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UPON THE BACTERIOLOGY

Progressive Cirrhosis of the Liver.

BY J. G. ADAMI, M.A., M.D., F.R.S.E.,

PROFESSOR OF PATHOLOGY, McGILL UNIVERSITY. MONTREAL, AND PATHOLOGIST TO THE

ROYAL VICTORIA HOSPITAL.

UKl'UINTi:i) FROM THK MONTKKAl, MEDUAI. JOUKNAI, AlKJUST, 1898.

.. ^vcf;'; .*>

UPON THE BACTBRIOLOGY

PROGRESSIVE CIRRHOSIS OF THE LIVER.

J. G. ADAMI, M.A., M.D., P.R.S.E.,

Professor of Pcathology, McGlll University, and Pathologist to the Royal Victoria

Hospital, Montreal.

IJP(JN THE BACTF:RT0L()({Y

PRUGIIESSIVE ClUltHOSlS OF THE LIVER.

J. G. Adami, M.A., M.D. F.R.S.E.,

ProfcsHor of PatholoRy, McGill University, and PatholoRist to the Royal Victoria

Hospital, Montreal

It is needless for nie hero to enter into a discussion of the various
theories which have been adduced to exphiin the development of
cirrhosis of the liver. I need only say that *^^he experience of a large
number of observers, who for weeks and months have 'noculated
and treated animals with various alcohols has shown that alcohol
itself induces at most the fatty liver with, it may be, a very slight
amount of fibroid change in the portal areas, and that not a single
observer has by this means been able to produce anything at all
resembling the extreme deposit of fibrous tissue which we meet with
in the hobnailed liver.

Alcohol in the main leads to the fatty liver, while on the other
hand the evidence has steadily accumulated, notably in India, that
extreme cirrhosis may attack children and adults who have not taken
a particle of alcohol either medicinally or otherwise.

Within the last few years, the French .school of pathologists headed
by Hanot, has regarded the enlarged cirrhotic liver with jaundice
as being of infectious origin, and it is common in France, now-a-days,
to speak of " ^e/b/c ivfectieux," but to the best of my knowledge
no one has as yet described any one micro-organism as being found
fretiuently associated with these cases of so-called infectious liver. At

' A paper read for tlu; author by Professor Osier, in the Section of Medicine, at
the meeting of the British Medical Association at Edinburgh, .July, 1898.

most, Levi' from a case of cirrho.sis in a 17 year old male, with marked
periportal fibrosis and enlarj^tMl spleen, (jUtained a diplococcu.s patho-
genic for f^uinea pigs. The age of the patient, the proliferation of
the hile ducts and thts absence of ascites, would indicate tliat his caae
was one of what is termed " Hanot's (!!irrhosis" but the bacteriology
is rendered somewhat doubtful in that there were also present l>ac-
terial end(jcarditis of the pulmonary valve and suppuvaUve meningitis.
Unfortunately I have not been able to obtain the original paptir,
nevertheless, this brief stat''ment of the main features of the case,
makes it at least po.ssible, as Paltauf has urged, that the endocarditis
and meningitis and the presence of diplococci in all the organs, may
have been due to a complicatitm.

On the other hand there is a somewhat suggestive relationship
between these cases of Hanot's cirrhosis and epidemic jaundice, in
some cases of which observers \\>wv noticed the presence of a diplo-
coccus or l)acillus with polar staining.

To the best of my knowletlge, no one has as yet i-ecognised the fre-
quent presence of any one form of mif-o-organisin in the connnone.st
form of hepatic cirrhosis — the so-called portal cirrhosis, tending to
the producti(m of the hobnailed liver, ".iiii or without marked atrophy
of the liver.

On V)ehalf of the Government of the Dominion, I spent the sum-
mers of 1894 and 1895 in Nova Scotia investigating a very remarkable
di.sease affecting the cattle in a limited area of the country — the .so-
called " Pictou cattle disea.se" — of which the main le.sion is a singularly
e.xtensive cirrhosis of the liver. The di.«ease is only found in a dis
trict spreading along the northern coast of the peninsula, in a tract
of country al)out 40 miles long iiy from 5 to 12 miles broad. Tlu.'re
apparently it has been noticed for some 40 years, now at one end of
this area now at another. The disease would .seem to be very chronic
and not to afl'ect all the cattle on a farm simultaneously, but unle.ss
due precautions are taken, in the course of three or foui* years most
of the animals upon a farm will, one after the othei', be affected. It
would seem further that the disease does not spread directly from
animal to animal, for there appears to be no s[)ecial incidence of cases
following upon the long winter sojourn of the animals in the byres,
which, with rare exceptions, are miserably dark and ill-ventilated, the
attempt being to keep these as warm as possible in con.siiijuence of
tiie .severity of the winter.

