. Although rheimaatic valvulitis is usually mild
and is of itself rarely dangerous, the secondary sclerotic
changes and retraction of the segments is an irremedi-
able and harmful sequel.

Myocarditis

Myocarditis is undoubtedly a common incident in
rheimiatic fever only recognized clinically when marked
cardiac incompetency occurs with or without dilatation.
Mild myocarditis alone due to infection with strepto-
cocci which have a pathogenic affinity for muscular tis-
sue undoubtedly occurs from chronic infectious foci.
The mild reaction excited by the streptococci of low
virulency in the walls of the heart is naturally in the
form of proliferative interstitial tissue changes.

ACUTE DISEASES 55

Pericarditis

Pericarditis may occur alone, in association with en-
docarditis, and may be involved in pancarditis in the
course of rheumatic fever. It may occur as a simple
fibrinous or serofibrinous type. Occasionally piu-ulent
pericarditis may occur with rheimaatic fever in chil-
dren. Pus in the pericardiimi or in a joint would indi-
cate a coincident infection with pyogenic bacteria or a
change in pathogenicity of the infectious agent,
for the streptococcus rheumaticus does not cause
suppuration. In rheumatic fibrinous and serofibrinous
pericarditis, the prognosis is good for recovery, but
adhesions of the pericardial layers is a common sequel
which later may cause nutritional disturbance of the
heart muscle.

CHOREA

Acute chorea is an infectious disease. Its casual re-
lation with rheumatic fever and the frequency of endo-
carditis of the simple rheirniatic type in chorea indicate
the infectious character and a common bacterial cause.
The incidence of the disease is much the same as rheu-
matism. The first attack occurs most frequently in
children between the ages of five and fifteen years.
Seasonal incidence is the same as rheumatism. An at-
tack of chorea may precede, occur with or follow an at-
tack of rheumatic fever. Recurrent attacks usually
occur. Pericarditis may occur. Recovery is the rule.
The nervous phenomena, ataxic movements, muscular
weakness, mental disturbances, mutism, etc., may occur
by hematogenous infection, with a type of the strepto-

56 FOCAL INFECTION

coccus rheumaticus which has a specific elective affinity
for the brain. Multiple cerebral bacterial embolism due
to a type of streptococcus of low virulence would cause
little anatomical disturbance, but could be provocative
of all the motor and sensory phenomena of the disease.
Indeed, gross embolism of the smaller cerebral vessels
has been found and has been the source of the etiologic
embolic theory. Simple verrucose endocarditis resem-
bling simple rheumatic endocarditis is the most conunon
morbid anatomical change in chorea. The cerebral
embolism theory is related to the associated endocar-
ditis, with alleged detachment of small emboli composed
of fibrin, blood cells, etc. During life one may not study
the tissues of the brain as in other hematogenous in-
fections of muscles, joints, lymph glands, etc. The
discovery of bacterial emboli in other infected tissues
of rheumatic fever, and the recognition of very slight re-
sulting tissue reaction, is presumptive evidence that bac-
terial cerebral embolism may be the cause of chorea.
Rothstein and others have isolated strains of strepto-
cocci post mortem from the meninges of choreic individ-
uals. Animal experimentation with specific strains
of the streptococcus isolated in rheumatic fever asso-
ciated with chorea has been followed by joint infection
and characteristic symptoms of chorea in the inoculated
animals.

ACUTE SYSTEMIC GONOCOCCUS INFECTION

Gonococcemia may result from a local infection
of the prostate, seminal vesicles, joints and tendon
sheaths, from infected thrombi of the veins contigu-

ACUTE DISEASES 57

ous to local gonococcus infection and also from in-
fected thrombi of the venous sinuses of the uterus in
the puerperium. Gonococcemia is a very serious con-
dition, usually fatal when the cause of malignant endo-
carditis and childbed fever. Like other bacteria the
gonococcus varies in degrees of virulence, and if mild
the patient may recover from a gonococcemia even
though the condition is associated with endocarditis,
puerperal fever or suppurative arthritis. Thayer (57)
has reported the recovery of two cases of gonococcus
endocarditis. I have seen two patients recover who had
suppurating multiple arthritis with gonococcemia. All
of the suppurating joints were opened and drained,
which doubtless aided recovery. The removal of the
focal cause in all systemic gonorrheal infection may
aid in overcoming the general disease.

Gonococcus Arthritis

Arthritis is the most frequent systemic expression
qf gonococcus focal infection. When monarticular the
knee joint is most frequently involved. Males suffer
in the proportion of twelve to one or two of females.
It usually occurs during an acute gonorrhea, but may
occur after the subsidence of an acute attack or from
a long existing focal infection of the genito-urinary
organs. For some reason the latent bacteria may take
on new virulence and cause the late systemic manifesta-
tion. In women the focal lesion may be difficult to
locate.

Anatomically it occurs as a synovitis, and peri-
arthritis, with bursitis and tenovaginitis. The synovial

58 FOCAL INFECTION

joint eflFusion is usually serofibrinous and occasionally
purulent. Purulent bursitis and tenovaginitis are more
frequent. Periarthritis of the wrist with suppuration
extending along the sheaths of tendons of the hands
may occur. Periostitis of the os calcis with resulting
exostosis and marked tenderness of the heel is a re-
markable condition due to the gonococcus.

The gonococcus is present in the infected tissues and
in the exudate of the joints, bursae and tendon sheaths
from which with proper technic it may be recovered in
pure culture. In chronic conditions the infection may
be mixed with streptococci and staphylococci.

It is a most damaging and seriously disabling disease.

When the exudate is purulent, early operative relief
may save the joint and tendon sheaths and preserve
function. In non-purulent conditions the tendency is
to a long obstinate course with resulting damage to the
blood vessels of the infected tissues. This results in
local malnutrition with the attendant metabolic changes
in the joint and tendons with resulting deformity and
loss of function.

Gonococcus arthritis is often mistaken for rheimaa-
tism. Unlike rheumatism it more frequently attacks
tendon sheaths and the exudate is sometimes purulent.
It may involve the intervertebral, temporomaxillary,
sternoclavicular and sacro-iliac joints while rheumatism
rarely does so. Both may be polyarticular. Gonorrheal
arthritis is often very painful in undue proportion to
the apparent local infection. As a rule the fever is not
high. The ordinary antirheumatic drugs do not alter
the clinical course. In many instances the removal of

ACUTE DISEASES 59

the infectious focus is followed by quick relief of the
systemic disease.

MALIGNANT ENDOCARDITIS

Malignant or ulcerative endocarditis, so called because
of the tendency to local tissue destruction and the high
mortality which it causes, may be acute or chronic. It
is always a secondary disease. It may be a local com-
plication of a systemic disease like pneumonia, typhoid
fever, epidemic cerebrospinal meningitis and rarely of
rheumatic fever, or it may arise from a focal infection
anywhere in the body due to the gonococcus, strepto-
coccus, staphylococcus and less frequently to other in-
fectious bacteria. There is always an associated bac-
teriemia. The bacteria which are most frequently found
in the infected heart tissues, vegetations and contained
thrombi, in the blood stream by cultures, are strepto-
cocci, pneumococci, gonococci and staphylococci.
Streptococci are the most frequent cause and reach the
blood stream and heart from septic wounds, the septic
puerperal uterus, and other streptococcus foci about
the head and elsewhere. While the streptococcus py-
ogenes is the strain which causes most of the acute types
arising from acute infectious foci, the streptococcus vi-
ridans may also cause the acute type, but usually is the
cause of chronic malignant endocarditis.

Bacteriemia associated with the general diseases
named or due to a focal infection may not involve the
heart. The normal endocardium is apparently resistant
while old sclerotic processes of the valves and congenital
deformities of the heart and proximal vessels predis-

60 FOCAL INFECTION

pose to malignant endocarditis. Hence malignant endo-
carditis most often occurs in individuals suffering from
chronic valvular disease and chronic cardiomyopathy.

AoBTic Valves
Streptococctts VnUDAVB
Man.

The morbid anatomy is essentially the same in all bac-
terial types of the acute form. Usually vegetations are
present, often massive, especially when due to the pneu-

i.k

^^H mococcu
^^" veo-etati

ACUTE DISEASES

mococcus, and streptococcus viridans. Occasionally the
vegetations are not large while necrotic destructive
lesions are dominant in very virulent infections and es-
pecially when staphylococci are the cause. From the cir-

aawKSSES^^'S*-

1^^

Fig. 10. — Section Tnaouou Vedeiationb on Mitral Valve Shown in
Fio. 9. Note the dark areas consisting of clumps of streptococci.

culating hlood thrombus formation occurs in the vege-
tations. Necrosis of endocardium, superficial and deep,
with perforation of valves and other destructive lesions,
may occur. The infectious bacteria are present in great
number in the vegetation^, thrombi and involved tis-

62 FOCAL INFECTION

When malignant endocarditis occurs as a local com-
plication of a general disease like pneimionia, rheu-
matic fever, cerebrospinal fever, or some other acute
disease, it may not be recognized because the severe
symptoms of the systemic disease may overshadow and
mask the manifestations of the local condition. As a
rule the other symptoms of the general disease are in-
tensified with evidence of failing heart, leading to a
rapid fatal issue. Frequently the severe endocarditis
is first recognized at autopsy.

There are, however, special and characteristic symp-
toms which may lead to the recognition of the condition
of the heart and especially if a bacteriemia is found by
blood culture. Detached small particles of the vegeta-
tions and of thrombi carried in the blood stream may
cause embolism in the various tissues and organs. Em-
bolism may give rise to deliriima, coma, paralysis, peri-
splenitis, with enlargement and tenderness of the spleen,
varying degrees of hematuria, gangrene of distal tissues
and petechiae, and at any point local abscesses may de-
velop from the infected emboli. Mycotic aneurism may
result. Embolism of lung followed by abscess may
occur if the right heart is involved. Usually the local
cardiac disease is manifested by endocardial murmurs,
but may be absent. The septic type is marked by chills
and an intermittent or remittent type of fever and severe
sweats. A typhoid type is characterized by a more con-
tinued type of fever, delirium, coma and rapid course.
In rare instances the clinical picture is that of cerebro-
spinal meningitis. The diagnosis may be difficult, but
is greatly aided by blood culture.

ACUTE DISEASES

Malignant endocarditis usually terminates fatally, but
recovery has been noted by Herrick (21) and others
In coroner's autopsy cases E. R. LeCoiuit has recog-
nized six or more instances of healed scars of ulcerative
endocarditis.

ACUTE NEPHRITIS

The types of acute infectious nephritis which usually
rises from a focal infection is embolic because the mode

Fig. II. — A Glomebulus Contain!

rabbit dying 7 days after inoculation. X 375 (after LeCount and
Jackson, Jour. Inf. Dis.).

of infection is hematogenous. It is, therefore, primarily
a glcmerulonepbritis. If the dose of infectious bacteria

64,

FOCAL INFECTION

reaching the kidney is large enough, the nephritis may
be diffuse. Usually the condition is expressed clinically
by bloody urine of varying degree, microscopic blood
is present with albuminuria and casts of various

after injettio;

1 (Hftcr LeCount

From rabliit dying 7 days
id Jackson, Jour. Inf. Dis.).

types. The urine is lessened in quantity in twenty-
four hours, soon a secondary anemia develops and
often within a short period a soft edema. Varying de-
grees of this type of nephritis occur from focal infec-
tion. The most usual site of the focal infection which
causes the nephritis is the throat. In the milder types

ACUTE DISEASES 65

of this form of nephritis apparent complete resolution
occurs after the removal of the focus of infection. BUl-
ings (9) has reported clinical ohser\'ations on the rela-
tion of focal infection to glomerulonephritis and the

Fig. 13.— a GLOMEBUT.ia in Which Ame Mashkb of Cocci Fim.i
OF CAPiLLASiEa. From a rabbit dying 9 days after inoculal
(after LeCount and Jackson, Jour. Inf. Dis.).

apparent resolution of the infection of the kidneys by-
eradication of the focus. LeCount and Jackson (35)
have shown the renal changes in rabbits inoculated with
streptococci. Of these animals six were inoculated with
strains of streptococci isolated from patients with epi-
demic septic angina. The kidney lesions were primarily

66 FOCAL INFECTION

of the vascular structures, glomeruli, intertubular ves-
sels and arcuate and interlobar veins. They noted a
pronounced perivascular exudate consisting chiefly of
lymphocytes and plasma cells. The tendency to repair
in the acute glomerular lesion, noted by LeCount and
Jackson, is very important when compared with the
tendency to recovery of clinical glomerulonephritis of
man, when the chief etiologic factor is removed.

ACUTE APPENDICITIS

Acute appendicitis due to focal infection located in
the throat and nose and sometimes in the jaws has been
noted by a great number of clinical observers, notably
among the French. Kretz ( 25 ) has shown the frequent
infection of the cervical lymph nodes with streptococci.
When the cause of the lymphogenous infection is acute
Kretz believes that the bacteria filtrate rapidly through
the lymph nodes, with resulting severe bacteriemia. In
less severe types of focal infection of the head and in
adults especially, the virulence and degree of bac-
teriemia is usually less. In these conditions, local or
general systemic infection may follow in the form of
acute multiple arthritis ( rheumatism ) , endocarditis,
pericarditis, osteomyelitis, nephritis, appendicitis,
cholecystitis and even streptococcus malignant endo-
carditis. He also believes that acute appendicitis and
cholecystitis are hematogenous in origin and never pri-
marily caused by infection within the lumen of the ap-
pendix and gall-bladder. Cannon (26) argues that
appendicitis and cholecystitis are hematogenous infec-
tions, and may be of focal origin. He believes that

ACUTE DISEASES 67

typhoid cholecystitis occurs through the blood stream.

