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of the relation between the basophil cells and thecardiovascular system is as yet unknown.

In recent papers Cushing (1933, 1934) suggests thatbasophilic invasion of the posterior lobe may bepotent in producing the features of his syndromeas well as the clinical conditions of eclampsia andessential hypertension. He was led into puttingforward this suggestion by finding, in addition to abasophil adenoma, an extensive infiltration of the

posterior lobe with basophil cells in a fatal case ofhis syndrome. In neither of our two cases was theamount of such infiltration as great as is often foundin normal subjects. Fig. 5 shows the largest areapresent-Case 2.

Summary(1) The clinical and pathological features are

described of two cases of basophil adenoma of thepituitary gland. (2) The syndrome described byCushing as "pituitary basophilism

" was imperfectly

manifested in both examples, especially in Case 2.

(3) The salient feature in both was cardiovascularhypertrophy. Obesity was present in both, but wasof atypical distribution in Case 2. In the femalethere was moderate hypertrichosis of masculinedistribution. (4) Bright’s disease was the cause ofdeath in Case 1, but in Case 2 cerebral haemorrhagecomplicated essential hypertension and primaryischæmic nephritis of moderate degree. (5) Inneither of our cases was there any abnormal invasionof the posterior lobe by basophil cells. (6) Theassociation between basophil adenoma and cardio-vascular hypertrophy is emphasised, but the natureof the association remains obscure.

Our best thanks are due to Prof. H. M. Turnbullfor his help in preparing this paper, and to Drs. W. W.Woods and A. B. Bratton for the necropsy reports.

REFERENCES

Bauer, J. : Wien. Klin. Woch., 1930, viii., 229.Berblinger, W. : Pathologie und pathologische Morphologie der

Hypophyse des Menschen (Handbuch derinneren Sekretion),Leipzig, 1932, vol. i., 909.

Bishop, P. M. F., and Close, H. G. : Guy’s Hosp. Rep., 1932,lxxxli., 143.

Broster, L. R., and Vines, H. W. C. : The Adrenal Cortex ;a Surgical and Pathological Study, London, 1933.

Craig, J., and Cran, Brennan: Quart. Jour. Med., 1934,n.s. iii., 57.

Cashing, H. : Bull. Johns Hopkins Hosp., 1932, l., 137.,, ,, : Arch. Internal Med., 1933, li., 487.,, ,, : Amer. Jour. Path., 1933, is., 539.,, ,, : Ibid., 1934, x., 145.

Kepler, E. J. (1933) : Vide Wilder, R. M., &c.Kepler, E. J., Kennedy, R. L. J., Davis, A. C., Walters, W.,

and Wilder, R. M. : Proc. Staff Meet., Mayo Clinic, 1934,ix., 169.

Kraus, E. J. : Med. Kiln., 1928, xxiv., 623, 662.Leyton, O., Turnbull, H. M., and Bratton, A. B.: Jour.

Path. and Bact., 1931, xxxiv., 635.MacMahon, H. E., Close, H. G., and Hass, G. : Amer. Jour.

Path., 1934, x., 177.Moehlig, R. C. : Jour. Amer. Med. Assoc., 1932, xcix., 1498.Russell, D. S. : A Classification of Bright’s Disease, 1929,

Med. Research Council, Spec. Rep. Ser. No. 142.Teel, H. M. : Arch. Neurol, and Psychiat., 1931, xxvi., 593.Vaughan, Janet : The Anæmias, London, 1934, p. 3.Wilder, R. M., Kernohan, J. W., Parker, H. L., Kepler, E. J., and

Walters, W. : Proc. Staff Meet., Mayo Clinic, 1933, viii.,97. (Case 2, p. 103 ; Case 4, p. 105.)

