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516 general condition. A week later nine injections of the serum manufactured by the Institut Pasteur de Paris were tried, but with no better result ; the temperature again oscillated widely, diarrhoea continued to be obstinate, and general anasarca ensued, death occurring on Oct. 1st from multiple embolism. Post mortem blood cultures were made from the splenic substance and numerous colonies of staphylococci were found but no streptococci. Remarks by Dr. GRIFFITH.-The chief interest of the above case lies in the later bacteriological examination which seems to confirm the value of the antistreptococcic serum, inasmuch as the streptococci which were present had disappeared, although the concomitant staphylococcic infec- tion proved too serious for the patient’s recuperative powers. Medical Societies. PATHOLOGICAL SOCIETY OF LONDON. Discussion on "Pseudo-tuberculosis." A MEETING of this society was held on Feb. 21st, the President, Dr. PAYNE, being in the chair. The PRESIDENT referred to the fund which was being raised as a memorial to the late Professor Kanthack. The laws of the society did not allow of any contribution being made from the funds of the society, but he wished to draw the attention of members to it. The capital is to be invested and Mrs. Kanthack is to receive the interest during her life, the fund ultimately being employed to encourage research. The secretary of the fund is Dr. Drysdale, 25, Welbeck-street. The PRESIDENT also referred with regret to the death of Professor Rutherford of Edinburgh and of Mr. Thomas Cooke. Dr. G. SIMS WOODHEAD, in opening the discussion on Pseudo-tuberculosis, stated at the outset that the term I pseudo-tuberculosis " had been responsible for a good deal of misunderstanding and the number of conditions classified under it were so numerous that pseudo-tuberculosis was no longer of the slightest value as a term in classification, for numerous pathogenic conditions, most varied as to appear- ance and etiology, were described by different writers as pseudo-tuberculosis. Dr. Woodhead first referred to a series of cases which came under his own observation during the investigations carried on for the Royal Com- mission on Tuberculosis and which were, for the sake of convenience, spoken of at the time as " pseudo-tubercular " and which might undoubtedly have been mistaken for true tuberculosis had not the conditions under which they occurred and the microscopic examination given such definite indica- tions to the contrary. In one case, that of a guinea-pig which died on the second day after injection of tuberculous meat, much too early therefore to show tubercle as the result of injection, the following conditions were found : venous con- gestion of the large intestine and c&aelig;cum; enlargement of solitary glands and Peyer’s patches with small hsemorrhages into their substance ; in these glands in the small intestine were white opaque points, sometimes scattered over the whole glandular patch; the mesenteric glands were slightly enlarged; the liver was mottled with small yellow patches ; in the lungs were two yellowish grey points ; the spleen was normal; and the mediastinal glands were evidently enlarged. The degenerated patches were much whiter than tuberculous nodules and the breaking down was more complete, so that on microscopic examination one could not make out even the outlines of any cells. No tubercle bacilli could be found in any of the lesions, but micrococci, especially in the form of diplococci, were numerous. As all the other guinea-pigs in the experiment were perfectly free from tubercle it was agreed to look upon it as some mycosis other than tuber- culosis. Without having recourse to microscopic examina- tion, however, Dr. Woodhead could not have satisfied himself that it was not a case of tuberculosis. In a couple of guinea- pigs inoculated with raw meat from the same cow small nodules were observed in the spleen resembling infarctions. On microscopic examination these nodules were found to have a central necrotic area of dead cells which had lost their outlines and had become fused into irregular masses. Short bacilli with polar staining, almost like diplococci, were fsonnd near the margin; around this central area was a zone of shadowy-looking splenic tissue, whilst outside this again was a distinct capsule of connective tissue and leucocytes. In the case of another guinea-pig injected with artificial tuberculous milk heated to 70" C. for one hour, at which temperature tubercle bacilli are: rendered innocuous-at any rate, as