A Case of Acute Ulcerative Endocarditis 
? 
Due to the Bacillus Dip therm. 
BY 
<r 
WILLIAM T. HOWARD, Jr., M.D., 
Y 
ASSOCIATE PROFESSOR OF PATHOLOGY, WESTERN RESERVE UNIVERSITY, ' 
CLEVELAND, OHIO. 
S'' 
(From the Pathological Laboratory of the Johns Hopkins University and, Hospital.) 
FROM 
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 
December, 1894. Reprinted from The American Journal of the Medical Sciences, December, 1894. 
A CASE OF ACUTE ULCERATIVE ENDOCARDITIS DUE TO 
THE BACILLUS DIPHTHERIAS. 
By William T. Howard, Jr., M.D., 
ASSOCIATE PROFESSOR OF PATHOLOGY, WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO. 
{From the Pathological Laboratory of the Johns Hopkins University and Hospital.) 
Although this case has been published elsewhere in abstract,11 wish 
to record it now in full, as it is not only the first reported case of endo- 
cardial lesion due to the bacillus diphtherhe, but it is the first time that 
this organism has been found associated with lesions of any of the in- 
ternal organs other than the lungs; and for these reasons it must be 
regarded as a unique case. 
The case occurred at St. Joseph’s Hospital, Baltimore, in the service 
of my colleague, Dr. Frank A. Warner, by whose courtesy I am enabled 
to report it. 
Constantine B., a Russian Pole, laborer, aged thirty-four years, mar- 
ried, was admitted to the hospital November 7, 1892, complaining of 
weakness, headache, and diarrhoea. 
Family history. His father is living and healthy. His mother died 
with some disease of the eye. He knew nothing of his grandparents. 
One brother and one sister died in childhood; cause unknown. One 
son died in infancy. The patient denied having had any previous dis- 
ease, and said that he had always been strong and healthy. His present 
disease began on November 1, 1892, when he was taken ill with severe 
chills, high fever, nausea and vomiting, diarrhoea, and with pains in the 
head, limbs, and abdomen. 
On admission, at 6 p.m., November 7th, his temperature was 100.5°, 
his pulse 84 per minute, and his respirations accelerated. The eyes 
appeared normal. The skin was hot and dry. There were no wounds, 
spots, or hemorrhages in the skin anywhere. The lips and mucous 
membranes were pale. The tongue was dry, its edges red, its dorsum 
coated with a yellowish-brown fur. The mucous membrane of the 
mouth and pharynx appeared normal The examination of the lungs 
was negative. The apex-beat of the heart was in the fifth intercostal 
space just within the nipple-line. The cardiac dulness began at the 
upper border of the fourth rib, the left sternal border, and extended to 
the apex. Both sounds were clear at apex and base. The second sound 
at the pulmonary cartilage was accentuated. The liver dulness extended 
from the upper border of the seventh rib to the costal margin in the 
1 Studies in Diphtheria. The Johns Hopkins Hospital Bulletin, April, 1893, No. 30. 2 
HOWARD : ACUTE ULCERATIVE ENDOCARDITIS. 
mammary line. The splenic dulness was obscure, the spleen was not 
palpable. The abdomen was resonant throughout. There was no gur- 
gling or tenderness in the right iliac fossa The urine was negative. 
A note made on November 18th showed that his state remained very 
much the same; but there was now some tympanites and some gurgling 
in the right iliac fossa. The tongue was dry and red. The tempera- 
ture had been ranging about 102° in the evenings, the pulse was 84 and 
of fair volume. Examination of the heart and lungs was negative. 
On November 21st he was worse, his pulse was 120 and of poor 
volume. Heart and lungs negative. 
November 24. The patient has lost ground steadily the last three days. 
His temperature was subnormal and his pulse 150° and very weak. 
Albumin was found in his urine to-day. He died during the night of 
the 24th. 
The autopsy was made by me eight hours after death. 
Anatomical diagnosis. Acute ulcerative endocarditis with extensive 
thrombus formation of the superior surface of the mitral valve. Slight 
vegetative endocarditis of the aortic valve. Congestion and oedema of 
the lungs. Acute and chronic nephritis. Acute splenic tumor. Em- 
bolism ot the splenic and renal arteries; infarction of the spleen and 
kidneys. Acute parenchymatous degeneration of the liver, kidneys, and 
heart. Septicaemia. 
Body 170 cm. long, well built; not emaciated. There are no oedema 
and no ecchymoses or other discoloration of the skin. The skin is pale. 
The pupils are dilated. 
The brain and cord not examined. The subcutaneous fat is well 
developed. There is no oedema of the abdominal or chest walls. The 
muscles are pale. 