BAD NAUHEIM: INTERNISTEN CONGRESS.—Over ahundred people took part in the Internisten Congressheld recently in Bad Nauheim, among them being doctorsfrom Spain, Sweden, Bulgaria, and Japan. The visitorswere received by Dr. Diehl in the name of the Reichs-statthalter. The director of the Balneological Institutedemonstrated some heart sound films, showing that bymodern methods it is possible to find out changes ofheart sounds much more exact than formerly, the changesbeing laid down in a curve, so that the improvement ordeterioration in the course of a year can be observed. Theguests also visited the William Kerckhoff Institute, wherethe director, Prof. Koch, explained to them the workingmethods employed for the investigation of cardiac disease.Entertainment at the Johannisberg concluded the visit.

SOME POINTS IN THE

TREATMENT OF RHEUMATIC DISEASES *

BY CHARLES W. BUCKLEY, M.D., F.R.C.P. Lond.PHYSICIAN TO THE DEVONSHIRE ROYAL HOSPITAL FOR

RHEUMATIC DISEASES, BUXTON

THE infective origin of rheumatic fever and rheu.matoid arthritis is now generally admitted, but theprecise mode in which the infective agent sets upthe disease is believed to be much more complexthan was supposed. While some strain of hæmolyticstreptococcus probably plays an important part itseems probable that other organisms may be capableof producing a symptom complex clinically indis-tinguishable from that attributed to the strepto-coccus, or may be associated with it. Gibson andThomson after a searching investigation arrived atthe following conclusions : Acute rheumatism isdue to some infective agent not yet defined, whoseentry into the body may be facilitated by infectionwith haemolytic streptococci. A possibility is thatthe late allergic manifestations of streptococcal’infection may damage the tissues susceptible torheumatic infection and facilitate generalisation ofthe specific agent." Continuing, they say : "Sucha theory correlates (1) the close epidemiologicalassociation of the haemolytic streptococci with acuterheumatism, and (2) the widespread distribution of

hæmolytic streptococcal infection and the com-

paratively limited distribution of acute rheumatism."These observations apply with equal appropriate-

ness to rheumatoid arthritis which is undoubtedlydue to some infective agent not yet precisely iden-tified, whose entry into the joints may be renderedpossible by allergic effects set up by a focus of infec-tion elsewhere either by the same microbe or by others.In expressing this view I am not unaware of thework of Cecil, Nicholls, and Stainsby 2 among otherswho have isolated from the blood by culture a

streptococcus, and claim to have set up arthritis byits inoculation into animals. -

INFECTION AND HYPERSENSITIVENESS

In a large proportion of cases of rheumatoidarthritis a septic focus can be discovered. ’Fromsuch a focus absorption of toxic bacterial productsgoes on, and the toxins gradually sensitise the tissuesuntil a point is reached at which rheumatic symptomsdevelop-whether by reason of the further action ofthe toxins themselves or by actual bacterial invasionhas yet to be demonstrated. It follows that theseptic focus should be removed at as early a stageas possible if it can be identified, but never in sucha way as to flood the system with toxins ; for anacute outbreak of arthritic symptoms has not infre-quently been known to follow wholesale extractionof teeth or tonsillectomy. A course of desensitisingtreatment by means of minute doses of a suitablevaccine may serve to avert such a catastrophe.

In such septic foci usually several different microbesare found, and even though it may some day beproved that certain types of arthritis are invariablyassociated with the presence of one definite organism,it is probable that the toxins of some prepare theway for others. Swift, Derrick, and Hitcheock,3who have done much important work on this subject,state that inoculation with non-haemolytic strepto-

* Abstract of a lecture given before the Furness Division ofthe British Medical Association.