regards guinea-pigs-- the animal died 11 days after injection. In some adenoid patches there were opaque areas which were found on micro- scopical examination to consist of tissue in an advanced stage of necrosis and at the margin micro-organisms were found, again in the form of short bacilli with polar staining. In another specimen injected with artificial tuberculous milk, heated as before to 70&deg; C. for ten minutes, the animal was killed 101 days after inoculation and a small, yellowish nodule was found near the surface of the liver and this was seen to be made up of a large mass of organising con- nective tissue in which not a single tubercle bacillus could be found. Dr. Woodhead described one or two other con- ditions which at first sight were mistaken for tuberculous I granulations but in which true tuberculous structure on the presence of tubercle bacilli could never be demon- strated. He next proceeded to discuss some conditions found in the lungs of sheep brought to him by a medical. officer of health who stated that he had had to confiscate large numbers of sheep showing this condition as tubercu- lous. Dr. Woodhead at once recognised the condition as what is called in Scotland "hoos"&mdash;small glistening pearly grey nodules produced by strongylus filari&aelig;. Microscopical examination showed that the nodules consisted of small nematode worms coiled and surrounded by proliferating connective cells. Here they had a perfectly distinct process. and one which should certainly not be called a pseudo- tuberculosis. Dr. Woodhead then called attention to Pro- fessor Muir’s article on Pseudo-tuberculosis in Birds, where at least six different conditions were referred to as having been described. Professor R. Muir of Dundee described a form. in birds which was probably the same as that described. by Malassez and Vignal, Nocard and Pfeiffer. Several of these forms of pseudo-tuberculosis had been separated from animals inoculated with material from patients sup- posed to be suffering from atypical tubercle. In others. again the guinea-pigs appeared to have been affected spon- taneously"-i.e., they had contracted the disease quite. apart from experimentation. This was a point of con- siderable importance in connexion with Dr. Woodhead’-, own observations on pseudo-tuberculosis which evidently occurred, in certain cases at any rate, independently of in- oculation, as in the animal that died two days after inocula- tion, whilst in another of his cases bacilli identical in appear- ance with those described by Nocard, Muir, and Pfeiffer were. found to give rise to this condition on the eleventh day. This corresponded very closely with the condition presented in the experiments of Professor Muir who pointed out that a very marked feature in this special form of pseudo-tuberculosis was that both leucocytes and connective tissue corpuscles undergo, a very rapid breaking-down and that caseation and softening both take place at a very early stage, the result being that the centre of a nodule becomes almost purulent rather than caseous. The proliferative changes in both Dr. Woodhead’s and Professor Muir’s cases were well marked and were confined almost entirely to the periphery of the nodule. There was an absence of giant-cells and the bacilli were usually found near the margin of the caseous centre. This accorded perfectly with what Dr. Woodhead observed in the, pseudo-tuberculosis of guinea-pigs described in the Report to the Royal Commission on Tuberculosis. In referring to old. cases found in museums labelled ’’ tuberculosis " but which more reoent investigators had recognised as being cases of actinomycosis, Dr. Woodhead called attention to a case described by Professor Boyce of Liverpool, which that writer very properly described as "aspergillo-pneumono" mycosis," a much better term than that of "aspergillar pseudo-tuberculosis" given by Kotljar to a similar condition. Kotljar divided pseudo-tuberculosis into two< groups, those of bacterial origin and those of mycotic etiology, these latter being produced by aspergilli. In com- paratively recent times they had passed from an anatomical pseudo-tuberculosis to a pseudo-tuberculosis bacillus. A serious question was opened, however, by the discovery by Frau Rabinowitch in milk, cream, and butter of a bacillus which morphologically, and in its staining reactions, but in. little else, was identical with the tubercle bacillus, and they had two positions from which it was absolutely necessary to extricate themselves. They had on the one hand organisms
Transcript
Page 1: PATHOLOGICAL SOCIETY OF LONDON