In each pleural cavity there are a few cubic centimetres of clear 
serum. The pleural surfaces are smooth and free from adhesions. Both 
lungs are crepitant throughout. They are congested, especially at the 
bases and posterior portions of the lower lobes. The mucous membrane 
of the bronchi is red and somewhat swollen. Both lungs and the bron- 
chial glands are deeply pigmented. On careful examination small 
ecchymoses are seen on the pleural surfaces. 
The pericardium contains about fifty cubic centimetres of clear serum. 
Both layers are smooth and present small points of ecchymosis, which 
are best marked over the epicardium of the left auricle. 
The left ventricle is rather strongly contracted. The heart is larger 
than normal and weighs 350 grammes. The myocardium is of a pale- 
red color and is less firm than normal. All the cardiac cavities contain 
dark fluid blood and yellowish-white clots. On opening the left auric e 
there is seen to project through the auriculo-ventricular orifice a granu- 
lar-looking and in some places mottled gray and red thrombus mass, 
which completely closes the orifice. This mass is everywhere intimately 
adherent to the superior or auricular surface of the mitral valve. On 
opening the ventricle the whole area of this surface of the valve is seen 
to be covered with this intimately adherent and generally grayish white 
thrombus mass, which presents in places a few granulations. This mass 
varies in thickness from 2 mm. to 1 cm. Oa incision it is found to be 
thickest about the middle of the valve. At many points it becomes 
thinner along the free margins of the valve, and is then often continued 
down on the chordae tendime. At the base of the valve toward the HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
3 
auriculo-ventricular ring on the superior surface the endocardium at the 
margin of this thrombus mass is curled up, leaving a red, roughened sur- 
face of ulceration. The thrombus is thickest over the anterior segment, 
and from here it sends down a teat-like projection, 5 mm. in diameter at 
its base, into the cavity of the ventricle. The two segments of the valve 
are bound together by the thrombus mass, which on incision is tough 
and dense and of a grayish-white appearance. At the point of juncture 
between the thrombus and the ulcerated valve the tissue is red and 
injected. 
The inferior or ventricular surface of the valve presents a few small 
granular elevations, which on removal leave a red ulcerated surface. 
Otherwise this aspect of the valve is normal. 
When the surfaces of the thrombus are brought together by closure 
the mass measures 17 mm. in diameter. At least half the diameter of 
the orifice is obstructed by the thrombus. 
Along the ventricular aspect of the aortic valve, just below the level 
of the corpora Arantii, there is a narrow row of exqusite, minute fresh 
vegetations of a light-red color. The rest of the valve is unchanged and 
there are no uncovered points of ulceration. 
In the meshes of the columnse carnse of the left auricle and ventricle 
there are soft grayish-white non adherent coagula. The parietal endo- 
cardium elsewhere is normal and presents no ulcerations. 
The right auricle and ventricle contain dark fluid blood and non- 
adherent coagula. The valves and the walls are normal. The auricular 
appendages contain non-adherent clots, but no thrombi. 
There is slight hypertrophy of the left ventricle. The circumference 
of the mitral valve is 9.5 cm.; of the tricuspid, 11 cm. ; of the aortic, 7 
cm. The coronary arteries are normal, as are the aorta and the 
pulmonary artery. 
The liver is large, and projects below the costal margin in the mam- 
mary line. The edges are round, the surface smooth. On section the 
surface is pale and opaque. The lobules are visible. There is no appa- 
rent connective tissue increase, and no areas of necrosis. The consistence 
is normal. In the gall-bladder there is a small amount of bile, of a 
syrupy consistence. The gall-bladder and the bile-duct are normal. 
The spleen is large, weighing 400 grammes and measuring 15 x 10 x 4.5 
cm. The surface in general is smooth, with here and there small scat- 
tered pale gray points in the capsule. The notch is well mahked. On 
section the organ is of a dark red color, in general, with here and there 
lighter areas. The organ is soft, but not diffluent, and throughout 
nearly its whole extent is the seat of infarction. The trabeculae are 
visible, the Malpighian bodies not. In the larger branches of the splenic 
artery there are white and red thrombus masses, which are often inti- 
mately adherent to the vessel wall. 
The kidneys are of about the same size and general appearance. 
They are smaller than normal, and together weigh 320 grammes. The 
capsules are readily removed. The main trunk of the renal artery of 
each side is normal; but in both kidneys in many of the branches of 
medium size there are grayish-white embolic masses which completely 
plug the lumen. Some of these masses can be pressed out, others are 
firmly adherent to the vessel walls. Beneath the surface of both kid- 
neys, scattered everywhere, there are points of ecchymosis. At the 
middle of the convexity of each organ there is a large, raised yellowish. 4 
HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
gray area, with dark red margins. These areas extend over a large 
surface, and the one in the left kidney involves fully one-sixth of the 
organ. On section of the kidneys these areas are seen to be irregularly 
triangular in outline. They are of a yellowish-gray color, and are firmer 
than the rest of the kidney tissue. These extensive infarcts involve both 
medullary and cortical tissue. Scattered over the surface and through 
the organs there are numerous smaller white infarctions, which, like the 
large ones, are surrounded by a dark hemorrhagic zone. These hemor- 
rhagic zones are especially well marked just beneath the surface of the 
organs. 