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cocci produces a hyperergic condition and increasedsusceptibility, not only to the same strain but alsoto more distantly related strains ; possibly, one mayadd, to entirely different microbes also.The view has long been held on the continent

that there is a type of rheumatoid arthritis whichis tuberculous in origin but much of the evidencehas been unconvincing. Positive reactions to suchtests as those of von Pirquet and Mantoux mayeasily be due to latent tuberculous foci in glandsor elsewhere, and the isolation of tubercle bacillifrom the blood in cases of acute polyarthritis by themethod of Reitter and Lowenstein has generallybeen unsuccessful in other hands. Recently, how-ever, some cases have been published in whichaffected joints diagnosed clinically as rheumatoidarthritis have been opened and synovectomy hasbeen performed, histological examination has demon-strated tuberculosis, and culture has in some casesbeen successful. 4 In two cases of my own of chronicpolyarthritis I have found tubercle bacilli in theeffusion from the knee-joints. It is stated that insome cases filter-passing types of the bacillus ofKoch of low virulence have been isolated, which oninoculation into guinea-pigs have set up a tuberculousadenitis but not a general tuberculosis.

It cannot be denied that the constitutional type,and the symptoms apart from the actual arthritis,in many cases are similar to tuberculosis. There isalso the possibility that a chronic tuberculous focusin the glands or elsewhere can sensitise the tissuesto and thus favour infection by streptococci, but itseems more probable that the sensitisation of thetissues is set up in the first case by streptococcalinfection and infection by tubercle follows.The sensitisation of the tissues brought about by

the absorption of toxins from a focus elsewhere inthe body is of great importance, inducing an allergiccondition. Rich 5 defines allergy as that state of

specific hypersensitivity which develops as a resultof the entrance of foreign protein into the tissues-with local tissue damage wherever the foreign proteinor a fraction (haptene) lodges in the sensitised tissue,and constitutional symptoms when the protein towhich the body is sensitised enters the blood stream.Some writers do not draw a distinction between

allergy and anaphylaxis, and the whole problem isdifficult and confusing ; but while sensitisation is

generally believed to be a stage in the developmentof immunity, Rich has shown that it is possible toseparate the two processes. Acquired immunity isan ability to inhibit the growth and invasion ofbacteria whose toxins have been the sensitisingprotein, and to neutralise these toxins. There maybe such a degree of immunity as can cope with asmall invasion, but an extensive extraction of teethor a tonsillectomy may release more of the specifictoxin or organism than can be dealt with, or sensitive-ness may be heightened by injudicious vaccinetherapy or otherwise, and fresh invasion takes placefrom the original focus or from secondary foci.Hypersusceptibility may of course result from

other causes-climatic conditions to which theindividual is ill-adapted, by no means the same foreveryone ; malnutrition from lack of suitable food,under which heading may be included vitamindeficiencies ; overwork or severe nervous or emotionalstrain, such, for example, as often results from longnursing of a sick relative ; shock ; endocrine defi-ciency ; bad hygienic conditions at home or in theworkshop ; and many others. All these conditionsmay be regarded as sensitising factors in the widestsense.

USE OF VACCINES

The specific treatment of the hacterial factor hasbeen the object of much research both at the bedsideand in the laboratory. Treatment by vaccines hashad a great vogue, and is based on the assumptionthat by the administration of a suspension of a

microbe believed to cause the disease we might raisethe resistance of the body and thus enable it toovercome the infection. While overwhelming clinicalevidence of the value of this procedure in securingprophylaxis is forthcoming no such claim can beadvanced for it as a method of treatment, and asTopley 6 says, "the practice of vaccine therapyrests on a very inadequate basis of experimentalevidence." As a method of treatment it has beenmore extensively used in chronic rheumatic diseasethan in any others, with the exception perhaps oflocal staphylococcal lesions where the conditions aredifferent. To the ordinary observer it seems illo-

gical, when the system is already invaded by somemicrobe, and has presumably mustered all its defen-sive forces to combat the invasion of the bacteriaand to neutralise their toxins, to inject further dosesof the same toxins. And yet good results haveundoubtedly followed such treatment in some cases,though I fear more cripples than cures have resultedfrom indiscriminate and injudicious vaccine therapy.To what, then, are the successes to be attributed ?It may be that the amount of toxin or bacteriaabsorbed from the septic focus is insufficient torouse the whole of the defensive forces of the body,and the vaccine produces a further or more powerfulstimulation ; but, on the other hand, the risk of

