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CENTENARY OF ST. MARY’S

St. Mary’s Hospital Medical School celebrates the

centenary of its foundation next month. It was, exceptfor the Royal Free School of Medicine, the last ofthe London undergraduate schools to be founded.When it came into being modern medicine was in its

infancy. The old system of apprenticeship combinedwith a short period of " walking the hospitals

" had

only lately been replaced by a prescribed course of studyand a compulsory period of hospital practice ; and nottill 1858, when the first Medical Act came into force,were those who wished to practise medicine required toobtain a recognised degree or diploma. The story of thegrowth of the school, and of the many triumphs ofits research-workers—among them Augustus Waller,Almroth Wright, Leonard Colebrook, and SirAlexander Fleming-are recorded by Sir ZacharyCope in a commemorative volume published lastweek.!

In 1830 Samuel Armstrong Lane, a surgeon andanatomist of wide experience, established a school of

anatomy near St. George’s Hospital which developed intoa complete medical school recognised by the newly formedUniversity of London. Its students did their clinicalwork at the nearby St. George’s ; and the project soonran into difficulties, as a rival school was started bvSt. George’s itself in 1836. Fortunately for Lane wide-spread development in Paddington called for a new

hospital in that area. He and three of the teachers fromhis school secured positions on the staff of this hospital,and funds for the erection of an associated school ofmedicine were quickly raised. The school, recognised byLondon University, opened in October, 1854, with justunder twenty students. At first only fifty beds wereavailable in the hospital for teaching; but within a yearthere were 150, and by 1867 the number had risen tonearly 200. The hospital continued to grow, and .withits associated hospitals it now provides over 800 bedsfor teaching.

’

The school was for a time less fortunate than the

hospital. When the 1914-18 war ended both its staffand its intake of students had been depleted, and itsfinancial position was precarious and the buildings wereout of date. This was the situation when, in 1920, Dr.Charles Wilson (now Lord Moran) was elected dean.Under his leadership not only was closer contact with theuniversity established and a higher standard of teachingsecured, but also funds were raised for the erection of thepresent commodious and well-equipped buildings, whichwere opened in 1933.When the school had started in 1854 all the subjects,

except chemistry and natural philosophy, were taughtby clinicians. One of the first full-time lectureships wasin physiology, and the post was first held by AugustusWaller. It was in a laboratory at the school that Wallerin 1887 demonstrated the electrical reactions of thehuman heart, thus laying the foundation of modernelectrocardiography. In 1902 Almroth Wright joined thestaff as bacteriologist and pathologist and built up a

department that was to be famous, first as the birthplaceof vaccine therapy, and, later, through Fleming’s dis-covery of penicillin. In the past thirty years the numberof university chairs in the school has steadily increased ;and the departments of medicine, surgery, pathology,bacteriology, chemical pathology, physiology, anatomy,and biochemistry are now all controlled by full-timeprofessors.

1. The History of St. Mary’s Hospital Medical School, or a Centuryof Medical Education. By Sir ZACHARY COPE. London:Heinemann. 1954. Pp. 257. 25s.

NATURAL IMMUNITY

RESISTANCE to infections is due to many factors, someof which are remarkably independent of physiologicalinfluences but remain the characteristic of the individualand his previous history. The blood-stream of the younginfant contains antibodies transmitted from the mother ;but these are lost within a few months, since no mechanismexists for their renewal. Even in the absence of obviousillness some immunity develops during childhood owingto exposure to subelinical infections. Such immunity islacking in some isolated communities from which infectiveagents are absent, and the introduction here of an

infection which in densely populated areas would havetrivial effeets may cause a major epidemic. Some non-specific immunity to infection is due to the white blood-cells, which dispose of many micro-organisms that findtheir way into the blood-stream ; and many tissues andsecretions contain lysozyme, which kills some bacterialinvaders. The presence of other non-specific immuneagents has long been suspected, but no-one is quite surewhy an animal such as the rat is apparently so much moreresistant to infections than the guineapig. Some experi-ments by Pillemer and his colleagues 1 may provide anexplanation.By a rather complicated process, based on previous

work with complement, these workers have isolated fromblood-serum a protein fraction which they call properdin(from perdere, to destroy). Properdin is a globulin of

high molecular weight, at least eight times greater thangamma-globulin ;* it is a euglobulin iiTsoluble in waterand represents less than 0-03% of the total serum-