After animal experinientation and a study of the

tissues and bacteria of appendicitis, Ghon and Namba

(27) conclude tliat if appendicitis occurs hematogenous-
ly it must be due to a specific strain of streptococci.

Adrian (28) has observed appendicitis as a focal in-
fection of general disease. He apparently considers
the bacteriemia of a focal infection a general disease.

ACUTE DISEASES 69

relation of the angina to appendicitis. The term
"anginal appendicitis" has been coined to express this
relation.

The confirmatory investigations of Rosenow (8) have
shown the occtn'rence of acute appendicitis from strains

of Ijmph foUiiJes.

of strept(jcocci, colon bacilli and other organisms which
have attained elective affinity for the tissnes of the
appendix. This elective tissue affinity has been acquired
by these microorganisms in the tissues of the appendix
during an attack, for when they are isolated from the

FOCAL INFECTION

infected tissues of the appendix and nascent cultures
are injected intravenously into animals, acute appendi-
citis occurs in the great majority of the inoculated
animals. The same affinity for tissues of the appendix
can be induced to appear in strains through variations
in culture methods and serial animal inoculation.

Fig. 17. — ^Diplococci in Peritoneal Coat of Appendix Shown in Fig. 16.

The invading organisms reaching the tissues of the
appendix hematogenously cause small hemorrhages in
the walls of the organ and if this invasion is great
enough the reaction of the tissues to the invading
organisms causes a positive chemotaxis with invasion
of leukocytes and plasma cells and consequent tumefac-
tion of the tissues and obstruction of the canal of the
appendix. With obstruction there occurs a condition
which invites the rapid increase in the numerous sapro-
phytic anaerobes and other bacteria usually present in

ACUTE DISEASES

the bowel and appendix with resulting increase of mor-
bid tissue change, varying in degree from edema to
necrosis and gangrene. Until these investigations of
Rosenow, the presence of colon bacteria and of various

other saprophytic organisms in the tissues of the normal
as well as the infected appendix, has led to the belief
that acute appendicitis has been excited by an infection
within the bowel by the various saprophytic organisms
usually found there. This secondary invasion of anae-

FOCAL INFECTION

- V ■'.• ' « •. •

robes and other bacteria often found in the tis-
sues closely related to the intestinal tract have been de-
scribed as the primary causes of appendicitis by Heyde
(29), Aschoff (30) and others. The argument from

^^^^^E^^^^^^^^t ^^^S^HH

■

"^ '-I^P

'^"vses^- Miy^^

■ '

li. 31.— He«obriiaoe, Necrosjb and Leitkocvtic Inf.m'hation

OF ApPE

^H Dix 94 Hours After Ikjection or Miked Citltdiib of Fus

FORM Ba- I

^H ciLLi A_si) Sthept(iccucj fbom Hujiak Appendix Shdwit m

Fis. 30.

-'^,-

'^' '

Fio. 23.— Smeptococci akd Fuwfobm Bacilli of Api'tsmx

SaoWH IK Fio. 31 34 HouBS Aftee Intbavesous Injection

FOCAL INFECTION

this point of view is that these facultative bacteria in-
vade the tissues from the himen of the bowel, when the
resistance of the body tissues is low. and especially when
the lumen of the appendix is partly or wholly closed
by fecal concretions, kinks of the organ or from other
causes. The more reasonable relation of these bacteria

Fio. i3. — Photosiicrooiaph of 3i Hot
Bmtii of a SraEPTOCoccuB Isolated f
CHOLBCvsnng. The raorpbolOBj, siie and grouping s
of strains from irholecyslitis. Gram stain.

to the disease is that of a mixed infection, secondary to
the primarj- hematogenous invasion usually by strepto-
cocci.

How much the lessened resistance of the tissues
of the appendix due to the presence of fecal stones and
other foreign bodies or to kinking of the organ may
have to do in attracting the streptococci in the blood
stream to the appendix, needs further investigation.

ACUTE DISEASES

CHOLECYSTITIS

Cholecystitis is unquestionably due at times to hema-
togenous infection with strains of streptococci and pes-

111

L-^lf^

OIC CHOIJCVSTITIfl IN DoO *tt HoiTlS Af-TEK I NTBAVE-

OF Streptococcdb Showit iif Fio. 23, fbom the
lKrii,T»*TED Wall of Humav Gall-bladdee Soon

Afttb Isolatioh,

sibly to other microorganisms. A patient in the Pres-
byterian Hospital who suffered from an attack of acute
cholecystitis was operated and it was noted that in the

FOCAL IXFECTIOX

fundus of the gall-ljladdcr there was a small softened
area which was excised. The gall-bladder also contained
some small soft concretions of bile. From the softened

One Abimal Passaoe.

tissues of the gall-bladder Rosenow isolated a strain
of streptococci which injected into animals produced
cholecystitis. This patient suffered from tonsillitis and
a short period before the onset of the attack of cholecys-

ACUTE DISEASES

titis had suffered from an acute tonsillitis. Strains of
the streptococci isolated from the tonsil had a like af-
finity for the gall-bladder in intravenously inoculated
animals.

Rosenow has shown also that strains of the strepto-
cocci attain an affinity for the gall-bladder similar to

Fra. 28. — Stseptococci in Lvhph Space or Edehatodb Wall of Gali^
a Shown in Fio. 35. Gram-Welgert stain.

that attained for other tissues, and that this affinity may
be lost and regained by varying methods of culture and
by serial animal passage.

There can be no question that cholecystitis may occur
through hematogenous infection by typhoid bacilli and
probably by other pathogenic microorganisms, but the
more frequent presence of streptococci than the other
pathogenic bacteria in the center of gall-stones removed
from patients, as shown by Rosenow, is suggestive of

78 FOCAL INFECTION

the more frequent occurrence of streptococcus cholecys-
titis.

ACUTE GASTRIC AND DUODENAL ULCER

Acute peptic, gastric and duodenal ulcer may be pro-
duced experimentally in animals by the intravenous

Fio. 37. — Phoiomicrogbafh op 34 Hodh AsciTEB-DExmoBe-BBoTH CuvTuax
OF Streptococcus from Human Ulceb at the Time the Sisaiit
Proved to Have the Affinity fob the Stomach When Intbate-
NODSLY Injected Into Animals. Grain stain.

injection of strains of streptococci which have an elec-
tive aflSnity for the stomach wall and Rosenow has
isolated this strain from the base of the ulcer and tissue
of the stomach wall of man. The strain, so isolated,
proved to have an elective affinity for the stomach wall
in animals intravenously inoculated. The mode of pro-

2* '■A ■

^^^

.^^"

j^^^P' ''—^'IH

i^B fli

^^tr!?^

Fig.
S

33.— Sectios of Wal.. of Si«.>iach of Habbit Showino W

ILAPED AllEA OF I S FILTRATION, HEMOnRIIACE AMD BeCIWSINO Ul

ON 4S Honaa Aftek iNTRArENOiTS Injection of Streptococci
ONSiL OF Patient with Herpes Zoster After One Animal Pa*

82 FOCAL INP^ECTION

duction of the nicer as noted animals is a strepto-
coccus embolic infection of the siibmucosa of the stom-
ach with resulting small hemorrhages into the surround-
ing tissues. In consequence of the hemorrhage and the

Fig. 33. — Stmbi'toii

presence of the infectious microorganisms in the sur-
rounding tissues, anemic necrosis so weakens the over-
lying mucous membrane that it Incomes digested by the
gastric juice. If the necrosis im'olves a vessel of suffi-
cient size, visible stomach hemorrhage may occur. If
the infection and injury is not great, healing takes place.
If the infection is more virulent, chronic ulcer results.

ACUTE DISEASES

ACUTE PANCREATITIS

Acute pancreatitis of serious degree always requires
surgical interference. When it is of mild deforce sur-

gical interference is not usually required, but if it be-
comes a chronic condition degenerative changes may

Www. AiT>h l!iLiiiAva«uu» [jiji

ACUTE DISEASES 85

lead to involvement of the islands of Langerhans with
disturbed function and diabetes mellitus may result.

There is a relation more or less close between the
strains of streptococci which have an elective tissue af-

Showinq DipLOCOCti IN Akea of Rovkd Cell
Partially Thrombosed Blood Vesbel of Fia. 35.

finity for the appendix, gall-bladder, stomach wall and

pancreas and this has been beautifully and graphically

■ shown in the table, which was presented in Lecture U.

ERYTHEMA NODOSUM

Erythema nodosum has been recognized as a condi-
tion which may occur with acute or subacute rheuma-
tism or as a part of the syndrome described by Osier
(17). The syndrome consists usually of polymorphic
skin lesions, hyperemia, edema, hemorrhage, quite fre-
quently associated with arthritis. At times there may

PiO. 37.— SL-BCUl-ANEOfB TlSSlES HIO.II EhYTIIE.HA NODOSUM ]N MaN. ScC-

tions showing a leukocytic ami rouud cell iiillltration along tissue
strands between the layers of fat._

a. 38. — SuBCUTAKEOVs Tissue fbom Ervthema Nodosi'M in Man. Sec-
tion showing red blood corpuscles, blood pigment, nuclei of disinte-
grated leukocytes and diplococci and diphtheroid baellli.

Fio. 39. — Sheab feom Sinole Colony in A scite a- Dextrose- Aoab 72 Honeg

AFTEB IsoCHLATION with the EMULSlOIf OF THE SvBCDTAHEora NoDi

Showing Diphtheroid Bacilli in Fio. 38.

88 FOCAL INFECTION

be viscera] crises, especially gastro-intestinal, endocar-
ditis, pericarditis, hematuria, nephritis, nodose erythema
and peliosis rheumatiea. The present knowledge of
the infectious nature of rheumatism, of endocarditis,
pericarditis and nephritis, point to a probable focal in-
fection as the cause of the syndrome, which has been

«f«

.- \

-1

diploc

FiQ. 39 Anra Os
in chains.

JCIKEA PlO iuJECTEll WITH CCLTimji

! AiriMAL Pabsaoe. Note the typical

discussed by clinicians in the past, as infectious, toxic
or metabolic.

The discovery of bacteria belonging apparently
to the members of the streptococcus-pneumococcus
group in fresh tissues isolated from the nodes removed
surgically from patients and the production of erythema
nodosum in the skin of animals intravenously injected
with the cultures so obtained, has been demonstrated
many times by Rosenow.

The removal of the apparent focus of infection in

FlO. 41, PlIOTOQBAPH ShOWINO CmCUHSCSIBeU lli:>ll>ltHir

OF THE Leos or A Rabhit i% HoL'u Aftgr ak Intsa

or CULTITBE OF DIPHTHEROID BaCTEBIA ShOWK IK FlO. 39, OBTAINED

Flou AK Ebtthematous Node ts Mak.

II Aspect
Obtained

Fio. 42. — Section ok Skjn of Rabbit Showino HEHonauAQE and Leu-
kocytic AND ROUSD CeI.1. IsflLTHATIOS Of St.-nCI.TTANEOl'S TISSUE 7i

HoUBS AfTEB Inteavenous Injec-tion or THE Dtphtiieboid Bacilli,
Showjt l>r Fio. 39. Note the complete absence of involvement of the
cutis and only sli§;ht infiltrstian of tlie corium.

Fig. W,— a TIip

Flo. 4l.-.SrtTi»K i.F TILE Ahtkkv iKciM TSIK \»e.\ lie Si-Bti-TANKoi-ii Hkm-
iiv.s IK Fio. 1,'. Xott llio iiiuriil iiggn-gutioii of leukocytes.

■y ,v V

Fjo. 46. — Photomichoobaph of 34 Hour Ccltithe in AeciTEB-DExmoss-
Bboth of a SniEPTococcuH Ibol.\ted rHOsi THE SpiSAL Flutd of a Rab-
bit Which Showed Hehpes After the IvtftAVDNous Injection
Stheptococccs Cultche fhom the Tonsil op a Man Who Suffebed
wiiH Hehfes ZoaTEB. The morphology is quite characteristic of the
strains from herpes zoster.

Sees on Undeh Surface of the Skih Over

-HE LOWEH

c Reoios of a Rabbit 31 Hodbs After an

1 NTH AVE-

OF Streptococcus Shown in Fie. M.

FOCAL INFECTION"

patients at the Presbyterian Hospital, suffering
from erythema nodosum, has been followed with relief
over periods of sufficient length of time to clinically
prove the etiologic relations of the focus of infection
to the systemic condition.

It has long been known that herpetic eruptions may
be induced in animals and that like lesions occur in man

Spinal Ganolton Cobdespoitd-
Fio. 47. Gram-Weigert stain.

from injury or infection of the ganglia on the sensory
root of the cranial and of the spinal nerves. That herpes
zoster may be the result of specific infection of the
ganglia of the posterior roots of the spinal nerves and
the etiologic infectious microorganisms may be isolated
from the infected tonsils and other foci has been dem-
onstrated with patients in our clinic. With these strains

Fio. 51. — DipiJ3cocci m Leukocyteb Withis a TiiBOMBoaEn Vein Shown
IN FiQ. 50. Grara-Weigert stain.

Fio. 53. — DipLocotci ix Hemohhhaoic and I.
Fid. 53. Gratu-Weigert stain.

Ahea Shown i

l-'it. 55.— Hehpes 111' Ski.n UK LufT Side of Face of a Kabbit 73 Horas
Aftee an Intrai-emous Injection of Streptococcus fioh tbe ToNSn.

iH Hehves Zosteh.'

Fio. S6.— Hemobbhaoe (a
Gasserian Ganomon

HoVRS AlTEH AN InTB

TosaiL IN- A Patiest '

THE Lit and Cheek.

102 FOCAL INFECTION

of the isolated bacteria, herpes zoster has been produced
in intravenously injected animals and the streptococci
have been recovered from the posterior root ganglia of
the inoculated animals.