At one place the infarcted area is extensively softened, and is bordered 
by a deep hemorrhagic zone, giving somewhat the appearance of a recent 
corpus luteum. The cortex of both kidneys, where not involved in 
infarctions, is swollen, pale, and opaque. The striae are indistinct, the 
glomeruli appear congested. The medullary portions of the kidneys are 
congested. 
The pelves, ureters, and bladder are normal. 
The pancreas, adrenal bodies, and testes are normal. 
The mucous membrane of the stomach is injected. The duodenum 
and the jejunum are pale. In the ileum and in the upper part of the 
large intestine the solitary follicles are swollen and congested, but pre- 
sent no sign of ulceration. The Peyer’s patches just above the ileo-coecal 
valve are swollen and red. 
The mesenteric glands are not specially enlarged. 
The pharynx, tonsils, and the mucous membrane of the larynx and 
trachea present no pathological changes. The nasal fossae and the vault 
of the pharynx were not examined. 
Fresh frozen sections of the heart, liver, spleen, and kidneys were 
studied, but as the various histological changes found showed very much 
better in hardened sections, a description of the microscopical appearances 
of the fresh tissues is omitted. 
Cover-slip preparations made at the .time of the autopsy from the mitral 
valve, the spleen, and the kidneys, showed in great numbers and in pure 
cultures a bacillus of the size and morphological appearances of the 
bacillus diphtherise. Cultures were made at once, with the usual pre- 
cautions, on plain agar-agar from the ulcerated surface of the mitral 
valve, and from the lungs, spleen and kidneys. After twenty-four hours 
in the thermostat there were numerous small isolated colonies in each 
tube. Cover-slip preparations from a number of these colonies showed 
always the' same organism, which had the same appearance as those seen 
in the cover-slip preparations from the fresh organs. 
The bacillus was non-motile. It varied in shape and size. It occurred 
both on coverslip preparations made from cultures and in sections from 
the mitral valve and the kidneys, usually as a straight rod with rounded 
ends, but it often assumed irregular and bizarre shapes. In some one or 
both ends were swollen ; in others, portions of the bacilli stained more 
deeply than others, giving a beaded appearance to the organisms. 
The bacillus from cultures and in the tissues stained well and clearly 
with Gram’s method and with Weigert’s fibrin stain. 
On glycerin agar-plates, after remaining twenty-four hours in the 
thermostat, the colonies were round or oval, elevated and coarsely 
granular, with ill-defined borders. The superficial colonies were large, 
very coarsely granular, and irregular in outline. With the naked eye HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
5 
the colonies were grayish-white in color. On slanting glycerin agar 
and plain nutrient agar the growth was abundant, and made up of small 
well-defined grayish-white colonies. The bacillus grew well on gelatin. 
In alkaline bouillon the growth occurred as small, irregular, grayish- 
white specks at the bottom and along the sides of the tube. The bacillus 
grew well on steamed potato, and could be cultivated for generations on 
this medium. The growth was, however, always invisible. There was 
a rapid and luxurious growth on blood-serum. 
The organism was cultivated on a variety of media side by side with 
cultures of the bacillus diphtherise obtained from undoubted cases of 
primary faucial diphtheria, and was always found to be identical in 
both its morphological and cultural properties with that organism. 
After repeated experiments this bacillus has failed to kill guinea-pigs 
and rabbits. 
Portions of the mitral valve, of the left ventricle, of the lungs, liver, 
spleen, and kidneys, and other organs were hardened in alcohol. Sec- 
tions of these were stained with hsematoxylin and eosine, methylene- 
blue and eosine, and with Weigert’s fibrin stain, and studied. 
