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 >/.^ 
 
 UPON THE BACTERIOLOGY 
 
 OF 
 
 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 
 
 OK 
 
 PROGRESSIVE CIRRHOSIS OF THE LIVER. 
 
 BY 
 
 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 
 
 OF 
 
 PRUGIIESSIVE ClUltHOSlS OF THE LIVER. 
 
 HY 
 
 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 
 
8 
 
 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 
 
9 
 
 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 
 
10 
 
 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 
 
 l\ 
 
 ^ 
 
11 
 
 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 
 
12 
 
 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- 
 
18 
 
 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. 
 
14 
 
 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, 
 
15 
 
 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 
 
16 
 
 (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 
 
17 
 
 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 
 
18 
 
 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. 
 
IB 
 
 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,