SPINAL MYELITIS

A recent interesting clinical observation and its re-
lated laboratory experiments as made by Rosenow is
worthy of record. A young man suffered for three
years from the mild but typical symptoms of spinal in-
sular sclerosis. When he was admitted to the hospital,
he suffered from ataxia of gait and station, greatly in-
increased knee kicks, slight nystagmus, but no intention
I tremor, and his spinal fluid was negative both as

I to abnormal cells and the serum tests. He had

periods of improvement and of worse conditions
associated with marked vertigo and falls without
unconsciousness. He had suffered from chronic ton-
sillitis for years. With a consideration of the possi-
bility of a relation of focal infection to the condition and
as no other site of infection could be located, the tonsils
were enucleated. The streptococci isolated from the ton-
sillar tissue, chiefly a strain of the green forming type,
was intravenously injected into two dogs. In both
animals focal hemorrhages were produced in the spinal
cord and the development of ataxic gait and partial loss
of power in all four extremities. From the focal soft-
ened areas of the spinal cord a like strain of strepto-
cocci was recovered.

The infectious etiology of focal hemorrhage and soft-
ening of the cerebrospinal axis has been recognized for

ACUTE DISEASES 103

a long time. The possibility that the condition may-
arise from a focus of infection is suggested by the ob-
servation and experiment just mentioned.

ACUTE OSTEOMYELITIS

Acute osteomyelitis is often ascribed to injury usually
involving the extremities. There can be no question
that the infectious organisms, usually tubercle bacilli,
streptococci and staphylococci, gain entrance into the
blood stream from foci in the head or lymph nodes and
that under certain conditions of increased virulence and
of lessened resistance upon the part of local tissues due
to injury of the bones, single or multiple osteomyelitis
may occur. Kretz (25) records clinical observation in
support of the focal origin of osteomyelitis.

THYROIDITIS

Thyroiditis is probably a much more frequent event
than has been heretofore noted. I have already called
attention to the frequency with which thyroiditis occurs
in rheumatism. Vincent (31) has shown the incidence
of 50 to 80 per cent, of swelling and tenderness of the
thyroid gland in the course of acute rheumatic fever.
There can be no question, too, that infection of the
gland occurs in other general infections. It also occurs
from focal infection about the mouth, throat, and nose.
We have observed many instances of thyroid enlarge-
ment, usually of chronic type, associated with evidences
of thyroid intoxication in many young women patients
with focal infection in the form of alveolar abscess, ton-
sillitis and sinusitis.

ff^^^'"'£. ,

g^S^^&i^^'^^

Fio. ST.— Section of Inis am. Cji.iahv Bodv op Haueit Showino Mahked

LeUKOCVTIC IsFII.THATIQN (a) 4 Davs AfTEII InTEAVENOUS InJECTIOK

OF Htheptococci from RuEusiATic Fever.

ACUTE DISEASES

IRIDOCYCr.ITIS

Iritis is not an unusual event in rheumatism, syphilis
and some other general infectious diseases. When
acute or subacute iritis occurs alone the cause has been
ascribed to infection, toxins, anaphylaxis and to faulty

Fid. fiS. — Photdhicboghapb of STHEPTOtoi
SHOim i»r Fio, 57. Gram-Weigert stain.

metabolism. That infection plays a much more constant
part in the causation of iritis is apparent from the expe-
rimental work of Rosenow (8), Irons and Brown and
others. Strains of streptococci in foci of infection
of the teeth, tonsils and sinuses have an unquestionable
relation to iridocyclitis alone as well as when the
eye infection is associated with rheumatic fever, chorea,
syphilis and other acute general diseases.

LECTURE IV

CHRONIC DISEASES RELATED TO FOCAL INFECTION

CHRONIC INFECTIOUS ARTHRITIS

Under the classification of chronic infectious arthritis
our present knowledge justifies the consideration of
chronic arthritis which may be due to various forms of
pathogenic bacteria. Investigation has shown that a
strain of the streptococcus, gonococcus, tubercle
bacillus, bacillus typhosus and spirocheta pallida are
the most common infectious causes of chronic arthritis.
When other bacteria are found in the infected tissues
of chronic arthritis and myositis, they may have etiologic
relations to the condition, but are probably present in
the tissues as a mixed infection or purely as parasites.

We shall confine the subject to streptococcus, gono-
coccus and tuberculous joint infections because of the
usual focal origin. The deformities which occur in
chronic arthritis due to the streptococcus and to the
gonococcus do not differ essentially because the morbid
anatomical changes which are produced in the chronic
type of infection due to the streptococcus and to the
gonococcus are essentially the same.

In both instances the mode of infection is hemato-
genous and from a focal infection. In both the obstruc-
tion due to endothelial proliferation or embolism in the

small arteries due to the hematogenous mode of infec-

107

108 FOCAL INFECTION

tion is practically the same. In both types of chronic
infection the virulence of the invading organisms is
not high. Consequently the tissue reactions excited by
the organisms is much less than in the more virulent
type of streptococcus and gonococcus. Consequently
instead of the production of a positive chemotaxis with
purulent exudates at the point of infection as with local
infections due to the streptococcus pyogenes and viru-
lent types of gonococcus, there is in these chronic con-
ditions a tendency to fibrinoplastic exudate and an
attempt to wall off an area of infection. The variation
in the virulency of the organisms which produce the
chronic types may result in serofibrinous exudates in
joints and tendon sheaths and to small hemorrhages in
subserous tissues and in muscles. The low virulency
of the organism, the embolic mode of infection of the
tissues, the resulting tissue reaction, all tend to lessen
the blood supply of the infected tissues through the
partial obliteration and destruction of small blood ves-
sels. In consequence there is a lessened blood supply
and oxygenation of the tissues which results in marked
malnutrition. Malnutrition leads to secondary meta-
bolic changes resulting in either hyperplastic or atrophic
changes in all joint structures, tendons and muscles.
These changes have been well described by Nichols and
Richardson (41) as both proliferative or hypertrophic
and degenerative or atrophic arthritis. Because of
these morbid changes, deformities result from muscular
contraction and from the changes which occur in the
bones, cartilage and other structures entering into the
joints.

CHRONIC DISEASES 109

Present knowledge is in accord with Nichols and Rich-
ardson in the statement they make that morbid changes
both proliferative and degenerative of joint tissue can-
not be differentiated etiologically.

If one considers that the infection of joint tissue is
hematogenous and that a sufficient dose of infectious
organisms in the blood stream may reach the peri-artic-
ular tissue or deeper tissue of the j oint — that is, the end
arteries in the subcapsular tissues — or through the
nutrient arteries and involve the medulla of the
epiphysis, one can harmonize the morbid anatomical
changes which have been so clearly described by Nichols
and Richardson.

The reaction set up in the tissues of the external joint
structures in the subcapsular region and in the medulla
of the bone will depend in all probability upon the
virulence of the infectious microorganisms and upon
the resistance of the general body structures and of the
joint tissues. They may be either proliferative with
virulent bacteria, especially in young or normal indi-
viduals, and necessarily the reaction will be less, or more
degenerative in kind in the joint tissues of individuals,
which are poor because of age, trauma and other con-
ditions which lessen the vitality of tissue.

Continued doses of infection from the focus would
necessarily add to the changes described in the joint
tissue. The repeated hematogenous infection destroys
more blood vessels, again and again traimiatizes the
infected tissue and continuously lessens the oxygen sup-

piy-

We now know that in chronic arthritis infectious

110 FOCAL INFECTION

organisms, whether streptococci or gonococci, have a
relatively low virulence. Of course the degree of viru-
lence varies and consequently the proliferative and de-
generative changes especially vary in different indi-
viduals.

With continued infection of the tissues malnutrition
necessarily increases, for the reasons named, and this
necessarily leads to retrograde metabolism.

Whether the retrograde metaboUsm is due solely to
the malnutritions or whether it is also due in part to
irritants in the tissues of bacterial or biochemic origin,
does not in any way alter the principles outlined. There-
fore, the proper understanding of chronic infectious
arthritis involves an understanding of the following
principles :

(1) The infection of the joints, muscles and other
involved tissues with pathogenic organisms which usu-
ally are members of the streptococcus group and the
gonococcus which are of relatively low virulence ; ( 2 ) a
hematogenous infection with embolism with resulting
ill jury of blood vessels and small hemorrhages into the
infected tissues; (3) lessened blood supply and oxy-
genation and consequent relative starvation of the in-
fected tissues and dependent upon the malnutrition^
favorable conditions for the continued life and multipli-
cation of the infectious organisms, and finally ( 4 ) retro-
grade metabolism due to the malnutrition.

In the chronic infections due to the streptococcus,
chronic arthritis may occur alone or associated with
chronic myositis and chronic myositis may also occur
alone involving single or groups of muscles. In chronic

CHRONIC DISEASES 111

gonococcus arthritis the muscles are rarely, if ever, in-
volved. Tenovaginitis is, however, more apt to occur
than in chronic streptococcus infection.

Various anatomical types of chronic infectious arthri-
tis may occur, which doubtless depends upon the de-
gree of bacteriemia, the degree of virulence of the in-
fectious organisms, the resistance of the tissues and the
fact that the mode of infection is hematogenous. Con-
sequently we may have a peri-arthritis, a synovitis, an
osteo-arthritis or a panarthritis. Any or all of these
types may exist in the same individual. The primary in-
fection may be severe enough to simulate acute rheu-
matic fever or mild rheumatic fever. Usually the dis-
ease begins insidiously, but there may be in many pa-
tients periods of increase in temperature usually of a
febrile type. There is always a great deal of soreness
of the infected tissues which is aggravated by anything
which disturbs the general or local circulation, as chilling
the body, fatigue and general nervous irritability. Be-
cause of the varying degrees of activity of the focus
there may be reinfection from time to time of the tis-
sues, joints, muscles, etc., with consequent aggravation
of the symptoms. Usually there is but little pain ex-
cepting with exercise of the involved organs. Chronic
gonorrheal arthritis is more apt to involve the interver-
tebral joints and ligaments, the sacroiliac, sternoclavic-
ular and temporomaxillary joints than the strepto-
coccus, but inasmuch as the streptococcus may also infect
the four named joints, involvement of them does not
necessarily indicate a gonococcus infection. Chronic
infectious myositis which may occur as a part of the

112 FOCAL INFECTION

chronic streptococcus arthritis or alone, is associated
with shortening of the muscle bundles due to the embolic
infection with subsequent hemorrhage and connective
tissue proliferation. At the time of infection there is
usually tenderness and pain when an attempt is made
to contract the muscles. When at rest there is usually
no discomfort. There is apparently an elective affinity
of the infectious organism for certain muscles, notably
the masseters, the biceps himieri, the hamstrings, the
anterior tibial and erector spinae groups. Other muscles
are sometimes involved and in some instances practi-
cally all skeletal muscles are included in the infection.

In all of these chronic types of arthritis and myositis
there may be general debility with anemia, emaciation
and nervous irritability due to the long continued infec-
tion. Often these general conditions are aggravated by
methods of treatment, in starvation diets and purges
which weaken the patient and by the overuse of drugs.
In recent years the irrational use of vaccines and of toxic
extracts of bacteria has added to the miserable condi-
tion of the patients.

These general weakening influences add to the con-
ditions which promote retrograde metabolism in the in-
fected tissues, so that in the patients who present the
worst type of the condition there is a tendency to such
a degree of retrograde metabolism that the connective
tissue group comprising aponeurosis, tendons and carti-
lage is changed into bone.

Chronic tuberculous arthritis is always associated with
focal or with general tuberculosis. It practically always
occurs as an osteomyelitis usually involving the epiphy-

CHRONIC DISEASES 113

sis. The evolution of the tuberculous process in the
epiphysis leads to infection of the joint with its char-
acteristic morbid anatomy. Tuberculous tenovaginitis
is usually a secondary infection from the periarticular
tissues, but may occur alone.

Spondylitis due to the typhoid bacillus probably
causes the same anatomical type as the gonococcus and
streptococcus.

Infectious neuritis or perineuritis due to a focus of
infection may occur alone or as a part of chronic ar-
thritis and myositis or with myositis without arthritis.
Usually the condition is a perineuritis. The nerves most
often involved are branches of the brachial plexus and
the sciatic trunks. Focal infection about the teeth, ton-
sils and sinuses is a frequent cause of neuritis. The
gonococcus may be the cause of neuritis or perineuritis.

CHRONIC INFECTIOUS NEPHRITIS

Chronic infectious nephritis due to focal infection is
very common. Probably it has first existed as a sub-
acute infectious nephritis and not infrequently occurs as
a hematogenous infection of the kidney from some focus
resulting in anatomical changes of various degrees.
Chronic infectious nephritis, like the subacute and acute
types, is usually due to strains of the streptococcus
which have a specific elective affinity for the kidney.
This specific afiinity may be attained in the focus of
infection. If the bacteriemia due to focal infection is
severe, undoubtedly nephritis either acute or chronic
may result from bacteria which have only general path-
ologic virulence. LeCount and Jackson (35) state that

114 EOCAL INFECTION

the moat important result of their work was the experi-
mental production of alterations, essentially subacute
and quite like thi; acute interstitial nephritis in human
kidneys, caused hy the acute infectious diseases, com-

X HIM) (after

plicated by or due to streptococcus infection. Of the
rabbits inoculated, eight, or 25 per cent, of the thirty-
three which died or were killed within the first two
weeks, showed chronic changes in the kidneys, while fif-
teen, or 62. 5 per cent., of twenty-four rabbits which lived

CHRONIC DISEASES 115

from fifteen to one hundred and eighty-six days, showed
chronic kidney changes. They conchide, therefore, that
chronic lesions of tlie kidney of a part of the inoculated

VeIK SpEBOtlNDED H"

Plasma Celij. From Ihe kidney of rabbit dying i2 days after inocu-
lation. X 35 (after LeCount and Jackson, Jour. Inf. Dis.),

rabbits resulted from the subacute nephritis caused by
the streptococci intravenously injected.

