General Hood Retires

524

Chemotherapy of Leprosy many remedies for leprosy advocated

over OF the the centuries only the oils of species of hydnocarpus have consistently maintainedtheir reputation up to the present day. They were originally given by mouth or inunction, and later a change was made to intramuscular, intravenous, or subcutaneous administration, but in the last few years intradermal infiltration into the actual lesions has been almost exclusively The original crude chaulmoogra oils have used. now been largely superseded by purified oils, their ethyl esters, and salts of their fatty acids, variously modified. In this issue Sir LEONARD ROGERS recalls some of his important earlier work on the treatment of leprosy with these drugs: The specificity of the chaulmoogra preparations in leprotic infection is questionable.Sir LEONARD ROGERS believes that they actually destroy leprosy bacilli within the lesions ; but the evidence that they are bacteriolytic is slight, and it is more probable that any action they exert results from counterirritation and the stimulation of a tissue response. In some cases the course of lepromatous leprosy appears to be modified by long-continued treatment with chaulmoogra, but in others there is no obvious benefit. When chaulwas the the available, moogra only drug drug treatment of leprosy was therefore unsatisfactory in the

extreme.

In the last seven years the introduction of the sulphones has substantially changed the outlook. In 1908 FROMM and WITTMAN1 prepared 4 : 4’ diaminodiphenylsulphone, and in 1939 RIST2 reported that this drug inhibited the growth in vitro of human and avian tubercle bacilli ; a year later he and his co-workers3 showed that it modified the course of avian ’tuberculous infections in rabbits. However, this sulphone, unfortunately, is relatively insoluble and too toxic for human use. In 1943 Faget et awl.4 reported the trial of ’Promanide ’ (known asPromin ’ in the U.S.A.), or p,p’-diaminodiphenylsulphone-N,

N’-didextrosesulphonate,

a more

soluble

compound,

in leprosy. This drug proved unduly toxic by mouth but could be given intravenously in doses of 5 g. daily, in some cases for long periods. The results were most encouraging : the disease was apparently arrested and actual regression of lesions was seen ; seldom, if ever, did the disease progress further while under treatment over several vears. In 1944 MUIR 5 described his results’ with " Diasone,’ disodium formaldehyde-sulphoxylate diaminodiphenylsulphone, in lepromatous leprosy in the West Indies. It was less toxic by mouth than promanide and could be given in tablet form in doses up to 2 g. daily for many months. As with promanide, clinical arrest or regression of the active manifestations of lepromatous leprosy attended its use. Other sulphone preparations are under investigation, notably ’ Promizole,’ 4,2’diaminophenyl-5’-thiazolylsulphone, andSulphe-

trone,’ 4:4’-bis

(y-phenyl-n-propylamino) diphenyl-

sulphone-tetrasodium sulphonate. 1. 2. 3. 4.

The relative value

Fromm, E., Wittman, J. Ber. dtsch. chem. Ges. 1908, 41, 2269. Rist, N. C.R. Soc. Biol., Paris, 1939, 130, 972. Rist, N., Bloch, F., Hamon, V. Ann. Inst. Pasteur, 1940, 64, 203. Faget, G. H., Pogge, R. C., Johansen, F. A., Dinan, J. F., Prejean, B. M., Eccles, G. C. Publ. Hlth Rep., Wash. 1943, 58,

1729. 5. Muir, E.

Intern. J. Leprosy, 1944, 12, 1.

of these various sulphones will emerge in due course, but the parent radical, common to all, appears to be the active therapeutic agent. In an extremely chronic disease like leprosy, characterised by spontaneous remission and exacerbation, years must elapse before any claim to cure can be established. Furthermore, treatment with the sulphones is not free from side-effects. Gastro-intestinal disturbances, hæmolytic anæmia, and hæmaturia are among the more severe toxic manifestations occasionally observed in ’the early stages of treatment, and at least one patient treated with diasone has died from agranulocytosis. Sometimes, too, an acute febrile exacerbation of the disease (lepra fever) is precipitated by the drugs. Most of these troubles can be averted by beginning treatment with very small . doses and cautiously increasing them over a period of weeks or months until tolerance is established. The full dosage must then be given for at least a year, with brief intermissions, before a clinical result can be

expected. Some American workers think that one of the antibiotics will ultimately be found to be therapeutically active in leprosy. Penièillin has been shown not to influence the course of a basic lepromatous infection, though it helps to overcome associated - secondary infections. Streptomycin has been given intramuscularly in big doses (250,000 units three-hourly) for four months by FAGET and ERICKSON s who believe that it benefited the leprotic lesions, though the results were not conclusive. The treatment is exacting, and the drug caused toxic manifestations necessitating its abandonment after this period. As Sir LEONARD RoGERS suggests, a combination of drugs -perhaps some antibiotic with a sulphone-may turn out to be more effective than any drug alone, since in tuberculosis, which has many features in common with leprosy, there seems to be no doubt that streptomycin and sulphones exert a synergistic action.7 Tocarry the analogy with tuberculosis still further, when p-aminosalicylic acid is more plentiful it might well be worth while to investigate its activity in leprosy. Though its use in tuberculosis is still in the early experimental stage this drug seems to be one of the few which combine a specific action on acid-fast bacilli with reasonable freedom from toxicity.