516

general condition. A week later nine injections of the serummanufactured by the Institut Pasteur de Paris were tried,but with no better result ; the temperature again oscillatedwidely, diarrhoea continued to be obstinate, and generalanasarca ensued, death occurring on Oct. 1st from multipleembolism. Post mortem blood cultures were made fromthe splenic substance and numerous colonies of staphylococciwere found but no streptococci.Remarks by Dr. GRIFFITH.-The chief interest of the

above case lies in the later bacteriological examinationwhich seems to confirm the value of the antistreptococcicserum, inasmuch as the streptococci which were present haddisappeared, although the concomitant staphylococcic infec-tion proved too serious for the patient’s recuperative powers.

Medical Societies.PATHOLOGICAL SOCIETY OF LONDON.

Discussion on "Pseudo-tuberculosis."A MEETING of this society was held on Feb. 21st, the

President, Dr. PAYNE, being in the chair.The PRESIDENT referred to the fund which was being

raised as a memorial to the late Professor Kanthack. Thelaws of the society did not allow of any contribution beingmade from the funds of the society, but he wished to drawthe attention of members to it. The capital is to beinvested and Mrs. Kanthack is to receive the interest duringher life, the fund ultimately being employed to encourageresearch. The secretary of the fund is Dr. Drysdale,25, Welbeck-street.The PRESIDENT also referred with regret to the death of

Professor Rutherford of Edinburgh and of Mr. Thomas Cooke.Dr. G. SIMS WOODHEAD, in opening the discussion on

Pseudo-tuberculosis, stated at the outset that the termI pseudo-tuberculosis

" had been responsible for a good dealof misunderstanding and the number of conditions classifiedunder it were so numerous that pseudo-tuberculosis was nolonger of the slightest value as a term in classification, fornumerous pathogenic conditions, most varied as to appear-ance and etiology, were described by different writers as

pseudo-tuberculosis. Dr. Woodhead first referred to a

series of cases which came under his own observation

during the investigations carried on for the Royal Com-mission on Tuberculosis and which were, for the sake ofconvenience, spoken of at the time as " pseudo-tubercular

"

and which might undoubtedly have been mistaken for truetuberculosis had not the conditions under which they occurredand the microscopic examination given such definite indica-tions to the contrary. In one case, that of a guinea-pig whichdied on the second day after injection of tuberculous meat,much too early therefore to show tubercle as the result ofinjection, the following conditions were found : venous con-gestion of the large intestine and c&aelig;cum; enlargement ofsolitary glands and Peyer’s patches with small hsemorrhagesinto their substance ; in these glands in the small intestinewere white opaque points, sometimes scattered over thewhole glandular patch; the mesenteric glands were slightlyenlarged; the liver was mottled with small yellow patches ;in the lungs were two yellowish grey points ; the spleen wasnormal; and the mediastinal glands were evidently enlarged.The degenerated patches were much whiter than tuberculousnodules and the breaking down was more complete, so thaton microscopic examination one could not make out even theoutlines of any cells. No tubercle bacilli could be found in anyof the lesions, but micrococci, especially in the form ofdiplococci, were numerous. As all the other guinea-pigs inthe experiment were perfectly free from tubercle it was

agreed to look upon it as some mycosis other than tuber-culosis. Without having recourse to microscopic examina-tion, however, Dr. Woodhead could not have satisfied himselfthat it was not a case of tuberculosis. In a couple of guinea-pigs inoculated with raw meat from the same cow smallnodules were observed in the spleen resembling infarctions.On microscopic examination these nodules were found tohave a central necrotic area of dead cells which had losttheir outlines and had become fused into irregular masses.Short bacilli with polar staining, almost like diplococci,were fsonnd near the margin; around this central area

was a zone of shadowy-looking splenic tissue, whilstoutside this again was a distinct capsule of connectivetissue and leucocytes. In the case of another guinea-piginjected with artificial tuberculous milk heated to 70" C.for one hour, at which temperature tubercle bacilli are:

rendered innocuous-at any rate, as regards guinea-pigs--the animal died 11 days after injection. In some adenoid

patches there were opaque areas which were found on micro-scopical examination to consist of tissue in an advanced

stage of necrosis and at the margin micro-organisms werefound, again in the form of short bacilli with polar staining.In another specimen injected with artificial tuberculousmilk, heated as before to 70&deg; C. for ten minutes, the animalwas killed 101 days after inoculation and a small, yellowishnodule was found near the surface of the liver and thiswas seen to be made up of a large mass of organising con-nective tissue in which not a single tubercle bacillus couldbe found. Dr. Woodhead described one or two other con-ditions which at first sight were mistaken for tuberculous