Ophiils (55) concludes that chronic nephritis is
usually of infectious origin, Klotz (54) states that a
form of acute interstitial nephritis induced in animals by

116 FOCAL INFECTION

the inoculation with strains of streptococci subsequently
gives rise to a renal sclerosis of the type known as chronic
interstitial nephritis. He believes that a similar process
is conunon in man.

In an article on the relation of focal infection to ne-
phritis, we gave the clinical history of a young woman
who suffered with hemorrhagic nephritis apparently due
to badly infected tonsils. After enucleation of the ton-
sils there was great improvement of the renal condition
and a restoration to apparent health. Occasionally,
slight albuminuria with the presence of hyalogranular
casts occurred. After one year evidences of chronic in-
terstitial nephritis became constant and three years fol-
lowing the removal of the tonsils and the greatly im-
proved condition, the patient died of renal intoxication
associated with a high degree of hypertension.

Every clinician of experience has observed patients
over long periods of time who have presented primarily
evidences of acute or subacute nephritis of infectious
origin and who have finally succumbed to chronic
nephritis. That a focal infection may be the
source of the kidney lesions and may lead to a
chronic irreparable renal disease must be emphasized.
Early removal of the etiologic focus may prevent fur-
ther anatomical insult of the kidneys and preserve renal
function and life.

CHRONIC CHOLECYSTITIS

Chronic cholecystitis with or without gall-stones is
the result of acute infection as a rule. As we have seen,
this may be due to hematogenous streptococcus infec-

CHROIS^IC DISEASES

117

tion. The streptococci, which lodge in the small area
of the fundus of the gall-bladder at the terminus of a
blood vessel, may cause hemorrhage and exciting tissue

Fia. G3.— Cbolectbtitib and Cholelithiasis if Doo Tek Days Afteh In-

THAVEN-OUfl InJECTIOV OF STBEPTOCOCCUS FltOH CeNTEH OF GaLI.-StONE

FBOM Hdhan Gall-Bladdeb. Note tlie black stones imbedded in the
edematous mucous mcmbrnne.

reaction which weakens the gall-bladder wall and may
rupture into the cyst. If the infectious organism is of
high virulency, acute purulent cholecystitis may occur

118 FOCAL INFECTION

or with a less virulent type the infection will he much
less in degree. If unoperated at the time of the acute
or suhaeute attack, gall-stones may form in the chroni-
cally infected gall-bladder. As long as the focal site
exists reinfection may lead to subsequent acute or sub-
acute attacks of cholecystitis.

As shown by Rosenow (8) the strain of strepto-
coccus, which seems to acquire an affinity for the tissue
of the gall-bladder, has a coincident affinity for muscles
particularly of the myocardium, and in confirmation
clinicians have noted evidences of myocardial weakness
in patients who suffer from chronic cholecystitis.

CHRONIC PEPTIC ULCER

Chronic peptic ulcers of the stomach and duodenum
are doubtless the sequence of acute ulceration and we
have already noted the mode of infection in acute ulcer

Fio. e*. — Stbeptococci and Leukocvtio Inkiltbation- in Peritoneal Coat
IN Pebfobatino Ulceb of the Stomach of Man.

Fio. 65. — Streptococci in Pehitoneai
Rasbit 5 Days After Imtbavehoi
Pebfi:«ati)ic> Ulcer of Stomach t

Coat of Ulceb of Stomach :
IjrjECTioM OF Stbeptococci rac
Man Shown in Fio. 64.

Fio. dfi. — Stbeptococci asd Leukocytic Infiltration in Chbonic Ulcix
or Max with Acute Esacebbation Shortly Before Opebacion.

Fib. tiS.— Chhonic Ui.cer of DronENiMi of Dou !3 Wekks Aiter a Sinqle

iNTHAVENUfS luJECTlUN OF STBEI'TUl'OCt [IS TROM HuMAN V IMKR. NotC

the dispiacemeiit of rauscuiar liiyer (u) by oonnectLve tissue and the
thickened peritoneal coat (b).

CHRONIC DISEASES 121

and the immediate morbid tissue changes which occur.
In the hematogenous embolic infection of the stom-
ach with a strain of the streptococcus which has an
elective affinity for the stomach wall, a local sub-
mucous hemorrhage occurs. In consequence of the
hemorrhage and infection, anemic necrosis results with
consequent lessened resistance and the necrosed tissues
of this small area are digested by the gastric juice. The
continued infection of the tissues around the acute ulcer
prevents the healing of the mucous membrane of the
stomach in all probability, for it is well known that
uninfected wounds of the stomach readily heal. The
continued action of the gastric juice upon the ulcer base
results in the characteristic anatomical picture of chronic
peptic ulcer.

CHRONIC INFECTIOUS ENDOCARDITIS

In 1903 Schottmiiller (10) reported the isolation of
a green- forming streptococcus in blood agar plates from
the blood of patients suffering from endocarditis. This
report was made in connection with the investigation
which Schottmiiller was at that time making of the
growth characteristics of streptococci upon blood agar.
He called this green-producing microorganism strepto-
coccus viridans. Its low virluency led also to the name,
streptococcus mitior.

The character of the endocarditis in which the strepto-
coccus viridans seemed to be the infectious agent has
proved to be one of a paradoxical nature in the sense
that the clinical course, in the early stages, is frequently
very mild and the patient is able often to be up and

122 FOCAL INFECTION

about, even attending to ordinary aifairs of life, but it is
progressive and in a few weeks or months, sometimes as
late as a year and a half, the patient usually suceiunbs
to the disease.

It is, therefore, a malignant type of endocarditis al-
though usually chronic in its clinical course. As I have
before stated the streptococcus viridans endocarditis
may sometimes be very acute and associated with a septic
type of temperature with a very high maximum and
low minimum temperature, and may run its entire clin-
ical course within two or three weeks. During the last
few years since routine blood cultures have been made,
the frequent incidence of this disease has become noted.
Osier (17),Horder (18),Libman (20), Lenhartz (22)
and others have reported a series of patients suffering
from what they have termed chronic infectious endo-
carditis, infective endocarditis, subacute infective endo-
carditis, subacute bacterial endocarditis and the report
which Rosenow and Billings made was under the title
of "chronic pneumococcus endocarditis."

The characteristics of this type of malignant endo-
carditis are usually a mild clinical course in which the
patient may complain of lessened strength and endur-
ance; usually a poor appetite; more or less dyspnoea
of exertion; slight to severe chills and fever in periods
often mistaken for malaria; cough, in some cases with
more or less expectoration, often with a septic type of
fever mistaken for tuberculosis, and in severe grades
sometimes treated for mild typhoid fever. The major-
ity of these patients have suffered at some time from
rheumatism and endocarditis or from endocarditis alone

CHRONIC DISEASES 128

and upon examination it is usual to find the evidences
of old valvular disease with varying conditions as to the
heart muscle. Those patients who have not previously
suffered from endocarditis may present no heart mur-
murs or other evidence of heart involvement. While
in bed the temperature is usually a mildly febrile one
of septic type and there may be rigors amounting at
times to severe chills. Sooner or later with involvement
of the left heart there are evidences of embolism in
petechia of the skin and elsewhere. Frequently there are
infarcts of the spleen manifested by enlargement and
tenderness of that organ. Infarcts of the kidney mani-
fested by hematuria usually microscopic (See Baehr
(23) and Lohlein (24) ) , embolism of brain with varying
degrees of sensory or motor disturbance and in some
patients embolism of sufficient size of the arteries of
the extremities to obliterate the pulse below the site of
the embolus and to cause gangrene of the extremities.
Mycotic aneurism may occur usually situated in the
smaller arteries. Death supervenes with severe embol-
ism of the brain or from exhaustion with mixed infec-
tion. The duration may be from two to three weeks in
the really acute types of the disease and may last for
eighteen or more months.

The streptococcus viridans may be isolated from the
blood and is characterized by the fact that in culture
media it soon loses its affinity for the heart and may be
converted, as shown in the immunological studies of
Rosenow (-8 ) , into any of the other types of the mem-
bers of the streptococcus-pneumococcus group.

The lesion of the heart in streptococcus viridans en-

124 FOCAL INFECTION

docarditis is characterized by the growth of massive
vegetations upon the valves and upon the mural endo-
cardium. (See Figs. 9 and 10.) It is not usually
attended with ulcerations, but there is an enormous
deposit of thrombus in the vegetations which serves as
a rich culture medium for the invading organism and
also because of the size and friability of the vegetations
and the thrombus formation is a ready source for the dis-
semination of emboli of all sizes through the systemic
vessels.

It is a non-pus-forming organism and consequently
suppuration does not foUow in the tissues involved in
the embolism. In rare instances the mycotic aneurism
may break into the surrounding tissues and in two pa-
tients under my observation abscesses formed and a
pneumococcus was obtained in pure culture therefrom,
while in the blood stream was found the streptococcus
viridans in pure culture.

The streptococcus viridans endocarditis is usually
fatal. Streptococcus viridans bacteriemia unassociated
with endocarditis, although there may be an endocardial
murmur present, is not necessarily fatal. The reports
of recoveries of streptococcus viridans endocarditis may
be of those patients who have streptococcus viridans bac-
teriemia without a real endocarditis. Libman has re-
ported recoveries, and in a series reported by Horder
the mortality was not absolute. In my own experience
only three patients out of more than one hundred who
haTehad a streptococcus viridans bacteriemia have recov-
mrmI l^ram tiiat oondition. In one of these there was no

\BUtt mummr and the condition was asso-

CHRONIC DISEASES 125

ciated.with streptococcus viridans infarct of the right
lung with suppuration, evacuation of abscess and recov^
ery. In another, a boy of sixteen, with a systolic mitral
munnur and moderate septic fever, the bacteria finally
disappeared from the blood and recovery ensued with
moderate mitral insufficiency fully compensated. In a
third patient, a Jewess, with mitral stenosis and mod-
erate septic fever of long duration mistaken before en-
tering the Presbyterian Hospital for tuberculosis of
the lung, the bacteriemia disappeared and five years later
the patient was entirely well except for the mitral sten-
osis, fully compensated.

Even with evidences of endocarditis in the last two
patients described, it was not proved that there was an
endocarditis of recent origin.

The character of the changes in the myocardium and
valves is so serious in this disease, very much like that of
the acute malignant endocarditis due to the pnemno-
coccus, that one can appreciate the fatal nature of the
condition.

That healing may occur though rarely cannot be
doubted when one examines the heart in an accidental
death with coroner's inquest where the enormous vegeta-
tions can still be recognized but so infiltrated with cal-
cium salts that a practical cure has resulted. This condi-
tion has been noted as I have stated previously in the ob-
servation of LeCount.

The focus of infection which undoubtedly causes the
streptococcus viridans bacteriemia and chronic malig-
nant endocarditis is often alveolar abscess. Of this we
have had numerous clinical examples. Coincident cul-

126 FOCAL INFECTION

tures from the alveolar abscess and from the blood
have yielded strains of streptococcus viridans. When
these nascent cultures were intravenously injected into
animals, typical endocardial lesions resulted. Doubt-
less a focus containing this* streptococcus may be lo-
cated in the tonsil or nasal sinus or elsewhere which
may be the source of the cardiac infection.

LECTURE V

TREATMENT

FOCAL INFECTION

Prevention of focal infection is an important prin-
ciple in the consideration of the treatment of the etio-
logic factor and the related systemic infections.

We may not hope so to modify the actions of indi-
viduals or of society that communicable diseases will dis-
appear or. that susceptibility to infection will be over-
come in the evolution of a mentally and physically bet-
ter developed race, for we cannot wholly prevent or
abolish the marriage or procreation of the unfit; vice;
alcoholic and drug addictions; poverty, unhealthful
domiciliary and occupational environment; the use of
contaminated food and drink ; community uncleanliness,
and other causes of mental and physical debility which
directly diminish the natural body defenses.

The control of these debility-producing factors is a
function of national, state and municipal public health
bodies. Politics, greed for wealth and ignorance are
influences which prevent the administration of well-es-
tablished laws which, if properly enforced, would do
much to abolish unhealthful conditions and disease.

As far as possible, as individuals and collectively, phy-
sicians should exert an influence to promote cleanliness
of mind and body and thus lessen the incidence of focal

127

128 FOCAL INFECTION

and systemic infection. The encouragement of per-
sonal cleanliness and especially the care of the skin and
its appendages, and of the mouth and throat should be
a duty of the family physician. The necessity of cleans-
ing the mouth, teeth and throat of aU particles of food
after eating should be taught as a prevention of local
infection, decay of teeth and of general disease. When
other measures fail the removal of the persistent over-
growth of lymphoid tissue, a good culture medium for
bacteria, of the nasopharynx and throat should be ad-
vised. Chronically enlarged pharyngeal tonsils, which
obstruct the upper respiratory tract and prevent proper
ventilation and drainage, invite local infection of the
mucous tracts of the head and should be totally re-
moved.