Heart. For histological study sections were made at several places 
perpendicularly through the mitral valve and the superimposed thrombus 
mass. These sections included, in addition to the thrombus and the whole 
extent of the valve, corresponding portions of the endocardium and the 
musculature of the left auricle and ventricle. The starting-point of the 
process on the valve could be best studied near the base of the valve, 
just below the auriculo-ventricular ring, for here it is more recent, and 
its various steps can be accurately traced. The lesion is somewhat 
irregular in extent, extending higher up toward the base of the valve in 
sections made from some places than in those made from others. In 
sections made through the posterior segment the change in the valvular 
tissue extends almost to the base of the valve, and in sections made from 
the anterior segment not quite so far. In these sections beginning near 
the base of the valve there are various changes to be noted in the endo- 
thelial cells of the endocardium. In many of them the nucleus stains 
poorly, and the surrounding protoplasm is swollen and granular; others 
have lost their nuclei; many of the cells are desquamated. In some of 
the cells bacilli can be made out. These are more numerous in the des- 
quamated cells. At this point there are no changes to be noted in the 
underlying tissue of the endocardium. Farther down, and beginning 
just above the thrombus mass, there is a large area very rich in cells, 
which extends through the entire thickness of the endocardium. Here 
the endothelial cells are entirely lost, only a few swollen, granular-look- 
ing, desquamated ones being made out. At this point there is seen in 
all the sections examined a considerable local reaction, shown by a great 
increase in the number of cells. These cells are for the most part poly- 
nuclear leucocytes, but there are a considerable number of round cells of 
about the size and appearance of large mononuclear leucocytes, and some 
more or less spindle-shaped cells. This cell-infiltration here involves the 
w'hole thickness of the endocardium proper, and in some sections the 
underlying muscle tissue as well. 
The cells are more numerous toward the free border, where the poly- 
morphous nuclear variety predominate, and they gradually lessen in 
number toward the muscle tissue and toward the base of the valve. 
Along the free edge and extending to some depth, there is a well-marked 6 
HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
nuclear fragmentation. Some of the cells have lost their nuclei, and the 
latter lie free in the tissue. These fragments may appear as round, 
highly refractive, intensely staining dots, or may assume very irregular 
and bizarre shapes. In places the tissue in which the cells lie is hyaline, 
staining diffusely with eosine, and showing characteristic threads of fibrin 
with Weigert’s fibrin stain. 
Both at the margin of this area, and extending a considerable distance 
into the tisue, bacilli can be made out. The bacilli lie both inside the 
cells and free in the tissue. This area is covered by a pseudo-membrane, 
that is continuous with that covering the rest of the valve and forming 
the thrombus mass. At this point the pseudo membrane is composed of 
a dense mass of fibrin laid down in succesive layers, and staining diffu- 
sively with eosine, and characteristically with Weigert’s fibrin stain. In 
between the meshes of the fibrin layers there are numerous cells, both 
large mononuclear cells and polymorphous-nuclear leucocytes, the latter 
variety predominating. Many of the cells contain bacilli in numbers. 
In the fibrin meshes there are also parts of disintegrated cells, free nuclei 
and fragmented nuclei. These latter often assume bizarre shapes, and 
they stain intensely with aqueous fuchsine and alkaline methylene-blue. 
Numerous bacilli appear in scattered clumps and in large zooglea masses. 
Below the area of cellular infiltration described in the endocardium, 
this membrane throughout its whole extent on the upper surface of the 
valve is hyaline, and stains diffusely with eosine, and very few nuclei can 
be made out. The endothelial cells on the free surface are entirely lost, 
and between this hyaline material and the thick thrombus mass there is 
an irregular, thick line, staining deeply with the aniline dyes, and which 
is made up of myriads of bacilli. As the free or unattached end of the 
valve is approached, in addition to the endocardial tissue, the underly- 
ing muscle tissue of the valve to a considerable depth is hyaline, and 
contains no well-preserved nuclei. There are some fragmented nuclei to 
be seen. This hyaline material stains diffusely and characteristically 
with eosine and with picric acid. At the edge of the valve, in sections 
made from various places, this hyaline tissue is covered with a mass of 
fibrin laid down in successive layers, and containing in its meshes numer- 
ous cells and bacilli. The cells here are in various stages of degenera- 
tion; many are swollen and granular, and contain bacilli. There is an 
intense nuclear fragmentation, and many free nuclei are seen. These cells 
are for the most part polymorphous nuclear leucocytes. At the margin 
of the free end of the valve, under this pseudo-membranous formation, 
there is a considerable local reaction, which is in many respects similar 
to the area described near the base of the valve. The chief point of 
difference is that here there seems to be a complete necrosis of the tissue 
of the part. The outlines of the cells are lost, the nuclei stain poorly, and 
there is an exquisite nuclear fragmentation, the fragments often taking 
bizarre shapes. The tissue stains diffusely with eosine and picric acid. 
The thrombus mass, which covers the whole of the upper or auricular 
surface of the valve, is composed of this fibrin formation containing cells, 
and of a diffusely staining mass of fibrin containing myriads of bacilli. 
These latter form a deep and irregular line along the free surface of the 
thrombus. Everywhere in the fibrinous material they are diffusely 
scattered in irregular clumps and in large zooglea masses. In sections 
stained with eosine and methylene-blue or hsematoxylin, the hyaline 
fibrinous material stains homogeneously, and the bacilli take up the HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
7 
nuclear dye intensely. With Weigert’s fibrin stain the hyaline material 
is seen to be made up of threads and bands of fibrin, and the bacilli 
stain deeply. In the outer portions of the thrombus but few cells are 
seen, and these are of the polymorphous-nuclear type only. 