I granulations but in which true tuberculous structure on

the presence of tubercle bacilli could never be demon-strated. He next proceeded to discuss some conditionsfound in the lungs of sheep brought to him by a medical.officer of health who stated that he had had to confiscatelarge numbers of sheep showing this condition as tubercu-lous. Dr. Woodhead at once recognised the condition aswhat is called in Scotland "hoos"&mdash;small glistening pearlygrey nodules produced by strongylus filari&aelig;. Microscopicalexamination showed that the nodules consisted of smallnematode worms coiled and surrounded by proliferatingconnective cells. Here they had a perfectly distinct process.and one which should certainly not be called a pseudo-tuberculosis. Dr. Woodhead then called attention to Pro-fessor Muir’s article on Pseudo-tuberculosis in Birds, where atleast six different conditions were referred to as having beendescribed. Professor R. Muir of Dundee described a form.in birds which was probably the same as that described.

by Malassez and Vignal, Nocard and Pfeiffer. Severalof these forms of pseudo-tuberculosis had been separatedfrom animals inoculated with material from patients sup-posed to be suffering from atypical tubercle. In others.again the guinea-pigs appeared to have been affected spon-taneously"-i.e., they had contracted the disease quite.apart from experimentation. This was a point of con-

siderable importance in connexion with Dr. Woodhead’-,own observations on pseudo-tuberculosis which evidentlyoccurred, in certain cases at any rate, independently of in-oculation, as in the animal that died two days after inocula-tion, whilst in another of his cases bacilli identical in appear-ance with those described by Nocard, Muir, and Pfeiffer were.found to give rise to this condition on the eleventh day.This corresponded very closely with the condition presented inthe experiments of Professor Muir who pointed out that a verymarked feature in this special form of pseudo-tuberculosis wasthat both leucocytes and connective tissue corpuscles undergo,a very rapid breaking-down and that caseation and softeningboth take place at a very early stage, the result beingthat the centre of a nodule becomes almost purulentrather than caseous. The proliferative changes in both Dr.Woodhead’s and Professor Muir’s cases were well marked andwere confined almost entirely to the periphery of the nodule.There was an absence of giant-cells and the bacilli wereusually found near the margin of the caseous centre. Thisaccorded perfectly with what Dr. Woodhead observed in the,pseudo-tuberculosis of guinea-pigs described in the Report tothe Royal Commission on Tuberculosis. In referring to old.cases found in museums labelled ’’ tuberculosis " but whichmore reoent investigators had recognised as being cases ofactinomycosis, Dr. Woodhead called attention to a casedescribed by Professor Boyce of Liverpool, which thatwriter very properly described as "aspergillo-pneumono"mycosis," a much better term than that of "aspergillarpseudo-tuberculosis" given by Kotljar to a similarcondition. Kotljar divided pseudo-tuberculosis into two<

groups, those of bacterial origin and those of mycoticetiology, these latter being produced by aspergilli. In com-paratively recent times they had passed from an anatomicalpseudo-tuberculosis to a pseudo-tuberculosis bacillus. Aserious question was opened, however, by the discovery byFrau Rabinowitch in milk, cream, and butter of a bacilluswhich morphologically, and in its staining reactions, but in.little else, was identical with the tubercle bacillus, and theyhad two positions from which it was absolutely necessary toextricate themselves. They had on the one hand organisms