The foregoing statements are applicable chiefly in
childhood, for children are especially susceptible to in-
fection of the tissues of the mouth, throat, nose, acces-
sory sinuses, middle ear and mastoid cells. We know
that freedom from streptococcus infection of the mucous
membrane and lymphoid tissues of the head would very
much lessen the incidence of rheumatism, chorea and
endocarditis in children and also in adults. We may not
as confidently expect to prevent acute appendicitis, pep-
tic ulcer, cholecystitis and nephritis by these measures;
still, the evidence of the etiologic relations of these dan-
gerous local infections to focal nose, mouth and throat
infection is so strong that the correction of these confined
infections is rationally indicated. I do not wish to seem
to be an advocate of unnecessary operations, for many
operations of all kinds are irrationally performed, in-

TREATMENT 129

eluding the removal of overgrowth of the tonsUs and
other lymphoid and mucous tissues of the nose and
throat. These conditions of the nose and throat may
disappear with a proper hygienic management. I believe
that tonsillectomy is often needlessly performed for the
relief of a systemic infection, when the real focal cause
is situated elsewhere. Doubtless the normal faucial ton-
sillar tissue has a beneficent function and uninfected,
should not be molested. But too often the tonsillar
tissue in children and also in some adults is a culture
medium of pathogenic bacteria and as such is a constant
source of danger as a portal of entry of infectious bac-
teria through the lymph and blood streams to the tissues
of the body. Infected tonsils cannot be successfully
sterilized by any known method of treatment and entire
removal is the only safe procedure. If necessary a prop-
erly directed surgical treatment of the easily recog-
nized morbid anatomical condition of the nasopharynx
and nares will establish normal ventilation and drainage
and lessen the incidence of middle ear, mastoid and
accessory sinus disease with the resulting possible sys-
temic involvement from these sites of focal infection..
Until recently the importance of pyorrhea dentalis and
alveolar abscess as an etiologic factor in systemic infec-
tion has not been recognized. Clinical and laboratory
observation and research have definitely settled the
question. As has been stated in the first lecture, the
members of the streptococcus group, but occasionally
other bacteria, are the pathogenic agents of pyorrhea
which cause systemic infection. The endameba buccalis
may have an etiologic relation to the pyorrhea of the

180 FOCAL INFECTION

teeth and alveoli, may intensify the destructive local dis-
ease and may he the agents of communicating the dis-
ease to others by direct personal contact or through fo-
mites. The existence of focal infection of the j aws in the
form of chronic alveolar abscess, without the manifesta-
tion of much discomfort, is remarkable. The condition
is often not discoverable by inspection and escapes the
attention of the physician and the dentist. It is only
when destructive lesions of the gum, tooth and alveolus
make the condition visible that a diagnosis is usually
made. Properly made Rontgen ray films of the jaws
will enable one to recognize the real morbid and ana-
tomical condition. The definite recognition of the con-
dition and the character of the mechanical dentistry
which should be practiced demands the use of Rontgen
ray films of the jaws. The use of emetin in the destruc-
tion of the endameba may rid the mouth temporarily of
an etiologic factor of pyorrhea, but the drug does not
remove the infectious bacteria in the focus, nor does it
restore the periosteum of the root of the tooth without
which the tooth ceases to be living bone and as a foreign
body invites added and continued bacterial infection.

In a consideration of amebic dysenterj^, Phillips (51)
states that emetin will kill the parasite in the active
stage, while the drug has but little or no effect on the
cysts. He suggests the hypodermic use of emetin in ten-
day periods, with gradually increasing intervals, until
repeated examinations finally fail to find endamebas in
the stooL Inasmuch as emetin destrovs endameba
buocaliSy the same method of management may more
ly rid the mouth of the parasite.

TREATMENT 181

^ Dentists everywhere are interested in the better man-
agement and correction of alveolar infection. We must
look to them for a treatment which will destroy the
focal infection of the jaws and safeguard the individual
from systemic infection. Deplorable as the loss of teeth
may be, that misfortune is justified if it is necessary to
obliterate the infectious focus which is a continued
menace to the general health.

Malnutrition and general debility due to chronic dis-
ease, old age, and other causes may lead to focal infec-
tion of the jaws. Such foci of infection tend to add in-
fection to already infected systemic tissues. These in-
fectious foci, which in a way are secondary to the sys-
temic disease causing the general debility, are just as
dangerous as primary foci and should be removed.

Persistent lymph node infections which do not dis-
appear with hygienic measures instituted to improve the
defenses of the body should be surgically removed as a
matter of protection against the further dissemination
of tuberculosis or of some other disease from the speciS-
cally infected nodes.

The conditions which may promote infection of the
gastro-intestinal tract are usually not brought to the
attention of the physician until too late to use measures
of prevention. Myriads of infectious bacteria are swal-
lowed in infected food, especially milk, and in the
muco pus of the nose, throat and bronchi. The gastric
juice and other digestive fluids probably destroy most
of these bacteria in robust individuals. The surviving
microorganisms may reach the tissues of the bowel
and the adjacent lymph nodes, under favor-

182 FOCAL INFECTION

able conditions may continue to have or may
attain pathogenic virulence, and cause local or
systemic disease. Habitual constipation, with or
without congenital or acquired anatomical de-
formities of the intestinal tract, may lower the natural
resistance of the tissues to invasion by the bacteria of
the intestine. Again the morbid anatomical conditions
which favor intestinal stasis may promote increased
general virulence or elective tissue afiinity of the in-
vading bacteria. Rosenow (8) has demonstrated an
acquired virulence and also an elective tissue affinity
for the appendix of a strain of colon bacilli isolated in
cultures from the exudate and tissues in patients with
appendicitis. When injected intravenously appendi-
citis developed in the inoculated animals. After a time
the general virulence and specific tissue affinity was lost
in subcultures of this strain. Beaussenat quoted by
Adrian (28) was unable to produce appendicitis by
the intravenous injection of ordinary strains of colon
bacilli without first injuring the mucous membrane of
the organ.

Infection of the digestive tract may be prevented
or at any rate its incidence may be diminished very
much by obliterating the sources of the mucopus in the
throat and nose, which at the same time removes the
foci of infection of the head, and also by avoiding in-
fected food.

Stasis of the bowels, whether due to habitual consti-
pation or to congenital or acquired anatomical condi-
tions, should have a proper medical management or, if
necessary, surgical treatment. I very much doubt if

mAi

TREATMENT 188

the removal of the entire colon is justifiable for ntestinal
stasis alone; certainly not to the degree practiced by
some surgeons. Chronic appendicitis with lessened tis-
sue resistance invites acute attacks, disturbs the gastric
digestion and may be a focus of systemic infection. The
same is true of chronic cholecystitis and especially as
the experiments of Roseno w ( 8 ) . seem to show that the
streptococcus strains, which acquire an elective affinity
for the gall-bladder, have also an affinity for muscular
tissue, especially the myocardium. This confirms the
clinical observation of the occurrence of cardiac muscle
disease with cholecystitis. Therefore, surgery is indi-
cated in appendicitis and cholecystitis to relieve the in-
dividual of a local menace to life, of reflex dyspepsia
and quite as important to remove etiologic factors of
systemic disease.

The morbid conditions of the rectum, which makes
it a dangerous source of lymphogenous and hematoge-
nous infection especially of colon bacilli and strepto-
cocci, should receive rational surgical treatment.

The focal acute and chronic infectious diseases of the
pelvic organs of woman, particularly of the uterus in
the puerperium and of the parametrium and fallopian
tubes, are so important that they should be rationally
managed and surgically treated when necessary to safe-
guard health and life.

The alleged etiological relation of chronic streptococ-
cus infection to cystic degeneration of the ovary needs
confirmatory bacteriologic research. This is especially
needed if the supposed infectious cause of diseases of the
ovary is accepted as an additional excuse for the too

184 FOCAL INFECTION

frequent sacrifice of the ovary for the numerous real
and fancied ills of women.

The infectious foci of the male pelvic organs requires
a management and surgical treatment which will re-
move a constant source of systemic diseases and in
gonorrheal infection in addition, a source of the most
frequent cause of pelvic disease of women, many of
whom are morally innocent wives. As demonstrated
by Sugimura (4) and Franke (5), lymphogenous in-
fection in addition to other spurces of hematogenous
infection of the ureter, kidney pelvis and kidney, from
the bladder, indicates additional reasons for effective
treatment medical or surgical to overcome acute and
chronic cystitis. So, too, may rational medical or surgi-
cal treatment of pyogenic and tuberculous kidney and
kidney pelvis infections prevent corresponding infection
of the ureter, bladder, other pelvic organs, and from all
of these sources a general systemic infection.

Infected wounds, often insignificant, of the skin and
mucous membranes and furuncles and purulent infec-
tion about the finger and toe nails should receive the
management which is indicated by the rare, yet often
serious, systemic infections which they may cause.

TREATMENT OF RESULTING ACUTE AND CHRONIC SYSTEMIC

DISEASES

In the treatment of disease it is an axiom to remove
the cause if possible. This law of good medical practice
is applicable in diseases due to focal infection. In some
acute diseases it is impossible to remove the focal dis-
ease, either because it is inaccessible or the serious con-

TREATMENT 185

dltion of the patient eontraindieates it. In bacteriemia
due to puerperal sepsis, or to an infectious thrombo-
phlebitis of the deep veins, surgery cannot be utilized
without danger of death from shock or from an over-
whelming degree of bacteriemia by a physical disturb-
ance of the infected thrombus or other tissue sources of
the infection.

In acute rheumatic fever associated with en-
docarditis, pericarditis or a pancarditis, the serious
condition of the patient usually eontraindieates tonsil-
lectomy for the removal of the most general etiologic
focus. Experience teaches that removal of the tonsils
during an attack of acute rheumatic fever usually does
not modify the clinical course. It is the better practice
to remove the focal cause, wherever it may be, in the late
convalescence.

In mild rheumatic fever and in chronic infectious
forms of arthritis the focal cause should be removed
early. Even in these mild and chronic types of infec-
tious arthritis and myositis one occasionally witnesses
serious results. A girl of eighteen who had suffered for
a year from a disabling chronic polyarthritis and myo-
sitis, due apparently to multiple chronic alveolar ab-
scesses, had many teeth extracted and the alveolar ab-
scesses curetted. Streptococcus bacteriemia developed
with acute hemorrhagic myositis, pleuritis, pericarditis,
myocarditis with submucous and subcutaneous hemor-
rhages and death. The streptococci isolated from the al-
veolar pus, the blood and after death from the muscles,
when injected intravenously into animals caused rheu-
matic arthritis, myositis, endocarditis and pericarditis.

186 FOCAL INFECTION

A girl of ten, now a patient in the Presbyterian Hos-
pital, suffered from a mild arthritis arid myositis. The
family physician had the enlarged and apparently inr
fected tonsils removed. Immediately, there developed
an acute general myositis, which gradually changed to a
non-febrile type with much deformity due to the shorten-
ing of the muscles. Experience of this kind affords proof
of the focal origin of certain systemic conditions and
that the operative technic of removal of foci of infec-
tions should be of a kind which will not overwhelmingly
inoculate the patient. In acute rheumatic infections the
removal of the original focus, usually tonsillitis, may
not prevent future attacks, for the streptococcus rheu-
maticus may occur in other focal sites, notably in
alveolar abscess and maxillary sinusitis. The prompt
removal of every recognizable local infection of the head,
in people who suffer from repeated attacks of acute
rheumatism, may prevent the disease. This result ex-
perience of recent years has conclusively proved. What
has been said of the treatment of the acute rheumatic in-
fections is also true of chorea. But experience has
shown that arsenic does modify the cause of chorea.
It is interesting to note, in this connection, that arsenic
has also a striking influence on the clinical course of
rheumatic pericarditis and pleuritis. I have used caco-
dylate of soda as a relatively non-toxic form of arsenic
in the treatment of chorea and of serofibrinous rheu-
matic pericarditis and pleuritis. From five to fifteen
grains in divided doses, each twenty-four hours, injected
deep in the muscles, has a remarkable effect within two
or three days. The uniformly constant result suggests

TREATMENT 137

a chemotherapeutic result similar to that of salvarsan
for spirochetes.

Salicylic acid seems to have a specific bactericidal
effect upon the streptococcus rheumaticus if it is given
in sufficient quantity in the first days. Large sterilizing
doses given early seem necessary. Perhaps the strepto-
coccus becomes immune to ineffectual doses of the drug,
and this may explain the lack of specific effect in the
prolonged clinical course. It is of interest to record
the apparent good effect of large doses of salicylic acid
during the first hours of acute appendicitis, which as
we have noted may be caused by a modified strain of
the streptococcus rheumaticus.

Acute gonorrheal arthritis must first be recognized
by the pathognomonic signs sometimes present, purulent
exudate in joints and tendon sheaths, the gonococcus
in exudates and blood and the recognition of a focus
in the genito-urinary tract. The specific von Pirquet
skin and the complement fixation tests are not always
to be relied upon in diagnosis unless suitably controlled,
according to Irons (36), Irons and NicoU (37). The
almQst uniform benefit of the early removal of the focal
cause is notable in systemic gonococcus infection. Even
with gonococcemia, if no involvement of the endocar-
diima occurs and if there is no gonococcus thrombo-
phlebitis, the removal of the focus is often followed by
recovery. Purulent exudates must be surgically treated.

Malignant endocarditis of all types is usually fatal
because the invading bacteria find lodgment and suit-
able conditions for growth and multiplication in large
vegetations filled with thrombi or in the necrotic tissue

188 FOCAL INFECTION

of the valves and heart walls of the ulcerative form. This
insures continued infection and increasing diminished
resistance of the patient. Multiple embolism and the
result upon all the involved organs hastens the fatal
end. Drug treatment is unavailing.

Infectious acute nephritis due to the specific elec-
tive tissue affinity of certain bacteria, especially mem-
bers of the streptococcus group, demands an early re-
moval of the focal cause. By this means death may be
prevented and if the anatomical injury of the kidney is
not too great the function may be preserved to a degree
consistent with health for many years. A woman
of thirty years under treatment for chronic arthritis
at the Presbyterian Hospital acquired coryza and
an acute frontal sinusitis. Hemorrhagic nephritis
immediately occurred, associated with some edema of
the face, legs and dependent portions of the body.
Drainage of the infected sinus was followed by rapid
general improvement and a gradual disappearance of
the albuminuria and the abnormal formed elements of
the urine. One month later the urine and functional
tests for phthalein, nitrogen and chlorid output were nor-
mal. A strain of streptococci, which was hemolytic,
isolated from the exudate of the sinus, when injected
intravenously into rabbits caused hemorrhagic ne-
phritis.