General Hood Retires IN the first phase of a long war the recommendations of the medical services seldom receive due attention : man-power seems plentiful, and the main business of all branches of the Forces is rapid expansion. It was towards the close of this phase that Sir ALEXANDER HOOD in 1942 succeeded Sir WILLIAM MACARTHUR as director-general of Army Medical Services, and his first achievement was to form at the War Office a group of people capable of fulfilling every task of the decisive stages of the war. Of the directorates, which soon increased to a dozen, all but one were headed by regular officers ; but in addition he had the help of a large number of civilians, eminent in their own line, who were asked not only tb advise on policy but also to take responsibility for providing 6. Faget, G. H., Erickson, P. T.

J. Amer. med. Ass.

1948, 136,

451.

7. Lincoln, E. M., Kirmse, T. W., De Vito, E.

Ibid, p. 593.

525

the specialist services that would meet the needs of all tection of the Geneva Convention. After long and careful thought HOOD decided that, if the Army was the armies in the field. United by their desire to in to have the best medical attention, its medical divided their belief, serve, these experts were by the importance of their own specialties, and they were services must dissociate themselves from everything mostly unaccustomed to the ways and aims of their not related to the preservation and promotion of the colleagues in the regular service. It says much for health of the soldier as a human being ; and all HOOD that he was able to build so much diverse inquiries into military efficiency were accordingly material into an efficient and smoothly running passed over to the Scientific Adviser to the Army machine. As its governor, he had to listen to the Council, under whose control medically qualified " proposals of each and all of his directorates, branches, officers could engage in aggressive medicine " withand consultants, and from these select and support out making any claim on the protection of the red Medical scientists applying their science to those that were practicable and compatible and cross. benefit to the in end most soldier. the would give purely military matters were rightly distinguished of his even control was from His genial, doctors bound by the Hippocratic oath and jovial, group service the firm : he attracted to the and sure solely concerned with promoting health and preventing his of and and associates, by loading complete loyalty curing disease. them with responsibility he extracted the greatest It can fairly be said that under General HOOD’S contribution each could make. Judged by results, direction the Army Medical Services disregarded no the medical service thu5, directed and conducted was advance in medicine, and reduced almost to a minias good as any army has known. mum the time-lag between discovery and application HOOD did more, however, than perfect a mechanism in the field. The effect of his work was a reduction inherited from his predecessor : he enlarged its scope. in pain, suffering, and mutilation, and he has the His innovating quality is revealed most clearly, privilege of knowing in his own time that what he perhaps, in the support he gave, often against advice, did was good. In doing it he attracted the affectionate to the development of psychiatry at a time when loyalty of those who served with him, and now thatthis had to contend with opposition not only from -too soon, it seems-he has stepped off the top of the powerful military authorities but also from powerful inexorable Service escalator they will wonder how his members of our profession. Another thorny question high talents can be further employed. It has been said was that of investigation into matters of health and that, even now, his capacity has never been fully military efficiency, requiring a modus vivendi with tested ; and certainly the best reward for a man who the Medical Research Council. From the beginninghas succeeded in one task is to give him another and of the war the council had placed its facilities at the harder. If we had to choose, we should suggest the disposal of the Forces, and when HOOD took office governorship of some part of the Empire where it was engaged in numerous inquiries for the Army. medico-sociological problems are paramount. MeanBelieving, however, that research must not be divorced while we can only wish the new director-general, from active service and become the monopoly of an Major-General CANTLIE, equal success-without the outside body, he felt that the best results would be opportunities of war. obtained by establishing, within his staff, a directorate of medical research, which should collaborate with the M.R.C. and facilitate the work of its operational Disabilities: and How to Live with research units. Serving officers were encouraged to Them propose and undertake investigations, and in order THE effect of a chronic disability depends on to help them, and. to supply a factual basis for administrative policy, a statistical section was its nature and extent, on the disabled person’s developed in the research directorate. Meanwhile, as age, financial standing, intelligence, occupation, and the war entered its later phase, the conservation of education, and on whether his family are a liability man-power became the major preoccupation of the or a help-for the burden will be immeasurably Army Council, and the preventive and health-pro- lightened if someone is able and willing to share it. moting activities of the Army Medical Department Besides these there are many less tangible reasons increasingly outweighed the purely curative. Ceaseless why the same lesion will make one man a querulous changes in the categorisation of personnel, more invalid while to another it acts as a stimulus to better systematic efforts at -reablement, and medical con- things. The series of fortnightly articles which begins tributions to the maintenance and improvement of in this issue will, we hope, reveal some of the factors morale were the order of the day ; and the change concerned ; but our primary aim in getting patients of emphasis was illustrated by HooD’s, inclination to to discuss their disabilities is to turn their experience change the name " medical services " to " health to the advantage of others who face similar difficulties. services " and his desire for the replacement of sickThe person whose happiness and efficiency depends on parades by a " doctor’s hour " comparable to the details of management must always make demands on " padre’s hour." At the same time, the application the imaginative insight of his doctor ; but there is, of scientific methods to the military art faced the we believe, a great store of private knowledge on which medical director-general with a difficult and almost they should both be able to draw in order to make the new problem. Medicine was now asked to concern best of a badjob. The first article, by a woman who itself not only with the health of the individual as was 23 when her spinal cord was damaged at the a human being but also with his efficiency as a fighting level of Tll-12, illustrates how much can be done and in of relevant information by a patient to minimise discomforts and dangers animal;’ pursuit officers of the Royal Army Medical Corps were led and to enlarge the remaining openings for an active into activities which must deprive them of the pro- life. ,