305

Discussion

The foregoing observations indicate that, contrary toprevious animal experimental work (McClean et al.), it isnot easy to demonstrate lecithinase or hyaluronidase inhuman infections with Cl. welchii. In only 4 cases werepositive lecithinase reactions observed, and in 3, sincethe material was obtained post mortem, the productionof toxin after death cannot be excluded. The reactions,moreover, were too delayed to be of any practical valuein the diagnosis and treatment of the disease in the living.It must be admitted, however, that our technique forextraction of infected tissue is not identical with thatemployed -by McClean. At the outset, McClean’scalcium borate buffer (pH 7-2) was used, and with it weobtained negative results from 2 fatal cases of gas-gangrene due to Cl. welchii in which no antitoxin hadbeen given. Later a more alkaline calcium borate buffer(pH 7 -8) was adopted. At the pH of both these bufferscalcium phosphate is precipitated, and, as alreadyindicated, toxin present during its precipitation will beadsorbed. We feared, therefore, that the techniqueused might have removed the lecithinase we were seekingif appreciable amounts of soluble phosphate were beingextracted from the muscle samples. But later experi-ments suggest that this is an improbable explanation ofour negative findings as compared with McClean’sresults in animals, unless the amount of phosphateextractable from gas-gangrenous muscle is much greaterthan normal. Dr. M. G. Macfarlane informs us thatthe phosphate content of affected muscle is, in fact,abnormally low, and her data are largely based onmaterial obtained from cases in the present series.

It appears more probable that any lecithinase pro-duced in the natural infection is rapidly fixed or removedin vivo. This is certainly ,true for lecithinase injectedinto rabbits. We have made many attempts to liberateany lecithinase so fixed in human material, but withoutsuccess. Finally, although we have obtained negativeresults in the absence of antitoxin, most of our cases had,in fact, received it ; and this is a factor that must beborne in mind when the merits of a diagnostic test

depending on free toxin are being considered.Of greater practical interest is the fact that in 9 cases

an excess of antitoxin in the blobd-stream for anythingup to 92 hours before death has failed to prevent a fataltermination to the disease. It is significant that in allthese cases the lesions were such that the surgeon wasunable to remove all the affected muscle at the time ofoperation, and that there was evidence that the localdisease had extended during the period of serum therapy.Therefore it must be concluded (a) that circulatingantitoxin is incapable of arresting the local spread ofgas-gangrene, and (b) that circulating antitoxin will notprevent death, apparently from toxæmia, as a result ofthis local infection. a

In connexion with the first conclusion, it is possiblethat the low antitoxin titre that we have observed innormal muscle may explain the failure of serum therapyto prevent the local spread of the disease. Antitoxinhas been shown to be present in much greater amountsin the exudate and in dead muscle, but the toxin willalso diffuse into normal muscle, presumably destroyingit and producing a further nidus for invasion by theclostridia themselves. The presence of antitoxin behindthe advance of the infection is of no benefit to the patient.With regard to the second conclusion-that antitoxin

will not of itself prevent death from toxæmia—thequestion at once arises whether death is due to the pro-ducts of tissue breakdown rather than the direct actionof bacterial toxin. And this is a problem which can bemore profitably discussed in the next paper.

SummaryBy the lecitho-vitellin reaction it is possible to make

sufficiently reliable titrations of alpha-toxin of Cl.welchii and its corresponding antitoxin for observationsin the field.As diagnostic procedures in early gas-gangrene neither

the lecitho-vitellin nor the hyaluronidase tests haveproved satisfactory.

, In 27 cases of gas-gangrene-almost all caused byCl. welchii-free alpha-toxin has been detected in 4.In only one instance, however, was a positive reactionobtained with material taken during life.

The possibility that the profound toxæmia of gas-gangrene is not due solely or even primarily to alpha-toxin has been discussed.

REFERENCES

Glennie, A. T., Hopkins, B. E. (1922) J. Hyg. Camb. 21, 142; (1923)Ibid, 22, 12, 37, 208.- Waddington, H. (1929) J. Path. Bact. 32, 275.

McClean, D.. Rogers, H. J. (1944) Lancet, ii, 433.- - Williams, B. W., Hale, C. W. (1943) Ibid, i, 355.

Macfarlane, R. G., Oakley, C. L., Anderson, C. G. (1941) J. Path.Bact. 52, 99.

Medical Societies

ASSOCIATION OF CLINICAL PATHOLOGISTS

THE summer meeting of this association was held inLondon on July 20 and 21, with Dr. ERIC WORDLEY,the president, in the chair. ’

Prof. J. H. DIBLE spoke on the pathology of infectivehepatitis with special reference to hepatic biopsy. Afterdemonstrating the method of liver puncture by the trans-pleural route with suction of a small piece of liversubstance into the cannula by means of an attachedsyringe, and describing the alcohol-free fixation topreserve glycogen, and the staining used, he produced aseries of slides illustrating the histological appearances ininfective hepatitis. The essential features were rare-faction at the centre of the lobule with derangement ofcolumns of cells, the appearance of bizarre forms withswollen cells associated with a cellular infiltration of thebile-ducts, and generally a reduction in the width ofthe lobule. There was, however, good -retention of thereticulin arrangement of the liver lobule. Dr. Dibledemonstrated varying degrees of these changes in variousforms of jaundice, including infective jaundice, serumjaundice, and neoarsphenamine jaundice, and suggestedthat the icterogenic agent was similar and that the toxicpathological changes seen after biopsy were also similar.