Many like examples of improvement or recovery from
acute hemorrhagic nephritis could be reported from
our observation and the experience of others recorded
in medical literature. So, too, one may cite examples
of nephritis which have progressed to a hopeless stage

TREATMENT 189

due to repeated anatomical insults of the kidney by
infectious microorganisms from the neglected focus.

Even types of chronic nephritis evidenced by albimii-
nuria, cylindruria and more or less hyperarterial ten-
sion show manifest improvement by the removal of
chronic focal infection of the dental alveoli, tonsils,
sinuses, gall-bladder, appendix and pelvic organs. A
rational after-treatment consisting of a properly selected
diet and attention to personal hygiene is of course an
important factor in the improved condition of these
patients.

Appendicitis, acute and chronic, requires surgical in-
tervention to conserve life and to obliterate a focal in-
fection which may seriously infect other tissues through
the lymph channel or blood stream. The incidence of
appendicitis may be reduced by the prevention of focal
infection about the head and by the early removal of
existing foci.

Acute and chronic cholecystitis demand early surgi-
cal treatment to relieve pain and dyspepsia and quite
as much to remove a dangerous focus of systemic in-
fection, especially of the myocardium. Babcock (40)
and others have noted the improvement of clinical chron-
ic myocarditis by the drainage of a coexisting chronic
cholecystitis. The prevention of focal infection of den-
tal alveoli, tonsils and sinuses and the early removal of
existing infection at these sites may diminish the inci-
dence of cholecystitis and of gall-stones.

In the treatment of gastric and duodenal ulcer the
experiments of Rosenow demand the primary removal
of the etiologic foci of infection as a means of preven-

140 FOCAL INFECTION

tion of the recurrence of the ulcer through reinfection.
A coincident rational medical management if consistent-
ly carried out, as advised by Sippy (56) , may be success-
ful in healing the ulcer. Surgical treatment is indicated
when the unhealed ulcer or the scar produces deformi-
ties which persistently interfere with gastric and
intestinal function and also when accidents, like
perforation and medically unmanageable hemorrhage,
occur.

Recurring erythema nodosum alone or as a part of
the syndrome described by Osier (17) may be entirely
controlled by the removal of the etiologic infectious
focus. A young woman of twenty-four years had re-
curring attacks of erythematous nodes of the arms and
lower extremities, associated with mild arthritis. She
suffered from a chronic maxillary sinusitis. Drainage
of the sinus gave coincident freedom from the nodes and
arthritis. After three months a recurrence of the sys-
temic disease proved to be due to a corresponding re-
currence of the sinus infection. Complete obliteration
of the sinus infection has been followed by the continued
absence of the attacks of arthritis and erythematous
nodes for three years.

A young married woman of twenty-six had recurrent
attacks of erythematous nodes and muscular soreness
for a year. She had also frequent mild tonsillitis and
pharyngitis. Enucleation of the tonsils was followed
by the absence of erythematous nodes for nearly a year,
then a recurrence. Re-examination revealed the pres-
ence of an infected lower pole of one tonsil. The re-
moval of the remaining portion of infected tonsil has

TREATMENT 141

resulted in the permanent cessation of the systemic dis-
ease.

The relation of focal infection to acute pancreatitis
often associated with cholecystitis has been noted. Early
surgical intervention to relieve the acute process is im-
peratively demanded. Chronic pancreatitis is of espe-
cial interest because of the relation the internal secre-
tion of the gland bears to carbohydrate metabolism. The
probable infectious origin of chronic pancreatitis as well
as the acute process from streptococcus foci, affords an
interesting problem for clinical investigation in the man-
agement of diabetes mellitus. We have removed exist-
ing focal infection about the head of diabetic patients,
have inoculated animals with the isolated streptococcus
strains, and have kept the patients under clinical ob-
servation. The results have not been uniform enough
to warrant a conclusive statement at this time.

Chronic pancreatitis which is etiologically related to
chronic cholecystitis and calculous cholecystitis as de-
termined by Opie (82) may disappear clinically by the
surgical removal of the etiologic factors.

Osteomyelitis may not be benefited by the removal
of the pyogenic bacteria containing focus of the tonsils,
jaws, sinuses and other tissues. Rationally the etiologic
focus should be removed coincidentally with the surgi-
cal treatment of the bone infection.

Infectious thyroiditis which occurs during a general
infection, like rheumatic fever, may subside during con-
valescence from the general infection. When infectious
goiter is due to a focal infection of the tonsils and alveo-
lar abscess, removal of the focus is usually followed by

142 FOCAL INFECTION

diminution in the size of the gland and by a disappear-
ance of the symptoms of thyroid intoxication. This has
been demonstrated in many individuals, chiefly young
women patients. The majority of these women were
overworked and often poorly nourished, with resulting
lowered immunity to the focal infection. Many of the
patients are under continued observation and without
exception there has been no instance of relapse of the
goiter or of hyperthyroidism.

Hematogenous focal infection of the nervous appa-
ratus, involving the gasserian and posterior spinal root
ganglia and spinal cord, affords confirmation of the
infectious nature of herpes, of insular sclerosis and
myelitis of the spinal cord. Removal of the primary
etiologic foci of infection about the upper air tract and
mouth may modify favorably the course of the spinal
cord infection.

The treatment of chronic types of infectious arthritis
and myositis is usually neglected or so irrationally con-
ducted that failure to benefit the sufferer is the usual
result. This unfortunate condition is due chiefly to a
want of knowledge by most physicians of the principal
factors which cause the morbid tissue changes. An
attempt was made to explain these principles in Lecture
IV.

In the treatment the primary necessity is to obtain
a knowledge of the patient's general condition and to
locate existing foci of infection which may have been
the chief primary cause, or still continue to be sources
of systemic infection. The result of rational manage-
ment will depend, partly in any event, upon the degree

TREATMENT 148

and character of the morbid tissue changes in the joints
and muscles, upon the command one may have in the
management and upon the age of the patient. Destruc-
tive lesions of bones and cartilege, bony ankylosis, ex-
tensive sclerotic changes and atrophy of muscles can-
not be repaired. Indeed because of the destruction of
blood vessels and the resulting want of nutrition, con-
tinued retrograde metabolism favors the change of the
connective tissue group, tendons, aponeurosis, ligament
and cartilage into bone. This is true of all types
of chronic infectious non-purulent arthritis of what-
ever bacterial type. Therefore, if the treatment is to
result in the arrest of the disease with advanced mor-
bid anatomical changes or in the recovery of those
with non-destructive morbid tissue changes, insti-
tutional care is required to insure the necessary
command of the patient over a sufficiently long pe-
riod of time to remove all focal sources of infection, to
build up general nutrition and to restore as nearly as
possible the blood circulation in the infected tissues. This
method of management is necessary to stop the sources
of systemic infection, to build up the body defenses
against the existing systemic infection and to improve
the general and local nutrition as the chief means of
arresting retrograde metabolism and at the same time to
promote resolution of the morbid infectious processes.
Rationally the younger the patient the readier will be
the response to the management.

In the preliminary general examination one may need
the aid of qualified specialists in the examination of the
nasopharynx, ears, accessory sinuses, pelvic organs and

144 FOCAL INFECTION

blood, and Rontgen films of jaws and plates of joints
to locate etiologic infectious foci and to determine the
degree of the joint changes. Microscopic examination
and cultures of blood, accessible exudates of joints and
of foci in the head, pelvis and elsewhere and of the urine
and feces may give valuable information of the char-
acter of the bacterial infection. Intravenous injection
of the nasQent cultures of the bacteria into animals may
produce lesions corresponding with the morbid changes
of the patients' tissues. With the consent of the patient
always, a harmless and, under local anesthesia, painless
removal of pieces of infected muscle, joint capsule,
fibrous nodes and lymph nodes proximal to the infected
tissues enables one to study the morbid histology and
with a proper technic to isolate the causative infectious
microorganisms from the tissues. But important as the
study of the exudates, tissues and bacteria may be, the
real and important principle is to know all that one
may of the physical condition of the patient. Follow-
ing this diagnosis the management includes :

1. The removal of all primary and, if necessary, all
secondary foci of infection. To make sure that all
sources of focal infection have been obliterated, repeated
examination should be made. Buried tonsillar tissue
may be left at the primary tonsillectomy. An infected
sinus may not have been adequately treated. Alveolar
abscess may finally require the extraction of the tooth.
An apparently cured gonococcus infection of the pros-
tate and seminal vesicles may recur. Constant vigilance
is necessary to insure the abolition of continued systemic
reinfection.

TREATMENT 145

2. To build up the natural defenses of the body. To
accomplish this involves close attention to important

principles including mental and physical rest, nourish-
ing food, restorative tonics when indicated, cheerful en-
vironment, good air and sunshine and with some patients
the use of suitable bacterial antigens as vaccines to stim-
ulate the formation of specific antibodies in the tissues
of the patient. Mental and physical rest must be ra-
tionally supervised to meet the idiosyncrasies of the indi-
vidual. Isolation and continuous bed confinement may
be exchanged for open ward and partial chair treat-
ment to meet the viewpoint of the patient and thus pro-
mote the most efficient rest of mind and body. This
absolute rest must be maintained until in febrile cases
all fever shall have disappeared and also until the severe
soreness of the joints and muscles aggravated by motion
jshall have diminished, for until then the exercise of in-
fected tissues lowers the natural resistance to infection
and thereby increases the infection of the joints and
muscles. Often the temporary application of restrain-
ing bandages, splints and casts may favor the diminu-
tion of the local infection. The usually poor general
nutrition of patients with chronic infectious arthritis
calls for a generous mixed diet including an abundance
of fats, oils, green vegetables and fruits. The emaciated
tissues demand a full allowance of protein-containing
food, both animal and vegetable. A plentiful amount
of water, milk, buttermilk, cream and fruit juices must
be taken.

When necessary, hematinic and other tonics, laxa-
tives, and simple analgesic palliatives, such as the sali-

146 FOCAL INFECTION

cylic acid compounds, may be judiciously given. There
are no specific drugs to be used and narcotics should
be avoided in these chronic diseases.

The mental depression of this class of patients re-
tards improvement, hence the need of a constant, cheer-
ful environment and an optimistic attitude of all who
come in contact with them.

With the sources of systemic infection obliterated, and
the existing systemic infection diminished or entirely
controlled by the management described, other measures
must be added to the treatment which may stop further
retrograde metabolism, and in favorable conditions
may result in the restoration of normal anatomical and
functional conditions of the tissues of the joints and
muscles.

These measures are so important that the failure
to apply them adequately means failure in the whole
management. The object of their use is to attempt to
restore nutrition to the starved tissues of joints and
muscles which have been deprived more or less of blood
and oxygen by the embolic mode of repeated infection
from the primary focus, for as long as the infected tis-
sues are starved, conditions exist which are favorable
to continued infection and furthermore, local malnutri-
tion leads to retrograde tissue metabolism.

In addition to the measures already advised to in-
crease the general nutrition, the local malnutrition may
be wholly or partly overcome by an improvement of
the general and local blood circulation. The measures
consist of hydrotherapy, active and passive exercise,
local application of superheated dry air and the Bier

TREATMENT 147

blood congestion method by the application of the rub-
ber bandage.

Hydrotherapy in the form of alternating hot and
cold shower or spray baths, applied daily for a few
minutes, flushes the blood to all the parts of the body
without fatigue to the patient. If the force with which
the water strikes the body is relatively high, the im-
provement of the circulation is greater. The tonic
effect upon the circulatory organs of the application of
cold water to the skin is well known. A cold plunge
bath is disagreeable to these enervated patients. The
alternating hot-cold spray repeated several times in a
few minutes, is borne without complaint, and the result
is quite as good as the use of the cold bath alone. In
the absence of facilities for applying shower or spray
baths, salt glows and alcohol rubs may be utilized as
poor substitutes of the cold bath.

Passive exercise of joints and muscles may be given
by nurses or more efficiently by individuals trained to
give massage. Mechanical aids in the form of the Zan-
der apparatus if rationally used give good results.

Active calisthenic exercises may be so taught that un-
der proper supervision each patient will have the bene-
fit of periods of exercise modified to meet individual
conditions.

Other active exercise, like walking, riding, driving,
swimming and gymnastic work, may be taken up at the
proper time. An individual qualified by education and
experience should have the supervision of the treatment
by baths, and mechanotherapy. Every general hospital
should have a mechanotherapeutic department with a

148 FOCAL INFECTION

qualified director for the treatment at the right stage
of the management of the large nmnber of patients, in
all communities, who suffer from chronic infectious ar-
thritis and of other chronic diseases. If rationally and
efficiently managed many would be restored to health,
while in others with more advanced morbid anatomical
changes the further progress of disease would be more
or less checked and an improvement of function would
be gained.

SERUM AND VACCINE THERAPY

Serum Therapy

The prophylactic and therapeutic use of antitoxic
sera in diphtheria and tetanus is established upon a sci-
entific basis. The specific neutralization of the poison
excreted by the exotoxic bacillus of diphtheria and bacil-
lus of tetanus, when the respective antitoxic serum is
properly administered, may be accurately ascertained by
clinical and laboratory methods.

