586 3 June 1967 Leading Articles urgent need of removal from home for diagnostic, protective, patients are often untutored in the problems of childhood or therapeutic reasons places in existing children's hospitals, and adolescence, and when already involved with a family or in hostels or other primarily non-medical child-care situation prefer to refer the younger members to a colleague Br Med J: first published as 10.1136/bmj.2.5552.586 on 3 June 1967. Downloaded from settings, may be more suitable than admission to a special working in another setting. school or unit, where, despite the fact that the majority of In these circumstances it would seem that child psychia- children rapidly become evidently less disturbed in their trists have an enormous responsibility for education and behaviour, the duration of stay may be as long as four years.10 consultation. Perhaps they should sacrifice some of the Economic factors are in any case likely to slow the further pressures and satisfactions of individual therapy and spend growth of special units, and the competing demands for more time giving training, consultation, and support to medical manpower make it unlikely that enough doctors of colleagues, both medical and non-medical, who are providing sufficient skill and experience will be available to staff a individual and family care in the community. At the same comprehensive child psychiatric service. Teachers and child- time they must try to ensure that adequate resources are care and probation officers, and others directly concerned invested in research. As well as including study of the origins with child care, must continue to carry a considerable share and development of childhood disorders, this should be aimed of the management of disturbed children. Their training in at evaluating the consequences of different forms of treat- the recognition and management of emotional disorders is ment. Our present child psychiatric services are so rudi- improving, but their greatest need is for continuing consulta- mentary that the buildings and staffing patterns of the next tion, guidance, and support in the management of their cases. decade may mould the development of services for the next Family doctors more than anyone have the opportunity to century. know families over many years and may be able to intervene before the development of overt disorder or to offer guidance The Registrar General's Statistical Review of England and Wales for the Year 1960, Supplement on Mental Health, 1964. H.M.S.O. in minimizing the effects of adverse situations. Unfortu- Ministry of Health H.M. (64) 4. H.M.S.O. nately undergraduate and postgraduate education does little 3 Blacker, C. P., Reurosis and the Mental Health Services, 1946. London. at present to equip the doctor for these tasks. Paediatricians Ministry of Education, Report of the Committee on Maladjusted and school medical officers are also more likely to see Children, 1955. H.M.S.O. Howells, J. G., Family Psychiatry, 1963. Edinburgh. disturbed children than the specialized psychiatric services, Caplan, G., Principles of Preventive Psychiatry, 1966. London. to these Ryle, A., Proc. roy. Soc. Med 1963, 56, 834. but are often reluctant attempt to deal with problems Rutter, M., and Graham, P., ifid., 1966, 59, 382. because of their uncertainty about their own capacity to offer * Shepherd, M., Oppenheim, A. N., and Mitchell, S., 7. Child Psychol. Psychiat., 1966, 7, 39. effective treatment and because of lack of available psychiatric sRoyal Medico-sychological AssocIation, Report on Schools and consultation. Psychiatrists practising in clinics for adult Hostels for Maladjusted Children, 1965. London. http://www.bmj.com/

The drug chosen for maintenance treatment of Which Hypotensive Drug? will also depend to some extent on the patient's state. Patients Hypotensive treatment improves the prospects of patients with severe or malignant hypertension will usually require with severe hypertension,' 2 and it is thought possible that the one of the more potent sympathetic blocking agents, while degree of benefit is related to the effectiveness of control of the blood pressure of patients with milder disease can often the blood pressure. be controlled with drugs that require less meticulous atten- on 24 September 2021 by guest. Protected copyright. Now that fMany hypotensive drugs are available, and more tion to dosage. Phenobarbitone has no place in the treatment appear every year, it becomes increasingly difficult to decide of hypertension.' 