One or two cases are on record in which the disease has broken out
in a neighbourhood after the body of a cow affected with the di.sease

1 Arch. Gen. de Med., March and April, 1894

has Im'i'ii washed down by oiu' of tho strcains and straiuhid upon the
farm hinds. Tho j^radual extension from farm to farm, throu^li any
fjjiven district, seems to be larj^ely brought about by the fact that
each farm has at the back of it a belt of woodhmd into which the
cattk; roam durin<^ tlie summer. The belts are badly fenced off from
each otiier, and here, if ati animal is aHected, it attempts to wander
ort" into the wocxlland and there die in some remote corner. Thus,
unless precautions are taken, the carcasses of these animals remain
uninterred and appear to act as centres of intV'ction. Undcrr the
present CJovernment ret^ulations, notitication is given of every sus-
picious animal, and the Government Inspector, if satisfied that it is
a ca.se of the tlisease, immediately destroys the beast and burns tho
carcass, or has it liuried in (|uicklim(^ By this means the number
of animals affected is rapidly being reduced, so that within the la.st
few years the nundtor of cases occurring annually has sunk from l')0
to under 80.

As for the .symptoms of the disease, the first symptom which is
noticed is that the milk has a somewhat acrid odour upon boiling and
acquires a pecular bitter taste ; within a few days the animal becomes
dry, it is weak and restless, the coat stare.s and the liudjs are dragged,
the bowels loose, the abdomen a little swollen, the eyes are staring,
the conjunctiva) suliieteroid. The animal becoming weaker and
weaker dies apparently in a condition of complete exhaustion. In
some few cases death is preceded by a period of intense excitement
almost maniacal in character, the animal rushintr al)out charfintr at
obstacles and then falling into a condition of paresis followed rapidly
by ileatli.

I killed and made post-mortem examinations upon .some 30 animals
during two years and fcjund, as Dr. Osier and Dr. Wyatt Johnston
previously determined, that the main lesions are an extreme condition
of generalised cirrhosis, not only periportal and pericellular, the
organ being somewhat enlarged and having a smooth and rarely a
finely granular surface. There is evidently an abundant production
of thin bile, for with scarce an exception the gall-bladder was found
very full and the fieees well stained. The periportal and abdominal
lymph glands in general are large and succulent, there is a moderate
amount of ascites, the fluid being perfectly clear and limpid, and
together with this there is a rather remarkable condition of a gela-
tinous (I'dema of the mesenteries and intestinal walls. A further
constant lesion is the presence of numerous follicular ulcers in the
4th or true stomach. These, save in the very acute case.s, are found in
a cicatrised condition, giving strongly the impression that the earliest

lesion ill till- ciiHf liii.s licfii j^iistric ami lias Itocii t'ltllowt'd \>y iiift-c'tion
of tlic alitliaiiinal lyiii|iliatic Hy.stciii ami tlit* portal aiva.

From all the animals which I killed, I was iiioro t'ortnnatc than
my priMJi'ci'Ssor.s in j^aininj^ a cliamotcriHtic niicro-ori^ani.sm. This
may have Im-i-ii diu! to the fact that I employed a Hoiiiewhat dillereiit
method of j,'ainin<f my ciiltiin's. Instead of taking' the me(lia and
inoculatinjf on the spot, all I employed was a series of sterilised ^dass
pipettes in which I collected relatively lar^'c amounts of the juices of
the various organs ; ascitic fluid, hlood, etc., ami tlien when hack in
my temporary lahoratory, either upon that or the followiii},' day, 1
inoculat(Ml my media. By this means, constantly from the lymph
juice of the altdciininal Inlands an 1 from tht* liver juice or hile and mon;
rarely frotn other organs and fluids, I obtained in each case growths
of a characteristic micro-organism ; snnll, polymorpliou.s, at timtis
appearing as a diplococcus and at others as a diplohacillus which \<y
its polymorphous character gave me a considerable amount of trouble,
until I found that employing the .same broth tube, at the end of 24
hours I obtained the one form, at the end of 4S, the other. Further
study showed me that this micro-organism was in reality a short
Iittcillus with polar staining, in this resembling to some extent the
micro-organisms of hiemorrhagic .septiciiMiiia in the lower animals, but
unlike them, pos.sessing a slight capsule. I was able to grow this
upon all the ordinary media of the laboratory. Into the character of
this micro organi.sm I will not here further enter, beyond stating that
I found it pathogenic for rabbits, guinea pigs and mice, ral)bits djing
in from 15 to 35 days, guinea pigs in from 30 to 35 on the average.

The characteristic features of this disease — the ascites without
jaundice, the gastric and intestinal disturbance and the condition of
the liver — led me .seriously to consider the points of similarity
between the course and symptoms of these cases and those present in
portal cirrhosis in man, and though it may seem a small matter, I
was especially struck by the fact that the first post-mortem which T
performed upon a case of atrophic ciirhosis upon my return from
Nova Scotia in 1895, presented the same gelatinous oedema of the
mesenteries and intestinal walls which was so prominent a feature in
the Pictou cattle disease.

Thus on and off for the last three years my attention has been
direct ' towards this pos-sibility of discovering bacteria in ordinary
progrt.-^sise portal cirrhosis. Upon three occasions I have thought
that I have gained .specific micro-organisms. In two, unfortunately,
the growth became contaminated with the colon bacillus, and as this
occurred on the eve of my vacation I was unable to co",titiue the

search t'lirtli*!!'. In the tliiiil, wliicli occurred a little over a month
ago, the growtli was very slight, and nlthough pure, it had apparently
(lied out on the fifth day and I was unaMe to gain any further cul-
tures, if ind«!ed what I saw was anything heyond the fre<|uent
prcHcnce of ilipiococci already existing in this livor juico at the time
of extraction.