In all the sections studied the muscle cells of the musculature of that 
portion of the auricle included in the sections are normal. There is a 
slight fibrous myocarditis. 
The muscle tissue of the valve itself presents a striking change. That 
portion of the muscle tissue just beneath the necrotic endocardium, 
toward the outer or free edge of the valve, is in all the sections studded 
hyaline, and stains diffusely. In several places there are small collec- 
tions of red blood-corpuscles that still preserve their form. 
In sections from one place there is on the under or ventricular surface 
of the valve near its free edge an area of cell infiltration, with loss of 
the endothelial cells and with nuclear fragmentation. There is a pseudo- 
membranous formation on the surface here. The process at this point is 
recent, and is similar to that seen on the upper surface near the base of 
the valve. At several places midway in the thickness of the valve there 
are focal areas of necrosis of the muscle-cells, with nuclear fragmenta- 
tion. About these areas there are polymorphous-nuclear leucocytes in 
various stages of degeneration. No bacilli are made out in these areas. 
In still other places there are areas of cellular infiltrations with prolifer- 
ation of the fixed cells and the presence of polymorphous-nuclear leuco- 
cytes. Many of the cells are degenerated, and there is considerable 
nuclear fragmentation. In the centre of one of these areas, which can 
be traced through a number of sections, there is a bloodvessel filled with 
a large zooglea mass of bacilli. There are few bloodvessels present in 
the sections examined, but those seen are large and evidently dilated. 
The bacilli described in the process on the valve are in pure culture 
and are morphologically identical with those in cover-slip preparations 
made in the fresh state and with those grown in the cultures made at 
the autopsy. 
Kidneys. Study of sections made from portions of the kidneys not 
involved in infarctions shows in some glomeruli thickening of the cap- 
sule of Bowman, with some desquamation of the capsular epithelium. 
The glomeruli show an increase of cells, and they nearly fill the capsules. 
In some very thin sections stained with eosine and methylene-blue the 
capillaries are seen to be distended with blood and to contain large 
numbers of polymorphous nuclear leucocytes. Here and there a few 
bacilli can be made out inside the capillaries. There is no necrosis of 
cells to be made out in the glomeruli. The afferent vessels are distended 
with blood. 
The intertubular connective tissue is increased in amount. The epi- 
thelial cells of the tubules are swollen and granular. The lumina of the 
convoluted tubules are in many places completely filled with these swollen 
and granular cells. In many tubules the epithelial cells are detached 
in large numbers from the basement membrane. The nuclei often stain 
badly and in some cells not at all. In some tubules scattered bacilli can 
be made out. There is no nuclear fragmentation. Scattered throughout 
the kidneys there are numerous areas of hemorrhage into the tubules. 
In these areas the tubules are distended with blood, and the epithelium 
is flattened out or completely lost, and inside some of the tubules so 
affected numerous bacilli are seen. These hemorrhagic areas are more 8 
HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
numerous in the cortex near the surface of the kidney. The vessels just 
under the capsule are distended, and here and there there is hemorrhage 
into the surrounding tissue. 
Sections cut across a large branch of the left renal artery present a 
peculiar appearance. In the side of the vessel nearest the cortex and 
occupying about one-fourth of the lumen of the vessel there is a mass of 
red blood-cells containing large numbers of polymorphous nuclear leuco- 
cytes, which are for the most part massed in clumps containing both free 
and fragmented nuclei. In this area a few bacilli are seen. The rest 
of the lumen of the vessel is filled with a mass of hyaline material stain- 
ing diffusely with eosine and showing characteristic fibrin threads with 
Weigert’s stain. In this material there are enormous numbers of bacilli 
usually in large zooglea masses. In the fibrin meshes there are many 
polymorphous-nuclear leucocytes, which are often massed together, and 
which show a well-marked nuclear fragmentation. These leucocytes are 
especially numerous and form a thick line at the junction of the line of 
red blood-cells with the fibrinous material. That portion of the vessel 
wall in relation with the mass of red blood-cells appears normal. The 
rest of the wall of the vessels presents an interesting picture. Here there 
are various changes met with in all three coats. 