Page 2: PATHOLOGICAL SOCIETY OF LONDON

517

of pseudo-tuberculosis which had the morphological andstaining characters of the true tubercle bacillus, butwhich pathologically appeared to be widely separated fromit ; whilst on the other hand they had a whole series oflesions which presented certain superficial resemblances totubercle, but which were not induced by the action of thetubercle bacillus. The protean forms of the histological lesionsin tubercle made it difficult to describe any single form astypical. Almost every new tissue at some period of itsdevelopment might be said to be like some stage of atuberculous process in the rapid infiltration of leucocytesand even the presence of giant cells. The phenomenaof endarteritis obliterans were seen also in many non-

tuberculous conditions. Taking the tubercle bacillus as

the etiological factor and basis of classification andtaking the investigations of comparative pathologists inrecent years who had found many lesions to be tuberclewhich were not previously so recognised Dr. Woodheadthought it very inadvisable that any nomenclature shouldbe brought in which could only ultimately lead to confusion,;and he hoped that the discussion would lead to the drawing upof an accurate and comprehensive nomenclature of many ofthose forms of disease which at present were practicallyunnamed. " Pseudo-tuberculosis " could no longer be

regarded as a pathological entity, and although it might benecessary, owing to the exigencies of use and wont, to retainthe term "tuberculosis," that term should be restricted asfar as possible to a process which had a distinct etiologicalfactor and they should minimise as much as possible theevil of the term by eliminating altogether such termsas "pseudo-tuberculous processes" or "pseudo-tubercular’organisms."

Dr. SIDNEY MARTIN said that his own personal experiencecovered much the same ground as that of Dr. Woodhead,being obtained through observations which he made inde-)pendently for the Royal Commission on Tuberculosis. Hehad repeatedly met with pseudo-tuberculosis or, as he

preferred to call it, "bacterial necrosis in guinea-pigs andrabbits. At first he was much troubled to diagnose thecondition as the specimens in the liver and spleen so closelyresembled those of true tubercle. But the appearances inother organs and the results of cultivation made it clear’that they were non-tuberculous. Besides, there was greatirregularity in the distribution of the lesions, although ininoculated tubercle there was a characteristically uniformmarch of infection along the lymphatics to the organs of thethorax and abdomen, and from each centre of infectiontubercle bacilli could be demonstrated, and each inoculatedinto an animal gave rise to true tubercle. Cases of pseudo-tuberculosis were very rare in man, most of the recordedcases being due to some aspergillus. There were three,however, recently published which appeared to be due to someform of streptothrix. The first was recorded by Dr. SimonFlexner and occurred in a negro, aged 70 years. The chieflesions were in the lungs. The upper lobes were consolidatedand there were scattered nodules in the lower lobe of the leftlung, the nodules being larger than in true tubercle, and havingundergone rapid softening. No cavities had been formed as inphthisis, the softened matter not being expelled. There wasalso infection of the omentum and peritoneum. No tuberclebacilli were discovered and inoculations did not give rise totubercle. On microscopic examination a typical streptothrixwas found in all the lesions. The second case was recordedby Buchholz. The patient was a man, aged 38 years, whohad an empyema and consolidation of the lung with forma-tion of cavities. The liquid material in the consolidated

’lung was traversed by branching hyphae, indieating infectionby a streptothrix. No tubercle bacilli were present. Thethird case occurred in a woman. There was cystitis at first-and then a number of small tumours appeared on the skinand suppurated. Later consolidation of the lungs occurred,supposed during life to be tuberculous. After death notubercle bacilli were found, but there were branched threadsof some streptothrix.