TIk! ditliculty that has pursued nie in this searcli has been that
which has prevented nie from puhlishing so far any extensive report
of my studies upon the Pictou cattl" disease, namely, the extra-
ordinary dilliculty in staining tim micro-organism in the tissues. I
have tried a very great niunl)er of metlKxIs, and wliile with many I
have been aide to rtfcogtiise the bacteria, the results obtained have
been so inconstant that I have felt that others following me might
veiy possilily have negative results ; thus I have been unwilling to
make any full .statement until I hIiouM be able to state clearly how
to be able to rccogni.se the micro-organism. While this micro-
organism stains deeply it appears to lose its stain even more
rapidly than does the ti.ssue. Sometimes Gram's or \Veigert's method
shows them perfectly, but while the iodine appears to have a deter-
rent ert'ect upon the decolorisation of the microbes, the stain is not
properly fixed by its means. And while again I have obtained good
results by staining with methylene l>lue dissolved in anilin oil, a
momentary pa.ssage of sections so stained, through a mixture of anilin
oil and xylol and so through xylol into Canada balsam, yet even here
the colour appears to fade out rapidly so that in a few days the micro-
organisms are unrecognizable. Eventuall}' the thought struck me
that bleaching in ilie suidight might be a possible means. By this
process there would be no diffusion currents set up, and if, as my
previous work had shown, the bacilli took up the stain with rapidity
then the deeply .stained sections would have so much of the dye in the
bacilli that, upon bleaching out, the bacilli would be left stained when
the tissue itself had become colourles.s.

My laboratory assistant, Mr. E. W. Hammond, prepared a large
.series of .sections in this way and obtained .some excellent results. He
found that, as I had suggested, strong staining with carbolised fuchsin
followed by bleacliing for a short time each day for a period of a fort-
night or more, <lemonstrated the bacteria admirably. While the
process is a slow one it has the undeniable advantage that each day
th(! mounted section can be exanuned to see how far the process of
bleaching has progressed. By this means I was able to find out that
in the Pictou cattle disease the micro-organisms, while present .scat-
tered through the new librous tissue, are present also in large numbers

within the .liver cells, and in the liver of a rabbit which had been
inoculated with the uiicro-organisin isolated by ine, although the animal
died before any marked cirrhosis had developed, the liver cells were
seen to contain these microbes in very great numbers. As to how the
micro-organisms enter these cells, that is a point on which at present I
can throw no light, but the appearances given, as will be seen in a
specimen under the microscope in the Pathological Exhibit, is that
these cells contain large numbers (>f extremely minute diplococci.

Recently, within the last month, a remarkable case of cirrhosis with
pigmentation unaccompanied by diabetes has again drawn my atten-
tion to the bacteriology of atrophic cirrhosis. Dr. Maude Abbott,
who is working in my laboratory at the Royal Victoria Hospital,
.showed me some sections of the nbdon)inal lymphatic glands, stained
by Weigert's tibrin stain in which, under high power, I noticed a
peculiar tine granulation, and upon examining under the LSth inch
immersion, these fine granules resolved themselves into minute diplo-
cocci.

Examining the liver stained the same way, I there noted large
numbers of the same micro-organism, and since then I have gone
through all my five cases of cirrhosis which I have had during the
last three years ; through specimens of four well marked cases of hob-
nailed liver receive<l from Profe.ssor Hektoen, of the Rush Medical
College, Chicago, and through a series of sixteen livers, some of well
marked atrophic cirrhosis, others of milder stag(\s of cirrhosis sent to
me by Dr. Flexner from the Johns Hopkins Hos})ital. So far in
every case of well marked portal cirrliosis whether of the small
shrunken type or of the large hobnailed type, whether as.sociated
with jaundice without ascites or with ascites without jaundice, I came
across constantly one characteristic form of micro-organism, olitain-
ing the best and most permanent results by the method already
mentioned, of staining in carbolised fuchsin and bleaching or partially
bleaching in the sunlight.

This micro-organism is extraordinarily minute; by the trained eye,
in well stained specimens, it can be recognised under the 12th inch
immersion, but for satisfactory work it is absolutely necessary to em-
ploy the 18th or 20th inch immersion len.s. According to the depth
of the stain, so does it appear either as an ovoid bacillus, which might
easily be mistaken for some stained deposit in the liver cells, or as a
minute diplococcus surrounded by a halo, the explanation being that
with strong staining the the bacillus and capsule are stained thi'ough-
out, with weak, the body of the micro-organism and the capsule are
decolorised, leaving simply the polar staining. Even in the tissues

this micro-organism is somewhat polymorplious, that is to say, that
at times one sees the two stained portions so close together as to re-
semble a minute edition of the gonococcus, at other times they are
furtlier apart and ap[)ear rounded like the coccus form of pneumo-
coccus, while in th(! same specimen a rare form may he seen in which
the two stained portions are even slightly elongated. These ar(^
present in greatest numhoi's within the ciills. A i'emarkal)le feature
about 'hem, and one which yeais ago I noted in connection with the
Pictou cattle dis(;ase, is wluitlier they be seen in the lymphatic glands
or in the liver, in the unstained condition many have distinctly a
brownish tinge, so that in the liver especially these ixulies may at
first sight be mistaken for minute granules of precipitated bile pig-
ment. They vary in number ; in two cases in which tlie disease
appeared to Ix; of very slow progress but few were present ; in those
cases in which the bands of portal connective tissue showed an abund-
ance of small round cells and in which the disease according to all
indications was active and progi'essing, the number was remarkable,
in fact so numerous were they that it was impossible for me to arrive
at any other conclusion than that there is a distinct association be-
tween the presence of this micro-organism and the development of
the disease.