On one side, at a point where the fibrinous material joins the mass of 
red blood-cells and between the latter and the vessel wall, the endothelial 
cells of the intima are for the most part desquamated. Those remaining 
attached are swollen and granular. The desquamated cells lie in the 
fibrinous material, are swollen and granular, and many have lost their 
nuclei. Some contain bacilli, which often have a transverse, beaded 
appearance. Extending from this point all the way around the side of 
the vessel until the mass of red blood-cells is reached again, the endo- 
thelial cells are lost over large areas. In many places the fenestrated 
membrane of the intima is stripped off. Around the whole of the three- 
fourths of the circumference of the vessel where these changes in the 
intima are noted there are large numbers of polymorphous-nuclear 
leucocytes and bacilli imbedded in the fibrinous material already de- 
scribed. Just here there are many leucocytes and endothelial cells con- 
taining bacilli. Throughout this three-fourths of the circumference of the 
vessel the media is the seat of a peculiar change. Here, forming a line 
between the junction of the intima and media, there are a large number 
of cells. These are especially numerous in those places where the fenes- 
trated membrane is lost. 
The muscle-cells at these points have lost their nuclei and stain dif- 
fusely with eosine; there is also considerable nuclear fragmentation, but 
it is never so extensive as that seen outside the intima and in the mass 
of fibrin. The cells above described are for the most part polymorphous- 
nuclear leucocytes; but there are also many large, round cells with large 
single nuclei. Here and there in these areas of cellular infiltration 
bacilli can be made out, but they are never numerous. In some places 
the leucocytic invasion can be traced down along the muscle bands to 
the adventitia. At one point and over a considerable area the muscle- 
cells of the whole thickness of the media are hyaline, have lost their 
nuclei, and there is considerable nuclear fragmentation. Here there are 
a large number of leucocytes, and a few bacilli can be made out here 
and there. The adventitia shows a recent proliferation of the fixed cells, HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
9 
and the tubules in the neighborhood are atrophied. Nowhere can one 
trace leucocytes entering the media from the adventitia. 
Sections cut through a large infarction extending through the medulla 
and the cortex of the left kidney show many interesting changes. The 
cells of the kidney tissue in this area are entirely necrotic and stain 
deeply with eosine. Only here and there do the nuclei stain at all. In 
many places the tubules are filled with a hyaline material which stains 
diffusely with eosine. In sections stained with Weigert’s fibrin stain 
these hyaline masses are seen to contain many fine threads of fibrin. A 
fibrinous network can also be made out between the tubules both in the 
intertubular tissue and inside of the small bloodvessels. These latter 
are distended and the nuclei of the cells of their walls do not stain. The 
cells of the glomeruli in this area are necrotic and their nuclei do not 
stain. The glomerular capillaries are often filled with threads of fibrin. 
All through the infarcted area there are great numbers of bacilli, which 
are seen in scattered clumps and in large zooglea masses. These lie 
inside of the tubules, in the intertubular tissue inside the capillaries 
and small vessels. Many of the glomeruli contain large masses of 
bacilli; indeed, in some glomeruli nothing can be seen but a large 
zooglea mass of bacilli. 
In the centre of the infarcted area no leucocytes are seen. Along 
the border of the infarct there is a dense infiltration, with polymorphous- 
nuclear leucocytes, with a great deal of nuclear fragmentation. In some 
places this leucocytic infiltration can be traced for some distance into 
the infarcted area. Here two appearances are met with. In some 
places about a dense mass of bacilli which lie in a glomerulus, in tubules, 
in capillaries, or, as often occurs, in the intertubular tissue, there is seen 
a dense infiltration, with polymorphous-nuclear leucocytes. Many of 
the nuclei of these cells lie free in the tissue, are fragmented, and show 
bizarre shapes. In most of these areas the tissue is hyaline and necrotic, 
and stains diffusely with eosine, and with Weigert’s fibrin stain fine fibrin 
threads can be made out. In other places, extending for some distance 
into the infarcted area, the capillaries and small bloodvessels are dis- 
tended, with large numbers of polymorphous-nuclear leucocytes. 
The area of infarction does not extend quite to the free border of the 
cortex, for nearly everywhere just under the capsule the tissue cells stain 
well. The vessels here are distended with blood, and some of the capilla- 
ries can be traced running down into the infarcted area. The endo- 
thelial cells of the walls of these vessels stain well; their lumina contain 
red blood-corpuscles and great numbers of polymorphous-nuclear leuco- 
cytes. In places there is hemorrhage into the tubules and into the 
intertubular tissue. Often polymorphous-nuclear leucocytes, free nuclei, 
and nuclear fragments can be made out in the hyaline contents of the 
tubules and in the intertubular tissue at this border of the infarction. 
In most of the sections studied the line of the infarction is clear cut. 
In some sections the leucocytic invasion extends for some distance into 
the infarted area. 
The bacilli seen in all the sections of the kidneys are invariably mor- 
phologically identical with those described on the heart-valve and ob- 
tained in the cultures. They are the only kind of bacteria present. 