The use of specific antisera in the treatment of dis-
eases caused by endotoxic bacteria has been far from
successful. The principle upon which the value of an-
tisera is based, is that when injected subcutaneously,
there will be aroused in the body of the patient specific
defensive forces, in the form of antibodies, leukocytic
phagocytosis and bactericidal substances which may fa-
vorably modify the course of the disease. In epidemic
cerebrospinal meningitis the specific antimeningococcal
serum of Flexner, when injected directly into the spinal
subarachnoid space, apparently has specific bactericidal
properties. The injected serum probably arouses tis-

TREATMENT 149

sue reactions, which mobilizes the defenses of the body,
increasing cellular phagocytosis, digestion of the invad-
ing meningococci and even acting directly as a bac-
tericide. Other therapeutic antisera obtained by im-
munizing animals with strains of the streptococcus,
pneumococcus, bacillus of dysentery and other endo-
toxic bacteria have not given uniform results. The fail-
ure of these sera generally now is recognized to be due
to several factors, including the existence of variant
strains of bacteria which may not be differentiated mor-
phologically. Moreover, there may be a marked dif-
ference in the various strains in pathogenicity and viru-
lence and in the tissue reactions of the infected individ-
ual. Each strain may arouse specific effects and the
results thereof will be influenced only by the therapeutic
serum obtained from an animal immunized with a like
strain. This principle has been successfully utilized by
Cole and his co-workers in pneumonia. They have clas-
sified the pneumococcus into four types, of which types
I, II and III represent single specific strains and type
IV a group of strains unlike the first three types. The
antiserum must be prepared by immunizing an animal
with the type of pneumococcus which is to be attacked.
The same principle has been proved to exist in reference
to the pathogenic strains of streptococci and of the
strains of the bacillus of dysentery. The principle of
the necessary possession of "type" specificity of the bac-
teria used in the production of antisera to obtain any-
thing like satisfactory therapeutic results has been ap-
parently established. While it may not prove to be a
principle to be applied to the preparation of antisera

150 FOCAL INFECTION

of all endotoxic, pathogenic bacteria, perhaps to a few
only, yet there is in its adoption the hope that a broader
field of specific antiserum treatment may be developed.
In our study of focal and systemic hifections we used
the antiserum of the horse immunized with strains of
streptococcus viridans in the treatment of streptococcus
viridans endocarditis and in chronic arthritis without
notable good effect. Apparently unavoidable anaphy-
lactic shock and other objectionable effects compelled
us to abandon its use. Therefore, the production of and
the use of antisera in the treatment of diseases due to
focal infection present problems which present knowl-
edge may not solve.

Vaccine Therapy

We know that a degree of immunity to some infec-
tious diseases may be produced in man and animals by
inoculation with non-lethal doses of living or dead path-
ogenic bacteria. In a few diseases, a mild form of in-
fection or intoxication is produced by the inoculation
with resulting immunity of variable duration. Attenu-
ation of the virulence of living virus used for inocula-
tion has been successfully practiced to produce a mild
disease which affords protection to the protean malady.
Vaccinia in man produced by inoculation with cowpox
protects against variola. Inoculation with living or
dead typhoid bacteria and paratyphoid bacilli with
proper technic will afford immunity of variable time
duration to typhoid and paratyphoid fevers. These ex-
amples of the use of vaccines in prophylaxis have a very
limited application in practice. Probably the field of

TREATMENT 151

application may become broader when we finally recog-
nize the specific etiologic microorganisms of all infec-
tious diseases which usually give a lasting immunity by
one attack. Then, as in typhoid fever, prophylactic
vaccination may become of the greatest use in preven-
tive medicine.

Vaccination with attenuated virus during a long in-
oculation stage of infection, as successfully practiced
by Pasteur in man bitten by animals suffering with ra-
bies, will probably not be applicable in other infections
which have comparatively shorter incubation stages.
The present use of therapeutic vaccines is based upon
less stable scientific principles. In 1902 Wright evolved
the use of autogenous vaccines in chronic infectious dis-
eases. He believed that the natural defenses of the
body, exhausted by long infection, would be increased
and mobiUzed by inoculation with microorganisms of
the same type and kind which caused the chronic disease.
He judged the improvement in the defensive forces of
the patient's body after autogenous vaccination by esti-
mating the opsonins in the patient's blood. He argued
that with an increase of specific antibodies in the blood
of the patient, the fibrinoplastic exudative barrier sur-
rounding local infectious processes, which afforded pro-
tection to the localized bacteria, would be broken down
by the mobilization of immune substances. The bac-
teria so exposed would then be readily overcome. Thus
f urunculosis of the skin, due usually to a staphylococcus,
was more readily overcome by autogenous staphylococ-
cus vaccine.

It would seem rational, too, that a general chronic

152 FOCAL INFECTION

infectious process would be more readily overcome by
the use of an autogenous vaccine which would increase
the natural defenses of the body which have become ex-
hausted by the long battle with the invading bacteria.
Unfortunately the question involves many unknown fac-
tors. A certain type of pathogenic bacterium, used as
an antigen, may excite the formation of antibodies in
the nature of opsonins, agglutinins, precipitins, leukocy-
tosis, phagocytosis and other offensive or defensive proc-
esses, but we may not depend upon a similar result with
other pathogenic bacteria etiologically related to other
infectious diseases. We cannot, from present knowl-
edge, definitely expect the same tissue reactions and re-
sulting formation of immune substances in man and
laboratory animals infected with the same type of in-
fectious bacteria. Indeed the resulting tissue reactions
and formation of defensive and offensive substances to
a strain of pathogenic microorganisms may differ in de-
gree and kind in human beings, dependent on age, race,
occupation and other factors. Variations of type of
strains of pathogenic bacteria with corresponding dif-
ferences in the tissue reactions of infected individuals,
is an important factor in immunological experimenta-
tion. We know that the pneumococcus and strains of
streptococci not only differ in type, but also differ in
virulence, and that each type probably arouses defensive
and offensive forces in the infected individual, differing
more or less for each type; and possibly the tissue re-
actions are still further modified by the degree of viru-
lence of the invading bacteria. Pathogenic bacteria may
possess a mono- or polytropism ; that is, an elective affin-

TREATMENT 158

ity for a certain kind of tissue or for several kinds of
tissues. Therefore, if specific vaccine is necessary to
arouse specific immune substances to combat offensively
or defensively the invading infectious bacteria, it implies
the use of an autogenous antigen. In this sense an au-
togenous vaccine means the use of dead bacteria, proved
to be of the same specific type in virulence and tropism
as that which causes the infection of the individual who
receives the vaccine. In chronic infectious diseases, it is
often difficult to isolate definitely the microorganisms
which are the real etiologic factors in a given case.
Without an accurate bacterial diagnosis one is unable
to discuss the other vexatious problems which must be
considered in the elaboration and use of the autogenous
vaccine.

In our work we have isolated the suspected bacteria
from the blood, lymph nodes, fibrous nodes, joint exu-
dates, joint tissues, muscles, skin and other infected tis-
sues of patients. To ascertain the tissue tropism we
have injected animals intravenously and from the in-
fected tissues of the experimental animals, have again
isolated the bacteria. Vaccines have been prepared from
cultures made from the microorganisms isolated from
patients and also from the cultures derived from pa-
tients after animal passage with especial regard to tissue
tropism. We have also sensitized some of these vac-
cines with antiserum.

We have used these autogenous vaccines in the treat-
ment of many types of chronic infectious disease. More
than five hundred patients suffering with infectious ar-
thritis have received the vaccines subcutaneously in doses

154 FOCAL INFECTION

varying from 10,000,000 to 2,000,000,000 and more,
given every five to seven days, and in rare instances
daily. The focal, local and general reaction of patients
was carefully noted. For two years the opsonic index
and the phagocytic index of each patient were estimated
painstakingly before and after each vaccination.

The difficulty of estimating the opsonins and the final
conclusion that the opsonic index obtained by the most
careful technic is unreliable led us to abandon that
method of estimating the results of autogenous vacci-
nation.

In place thereof we managed some patients with and
some without vaccination, but all of them upon the same
hygienic treatment. The final result was quite as satis-
factory without as with vaccine, in patients suffering
with chronic infectious arthritis and acute rheuma-
tism.

Patients suffering with chronic streptococcus viridans
endocarditis were not benefited by autogenous vaccines.
Indeed I believe some of them were made distinctly
worse when moderately large doses of vaccines were
used.

The problems which confront the clinician in the use
of therapeutic vaccines, must be solved by the immunolo-
gist. The views of Theobald Smith (39), Richard M.
Pearce (38) and others in regard to therapeutic vac-
cines should be read by every clinician.

Based upon the work of Wright, but disregardful
of the principles developed by him, therapeutic vacci-
nation has progressed in this country into an irrational
fad which is intensified and made degrading to the mod-

TREATMENT 155

ical profession and harmful to the patients by commer-
cial greed.

We are forgetful of the principles of medical practice
of our fathers. They recognized the influence of old
age, exposure to extreme cold, poverty and poor nutri-
tion, physical and mental exhaustion, faulty personal
hygiene and other debility-producing factors in the cau-
sation and also in the prolongation of infectious and
other diseases. They also recognized the necessity of
the removal as far as possible of all these contributory
etiologic factors in the management of the patient.
The modern vaccinationist pins his faith on the adver-
tised specific virtues of stock vaccines, which he may em-
ploy in polyvalent form to insure a sure-shot eff'ect.
He believes vaccines will arouse specific defenses in the
tissues of the patient in spite of all contributory etio-
logic factors of disease. Therefore, the rational diet,
proper baths, passive and active exercise, correction of
personal uncleanliness and alcohol misuse are neglected.
The practitioner usually is ignorant of all laws of im-
munology. It is this want of knowledge which makes
him believe the ridiculous statements made by the manu-
facturers of vaccines.

Modern experimental investigation of the physiologic
action of drugs has done much to restrict the abuse of
drug therapy of the past. So, too, must the practitioner
be made acquainted with what we know and do not know
of inmiunology. We must restrict the therapeutic use
of bacterial antigens to those conditions which the
known laws of inmiunity and scientific clinical experi-
ence have proved to be safe and of value.

156 FOCAL INFECTION

The Therapeutic Use of Non-specific Protein Anti-
gens Injected Intravenously

In recent time the intravenous injection of non-spe-
cific proteins (bacterial and others) has been used in
the treatment of both acute and chronic infectious dis-
ease. The phenomena aroused by a proper intra-
venous dosage consist of a chill followed by high fever,
great general discomfort, usually a relatively slow pulse
rate, leukocytosis sometimes of a high degree, not in-
frequently preceded by an immediate leukopenia. Gay
and Chickering (49) have used the protein, non-toxic
remnant of the typhoid bacillus by intravenous injec-
tion in the treatment of typhoid fever. The characteris-
tic phenomena noted above resulted. When used after
the first week of typhoid fever, the reaction was fol-
lowed by. a critical fall of the temperature and conva-
lesence was established in 41.5 per cent. A gradual fall
of temperature occurred with abbreviation of the course
in 24.5 per cent, and no permanent benefit occurred in
84 per cent, of the patients treated. We have used the
non-toxic protein remnant of pneumococci obtained by
autolysis of the bacteria, first suggested by E. C. Rose-
now, in pneumonia. When injected intravenously, the
typical phenomena occurred with apparent beneficial
effect, which was most marked if used early in the
course of the disease.

In acute rheumatism and also in chronic infectious ar-
thritis, astonishing beneficial effects have been noted
in a few instances from the intravenous injection of ty-
phoid, of colon and of other non-specific protein anti-

TREATMENT 157

gens. Jobling and Peterson (48) injected animals in-
travenously with dead bacteria and found that non-spe-
cific ferments were mobilized. They believe that these
ferments are bactericidal and that at the same time toxic
substances are rendered non-toxic. The suggestion has
been made that the severe reaction caused by the intra-
venous injection of a foreign protein, is followed by a
condition of refraction ( anti-anaphylaxis ) and the or-
ganism fails to react to the invading bacteria. Jobling
believes that it will be possible in the near future to use
intravenously the non-toxic portion of protein to ex-
cite the mobilization of the helpful ferments without the
painful, disagreeable and even dangerous clinical phe-
nomena which attend the intravenous use of unmodified
protein antigen. The mode of action of the non-specific
albumose antigens, injected intravenously, is not well
understood. Their use in acute and chronic infectious
diseases affords a fruitful field of combined research by
the immunologist and clinician.

BIBLIOGRAPHY

1. Bass, C. C, and Johns, F. M. "Pyorrhea Dentalis and

Alveolaris." The Jour. A. M. A., 1915, LXIV, 553.

2. Barrett, M. F. Preliminary Report, Dental Cosmos^

1914, LVI, 948.

3. Smith, Allen J., Middleton, W. S., and Barrett, M. F.

"Tonsils as a Habitat of Oral Endamebas," The
Jour. A. M. A., 1914, LXIII, 1746.

4. SuGiMURA, S. "Ueber die Beteilung der Ureteren an den

akuten Blasen entziindengen nebst Bemerkungen iiber
ihre Fortleitung durch die Lymphbahnen der Ure-
teren." Virchow Arch., CCVI, W.
6. Franke, Carl. "Die Koliinfection des Harnapparats und
deren Therapie." Ergabniss d. Chirurg. u. Ortho-
pod., 1913, VII, 671.

6. DicK, Geo. F., and Dick, Gladys R. "The Bacteriology

of the Urine in Non-suppurative Nephritis.'* The
Jour. A. M. A., 1915, LXV, 6.

7. KoLLE, W., and Wassermann, A. "Latency of In-

fectious Bacteria." Hand Bu4;h der Path. Mikro-
organismen, 1903, I, 147.

8. RosENOw, E. C. "Immunological and Experimental Studies

on Pneumococcus and Streptococcus Endocarditis"
(Chronic Septic Endocarditis) . Jour. Inf. Dig., 1909,
VI, 245.

. "A Study of Pneumococci from Cases of Infectious

Endocarditis." Jour. Inf. Dis., 1910, VII, 411.

. "Immunological Studies in Chronic Pneumococcus En-
docarditis." Jour. Inf. Dis., 1910, VII, 429.