Dr. WASHBOURN said that it would be advisable to discardthe term ’’ pseudo-tuberculosis

" as it was misleading. By

some observers several bacilli which resembled the tuberclebacillus in morphology and in staining reactions would becalled "pseudo-tubercle bacilli." They were of importancefrom the point of view of clinical diagnosis, for by relyingupon a microscopical examination alone they might easily bemistaken for the tubercle bacillus. In the urine pseudo-tubercle bacilli of this nature were by no means uncommon.It was on this account that inoculations were necessary for

the diagnosis of tuberculosis of the genito-urinary tract.The term " pseudo-tuberculosis " was usually applied in quitea different sense to the above. It was used to denotediseases which resembled tuberculosis in morbid anatomybut which were caused by other organisms than thetubercle bacillus. Of late a large number of suchdiseases had been described. There were many organismswhich produced similar anatomical lesions to those producedby the tubercle bacillus. These organisms were of widelydifferent character. There were bacilli such as the bacillus

pseudo-tuberculosis, giving rise to caseating tubercles in

many animals ; the bacillus pseudo-tuberculosis murium,causing caseating tubercles in mice; and the bacillus pseudo-tuberculosis liquefaciens, causing tubercles in the peritoneumin the human subject ; and similar lesions in rabbits. Therewere various kinds of streptothrix such as the one describedby Dr. Flexner in the human being. There were also organ-isms which did not belong to the class of bacteria. A form ofmould, the aspergillus, had been described as causing atuberculous lesion in the human lungs and even nematodeworms might produce tubercles consisting of giant cellsand epithelioid cells in the lungs of cats and the

kidneys of dogs. There was a skin disease describedby Gilchrist and Stokes which was of especial interest. Itresembled lupus vulgaris in its clinical aspect but itwas caused, not by the tubercle bacillus, but by a blastomyceswhich they obtained in pure cultivations and which producedin animals by inoculation tubercles consisting of epithelioidcells and giant cells. It was quite probable that many of thecases of so-called tuberculosis of the skin were due to otherorganisms than the tubercle bacillus, as in a case seen latelyin which tubercle bacilli could not be demonstrated eitherby microscopical examination or by inoculation. It was

quite clear that the lesions caused by the tubercle bacilluswere by no means specific, for many organisms might produceexactly the same changes. Again, the lesions produced bythe tubercle bacillus were not constant; sometimes there wasmuch caseation with formation of giant cells, while in othercases there was the production of a granulomatous tissue ;in fact, the tubercle bacillus and the other pathogenicorganisms mentioned obeyed a general law. They set up amore or less chronic form of inflammation the characterof which depended partly upon the virulence of the organ-ism and partly upon the relative susceptibility of the animal.Thus the same pathogenic organism might produce severaltypes of inflammation and the same type of inflammationmight be produced by several pathogenic organisms.The most important lesson to be learnt from thisdiscussion was the importance of making a systematicbacteriological examination of every case in the post-mortem room-a procedure very much neglected in London.

Dr. JAMES GALLOWAY said that Dr. Murray of Glasgowhad described a case in which mycosis fungoides andlater general infection followed a kick from a sheep. Anorganism was isolated which appeared to be a streptothrix.Dr. Galloway also referred to two rare skin diseases. Thefirst, "xanthoma with giant cells,’’ had been called by Unna" pseudo-tuberculosis of the skin." The disease was infectiveand usually appeared first on the lower lid. The giant cellswere arranged in a layer just beneath the epidermis. In onecase several of these tumours formed on the face. Notubercle bacilli could be found in the sections. The secondform of skin disease was characterised by the appearance oftumours over the surface of the body in which giant cellswere present in very large numbers. They closely resem-bled sarcomata but after some months they disappeared asrapidly as they had come. It was clear that histologicalevidence alone could not be relied on for diagnosis, butexperimental evidence from inoculation must be forthcomingas well.

Dr. WOODS HUTCHINSON had several specimens of theconditions which would come under the heading "pseudo-tuberculosis " which he had obtained from the ZoologicalGardens. One was a lung in which the lesion was due to anaspergillus taken from a trumpeter bird and he had met withsimilar specimens in ducks and parrots. It did not appearto be of a very highly toxic character. The other was a

monkey’s lung showing what was known in Germany as" worm knots " and which could be seen to consist of a massof coiled worms, probably either strongyli or niarias. This

monkey also had many thread worms in its peritoneal cavitywhich did not appear to have given rise to any disturbance.On the motion of Mr. SHATTOCK the discussion was

adjourned to March 6th.


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