Major C. E. VAN RooyEN described the rapid diagnosisof smallpox by demonstration of elementary bodies fromthe vesicles. From his experience of several hundredcases in the Middle East he maintained that this was asimple matter and their recognition to a trained observerwas reliable. The findings had been proved correct inseveral cases in which they were doubted because at firstthe clinical appearances were atypical. A second paperdealt with rickettsial agglutination tests in typhus.

Prof. A. D. GARDNER read a paper on the laboratorydiagnosis of Weil’s disease. He had investigated materialfrom 900 suspected cases and had found 150 positive.From his records it was clear that -jaundice was notalways present and that the non-icteric cases probablyhad a better prognosis. Case-mortality in the seriesdiffered with age ; in old people it was 50% but in

young people only 5%, the overall mortality being 12%.The agglutination tests had been carried out withformolised suspensions of the leptospira which had beengrown in 12% rabbit serum in glass-distilled water.These suspensions had remained stable iri his hands foryears. Dr. Gardner expressed the hope that now thatpenicillin shows such great promise in the treatment ofthe disease, attempts at diagnosis will be made earlierin the disease without waiting for jaundice, which some-times occurred in this series as late as the 8th or 9thday, although it was commonest on the 5th.

Squadron-Leader E. M. DARMADY’S paper on the trau-matic urœmia syndrome produced an excellent discussionin which various contributors showed how the syndromewas produced by many factors, including trauma, crush,and severe transfusion reactions, all of which gavesimilar histological appearances in the kidneys. In thisdiscussion Dr. JOAN Ross described cases of anuria shehad collected from the battle areas.

Dr. G. R. OSBORN dealt- with the action of thiouracil ongoitres and showed a series of sections demonstrating themain changes. Macroscopically the tumour was oftenhard, pure white, with no appearance of colloild-verysuggestive in appearance of carcinoma. Even micro-scopically the changes frequently included large cellswith hyperchromatic nuclei which also might be mistakenfor a carcinoma. Dr. Osborn agreed that thiouracil was.now the best preoperative means of treatment in thediffuse toxic goitre.

306

Dr. W. H. GRACE described a long series of cases ofsudden death in infancy, and explained the difficultieswith which even an experienced forensic pathologistmight be faced when presented with a " dead infant."Asked whether he believed in status lymphaticus heanswered that he regarded this as the fifth ace, to be keptup the sleeve for special emergencies.

Papers were also read by Dr. M. 0. SKELTON, whodemonstrated fatal tracheo-bronchial diphtheria in aninfant of five weeks. Dr. R. A. 0. WILLIAMS spokeon the value of preliminary fluid culture for the isolationof pyogenic cocci when a larger yield is desired: Dr. A. F.SLADDEN spoke on the roictme examination for diphtheria,using a tellurite-Loeffler medium which he claimed as -asimple and effective substitute for the elaborate medianow in use. Dr. K. B. ROGERS described a method ofsuspending sedimentation tubes in a jar of water at acontrolled temperature because of the discrepancieswhich occurred as a result of temperature variations inthis test. A discussion was opened by Dr. E. N. DAVEYfollowed by Dr. S. C. DYKE on the investigation of theallergic state. Some doubt was thrown by followingspeakers on the value of skin tests in demonstratingsensitivity, but generally it was held that they are ofgreat value in indicating particularly single-allergensensitivity.The meeting ended with a paper by Dr. H. N. STAFFORD

on the corpse, the pathologist, and the coroner. Expound-ing the duties and limitations of the pathologist in regardto the coroner, he gave his interpretation of the 1887Coroners Act with the amending act of 1926. He madeit clear that a pathologist may make a post-mortemexamination if he considers, or is told, that the death isdue to natural causes, and that in any case no

" assault "can be committed on a corpse by so doing. The over-riding consideration was that there should be cooperationbetween the medical men and the coroner, and thecoroner must certainly not be obstructed in his duties.

During the two days there were also many demonstra-tions which were well attended. At the society’s dinnerthe guests included Major-General L. T. Poole (directorof pathology, War Office) and Professor Gardner.

Reviews of Books

Index of Differential Diagnosis of Main Symptoms(6th ed.) Editors : HERBERT FRENCH, CVO, CBE, DM OXFD,FRCP ; ARTHUR H. DOUTHWAITE, MD LOND., FRCP.

