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ever has a cerebral haemorrhage. Similarly he oftensuffers from general paralysis of the insane but hardlyever from tabes dorsalis ; BILLINGTON 17 has recordedone case. Liver disease is almost the rule amongAfricans, and a completely normal liver is seldom seenat autopsy. Hepatitis accompanies many, knownbacterial infections 18 and some cases are doubtless

examples of infective hepatitis ; others have anuncertain aetiology and may reflect protein deficiency.Cirrhosis is common, even in young adults ; it isoften portal in type, but almost as frequently thefibrosis is coarse and there are large areas of hyper-plasia, which suggests postnecrotic scarring. GILL-:may and GILLMAN 19 in South Africa have demon-strated by liver biopsy the relationship of fattyliver to the kwashiorkor syndrome. From all partsof Africa primary hepatic carcinoma, grafted oncirrhosis, is often reported, whereas it is almostunknown in Europe. EVANS 20 and others 21 haveestablished the frequency of sickle-cell disease andsickle-ansemia in Africa. Anaemia appears to bealmost universal and reflects the strain of parasitesand deficiencies of iron and extrinsic factor in thediets of the Africans.22

It is generally agreed that Africans are poorly fed._-BNDERSON 23 has observed the beneficial effects of

giving a liberal diet, containing 3100 calories and120 g. of protein daily, to African soldiers. Even onthis diet, however, it was impossible to producedynamometer readings which could be favourablycompared with those of British soldiers-in otherwords, it was impossible to repair the damage done bymalnutrition during the period of growth. " TheAfrican," OGILVIE writers, " is occasionally a finephysical specimen, but more often he is stunted andweakly. If dietetic measures are to correct this stateof affairs in the African adult they must be appliedin childhood-or even in intrauterine life."

Headache in Malaria

A REPORT trom America 4 suggests tnat nicotinic acidwill sometimes relieve the intractable headaches occurringin the intervals between malarial attacks. To 25 menwho complained of headache which was attributed bythe examiner to malaria, 100 mg. of nicotinic acid wasgiven by mouth. Complete relief some thirty to fortyminutes after taking the drug was reported by 10 patients ;partial relief was reported by 7 ; while in the other 8it had no effect. Duration of relief varied, but usuallyit continued for several days. Where the headacherecurred every day, 50-100 mg. of nicotinic acid afterbreakfast every morning provided effective relief ; thedose was determined by individual requirements. Zeligshas found all other remedies useless in this type of head-ache ; he suggests that nicotinic acid should be givena wider trial, particularly in view of its safety. Thetreatment aims at obtaining cerebral vasodilatation, inview of the isoagglutination and capillary stasis knownto occur in cerebral malaria.

17. Billington, W. R. Ibid, 1942, 19, 197.18. Muwazi. E. M. K., Trowell, H. C. Ibid, 1942, 19, 40. Stephen-

son, R. W., Kirk, R. Trans. R. Soc. trop. Med. Hyg. 1943,37, 189.

19. Gillman, J., Gillman, T. Nature, Lond. 1944, 154, 210; Arch.intern. Med. 1945, 76, 63; J. Amer. med. Ass. 1945, 129, 12.

20. Evans, R. W. Trans. R. Soc. trop. Med. Hyg. 1943, 37, 281;Ibid, 1945, 39, 207.

21. Smith, E. C. Ibid, 1934, 28, 209. Trowell, H. C. E. Afr. med. J.1945, 22, 34. Reid, R. D. West Afr. med. J. 1936, 9, 15.

22. Trowell, H. C. Trans. R. Soc. trop. Med. Hyg. 1942, 36, 151;Ibid, 1943, 37, 19.

23. Anderson, T. F. E. Afr. med. J. 1943, 20, 207.24. Zeligs, M. A. J. Amer. med. Ass. 1945, 129, 796.

Annotations

SIXTY YEARS OF MEDICAL DEFENCE

THE diamond jubilee of the Medical Defence Union wascommemorated last week by a luncheon in London.The president, Mr. St.J. D. Buxton, recalled that it wasincorporated in 1885 by C. F. Rideal and a group of

laymen, whose purpose was to provide doctors withinsurance against prosecutions for malpraxis and attacksby libel or slander ; and to suppress practice by unregis-tered persons. The next year a Midlands branch wasformed under the chairmanship of the well-known

Birmingham surgeon, Lawson Tait. In 1887 he waselected the first president, and in the following yeararticles of association were adopted and the unionbecame an entirely medical organisation. The firstdecade of its existence was stormy, but by the turn ofthe century it had become firmly established, with amembership of 4604 and a reserve fund of JE7637. Apartfrom a slight setback in the war of 1914-18, its recordhas since been one of steady development ; its member-

ship now approaches 30,000 and its funds exceed £ 150,000.In the course of the years the work of the M.D.U. hasbroadened : apart from helping practitioners with allmanner of individual medicolegal difficulties, it hasdeveloped the collective defence of the profession. AsSir Alfred Webb-Johnson, P.R.c.s., observed in proposingthe toast of The Union, the kind of protection its offersis essential to every medical man and woman.