protein. It is not a component of the hæmolytic comple-ment system of blood, although it requires the presenceof complement- for its activity ; but, on the contrary,in conjunction with a polysaccharide residue from yeast,it destroys the third component of complement. Properdinparticipates in various of the bactericidal, virus-neutralis-ing, and hæmolytic activities of blood-serum which arenot due to specific antibodies. Perhaps the most signifi-cant fact about properdin is its distribution amongdifferent animal species. The serum of the relativelyresistant rat contains between 25 and 50 units per ml.,whereas the serum of the susceptible guineapig containsonly 1-2 units ; human serum, containing 4-8 units perml., is intermediate. The natural resistance of the cowand pig is usually regarded as greater than that of sheep,and their serum-properdin levels are somewhat higher.These serum-properdin determinations have been madeby measuring the bactericidal effect on dysentery bacilli,but there is no information yet about its effect on otherinfective agents. It is difficult as yet to assess the roleof properdin in resistance to infection, and it is not easyto forecast whether it may prove of value in treatment orprophylaxis ; immunologists and protein chemists willcertainly want to find out more about this interestingserum-protein fraction.

Other recent work indicates the possible importance ofimmunity not due to the production of specific anti-bodies. Evans and Perkins 2 find that a single intra-peritoneal injection of pertussis vaccine produces in micewithin a few hours substantial immunity to an intra-cerebral infection of virulent Hœmophilus _pertussis.This immunity is not due to the presence of circulatingantibodies-indeed it appears long before antibodiescould be formed-and yet the effect is specific for

pertussis vaccine. Possibly such immunity may be

comparable to the interference type of resistance con-ferred by some viruses, in which immunity sometimesseems to be associated with a continued latent virusinfection rather than with antibody formation ; thepresence in cells of the latent virus apparently excludes1. Pillemer, L., Blum, L., Lepow, 1. H., Ross, O. A., Todd, E.,

Wardlaw, A. C. Science, 1954, 130, 279.2. Evans, D. G., Perkins, F. T. Brit. J. exp. Path. 1954, 35, 322.

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infection with some other virulent infective agents. Forinstance, vaccinia virus has been reported 3 to induoeresistance in mice to intracerebral infection with H.

pertussis. Whether such immunity is confined to certainintracerebral infections is still unknown.Knowledge that resistance to infection is generally

associated with the presence of circulating antibodiesdoes not exclude the possibility that other immunemechanisms may prove important.

3. Dalldorf, G., Cohen, S. M., Coffey, J. M. J. Immunol. 1947,56, 295.

4. Morrow, J. D., Schroeder, H. A., Perry, H. M. jun. Circulation,1953, 8, 829.

5. Dustan, H. P., Taylor, R. D., Corcoran, A. C., Page, I. H.J. Amer. med. Ass. 1954, 154, 23.

6. Lindauer, M. A., Hafkenschiel, J. H. Cited by Turner andLansbury (footnote 4).

7. Turner, L. W., Lansbury, J. Amer. J. med. Sci. 1954, 227, 503.

A DRUG-INDUCED RHEUMATIC SYNDROME

ADMINISTRATION of 1-hydrazinophthalazine hydralla-zine hydrochloride, (’Apresoline’) may lead to a reactionwhich mimics rheumatoid arthritis or systemic lupus ery-thematosus. This syndrome occurred in 7-2% of hyper-tensives treated with a combination of hexamethoniumand 1-hydrazinophthalazine.4 It developed four to

twenty-three months after the beginning of treatment,tending to affect the distal joints of the upper limb ; in

progressive cases the condition eventually included suchfeatures of systemic lupus erythematosus as fever, rashes,haematuria, anaemia, leucopenia, adenopathy, spleno-megaly, hyperglobulinaemia, and signs of hepatitis. Only1 patient had all these abnormalities, and in none couldthe " L.E. phenomenon " be demonstrated. All these

signs regressed when the hypotensive drugs were with-held, and their relation to 1-hydrazinophthalazine seemedto be confirmed in some patients by their reappearanceafter a single test dose. The arthritis was rapidly relievedby cortisone. Similar syndromes were noted in about10% of 139 cases treated with 1-hydrazinophthalazinealone. 5 The mean time of onset was one year after the

drug was first given. Rheumatic " and " febrile "

phases were distinguished. In the rheumatic phase therewas migratory arthralgia, most often involving the inter-phalangeal joints and less often the wrists, elbows,shoulders, and knees. The affected joints were stiff,tender, swollen, warm, and sometimes red. In some

patients the erythrocyte-sedimentation rate was increasedand alpha and beta globulin levels were raised. Symp-toms subsided about a week after treatment was stopped,but they nearly always recurred if 1-hydrazinophthala-zine was given again. 5 patients passed from the" rheumatic " into the " febrile " phase, with the addedfeatures of prostration, pain in the chest and abdomen,and sometimes erythema of the hands and forearms,polyserositis, and non-specific pneumonitis. In 1 patientin this group the L.E.-cell test was positive. A third