Liver. The liver cells are swollen and granular, but their nuclei stain 
well. In many places the cells are filled with bile pigment. The capilla- 10 
HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
ries are wider than normal, and contain red blood-cells and large numbers 
of polymorphous-nuclear leucocytes. The central veins of the lobules 
generally are distended; some are very much so. In some sections the 
lumina of the central veins, beside red blood-cells, contain many large 
cells of the size and appearance of liver-cells. The nuclei of these cells 
do not stain with the nuclear dyes, and the cell bodies stain diffusely 
with eosine. In these areas the liver cells around the central vein, to 
the depth of several rows, present the same characters. In these areas 
there is no nuclear fragmentation and no leucocytic infiltration. In one 
section there is an area near a central vein in which the nuclei of the 
liver-cells do not stain ; the cell bodies here stain deeply with eosine. In 
this area there is no leucocytic invasion and no bacilli are seen. 
A few scattered bacilli can be made out here and there in the liver 
capillaries. In some sections large zooglea masses are seen. In sections 
stained with Weigert’s fibrin stain no fibrin can be made out in the liver. 
There is some increase of connective tissue in the portal systems. 
Spleen. In the infarcted areas of the spleen the tissue is filled with 
red blood-cells and polymorphous-nuclear leucocytes, accompanied by 
an extensive nuclear fragmentation. Tissue stains deeply with eosine, 
and in sections stained with Weigert’s fibrin stain a great deal of fibrin 
is seen both in and outside of the capillaries. Bacilli are seen in great 
numbers, both in scattered clumps and in large zooglea masses, both in 
the bloodvessels and free in the tissue. Scattered in the splenic pulp 
there are numerous peculiar crystalline masses. They are of an orange 
color, and have the appearance of a mass of thread-like lines radiating 
from a common centre. 
Lungs. Microscopical examination of sections of the lungs shows 
nothing of special interest. There is a slight amount of chronic inter- 
stitial pneumonia, with deep pigmentation. In places, small hemorrhages 
into the pleura cannot be made out. The bloodvessels about these areas 
are dilated. 
The epithelial cells of the bronchi are swollen, and in some places 
desquamated. No bacilli are seen in the capillaries or in the larger 
bloodvessels. 
The bacillus found in such great numbers in this case has been care- 
fully studied by Prof. Welch, by myself, and by several other workers 
in his laboratory, and none of us has been able to distinguish any differ- 
ence between it and the bacillus diphtherise obtained from typical cases 
of primary faucial diphtheria, either morphologically or by cultural 
methods. It has invariably reacted typically to all the cultural and 
staining tests known. 
Dr. A. C. Abbott, of the Laboratory of Hygiene of the University of 
Pennsylvania, has also failed to distinguish it by these methods from the 
ordinary bacillus diphtherise. Furthermore, he has found that the 
bacillus of my case shows the same reaction described by him as to 
change of form as does the ordinary bacillus diphtherise on changing it 
from blood-serum to glycerin agar-agar, and vice versa. Abbott1 has 
found that the long, clubbed, irregularly staining individual bacilli 
1 Abbott: Journal of Pathology and Bacteriology, October, 1893., HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
11 
diphtherise seen in cultures made on blood-serum, when transferred to 
and grown on glycerin agar-agar are far less voluminous, much shorter, 
and many-shaped. The reverse he found to occur when bacilli previously 
grown on glycerin agar-agar were transferred to blood-serum. 
The bacillus of this case, even when large doses were used, has not 
proved pathogenic for guinea-pigs or rabbits. Animals kept for months 
after inoculation are alive, and show no paralysis. 
These facts bring up the interesting question of the existence of a true 
bacillus diphtherise pathogenic for human beings and not for animals. 
Abbott,1 in August, 1891, reported two cases of primary faucial diph- 
theria which bear upon this point. In the first case he obtained a 
bacillus, the only difference between which and the bacillus diphtherise 
was that it was not pathogenic for animals. The bacillus of the second 
case showed a more luxuriant growth than usual on various media and 
a visible growth on potato, and also failed to kill animals. 
Abbott2 has lately reported two cases of membranous rhinitis, in both 
of which the bacillus diphtherise was found. Cultures from one case 
killed guinea-pigs in forty-eight hours, and cultures from the second 
case failed to kill these animals. 
The behavior of the bacillus found in my case goes to strengthen the 
argument that the intensity of the virulence of the bacillus diphtherise 
fluctuates. 
The fact that the patient was affected twenty-four days before death 
occurred, and the absence of any mechanical interference to the circula- 
tion on account of the valvular lesion, together with the histological 
appearances of the process on the mitral valve, would seem to show that 
the organism concerned in the etiology of the affection was not possessed 
of a high degree of virulence. These facts, added to the state of the 
process in other organs, point rather to a gradual loss of resistance on 
the part of the individual, which finally allowed such a rapid multipli- 
cation of the bacilli on the heart valve as to produce a genuine septi- 
caemia, and finally extensive infarctions in the spleen and kidneys. It 
is probable that the large area of renal territory comparatively suddenly 
thrown out of use as the result of the numerous and large infarctions, 
together with the acute nephritis present, was the immediate cause of 
death. The individual was able to resist the bacilli for some time, and 
it was only after this resistance was exhausted by a prolonged struggle 
that the bacilli and their products were capable of multiplying to cause 
septicaemia and embolic processes. 