80 minute are these micro-organisms that it is difficult to focus
them, and I would strongly urge those attempting to confirm these
observations to take, if ^necessary, h'om twenty minutes to an hour
studying an individual field of the mic •o.scope before arriving at any
definite conclusion.

Here, perhaps, I should correct myself. In the fully stained condi-
tion the micro-organisms while small are not so very much smaller
than the ordinary run of pathogenic bacteria. But in this fully stained
condition, as already stated, they are very difhcult to distinguish from
granules scattered through the cell protoplasm ; it is in the partly
decolorised condition in which the polar staining alone is recognisable
and is peculiarly charactisristic, that they appear so very minute.

* Indeed, I know of no form so minute, save that recently described by

Nocard and Roux as being the causative agent in the contagious

pleuro-pneumonia of cattle, and the strain upon the eyes in studying

, these microbes is most .severe. This adds greatly to the difficulty of

I photographing the micro-organisms.

I am indebted to Dr. Pati'ick, th(! photographer of our hospital, for
the accompanying lantern slides, in which despite great difficulties he
has managed, I think succe.ssfully, to demonstrate the oi'ganisms in
the tissues ; but with regard to this I may .say that where he shows

one micro-organism the slightest change of focus would bring others
into view, so that his slides show but about l-20th of the number
recognisable in any given field.

As to whether the micro-organisms in the human and in the bovine
liver are identical it is impossible for me to affirm. At Johns Hopkins,
as in our own hospital and in a large number of foreign hospitals,
not to mention the leading hospitals in the old country, it is now the
custom to obtain cultures' from half a dozen or more regions, includinsf
the liver, in every autopsy performed within fifteen hours after death.
And, while the methods employed for obtaining cultures are in many
cases faulty, to the extent that an insufficient amount of tissue juice is
taken, it seems to me unlikely that had this form been cultivable
upon the ordinary media, it would not before now have been isolated.
Nevertheless, there is this to be said, that very frequently the colon
bacillus grows upon cultures made from the liver ; isolated colonies
of the micro-organisms from the Pictou cattle disease, while growing
more slowly, are not unlike those of the colon bacillus, and thus pos-
sibly the micro-organism if growing in a manner similar to that of
the Pictou cattle disease, might be neglected on account of this simi-
larity in appearance.

It so happens that here in Montreal cases of the disease are few and
far between ; five cases only have come under me in four years, and
in a seriss ot 934 autopsies made during twelve years at the Montreal
General Hospital and indexed by Professor Wyatt Johnston, I find
that altogether 31 cases of cirrhosis of the liver are recoi'ded and 14
of the cirrhotic and fatty liver, with one; recoi'ded as " hypertrophic
cirrhosis." I have thus thought it wise to pul)lish these ob.s-:>rvations,
even though I can at the present moment make no alxsolute statement
with regard to the i.solated micro-organism and its character, beyond
the statement that, as already mentioned, in one agar tube made from
the live juice, I was able to recognise the form, although in iiot v<!ry
great numbers and with the absitnce of any visible growth.

Lastly, as to the cases in association with which I have found this
micro-organism. If future observers confii-m the observations given
above, then we must conclude that many of the divisions and distinc-
tions attempted to be drawn between the forms of advanced ciirhosis
of the liver, must bo broken down for, in the fii'st place, I have found
the same appearance in the large liver with moderate granulation or
slight hobnailed condition, which some would speak of as " hyper-
trophic cirrhosis," as again in the small contracted typical hobnailed
liver ; in cases frankly multilol)ular with sharply defined bands of
connective tissue cutting off relatively large areas of liver substance

and showing relatively few bile ducts ; as again in cases of the more
unilobular type with iil-detined edges to the lobules and abundant
bile ducts ; in cases which have shown jaundice without ascites, ascites
without jaundice, and again both jaundice and ascites ; lastly, incases
with a pronounced alcoholic history and others in which no history of
alcoliolisni could be obtained.

I am far from wishing it to be understood that I am here laying
down that all cases of fibroid change in the liver present these minute
micro-organisms ; to make any such suggestion would be absurd.
Nor again am I prepared to say that Hanot's cirrhosis affecting the
young adult and presenting the enlarged liver with smooth surface
II '"^J accompanying this, crises of icterus, is identical with the more

(| ordinary form of progressive cirrhosis affecting the adult. It may be

so or it may not. All that I at present am prepared to lay down
IS this, that the progressive and extensive cirrhosis affecting the
adult at or after forty years of age is, according to my investigations,
accompanied by the presence in the liver cells, as again in the newly
formed connective tissue, of an extraordinarily minute bacillus, having
a polar staining and resembling greatly in its appearance under the
microscope a form which I have isolated from cases of infective cirrhosis
among cattle.