EVALUATION OF CHOLERA VACCINATION

CHOLERA is perhaps the most easily controllable ofthe pestilences that have in the past swept across theworld. It has not appeared in the United States forover seventy years, or in Europe for the last two decades.Yet in India and in China it is still one of the majorepidemic diseases and in India alone it claims an averageof 200,000 victims a year. It could almost certainly bebanished from these countries also by suitable sanitaryreforms, notably by the provision of protected water-supplies for their teeming millions. In the course oftime, measured by generations, these reforms will nodoubt be carried out, and then cholera may disappearfrom the world; but in the meantime the public-healthauthorities in the affected countries have been compelledto adopt palliative measures, one of the most popularof which has been prophylactic inoculation. This hasbeen practised widely in India since its introduction byHaffkine over fifty years ago, and has seemed to be verysuccessful, but the sceptics have often pointed out thatits value has never been established on sound statisticalevidence.To meet this criticism advantage was taken of a severe

epidemic in 1942 and 1943 in Madras Province to make ascientifically planned and carefully executed statistical

investigation of the results of anti-cholera inoculation.The area investigated had a population of about threemillion, of whom about a quarter were inoculated and thebalance were used as controls. The vaccine was madeat the King Institute, Guindy, from " Agawa " and" Inaba " strains of Vibrio cholerx ; a single dose of1 c.cm. containing 8000 million organisms was given toadults and half this dose to children. Of 709,977"protected" persons, 1118 developed cholera, and

among 2,119,568 uninoculated persons there were

34,336 cases of cholera. Analysis of these results suggeststhat " protected " persons are 12-14 times less likelyto get cholera than the unprotected, that immunity isestablished even on the third day after inoculation andincreases progressively for at least five weeks, and thatthe immunity conferred lasts up to a minimum of five

1. Report of the Scientific Advisory Board of the Indian ResearchFund Association for 1944.

135

months and probably as long as ten to twelve months.There was some evidence that inoculated persons whodeveloped cholera were less likely to die of the diseasethan those who had not been inoculated, but thedifference in fatality in the two groups was not great,and the main value of the vaccine lies in the fact that theinoculated are less likely to get the disease.

There was also evidence, derived from villages whichwere visited more than once by cholera during theepidemic, that inoculation during the first outbreak

produced a herd immunity that had a favourable effecton subsequent outbreaks. In this observation lies some

hope that inoculation may prove more than a palliativemeasure of control, but it is rather a slender hope in viewof the relatively short duration of the protection providedby inoculation. It might be possible to banish cholerafrom an endemic area by a very extensive inoculationcampaign, but unless the fundamental sanitary defectswere corrected it would still be liable to reinfection from -a neighbouring endemic area.

It is good to know that in cholera vaccine we have amethod of prevention of proved value, since there aremany circumstances in which it is obviously the methodof choice ; but it will be a pity if vaccination is allowedto claim the attention of public-health authorities to theexclusion of the more permanent methods of controllingcholera and incidentally many other intestinal infections-the provision of safe water-supplies for all the inhabi-tants of cholera endemic areas.

INDUSTRIAL ABLEMENT AND REABLEMENT

AT the official opening last week of the first residentialindustrial rehabilitation centre started by the Govern-ment, Mr. Ernest Bevin, the Foreign Secretary, expressedthe hope that doctors would familiarise themselves withthe work of this and similar centres. It is hoped thatthis is but the,forerunner of many Ministry of Labourcentres throughout the country. The centre near

Egham was established almost two years ago for thephysical and mental rehabilitation of men disabled inthe Forces and industry, and since then a thousand menhave passed through it. Of these about half havereturned to their former jobs or other suitable occupa-tions, and most of the remainder have proceeded toother establishments for further training. The new-comer to the centre is medically examined on arrival.The first part of his stay is spent in physical and mentalreablement and in regaining confidence ; at this stagehe is engaged largely in physical training and physio-therapy. At the end of this period he has a talk withthe industrial manager, who is guided in advising a

career by the medical report, the man’s aptitude, andthe availability of jobs in industry. Whether it isdecided that he should return to his former occupationor embark on a new one, he can acclimatise himself tohis work by using the workshops and other facilities inthe centre. When he leaves Egham to start work, orfor a further course of training, he does so knowing whatto expect and what he is capable of accomplishing.No-one will deny that there is a place for such centres.