report 6 of these toxic effects of 1-hydrazinophthalazineincludes a description of a case with the characteristicbutterfly rash of systemic lupus erythematosus and,again, a positive L.E.-cell test.The authors of these reports believe that the reactions

were due to a direct metabolic effect of the drug, ratherthan to hypersensitivity. Patients showing these reac-tions all had a vigorous hypotensive response, suggestingthat both effects resulted from a single metabolic actionof 1-hydrazinophthalazine.4’ The ability of any substanceto produce a syndrome resembling rheumatoid arthritisis bound to excite interest among students of this enig-matic condition ; and Turner and Lansbury have builtthis new finding into a hypothesis to explain the naturallyoccurring disease. The rheumatic syndrome induced by1-hydrazinophthalazine may simply illustrate that jointshave a restricted repertoire of pathological reaction ; butinformation about the microscopic appearances ofaffected joints and the agglutination titre of the serumfor sensitised sheep cells would be of considerable interest.

WHAT THE DOCTOR ORDERS

Mr. H. Davis, PH.D., in his chairman’s address to theBritish Pharmaceutical Conference at Oxford last Monday,gave some further statistics on prescribing habits. Froman analysis at the Ministry of Health of a large sampleof National Health Service scripts for 1953, it seems

that doctors now prescribe fewer mixtures and lotions,more tablets and pills, and twice as many proprietarypreparations as in 1948 ; more than a quarter of all

prescriptions are now for such preparations. Only oneof every sixteen scripts examined was a prescriptiondispensed to the prescriber’s own formula rather than toa formula in a standard work of reference.

Every clinical teacher already suspects that medicalstudents do not know how to write prescriptions, and itlooks as though some doctors must have almost abandonedthe practice. But a prescription may be none the worsefor being ready-made ; and the many acceptable pre-scriptions in the National Formulary and other compendiaare one of the best safeguards against extravagance inprescribing. So long as the tradition continues that theconsultation shall end with a prescription, so long shallwe be called on to study the statistics of gargantuanconsumption of drugs. The general practitioner isusually accused of over-prescribing, and no doubt if wewould cast him as clinical pharmacologist the charge isjust. But many subtler considerations may lead him towrite a prescription for a cough medicine or a tonic. In

reading Dr. Davis’s figures we should think of the linesof Robert Burns :

What’s done we partly may compute,But know not what’s resisted.

1. Takayashu, M. Acta, Soc. ophthal. jap. 1908, 12, 554.2. Caccamise, W. C., Whitman, J. F. Amer. Heart J. 1952, 44, 629.3. Lewis, T., Stokes, J. Brit. Heart J. 1942, 4, 57.4. Ask-Upmark, E. Acta. med. scand. 1954, 149, 161.

THE PULSELESS DISEASE

THE names of many rare and strange diseases comequickly to the tongue because of their oddness, rhythm,or descriptive power. Such a one is "the pulselessdisease " or TakaTasl1u’s ATndrome.1 First described inJapan, where, according to Caccamise and Whitman,258 cases have been published, it has more recently beenrecognised in Europe, particularly in Scandinavia andthis country.The disease is predominantly one of young women

(the average age is 30). It consists of a slowly progressive,obliterative panarteritis affecting the thoracic aorta andits branches. The innominate, carotid, and subclavianarteries are most often involved, although the obliterativearteritis can also affect the large intracranial, cardiac,pulmonary, and mesenteric arteries. The occlusion ofthe branches of the thoracic aorta results in an " invertedcoaretation," and, to compensate for the deficient blood-supply to the head and arms, a collateral system developsby which blood is carried from the descending aorta,through intercostal and diaphragmatic arteries, to thesubclavian system. Crenations of the lower ribs, producedby the enlarged and serpiginous intercostal arteries, weredescribed by Lewis and Stokes.3 The ischaemia resultingfrom this abnormal circulation gives rise to the charac-teristic absence of pulses in the arms and head andneck, and to intermittent claudication in the arms andjaw. The hands and arms show the classical colourchanges of chronic isohcemia, and repeated svncope fromcerebral ischaemia may dominate the clinical picture.The carotid sinus, when involved in the arteritis, showsundue tactile irritability ; and syncope on palpating orflexing the neck has often been observed. Cardiacenlargement, arterial hypertension in the legs, and a

persistently high erythrocyte-sedimentation rate completethe picture. The course of the disease is chronic andprogressive, although survival for as long as 14 yearsafter diagnosis has been recorded. 4