I cannot conclude without again expressing the debt under which
I labour to several helpers. To Dr. Maude Abbott and Dr. Patrick ;
to my Laboratory As.*istant at the University, Mr. E. W, Hammond,
who aided me very materially in Nova Scotia ; Mr. Howell, my assis-
tant at the Royal Victoria Hospital, but for whose energy I should
have l)eeji unable to prepare and examine all my material ; to Mr-
Nicholson, who has most gladly crossed the Atlantic to demonstrate
my specimens during the course of the meeting ; and -ibove all, on
this occasi(m am T indebted to a member of McGill University, my
predecessor not only in the teaching of Pathology, but also in the inves-
tigations in the Pictou cattle disease, than none, not even myself could
moi-e willingly or more appropriately, or better, have brought this
* subject before von.

!\ ■ ^

■ » Appendix, {July mii, IMS.)

I By a remarkable coincidence, upon the afternoon of the day upon

which 1 completed the dictation of the foregoing in order that \ might
have it complete for Dr. Osier to take with him to Edinburgh, I was
called to perform a post-mortem upon a case apparently of heart
failure whicii turned out to be (me of atrophic cirrhosis of the liver.
I sIkjuUI here aild that a diagnosis of cirrhosis of the liver had been

considorod and Imd boon left in doubt ; while clearly, from the con-
dition of the lieart, death had resulted from failure of that organ.

Not to enter too fully into the details of the case, for the clinical
notes of which 1 am indebted to Dr. James Stewart, I may say that
the body was that of a female of 5G, who had always lived in Canada,
and who, after the diseases of childhood had, until two years previously,
enjoyed good health. She had 10 children with no miscarriages, and
there was no history of inherited disease. She gave a moderate his-
tory of alcoholism, stating that .she chietly di-ank beer, but if one may
base any argument upon the fre(|Uent pre.sence of minute whitish
phujues which were found .scattered along the ovsophagus, she was a
pronounced alcoholic.

For the la.st two years she had not l)een well, dating her impaired
health from a fall while out walking, when she injured her back
somewhat. B^or the last year her heart had been very weak and upon
exercise her feet and legs became swollen. Since last April, the
weakness, swelling of the legs and abdomen, shortness of breath and
palpitat'on have been much worse, and for three days before admis-
sion, dyspn(ra, sleeplessness and weakness had been extreme, while
for months she hail steadily been losing flesh.

Upon examination .she was found .sallow, with moderate ansBmia of
mucous membranes, the sclerotics wei-e icteroid with distension of the
supm-ficial vessels ; the face was enmciated and there was orthopnea ;
the temperature was normal, the pulse rapid and the respirations were
36. The skin, more especially the face, neck and arms, was of a peculiar
ashy colour ; this, she stated had been noticeable for some years ;
there was sliofht srcneral (inlema, marked cedema of the lower ex-
tremities, and definite ascites. The pulse was 100. very irregular in
volume and rhythm ; the apex beat was unrecognisable ; there were
no murmurs. There was evidence of right-sided plenri-sy and numerous
coarse and fine rales with expectoration of frothy mucus. There was
frequent vomiting and retching, though this had l)egun only a few days
before admission to hospital. The urine was dark, amber coloured,
with flocculent sediment, a fine ring of albumin and contained some
bile. For a week oi" moie her condition improved ; the heart became
more powerful, the a.scites diminished. Suddenly upon the 6th, the
patient died.

The autopsy was held six hours after death, and showed the fol-
lowing conditions .

Heart. — Large, full, with dilatation of the cavities, the mu.scle being
somewhat atrophied and fibroid. The coronary vessels were athero-
matous. All the valves were norm.il and in both auricles were puri-

form and braakini^ down hall thron»l)i indicating a very feeble circu-
lation.

Lungs. — Both showed adhesions to the diaphragm and elsewhere,
and on section pi-esented little beyond (t^denia, ,s ,\e that the lower
lol)o of tlie right lung was almost completely compressed and airless
as a result of the riglit-sidcsd pleursy. The right pleural cavity C(m-
tained about 700 rem. of red stained il'ild without Hocculi.

Abdomen.— Thii abdomen contained between 900 an<l 1,000 ccm.
of turbid and greenish ascitic fluid. Neither liver nor spleen were
visible,

Sloiinicli. — This was long and narrow with mucosa thickened, the
cardiac portion having a curious .strawberry-like appearance with Hue
white dots .standing out, Itut not projecting from the generally red-
dened surface. This faded off' in the pyloric portion of the stomach
where there was a fair amount of nuicus.

Ditodeniim. — The first three inches presented an identical straw-
berry-like appearance to that .seen in the cardia.

Intestives. — The small intestines in general were congested and the
last three inches befox-e the ileo-csucal valve showed large prominent
solitary follicles. The walls of the small intestine had a distinctly
brownish tinge as of von Recklinghausen's Hemochromatosis. The
mesentery of the .small intestine was distinctly fatty and swollen,
and upon section abundant milky lymph poured out wherever it was
cut.