sensitising the tissues further is a very grave one,and in consequence dosage must be extremely smallto begin with if it is thought desirable to use suchtreatment. A vaccine administered in very smalldoses at suitable intervals, or in such a way as tosecure very slow absorption as by the intradermalmethod, appears to act not by stimulating antibodyformation but by inducing desensitisation.An example of this method of desensitisation is

found in the prophylaxis and treatment of hay-fever and asthma-typical allergic states-by theinjection of minute doses of the protein or othersubstance to which the victim is susceptible. Itdoes not appear essential for desensitisation thatthe vaccine should be autogenous, and as proof is

yet lacking as to the exact nature of the infectingorganism it seems hardly justifiable to speak of anautogenous vaccine if by that it is claimed to be avaccine of the infecting microbe. All that can besaid is that it contains some of the microbes fromthe patient’s own focus, and may therefore be moreeffective in desensitisation in the particular case.

The intradermal use of vaccines for desensitisationhas been tried, particularly in France, with somepromising results. The method has three features-slow absorption of minute doses of a mixed antigen ;the stimulation of the deeper layers of the dermis toproduce antibodies, which some regard as a pointof importance ; and polyvalency with the inclusionof tuberculin which is regarded as a universal non-specific antigen-and this may be the most importantfeature. The possibility of a tuberculous basis insome forms of arthritis to which reference has alreadybeen made receives support from the good effectswhich I have known to follow treatment by thismethod. It is necessary to study the effects care-fully, increasing the intervals gradually, especiallyif there is reason to suspect the existence of tuber-culous foci, active or latent, in the system. If there

248

is no sign of benefit after three or four inoculationsit is better to try some other method, but I havenoted in several cases marked improvement mani-fested by a rise in the sedimentation-rate as well asin the general symptoms. A course of ten or fifteeninoculations seems to be the best. followed, if neces-sary, by chrysotherapy.

This method of using vaccines as desensitisingagents has the advantage of being reasonably freefrom risk, but none the less requires care, and it isdesirable that a chart of the temperature should bekept and the character of any reaction noted care-fully upon it ; with such precautions the dose maysteadily be increased, but any sign of increasingreaction without a proportionately increased dosecalls for a temporary cessation of the treatment orthe trial of some other method. In my opinion, thesuccess which is claimed for a vaccine which is sup-plied commercially, and has attained considerablepopularity for the undoubtedly good effects whichhave resulted in many cases, is due to its action as adesensitising agent.

In regard to the intradermal use of a vaccine, theobservation of Auer is of interest ; he found thatinjury to the skin of a sensitised animal when antigenwas in the circulation might produce a local reactiondue to the actual excretion of sensitinogen into theinjured area. Jenkins 8 has suggested that fromthis observation it may be inferred that once a jointis damaged a more or less continuous irritation isset up by the antigen in the blood, and a viciouscircle is started which can only be broken by theremoval or neutralisation of the circulating antigen.The use of vaccines in the ordinary way is believed

by some to be simply a form of protein shock therapy.However produced, so-called protein or peptoneshock sets up an anaphylactoid reaction differing insome details from true anaphylactic shock ; but theresemblance to the shock effect produced by antigen-antibody reaction is striking. This is due to theliberation of a histamine-like substance, and theinfluence of histamine in the treatment of arthritisis receiving considerable attention. As a localmethod it has proved of definite value.

REFERENCES

1. Gibson, H. J., and Thomson, W. A. R. : Edin. Med. Jour.1933, xl., 93.

2. Cecil, Nicholls, and Stainsby : Jour. Exper. Med., 1929, l.,617.

3. Swift, Derrick, and Hitchcock : Jour. Amer. Med. Assoc.,1928, xc., 906.

4. Cooperman, M. B. : Ann. of Surg., 1932, xcvi., 1065.5. Rich, A. R. : THE LANCET, 1933, ii., 521.6. Topley, W. W. C. : Outline of Immunity, London, 1933.7. Auer : Quoted by Jenkins (ref. 8).8. Jenkins, C. E. : Brit. Med. Jour., 1934, i., 186.