(Wright. Pp. 1128..E4 4s.)THERE is an old-world charm about this reference book

that places it in a category by itself. It recalls thosespacious pre-1914 days when top hats and frock coatswere still de rigueur and the clock was not the tyrant ithas since become. Merely to delve into the index is apleasure : ’‘ bilberries, melsena due to"; " flatulence,inflammable gas in " ; "-Turkish-trouser disease." Howmany modern practitioners could give the six tests fordeath mentioned here or the 47 causes of haemoptysis ?On the other hand, it is surprising to find neither Grocco’snor Graham Steell’s names among the " Proper Names

"

indexed. Subsultus tendinum is another unexpected omis-sion. Dr. Douthwaite has assisted the veteran senioreditor in the preparation of this edition, but obviously theprinciple that has been adhered to is that nothing old ofvalue should be discarded in favour of what may proveto be transitory among recent advances. It is typicalof the book that twelve of the nineteen contributorsshould be of the generation that has either

" passed on "or is now on the consulting staff of our medical schools.The young may scoff at such a work; yet with experiencethey will sooner or later realise that a book like this is anessential occupant of the library of every doctor. Agecannot wither nor custom stale its infinite variety.Handbook of Physiology and Biochemistry

(38th ed.) R. J. S. McDowALL, MD, D so, MRCP. (JohnMurray. Pp. 898. 25s.) -

IN spite of its gradual evolution this book retains itsessential character of treating the field of biochemistryand physiology which the medical student is expectedto cover in a reasonably short space. It is somewhatdidactic and although references to authoritative workshave now been introduced it is questionable whether the

reader’s curiosity will be aroused sufficiently to make himlook them up. However, the problem of how to makemedical students think about physiology, instead oftrying to

" learn " it, is a difficult one, and perhaps oneshould not expect to find the solution in a textbook.The author has improved the illustrations in thisthoroughly revised edition.Man and His Fellow Men

SAMUEL LowY, MD PRAGUE. (Kegan Paul, Trench,Triibner & Co. Pp. 194. 15s.)

THE sub-title of this book is " Modern Chapters onSocial Psychology," but there is a wide gap betweenDr. Lowy’s approach and that now customary inAmerican and English schools of social psychology. Hebases his study on the observations he made whilepractising as a psycho-analyst in Czechoslovakia andother European countries : his book is reflective andliterary rather than scientific, and discursive rather thanexact. The humane dispassionate tone of the writingattests the author’s sincerity and his medical outlookupon the troubles of human conduct. Many readerswill, however, agree with Mr. Herbert Read who, in anintroduction, takes exception to Dr. Lowy’s opinion thatmen need to be guided and compelled by an externalsuperior authority, the State, if they are to arrive at thehigh intellectual and moral achievements of which theyare capable. At’the end of his book Dr. Lowy has achapter,

" Suggestions on General Reform," which putsthis doctrine in persuasive form ; he would have theState insist on tolerance and " social decency," so thatit would penalise exploitation, bullying, and prejudice.But perhaps he trusts the State, that headstrong instru-ment and master, too much.

New Inventions

APPLICATOR FOR PENICILLIN CREAM

A SATISFACTORY method has been devised for theintroduction of penicillin cream, into the depths of smallabscesses of the fingers. The cream is contained in apiece of glass tubing about 5 cm. -long and 5 mm. ininternal diameter. One end of the tube is plugged withcotton-wool, andthe cream is ex-pelled from thetube by pushingon the cotton-wool with anordinary woodenswab-stick. Theopen end of thetube should beslightly turned in, by holding it in a flame for a few seconds,so that the cotton-wool plug cannot be pushed into thewound. It is convenient to put up each tube with onewooden stick in a wide-mouthed I-oz. screw-capped bottle.The bottle, containing the glass tube, plugged at one

end, and the stick, is autoclaved ; the penicillin cream(or ’ Penagar ’ if preferred) is introduced into the tube,lying flat in the bottle, from a serum syringe fitted witha wide-bore aspiration needle. When Lanette wax’creams are used, it is best to have the cream base dis-pensed and sterilised in the barrel of the syringe and’tomix the penicillin solution with it in the barrel. Penagaris sufficiently fluid to be sucked up into a syringe aftermixing in a bottle. It is important to store the tubesin a horizontal position, as otherwise the cream. tends torun out ; with penagar it is particularly important tokeep the tube horizontal until the agar has set.

For use, the tube and stick are tipped out into asterile dish ; the open end of the tube is inserted intothe wound, and the cream is expelled by pushing withthe stick on the cotton-wool plug at the other end.The advantages of the method are : (1) the cream

can be introduced into the depths of the wound ; (2)the dosage can be easily controlled ; one tube holdsabout 0-5 c.cm. of cream, but more than one can be usedfor large abscesses ; (3) there is no risk of contaminationof the cream, as is liable to happen if more than one dose istaken from a container; and (4) there is very little waste. ,

Tube and stick contained in bottle.

R. E. O. WILLIAMS, M D, B SC LOND.Medical Research Council Wound Infection Unit,

Birmingham Accident Hospital.