The abdominal lymph glands were in general reddened and succu-
lent. The retroperitoneal glands, especially those in the neighbour-
hood of the portal fissure and of the pancreas, were markedly enlarged.

Liver. — The liver was distinctly small, weighing 1045 grams or a
little over two pounds ; the two lobes were correspondingly diminished
in sisie, the organ was pale and had a finely gi-anular surface ; there
were abundant old fine veil-like adhesions over the upper surface to
the diaphragm. On section the organ cut fairly firudy more especially
along the lower half of the right lobe and the under surface. On the
whole the ajjpearance on section was more fatty than fibroid. Micro ■
scopically, the organ presented along with fibroid thickening of the
portal sheaths, a somewhat difiuse cirrhosis, the bands of fibrous
ti,ssue not being sharply cut and being infiltrated with a considerable
number of small round cells. The cirrhosis was very obvious but not
of the more usual type and the difiuse nature of the change may
explain why the surface was finely gi-anular rather than distinctly
hobnailed.

Gall Bladder. — This had (edematous thickened walls.

Sjileen. — Of normal size nn<l ratlier soft, although on section the
trabecula) were seen larger and more prominent than usual.

Pancreas. — Viiluminous and moderately firm.

Suprarenals. — Of fair size.

Kidneys. — These were Uie hog-hacked type of mixed interstitial
and parenchymatous nephritis. This so-called ' hog-backed ' appear-
ance, is that which, as I believe, Formad of Philadelphia, was the first
to point out, is the more common form of alcoholic kidney in North
America. The organs were large with a finely granular surface and
full and firm corte.x. There were white infarcts both in the kidney
and the spleen.

The body was still warm at the time of autopsy and I obtained
numerous sterilised pipettes of tissue juice from the liver, spleen,
kidneys, abdominal lymph glands, ascitic fluid, pleural fluid, pericar-
dial fluid, blood, and lymph from the mesentery, and with these made
a series of inoculations on the surface of sloping glycerinated agar
tubes, as also some into broth.

Portions of the collected ascitic and pleural fiuid were centrifugal-
ised, the cellular debris dissolved by caustic potash and after further
centrifugalisation the deposit examined under the microscope after
staining with carbolised fuchsin. This deposit showed rather rare
minute diplococcus fornis with a slight halo round them, similar in all
respects to those recognised in the ti-ssues.

A series of slide preparations were made from the various pipettes
direct, fixed in the usual method and stained with carbol fuchsin,
which was warmed until definite vapour was given ott", then washed
with watei- just cool enough to bear the hand in it, and mounted. As
a result the characteristic diplococcus form was found in the prepar-
ations made from the liver, lymph from the mesentery, th(! ascitic
Huid, the heart blood, the left kidney and the mesenteric glands ; they
were not found in the pleural cavity, the bile or the pericardial fiuid.

Next, using a fair amount of the fiuid out of each j)ipette, I allowed
this to flow over the surface of slanting glycerinated agar tubes, my
experience with the Pictou cattle disease having shown me, that
while the fiuid in the pipettes could show numerous diplococci, appar-
ently the majority of those are dead, and only a few remain alive.
By this means, in 24 hours I obtained fairly fre(iuent growths in
tubes from the spleen and left kidney, and rai'e growths in the mesen-
teric glands and heart blood. Four colonies only appeared upon the
tul)e prepared from the liver, and two from the ascitic fiuid and the.se
latter did not sliow clearly till the expiration of 4M hours.

Subcultures made again directly upon the glycerinated agar surface,

showed a fine rather thin growtli at first uf n)inute discrete colonies;
hiter these ran to^'ether into thin waxy lines which nixtn the expira-
tion of four or five days assumed a i'aint yellowish tinj^e. Other
tuhes were made directly from the pipettes of the kidney and spleisn
into beef broth. 'J'his upon the following day showed a faint turbidity,
which, just as in the case (jf the I'ictou cattle disease, if anythinj,',
.lessened with further -rrowth. whih; a whitish depo.sit foriiieil at the
bottom. Since then, usinir the remaininj.1' pipettes, I have obtained a
j,'reat mnnber of broth cultures, the <,n-owth beinj,' much more free
upon this medium than upon the agar, and further, yielding forms
which are more characteristic and less Hal )le to cause confusion ; for
the nncro-organism is most remarkable in its characters.

Ui'own upon broth, in 24 hours it is present in the form of nnnute
diplococci surrounded with a faint halo or capsule. Often these tend
to bo arranged in irregular chains in which the separate appearance
of the dots arc not (piite regularly arranged, the long axis joining the
two dots not of necessity coinciding with the long axis of the chain.

Grown upon glycerinated agar, the appearance is most puzzling,
and although I had similar (3xperience when working (jut the charac-
ter of the micro-organism of the Pictou cattle disease, the.se agar
cultures have given me a week of profound anxiety, until within the
last 24 hours I have solved the problem. A 24 hour culture at 37'
upon glycerinated agar, reveals minute forms which upon careful
staining with fuchsin, not too deep, are clearly forms of diplococci.
One gets every transition from the frank diplococcus form through one
in which only very careful focussing shows that the somewhat oval
bacterium has at either pole a deeper stained mass, to forms in which
the polar staining cannot be made out so that one appears to deal
with true short bacilli. Add to this, a certain number of oval forms
can be seen still smaller than the diplococcus, in which the distinction
between the two ends cannot be made out.