5 A type of diuretic is usually the which drug should be given to any patient. Indeed, the multi- first choice for patients with mild hypertension provided there plication of remedies means that' no single one is entirely is no risk from gout or diabetes. There is no evidence that satisfactory. Side-effects and other hazards must always be any single diuretic is superior to the others in respect of balanced against possible benefits. efficacy or freedom from side-effects. There is little point in The drugs used will depend in part on the patient's con- increasing the dose if adequate control of the blood pressure is dition. In hypertensive emergencies, such as encephalopathy not achieved. Potassium supplements will be required, par- or left ventricular failure, the blood pressure must be reduced ticularly if the patient' is receiving digitalis. If adequate rapidly. For this purpose parenteral or control is not obtained, it is probably reasonable to add small may be given, provided the patient is either doses of a rauwolfia alkaloid. This combination is usually sitting up or tilted feet downwards. Intramuscular reser- more effective than a diuretic alone, though the rauwolfia pine or intravenous frusemide or ethacrynic acid may likewise alkaloid may cause depression or retention of sodium. There be employed unless there is reason to believe that the patient is again no unequivocal evidence that one rauwolfia compound has obstructive disease of the urinary tract or severe renal is superior to the others. One major advantage of diuretics failure. Parenteral treatment with has been and rauwolfia compounds is that they do not cause postural advocated, but it can occasionally cause a transient rise of hypotension. The same is true of propranolol, which has a arterial pressure' and is probably better avoided. Patients moderate hypotensive action.' It may, however, cause cardiac requiring this kind of treatment will almost invariably need failure, and its place in the routine treatment of hypertension continuous control of their blood pressure thereafter unless is not yet established. the emergency is due to a self-limiting condition such as acute If the above drugs fail to control the blood pressure, or if glomerulonephritis. the patient has severe hypertension, one of the agents affecting 3 June 1967 Leading Articles BRnITH 587 sympathetic efferent function should be given. These com- pathetic blocking agents will give better results than a single prise the ganglion-blocking agents, of which only mecamyl- one.'4 Good results depend to a great extent on the care with amine and are now used in any quantity, methyl- which the regimen is managed: this is usually more impor- Br Med J: first published as 10.1136/bmj.2.5552.586 on 3 June 1967. Downloaded from dopa, and the drugs which block sympathetic fibres at the tant than the initial choice of drug. neuro-effector junction-, , bethan- idine, guanoxan, , and . has an effect similar to these drugs on arterial pressure,' but should not usually be prescribed for the maintenance treat- ment of hypertensive patients because it is a monoamine- oxidase inhibitor, and patients receiving drugs of this type may suffer dangerous reactions after some other drugs or Rubidomycin in Acute Leukaemia foods. The ganglion-blocking drugs affect parasympathetic as well as sympathetic functions and thus may cause addi- Rubidomycin is the first antibiotic to show therapeutic effect tional side-effects. Few people would now consider them the in management of acute leukaemia in man. It is produced first choice for the treatment of severe hypertension, though from a strain of Streptomyces coeruleorubidus, and it is active they may be very useful if other drugs fail. Bretylium has in all forms of acute leukaemia. J. Bernard and his now fallen into disfavour because many patients become colleagues,' in an extensive clinical trial, have found it useful tolerant of its hypotensive effects. in the treatment of acute lymphoblastic leukaemia and have In the B.M.7. this week Dr. V. Vejlsgaard and his col- also been able to obtain remission in more than half their leagues report a double-blind comparison of four drugs- patients with acute myeloblastic leukaemia. This is the first namely, guanethidine, methyldopa, guanoxan, and guanoclor. time that the use of one drug alone has resulted in such a Most studies of different ganglion-blocking agents have con- satisfactory remission rate in acute myeloblastic leukaemia, centrated on the severity of postural hypotension, and the and the duration of the remissions appears to be at least incidence of side-effects over a relatively short period of time. several months. The present workers found methyldopa the most satisfactory Several schedules for the administration of rubidomycin in these respects. In a similar comparison between methyl- are being tried, and it is not yet possible to define the most dopa, guanethidine, and pargyline7 the same conclusion was satisfactory method. It