BACILLARY DYSENTERY OF THE

NEWCASTLE TYPE

BY HENRY WHITEHEAD, M.D. Manch., D.P.H.MEDICAL OFFICER OF HEALTH, WIGAN

With a Note on the BacteriologyBY W. M. SCOTT, M.D. Edin.

A MEDICAL OFFICER OF THE MINISTRY OF HEALTH

ON Jan. 15th, 1934, Dr. R. J. Ormsby, medicalofficer of health for Standish, called at my officeand asked me if I would admit to the Wigan InfectiousDiseases Hospital two cases of probable food-

poisoning. He informed me that four people had been

affected in one house in his district, a mother andher three children. The two children referred byDr. Ormsby for admission had partaken of cornedbeef none of which was left for examination. Themother and the other child had not partaken of it.This third child, a boy, J. S., aged 12, had been sentto the Wigan Infirmary with marked cerebral symp.toms in addition to frequent vomiting, abdominalpain and diarrhoea. He had a history of havingfallen on his head a week before and, as the cerebralsymptoms pointed to possible compression, he wastrephined. He died on Jan. 15th, and post mortemmarked inflammation of the intestinal tract wasfound. I advised Dr. Ormsby to call at the localinfirmary and ask Dr. W. E. Cooke, the pathologistto this institution, if he would kindly forward toDr. W. M. Scott, of the Ministry of Health, specimensof liver, kidney, spleen, stomach and intestines fromthe case according to the recommendation of the

Ministry of Health in cases of possible food-poisoning.This material was sent as requested.The other two children were admitted to the Wigan

Infectious Diseases Hospital on Jan. 15th, 1934. The

boy, F. S., aged 8, was extremely ill on admission withvery frequent vomiting, abdominal pain, diarrhoea andsymptons of cerebral irritation. His temperature rose to103° F. on the second day and there was some deliriumand violent headache. His colour was poor and his pulsevery weak, with sighing respiration. He still complainedof severe abdominal pain and there was much abdominaltenderness and rigidity. The vomit was very offensiveand the stools, green and very foul smelling, showedoccasionally mucus with traces of blood.The other child, a sister, E. S., aged 11, was not so

acutely ill on admission but had had very similar symptomsbefore that. She complained of severe headache but thevomiting and diarrhoea had subsided ; there was somemucus in her stools. She made a rapid recovery.The treatment was symptomatic together with rectal

salines and glucose. Six days after admission the boy,F. S., had completely recovered. Specimens of his vomitand fseces were sent to Dr. Scott and specimens of hisblood and that of his sister a fortnight later for agglutinintests.

There is no evidence that any particular article offood conveyed the disease ; no other similar casesare known to have occurred in the neighbourhoodOne may hazard the guess that the source of infectionof this family may have been an undiscovered carrier.

Note on the Bacteriology. (By Dr. SCOTT.)The colon of J. S. received on Jan. 18th showed

definite congestion with minute haemorrhages in themucosa.

MacConkey plates inoculated with scrapings fromthe mucous surface yielded only one non-lactose-

fermenting colony (among many typical coli colonies).With the faeces from F. S., however, MacConkey plateswere obtained showing numerous non-lactose-fer.

menting colonies. The two strains thus isolated,J. S. and F. S., behaved exactly alike in culture ;they were non-motile, produced no indole andfermented dextrose and dulcitol but not lactose,sucrose or mannitol. The dextrose fermentation wasevident after 24 hours but the dulcitol not till afterfive days at 37° C. With both "sugars " a smallbubble of gas was produced as well as acid. Agglu-tination tests were negative with sera of the salmonellagroup and of the Flexner and Sonne dysentery types,but were positive to full titre (1600) with serum pre-pared with a strain of the Newcastle bacillus describedby Clayton and Warren,’ as well as with sera preparedwith strains, regarded as serologically identical,isolated (1) by Downie and Wade 2 near Manchester,