In 48 hours, and still more in 72 hours, the same culture which had
given this appearance at the end of 24 houis appears to be contamin-
ated by the presence of long distinct bacilli ; that is, if sections be
well stained with fuchsin, while this is .still more the case after stain-
ing with Loefi^er's methylene blue. At first sight, a cultr from
this variety showing these bacilli of irregular length with rounded
ends, often lying side liy side, appears to be untloubtedly of the colon
bacillus or .some allied form. And here I gain an explanation of the
contrary results obtained l)y a bacteriological covfrere and myself in
London two years ago. I took to him cultures isolated from two
cases of cirrhosis which, on examination in Montreal, seemed to be

(liplococci, and his statt^nient timt hv found only colon Itacilli niiuie
n>e cause my invcstifjations for tlie tiuio. I can now well understand
liis most pardonable mistake.

Yesterday upon examinin;^ the agar plate culture from the spleen
which had been made upon the 7th inst, and had been left for 24 lumrs
in th J incubator and there apparently yielded no (growths and which
thus had remained for four days at the ordinary temperature in the
shade, I recognised one form of growth alone present, extremely minutei
the colonies well separated from each other.

Upon renu^ving one colony and making a coverslip preparation
stained with fuchsin, I found that I had to deal with long chaindike
bacilli interspersed with some shorter forms of the same brea<lth.
The appearance was so wholly unlike anything that I had previously
made out in the broth cultures, that I neglected this colony and made
a culture from another identical in appearance and eciually isolated,
and in this case after staining with fuchsin, and as T thought over-
staining, I washed in absolute alcohol. The result obtained was most
remarkable. The long bacillary forms could still be recognized in
this as in the other specimen and if anything they were longi'r, but
each long filament showed a discoloured sheath in which, scattered at
perfectly regular intervals, were pairs of dots deeply stained. In
.sqme places individual dots could be clearly recognised elongated
and replacing the pairs. These pairs of dots in size resembled
the diplococcus-like forms seen in the broth cultures and in the
tissues to which I have already so fre(iuently drawn attention.
I regret that time has forbidden that I should obtain photographs of
this very curious appearance so that they could be demonstrated with
the lantern. In the series of preparations which will be found in the
Pathological Museum, this form will be placed under the nnero.scope
and there will also be a .series of sketches made by me under Zeis,s's
Camera Lucida showing this appearance.

I touched the same colony with a platinum needle and inoculated a
broth tube from it and eight hours later, the broth, which hail in the
meantime been kept at 87*^, .showed a faint turbidity, and ninv some
specimens treated with carbolised fuchsin in the same way, showed
in place of the singularly long filaments, numerous diplococcus forms,
fairly large, in which the connecting more colourle-ss portion could be
well seen, while here and there a rarer form showed three instea<l
of two dots along the course of the bacillus. These observations
satisfactorily explain the curious condition of affaii's.

The microbe which is seen in the tissues as a diplococcus surrounded
by a faint halo, is in broth after 24< hours pre.sent also as a diplococcus

but mtluT lartjer, .tliowiur,' or not showinf^ th« halo acconlin;,' to
tho extent of the stain.

Upon ajjjar a^mr, wliih; first present as a diplococcus form, it grad-
ually extends and eacli day is seen as a longer hacillary fonn, but if
stained and decolourised witii carlxjlised fuchsin and decolourised to
the right extent, each lotig Hlanicnt is seen to he niaile up of diplo-
coccus-like meinhers lying in the common sheuth. I made out a
similar condition of atiairs in connection with the Pictou cattle
disease, but do not remember to have come across such Ion"' tillamen-
tous forms.

We seem thus to be dealing with a form totally unlike any which
to the best of my knowledge, has been described ; the polymorphism
is remarkable. It is most difficult, however, to determine how to
describe the appearances seen, and I am at a loss whether to state
that we are dealing with an encapsuled diplococcus or with a bacillus
having inclusions taking a peculiar deep staining, just as in the
ordinary cell, the nucleus stains deeper than the surrounding proto-
plasm. The general appearance in the tissue is certainly that of an
encapsuled diplococcus, but on the other hand, grown outside the body
and upon agar and then treated with Loeffler's methylene blue, the
whole of that [ )rtion which plays the part of a capsule to the <liplo-
cocci takes on a stain with as gi-eat intensity as do ordinary bacteria.
On the whole at present, I am inclined to the latter view, because
examining tubes in which proliferation is most rapidly proceeding, I
find upon staining with carbol fuchsin and decolourising with alcohol,
that one has in the youngest ovoid forms what is most sugo-estive
of the polar staining such as one sees in the bacteria of luejuorrhagic
septictemia, that is to say, there is at either pole not a complete coccus
form, but a generally deep staining concavo-convex segment, the two
parts being .separated by a clear space and the membraiu- joining the
ends of the opposite! crescents being clearly visible.