. "Transmutation Within the Streptococcus-Pneumococ-

cus Group." Jour. Inf. Dis., 1914, XIV, I.

159

160 BIBLIOGRAPHY

RosENOw, E. C. "The Etiology of Acute Rheumatism, Ar-
ticular and Muscular." Jour. Inf. Dis., 1914, XIV,
61.

. "The Bacteriology of Appendicitis and Its Production

by Intravenous Injection of Streptococci and Colon
Bacilli." Jour. Inf. Dis., 1915, XVI, MO.

. "The Etiology and Experimental Production of Ery-
thema Nodosum." Jour. Inf. Dis., 1915, XVI, 367.

8. RosENow, E. C, and Sanford, A. H. "The Bacteriology
of Ulcer of the Stomach and Duodenum in Man."
Jour. Inf. Dis., 1915, XVII, 219.

8. RosENow, E. C. "The Newer Bacteriology of Various
Infections as Determined by Special Methods." The
Jour. A. M. A., 1914, LXIII, 903.

. "Bacteriology of Cholecystitis and Its Production by

Injection of Streptococci." The Jour. A. M. A„
1914, LXIII, 1835.

8. RosENow, E. C, and Ofterdal, Sverri. "The Etiology
and Experimental Production of Herpes Zoster."
The Jour. A. M. A., 1915, LXIV, 1968.

8. RosENow, E. C. "Iritis and Other Ocular Lesions on

Intravenous Injection of Streptococci." Jour. Inf.
Dis., 1915, XVII, 403.

9. Billings, Frank. "Chronic Focal Infections and Their

Etiologic Relations to Arthritis and Nephritis."

Arch. Int. Med., 1912, IX, 484.
. "Chronic Focal Infections as a Causative Factor in

Chronic Arthritis." The Jour. A.M. A., 1913, LXI,

819.
. "Chronic Infectious Endocarditis." The Arch. Int.

Med,, 1909, IV, 409.
. "Clinical Aspect and Medical Management of Arthritis

Deformans." III. Med. Jour., 1914, XXV, 11.
. "Focal Infection : Its Broader Application in the Etiol-
ogy of General Disease." The Jour. A. M. A., 1914,

LXIII, 899.

BIBLIOGRAPHY 161

B1LLIN6S9 Frank. "Systemic Diseases of Focal Origin.''
Forchheimer^s Therapeusisy 1914, V, 169.

10. ScHOTTMULLEE, H. "Die Artuntersuchendung der fiir

Menschen Pathogenen Streptokokken durch Blu-

tagar." Munch. Med. Wchnschr., 1903, L, 849.
. "Ziir Aetiologie der Pneumonie Cruposa." Munch.

Med. Wchnschr., 1905, LII, 30.
. "Endocarditis Lenta." Milnch. Klin. Wchnschr.^ 1910,

880 (quoted by Libman).

11. Cole, Rufus, and Dochez, A. R. "Report of Studies

in Pneumonia." Trans. Assn. Am. Phys.y 1913,
XXVIII, 606.

12. Haessli, Hans. "Der Verhalten der Streptokokken

Gegeniiber Plasma und Serum und ihre Umziichtung."
Mitth. a. d. Harnb. Staats KranJcenamst, 1910, XL,
10.

13. FoRSSNER, G. "Renale Lokalisation nach intravenosen

Injektionen mit einer dem Nierengewebe experimental
angepassten Streptokokken cultur." Nord. Med.
Arkiv., 1902, XXXV, 1-56.

14. PoYNTON, F. J., and Paine, A. "The Etiology of Rheu-

matic Fever." The Lancet, 1900, II, 861.

. "A Further Contribution to the Study of Rheumatism ;

the Experimental Production of Appendicitis by the
Intravenous Inoculation of the Diplococcus." The
Lancet, 1911, II.

. "Observations Upon the Arthritis Produced in Rabbits

by the Intravenous Inoculation of a Diplococcus Iso-
lated from Cases of Rheumatism." Trans. Path. SocJ
London, 1904. •

. "Observations Upon Certain Forms of Arthritis." Br.

Med. Jour., 1902, II, 1414.

. "The Pathogenesis of Rheumatic Fever." Trans. Path.

Soc, London, 1901.

. "The Relation of Malignant to Rheumatic Endocar-
ditis." The Lancet, 1902, I, 1036.

162 BIBLIOGRAPHY

PoYNTON, F. J., and Paine, A. "Remarks on the Infec-
tious Nature of Rheumatic Fever, Illustrated by
the Study of a Fatal Case.'* Br. Med. Jour.y
1904, I.

. "Some Further Investigations and Observations Upon

the Pathology of Rheumatic Fever." The Lancet^
1910, 1, \6M.

15. Beattie, James. "Acute Rheumatism.'* Edinb. Med.

Jour., 1904.

16. Walkee, E. W. a., and Ryffel, J. H. "The Pathology

of Acute Rheumatism and Allied Disorders." Br.
Med. Jour., 1903, II, 659.

17. OsLEE, Wm. "Chronic Infectious Endocarditis." Quar.

Jour. Med., 1909, II, 219.

. "On the Visceral Complications of Erythema Exu-

dativum Multiforme." Am. Jour. Med. Sci., 1895,
CX, 629.

18. HoRDER, Thomas J. "Infective Endocarditis." Quar.

Jour. Med., 1909, II, 289.

19. LiBMAN, E., and Celler, H. L. "The Etiology of

Subacute Infective Endocarditis." Jour. Am. Med.
Sci., 1910, CXL, 516.

20. LiBMAN, E. "A Study of the Lesions of Subacute Bac-

terial Endocarditis with Peculiar Reference to Heal-
ing or Healed Lesions, with Clinical Notes." Jour.
Am. Med. Sci., 1912, CXLIV, 313.

21. Her2,ick, James B. "The Healing of Ulcerative Endo-

carditis." Med. News, 1902, XXXI, 10.

22. Lenhartz, H. "Ueber die Septische Endocarditis."

Munch. Med. Wchschr., 1901, XLVIII, 28.
28. Baehr, Geo. "Glomerular Lesions of Subacute Bacterial

Endocarditis." Jour. Am. Med. Sci., 1912, CXLIV,

327.
24. LoHLEiN, M. "Ueber hamorrhagische Nieren Affektionen

bei Chronischer Ulcerosen Endokarditis." Med.

Kim., 1910, VI, 10.

BIBLIOGRAPHY 168

25. Kbetz, Richard. "Angina und Septische Infektlon.'*

Zeitschr. f. HeUkund.; 1907, XXVIII, 296.

26. Cannon, Dr. "Ueber die Frage der hamatogenen In-

fektion bei Appendicitis und Cholecystitis." Deutsch,
Zeitschr. f. Chir., 1908, XCV, 21.

27. Ghon, a., and Namba, K. "Zur Frage iiber die Genese

der Appendicitis." Beitrag. z. Path. Anat, u. z.
Algem. Path., 1912, LII, 130.

28. Adrian, C. ."Die Appendicitis als Folge einer AUgemei-

nerkrankung." Klinisches und Experimentelles. Mit"
teUy a. d. Grenzgeb. d. Med. u. Chir., 1901, VII,
407.

29. Heyde, M. "Bakteriologische und ExperimenteUe

Untersuchungen zur Aetologie der Wurmfort-
satzentziingen (mitt besondere Beriicksichtigung der
Anaeroben Bakterien)." Beitr. z. Klin, Chir., 1911,
LXXVI, I.
SO. AscHOFF, L. "Pathogenese und Atiologie der Appen-
dicitis." Ergehnisse d. Inner Med. u. KinderheU-
kwnd, 1912, IX, 1.

81. Vincent, H. "Sur la thyroidism dans la rheumatisme

aigu, et sur Porigine rheumatismale de certain cas
du goitre exophthalmique." Compt. rend. Soc. de
Biol, 1907, LXIII, 389.

. "Rapports de la maladie Basedow avec la rheumatisme

aigu." BuU. de la Soc. Med. de Paris, 1907, XXIV,
l%SQ\Semain£ Med., 1907, Mar. 20, 143, Ihid., 1907,
Nov. 21, 575; Ibid., 1908, Jan. 1, 47; Ibid., 1908,
Oct. 28, 527.

82. Opie, E. L. "The Etiology of Acute Hemorrhagic

Pancreatitis." /. H. H. BvU., 1901, 182.

88. Davis, D. J. "Bacteriological and Experimental Ob-
servations on Focal Infection." Arch. Int. Med.,
1912, 505.

84. Jackson, Lema. "Experimental Rheumatic Myocar-
ditis." Jour. Inf. Dis., 1912, XI, 240.

164 BIBLIOGRAPHY

85. Le Count, E. R., and Jackson, Lelia. "The Renal
Changes in Rabbits Inoculated with Streptococci/*
Jour. Inf. Dis., 1914, XV, 389.

36. Irons, Ernest E. "Bacteriology and Immunity. Studies

in Gonococcal Immunity." Trans. XVIIth Internat.
Med. Cong., 1913, 87.

37. Irons, Ernest E., and Nicoll, H. K. "Complement

Fixation in the Diagnosis of Gonococcal Infections."
Jour. Inf. Dis., 1915, XVI, 303.
88. Pearce, Richard M. "The Scientific Basis of Vaccine
Therapy." The Jour. A. M. A., 1913, LXI, 2115.

39. Smith, Theobald. "An Attempt to Interpret Present-

Day Uses of Vaccine." The Jour. A. M. A.y 1913,
LX, 1591.
. "Theobald Smith and Phenomena" (Anaphjlaxis). Re-
ferred to by many experimental workers. See Jour.
A. M. A., 1906, 1910, and Lewis, P. A., Jour. Exper.
Med., 1908, X, 1.

40. Babcock, Robt. H. "Chronic Cholecystitis as a Cause

of Myocardial Incompetence." Jour. A. M. A.,
1909, LII, 1904.

41. Nichols, Edward H., and Richardson, Frank L.

"Arthritis Deformans." Jour. Med. Research, 1909,'
N. S., XVI, 149.

42. Weil, Richard. "Anaphylaxis and Its Relation to Prob-

lems of Hiiman Disease." Cinn. Lancet Clinic, 1913,
Nov. 19.

. "Studies in Anaphylaxis. Desensitization ; Its Theoreti-
cal and Practical Significance." The Jour, of Med.
Research, 1913, New Series, XXIV, 233.

. "Studies in Anaphylaxis." The Jour. Med. Research,

1914, New Series, XXV, 299.

43. VON Pirquet, C. E. "Allergy." Arch. Int'. Med., 1911,

VII, 259.

44. Rosenau, M. L., and Anderson, John F. "Hypersus-

ceptibility." Jour. A. M. A., 1906, XLVII, 1007.

BIBLIOGRAPHY 165

RosENAu, M. L., and Anderson, John F. "A Study of the
Cause of Sudden Death, Following' the Injection of
Horse Serum." 1906, Hygiemc Laboratory Bul.y
No. 29.

. "Studies on Hypersusceptibility and Immunity." 1907,

Hygiemc Laboratory Bui., No. 36.

. "Further Studies Upon the Phenomenon of Anaphy-
laxis." 1909, Hygienic Laboratory Bui., No. 50.

45. Vaughan, V. C. "Protein Split Products in Relation to

Immunity and Disease." Lea & Febiger, Philadel-
phia, 1913.

46. AuER, J., and Lewis, Paul L. "Acute Anaphylactic

Death in Guinea Pigs." Jour. A.M. A., 1909, LIII,
458, and Jour. Exper. Med., 1910, XII, 151.

47. Park, W. H. "A Critical Study of the Results of Serum

Therapy in the Diseases of Man." The Harvey Lec-
tures, 1905-6, 101, Lippincott.

48. JoBLiNG, James W., and Petersen. "Bacterio Therapy

in Typhoid Fever." Jour. A. M. A., 1915, LXV,
515.

49. Gay, Frederick P., and Chickering, Henry T. "Treat-

ment of Typhoid Fever by Intravenous Injections of
Polyvalent Sensitized Typhoid Vaccine Sediment."
The Arch, of Int. Med., 1916, XVII, 303.

60. Hastings, T. W. "Complement Fixation Tests in Chronic

Infective Deforming Arthritis and Arthritis De-
formans." Jour. Exper. Med., 1914, XX, 52.

• "Concerning a Polyvalent Antigen for the Complement

Fixation Test for Streptococcus Viridans Infection."
Jowr. Exper. Med., 1914, XX, 72.

61. Phillips, Llewellyn. "Emetine in Amebiasis." Jour.

Trop. Med. and Hygiene, 1914, Aug. 15.
52. Meltzer, S. J. "Bronchial Asthma as a Phenomenon of

Anaphylaxis." Jour. A. M. A., 1910, LV, 1021.
63. JoBLiNG, J. W., Petersen, W. F., and Eggstein, A. A.

"The Mechanism of Anaphylactic Shock. Studies

166 BIBLIOGRAPHY

on Ferment Action." Jour, Exper, Med.^ 1914, XX,
401, and 1915, XXII, 401.

64. Klotz, Oskar. "Experimental Bacterial Interstitial

Nephritis." Trans, Assoc, American Physicians,
1914, XXIX, 49.

65. Ophuls, W. "Subacute and Chronic Nephritis as Found

In One Thousand Unselected Autopsies." Arch. Int,
Med., 1912, IX, 156.

66. SiPPY, B. W. "Gastric and Duodenal Ulcer, Medical

Care by an Efficient Removal of Gastric Juice Cor-
rosion." Jour, A, M. A., 1915, LXIV, 1628.

67. Thayee, W. S. "On Gonorrheal Septicemia and Endo-

carditis." Amer, Jour. Med, Sci.^ Nov., 1905, new
series, CXXXI, 751.

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BS9 Focal Infection
1916

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