The only doubt can be why they were not establishedlong ago for the benefit of the injured and the misfitsin industry. And why should the system be restrictedto righting damage already done ? The war has broughtout the supreme importance of selection for the varioustypes of Army employment ; the time has come whenexperts in job-analysis will play an increasing part inindustry. Why should not centres similar to that atEgham be set up to help youths choose their job beforethey start work ? ’ Such centres would be analogous tothe primary training centres which have operated suc-cessfully in the Army.! Too often, youth has its futuredecided by local availability of work, by family tradition,

1. Rees, J. R. Brit. med. J. 1943, i, 1.

or by casual lack of consideration. Selection centresshould be available to all, but compulsory for none.Formal intelligence and aptitude tests can provide no rigidguide ; but if these were reinforced by practical facilitiesfor boys to show themselves and others where theirbent lay an immense contribution would be made toindustrial efficiency and happiness.

SINGLE MASSIVE DOSES OF SULPHONAMIDES

EHRLICH originally thought that organic arsenicalsshould be administered to patients with syphilis in onemassive dose (therapia magna sterilans), and for someyears a few injections were believed to effect a cure.After the last war, however, the view grew up that apermanent cure can only be obtained by maintaining aneffective level of the drug over a long period. In the lastfew years, particularly in the United States, intensivearsenical therapy has returned to favour, and satisfactory

- early results have been reported after a seven-daycourse of Mapharside’ and bismuth subsalicylate.1Similarly with penicillin, good early results in syphilishave followed a five-day course totalling 9,000,000 units,2and in gonorrhcea 3, spectacular success has been obtainedwith 100,000 units given in 5 or even 3 injections two-hourly, though a single-injection technique has been lesssatisfactory.

In the sulphonamide therapy of bacterial infections,Golden and Meyer 4 now advocate the administration of asingle " massive " dose of 9 g. by mouth. They base thisview on their experience with sulphonamides appliedintraperitoneally in cases of peritonitis. They are satis-fied that a single dose of 9 g. applied in that way hasproved effective without any subsequent maintenancedosage, though it is less than the amount usually advo-cated for the first 24 hours of sulphonamide therapy,6 halfof which is commonly given as an initial dose. In this

way they claim to counter the tendency of organisms tobecome resistant to sulphonamides, and to avoid the"

masking " of symptoms which continued administra-tion may cause. A strong case must, however, be madeout before the clinician can be advised to abandon themaintenance dosage, controlled by blood-level determina-tions, which has proved so successful in practice.Most of the sulphonamides are fairly rapidly excreted

in the urine, especially sulphanilamide which Golden andMeyer use as " a typical sulphonamide." When a

single dose is given, a maximum level is reached in theblood and tissue fluids within a few hours ; the concentra-tion rapidly falls to an ineffective level and finally tozero when the drug is completely cleared from the body.The object of maintenance dosage is to keep the sulphon-amide concentration in the blood between 5 and 10 mg.per 100 c.cm., which has been shown to be the minimumbacteriostatic level, for a long enough period to allow thebody tissues to develop antibodies. If we still acceptthat the action of the sulphonamides is mainly bacterio-static, success must depend on the host completing thekill, except when the infecting organism is highly suscep-tible. The clinical experience has been that infectionstend to relapse unless sulphonamide therapy is continuedfor 4-5 days. It has been demonstrated that thebacteriostatic effect is not directly proportional to theconcentration in the body fluids, and little therapeuticadvantage is gained by increasing the sulphonamideconcentration beyond 10 mg. per 100 c.cm., until thevery high concentrations that occur with local applicationare attained. The dangers of ineffective sulphonamideconcentrations have been emphasised by many writersand are avoided by the accepted dosage methods. The

1. See Lancet, 1944, i, 280.2. Lourie, E. M., et al. Ibid, 1945, ii, 696.3. Leading article, Ibid, Jan. 12, 1946, p. 58.4. Golden, B. I., Meyer, S. W. J. int. Col. Surg. 1945, 8, 225.5. M.R.C. War Memo. no. 10, London, 1945. Spink, W. W.

Sulphanilamide and Related Compounds in General Practice,Chicago, 1943.