is now agreed, however, that remission reached, though there was much variation between patients. should be induced by the shortest possible course and that About two-thirds of the patients were better controlled by maintenance therapy is contraindicated because of the drug's methyldopa than either of the other drugs, but one-third of toxic effects on the heart. Remissions may be induced by the them did better on one of the other agents. This merely intravenous administration of the drug dissolved in saline and underlines the fact that no ideal drug exists. Vejlsgaard and injected into a fast-flowing infusion. The injection is given his associates have shown convincingly that guanoclor is a daily in a dose of 1 to 2 mg. per kilogram body weight per difficult drug to use for the maintenance treatment of hyper- day, the length of the course depending on how well it is tolerated. The maximum dose that should be given is about tension, and it seems unwise to employ it unless others fail http://www.bmj.com/ to give satisfactory results. Though guanoxan performed 20 mg. per kilogram body weight, the average dose before fairly well in their hands, impaired liver function has now been side-effects are encountered being 6 to 10 mg. per kilogram. observed in many patients receiving it,8-0 and it may be wise So far the major complications encountered have been to give it too only if other agents fail. cardiotoxicity and bone-marrow aplasia. Toxic effects on This leaves methyldopa, guanethidine, , and the heart first show themselves by tachycardia, which leads debrisoquine. The last two have not been formally com- rapidly to pulmonary oedema and death. Death from pared with other drugs, but of the first two methyldopa myocardial degeneration induced by rubidomycin has appears to have a marginal advantage." However, it also occurred in about 10% of patients treated so far.' 2 The on 24 September 2021 by guest. Protected copyright. has some drawbacks. Between 10% and 30% of patients onset of this complication does not appear to be preceded by receiving long-term treatment develop a positive reaction to electrocardiographic abnormalities, and heart failure when it the Coombs test, and a small proportion of these have haemo- occurs is of sudden onset and intractable. Its occurrence is lytic anaemia.'2 There is also a risk of drug fever and liver related to the total dose given and has been seen in patients damage." In some patients it is impossible to control the given maintenance therapy or when a large dose was required blood pressure with methyldopa, even in combination with a to obtain a remission. diuretic. Many different remedies will need to be tried in Aplasia of the bone marrow is severe and occurs in a large difficult cases, and sometimes a combination of two sym- proportion of patients treated, G. Mathe having noted an Leishman, A. W. D., Lancet, 1963, 1, 1284. incidence as high as 90%.' It is more likely to occur in those 2 Hamilton, M., Thompson, E. N., and Wisniewski, T. K. M., ibid., patients who have had a number of chemotherapeutic agents 1964, 1, 235. Levine, R. J., and Strauch, B. S., New Engl. 7. Med., 1966, 275, 946. before starting rubidomycin, or in whom bone-marrow smears Cooper, E. H., and Cranston, W. I., Lancet, 1957, 1, 396. are not very cellular at the start of therapy. Aplasia Chesrow, E. J., Bernstein, M., Wiess, D., and Marquardt, G. H., Amer. 7. med. Sci., 1966, 251, 166. commonly arises during the second week of treatment and Prichard, B. N. C., and Gillam, P. M. S., Brit. med. 7., 1964, 2, 725. requires with Oates, J. A., Seiann, A. W., Clark, M. A., Rousseau, P., and Lee, supportive therapy antibiotics and transfusions R. E., New Engl. 7. Med., 1965, 273, 729. of platelets and white cells. The alternative is to nurse the ' Montuschi, E., and Lovel, T. W. I., Lancet, 1964, 2, 1339. ' Sheps, S. G., Schirger, A., Osmundson, P. J., Kavanaugh, G. J. patient in a germ-free environment and to give blood and Fairbairn, J. F., and Burbank, M. K., Mayo ClGn. Proc., 1966, 41, 577. platelet transfusions when necessary. 10 Cotton, S. G., and Montuschi, E., Brit. med. Y., 1966, 1, 51. Johnson, P., Kitchin, A. H., Lowther, C. P., and Turner, R. W. D., Hence rubidomycin is a very powerful therapeutic agent ibid.? 1966, 1, 133. which warrants further Carstairs, K. C., Breckenridge, A., Dollery, C. T., and Worlledge, tial. Its use at the present time S. M., Lancet, 1966, 2, 133. 3 Sjoerdsma, A., in Antihypertensive Therapy, ed. F. Gross, p. 321. XBernard, J., Jacquillt, C, Boiron M., Najean, Y.I Seligmann, i., 1966. Berlin. Tanzer, J., Wel, M., and L1ortholary, P., Presse med., 1967a,7, 951. ". Breckenridge, A., and Dollery, C. T., Lancet, 1966, 1, 1074. 2 Mathi, G., unpublished observations.