The length of time that the bacilli remained in the body may explain 
their lack of virulence for animals. The fact that the bacilli found in 
this case were not pathogenic for rabbits and guinea-pigs strengthens the 
1 Abbott: Johns Hopkins Hospital Bulletin, August, 1891. 
2 Abbott: Medical News, May 13, 1893, vol. lxii., No. 19. 12 
HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
position of those observers who hold that the lack of pathogenicity for 
animals in a bacillus otherwise identical with the bacillus diphtherise is 
not sufficient ground for classing it with the “ pseudo-diphtheria bacillus.” 
It is well known that various bacteria obtained from a variety of 
lesions in the human being often fail to kill animals. I have several 
times found that large numbers of pneumococci obtained from the lungs 
of fatal cases of pneumonia have failed to kill, or even to produce local 
reaction in rabbits. 
It is now generally recognized that bacteria when obtained from old 
lesions, as, for instance, pneumococci from the gray hepatization of pneu- 
monia, frequently lack virulence for animals. What happens with the 
pneumococcus and other pathogenic bacteria in this regard may well 
obtain for the bacillus diphtheriae. 
While this is the first case in which the bacillus diphtheriae has been 
obtained from lesions of internal organs other than the lungs, Frosch1 
has cultivated this organism from various internal organs in ten out of 
fifteen cases of ordinary diphtheria. Other observers have reported 
single cases in which they have gotten similar results. 
Booker2 has lately published a case of primary laryngeal diphtheria, 
in which he obtained pure cultures of the bacillus diphtherke from one 
of the submaxillary glands and from the spleen. 
When the suggestion of Frosch, that comparatively large pieces of 
organs are to be used in making cultures in these cases, is generally 
adopted, it will probably be found that the bacillus diphtheriae obtains 
entrance into the circulation, in fatal cases at least, with greater frequency 
than is commonly supposed. 
The absence of any demonstrable infection atrium in my case leaves 
us in the dark as regards the mode in which infection took place. 
Not until other cases of infection of internal organs by the bacillus 
diphtheriae have been observed can the interesting question of the modi- 
fication of the virulence of this organism when subjected to prolonged 
habitation in the human body and the action of the blood-serum be 
cleared up. 
The examination of sections from the various organs affected shows 
that the lesions due to, and the reaction of the tissues to, the organism 
found are identical with those described by Oertel3 for diphtheria in 
man, and by Welch and Flexner4 for experimental diphtheria in animals. 
It is interesting to note that the lesions found in the thrombosed renal 
artery were identical with those described on the mitral valve, though 
1 Frosch: Zeit. f. Hygeine u. Infectionskrankheiten, 1893, Band xiii., pp. 49-52. 
2 W. D. Booker: Archives of Pediatrics, August, 1893, vol. x., No. 8. 
3 Oertel: Die Pathogenese der epidemischen Diphtheria. Nach ihrer histologischen begrun- 
dung. Mit Atlas. Vogel, Leipzig, 1887. 
4 Welch and Flexner: Johns Hopkins Hospital Bulletin, No. 15, August, 1891. Also ibid., 
No. 20, March, 1892. HOWARD: ACUTE ULCERATIVE ENDOCARDITIS. 
13 
evidently of more recent date. The great number of bacilli seen in the 
infarcted areas in the kidneys cannot have been due solely to conveyance 
by emboli, but must have in large part depended upon a rapid multipli- 
cation of the organisms brought to the tissue with the embolic masses 
after the normal resistance of the tissues was destroyed by the necrosis 
resulting from the infarction. 
The hemorrhage into that part of the kidneys not involved in infarc- 
tions is readily explained by the direct action of the bacilli and their 
products upon the cells of the vessel walls. The destruction of renal 
tissue by the action of the bacilli and their toxines was extensive. 
The histological changes in the liver were not so marked or so far 
advanced as the lesions usually occurring in this organ as the result of 
the toxines of the bacillus diphtherise, but there was a considerable 
amount of focal necrosis of liver cells, especially about the central veins 
of the lobules. There was no leucocytic infiltration of these areas. 
It is interesting from the clinical side to note that there were no 
positive signs of valvular disease. No murmur was heard; there was 
absence of cardiac embarrassment, and the pulse was regular and but 
little accelerated until the last few days of life. Yfye An}erica]Q Jelirijal 
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