If this form coincides in other re.spects with the miero-oi-gaiiism of
Pictou cattle di.sease, it will grow rather more easily upon slightly
acid media, it will grow upon serum and very slowly in gelatine with-
out tnarked liquifaction, and will l)e fatal for animals of the labora-
tory at a relatively long period after inoculation.

It so closely resembles the micro-organism of the Pictou cattle
disease that I feel that I may safely prophesy this, for the time
taken in unravelling the nnitability of growth upon agar agar has pre-
vented me from working out these points till the last few days.

The great similarity in appearance presented by growths upon agar
agar under ordinary staining to the colon bacillus may perhaps make

it nnpossary to say a few words about tlio rdationsliip of tin* micro-
oi'iraiiiHiii isolated l>y iik;, to tin* liacillii.s in (|m'stion.

I have iiiathi j^rowtlis sltlc by side, and tiiul that in lirotii the colon
causes a greater turbidity and appears to j^row more freely upon ajjjar
afijar and also to be endued with j^reater motility. While upon stain-
ing' an bS hour broth culture of tiie micro-organism by the Nicolle
Nb)rax method, in order to demonstrate Haj^ella, I found that the
niicro-or<,'anism, which are even stumpier than tlie colon biicillus,
under similar circumstances to be possessed of termuial tiagella, either
one or two, and not of hiteral. This, if it were necessary, woultl seem
distinctly to prove that the micro-or;,'anism is wholly distinct from
the colon f^roup. However, I make this statement provisi<»nally, and
will give fuller details as to the characters of the micro-orj^anism
within the next few months, probably in the Jouimai of Kxpen-
menUd Medicine.^

I trust, however, that I have said sufficient to prove: 1st, That in
at least a very large number of well-marked cases of progressive
cirrhosis in man, there is to be found largely within the liver cells,
also in the lymph spaces in the newly formed connective tissue, a
peculiar and very minute form of micro-organism, present on stain-
ing to the proper extent, as a diplococcus surrounded liy a faint
halo, or when stained deeply, l)eing a rather obscure fmcterium, which
may easily be mistaken for stained deposits within the cells.

2nd. That in the infective cirrhosis of cattle, a very similar micro-
organism is recognisable, present in like positions within the tissues
and showing .similar appearances when stained.

3rd. That from at least 80 cattle affected with this disease I have
been able the isolate the micro-organism — from the liver, bile, abdom-
inal lymph glands, and in some cases from the various organs of the
body.

4th That the micro-organism isolated is a polymorphous micro-
organism, appearing as a small diplococcus when grown in broth,
tending to assume a distinctly l»acillary form when grown for a few
hours on other media, or in broth for a longer period.

5th. That this micro-organism is pathogenic for the animals of the
laboratory, and that in them it is to be recognised within the hepatic
cells as in other regions.

' August 20th.— Fuller studies have Hhown me that these statements need
amending. While the bacilli at first caused no fermentation of glucose and lactose
broths, later growths gave definite gas production, though not so extensive as the
atypical colon bacillus. The broth growths also remain atypical, but undoubtedly
the bacilli when growing freely have, like the colon bacillus, iatcriil tlagelhi. The
germ tielongs to the colon group. Fuller details of its characters will be given in a
later communication.

Gtli. That from a caso of distinct atrophic cirrhosis in tho human
bein;^, I liave ht'cii al)lt' to isolatf from varicjus or<^ans of tho luxly a
siniihvr micro-ori^aniHin, wliich j^rown in brotli lias a diplococcus form,
grown upon agar, is present as a short or longer bacillus according to
the age of growth.

This is not the occasion for me to discuss at lenjjfth the bearinsf '>^

try o

these observations upon the nature of progressive cirrhosis in man.
It is only necessary for me to say that if they are confirmed, as per-
sonally I feel they must be confirmed by everyone who proceeds with
sufficient caution to fcjllow tho methods employed by me, then cirr-
hosis of the liver assumes an entirely new aspect. We gain a .satis-
factory explanation at once of such phenomena as the enlargement of
the spleen, which, as has already been noted by more than one
observer, may be made out before there is any sign of portal olistruc-
tion ; we see wliy .so fre(juently there should l»e right-.sided pleurisy,
and may oven find that the (piestion as to whether a case is compli-
cated with ascites or jaundice, depends upcm this micro-organi.sm ;
depends upon whether it sets up a low infiammation of the peri-
toneum, or whether it more especially affects the liver cells and bile
ducts ; while disturbances which may occur not immediately in con-
nection witii tho liver, in the pancreas and in the kidney, would seem
to gain a possible explanation from the fact brought out by me, that
this micro-organism, connnon in the liver cells, is in an advanced
case to be gained from the heart blood and from the kidney.

That the micro-organism only causes cii-rhosis, I do not believe ;
indeed, we may find that it is the cause of more than one disturbance
in the livex', and indeed in other organs. This I base upon the fact that
in the case in which I have isolated this allied form from man, the
micro-organism shows itself capable of existing in several regions of
the body ; in fact of setting up what bacteriologically we regai'd as a
septicemic condition.

The illustrations referred to together with a further note on the
subject, will appear in the next number of the Jouknal,