686

We had planned a case-control study and we interviewed 13 men, from the same clinical practice as the men with KS, who were known to have had sex with other men but had no evidence of KS or HIV infection. It became clear, however, that appropriate controls would not be obtained. The men with KS were identified as being homosexual or bisexual after they were found to have KS. Because KS is linked with AIDS and homosexuality, these men may not have been openly homosexual and may not have even regarded themselves as such. If controls were selected from men who were known to be homosexual or bisexual, they may well have been more openly homosexual and more sexually active than the population from which the men with KS were drawn. Our hypothesis was that cases would report frequent sexual contacts involving exposure to faeces, but 3 men reported no history of insertive analingus, fisting, or insertive anal intercourse. Only 5 reported insertive analingus, but 9 reported receptive analingus. If KS is caused by a sexually transmitted agent, its transmission may not be limited to the faecal-oral route. These men constitute an important population for epidemiological and laboratory studies of the aetiology of this neoplasm. Division of STD/HIV Prevention, National Center for Prevention Services, Centers for Disease Control, Atlanta, Georgia 30333, USA

THOMAS A. PETERMAN

Department of Dermatology and Microbiology, New York University Medical Center

ALVIN E. FRIEDMAN-KIEN

Division of HIV/AIDS, National Center for Infectious Diseases, CDC, Atlanta

HAROLD W.

ICRF Cancer Epidemiology Unit, University of Oxford, Oxford, UK

VALERIE BERAL

JAFFE

TA, Berkelman RL, Jaffe HW. Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? Lancet 1990; 335: 123-28. 2. Jacobson LP, Munoz A, Fox R, et al. Incidence of Kaposi’s sarcoma in a cohort of homosexual men infected with the human immunodeficiency virus type 1. J Acquir Immune Defic Syndr 1990; 3 (suppl 1): 524-31. 3. Friedman-Kien AE, Saltzman BR, Cao Y, et al. Kaposi’s sarcoma in HIV-negative homosexual men. Lancet 1990; 335: 168-69. 1. Beral V, Peterman

Use of cyclosporin for psoriasis in

HIV-positive patient SiR,-HIV selectively attacks CD4-positive T helper lymphocytes, and their numbers gradually decrease, resulting in the clinical features of AIDS. The administration of cyclosporin to such patients might therefore be contraindicated since the drug is believed to exert its immunosuppressant effect mainly by inhibiting activation of these same CD4 lymphocytes. However, a report of a transplant patient who was HIV positive and received cyclosporin for 8 years without detriment indicated that this is not necessarily so.t In HIV-positive patients who also have psoriasis the skin disease is often severe and intractable, which is paradoxical since there is evidence of an increase in activated CD4 lymphocytes in the lesions2 and the response to treatment with cyclosporin is often very good.3 Cyclosporin has generally been avoided in HIV-positive psoriatic patients and its use has not been evaluated. We report findings showing that it may be beneficial rather than harmful. A 48-year-old homosexual man had had his first attack of psoriasis in 1977 and had one hospital visit for this in 1982. Otherwise the condition had caused little inconvenience. He was known to have acquired HIV infection in 1986 during a visit to Boston. In 1988 his psoriatic lesions recurred and although at first minor were nevertheless resistant to standard topical therapy. During the next year the problem steadily worsened and he had to give up work. Several hospital admissions for intensive therapy, which included zidovudine, methotrexate, and etretinate combined with topical corticosteroids, were of marginal benefit. Such was his distress that in August, 1990, when his CD4-positive lymphocyte count was as low as 0 04 x 10/1 he was given cyclosporin in a dose of 5 mg/kg, on the basis that the effects of cyclosporin would be rapidly reversible if his skin was not improved or his general condition worsened. There was immediate benefit with rapid clearing of the

psoriatic lesions and a pronounced improvement in his wellbeing, although his CD4 count remained low. Almost complete control of his skin problem was achieved and maintained for 12 months with 200 mg cyclosporin daily, before he eventually died from neurological complications in August, 1991. No opportunistic infections occurred apart from one brief episode of oral thrush that responded to nystatin. He showed no signs of the rapid deterioration in his general condition that was initially feared would result from additional immunosuppression by cyclosporin. In this patient, in addition to unequivocal clearing of the psoriasis, there was a distinct impression of general benefit from treatment with cyclosporin. This is not the first time such an observation has been made. Striking improvement was recorded with cyclosporin in a 38-year-old patient with end-stage AIDS but later the conclusion that cyclosporin could "cure" was thought to be premature after a report of one week’s trial in six patients without controls.4 Nevertheless there is evidence that cyclosporin could be of benefit in HIV infection. Duesberg5 pointed out that less than 1 % of T lymphocytes are infected with the virus and claimed that there must be an explanation, other than straight cytotoxicity by the retrovirus, for the steady drop in CD4 lymphocytes. An autoimmune reaction against T lymphocytes triggered by the virus is one possibility. This suggestion has been lent support by the fmding that macaque monkeys inoculated with human T lymphocytes are protected from infection with SIV, a disease widely used as an animal model for HIV.6 Additionally, the HIV glycoproteins gp 120 and gp 41 may closely resemble class II MHC proteins.7 This implies that an immune reaction against HIV might crossreact with antigens expressed on activated lymphocytes, the result of which would be a steady destruction of CD4 cellsIf this proposal is correct cyclosporin could, by inhibiting activation of

lymphocytes and the beneficial in AIDS.

expression

of class II MHC

antigens,

be

Department of Dermatology, University Hospital, Queen’s Medical Centre, Nottingham NG7 2UH, UK

B. R. ALLEN

Jacobson SK, Calne RY, Wreghitt TG. Outcome of HIV infection in transplant patients on cyclosporin. Lancet 1991; 337: 794. 2. Borel JF. Mechanism of action and rationale for cyclosporin A therapy for psoriasis. Br J Dermatol 1990; 122 (suppl 36): 5-12. 3. A consensus report: cyclosporin A therapy for psoriasis. Br J Dermatol 1990; 122 (suppl 36): 1-3. 4. Walgate R. Politics of premature French claim of cure. Nature 1985; 318: 3. 5. Duesberg P. AIDS epidemiology: inconsistencies with human immunodeficiency 1.

virus and infectious disease. Proc Natl Acad Sci USA 1991; 88: 1575-79. 6. Stott EJ. Anti-cell antibody in macaques. Nature 1991; 353: 393. 7. Fleury S, Lamarre D, Meloche S, et al. Mutational analysis of the interaction between CD4 and Class II MHC: Class II antigens contact CD4 on a surface opposite the gp120-binding site. Cell 1991; 66: 1037-49. 8. Maddox J. AIDS research turned upside down. Nature 1991; 353: 297.

In-vitro activity of zidovudine against

mycoplasma SiR,—Dr Lafeuillade and colleagues (Jan 11, p 131) report that growth of mycoplasmas is inhibited by zidovudine in vitro, and the topic of mycoplasmas in AIDS has generated much debate.’ We have investigated the mycoplasmastatic or mycoplasmacidal activity of zidovudine. One of us first used the metabolism-inhibition technique 25 years ago to determine the antibiotic sensitivity of mycoplasmas2 and we have since had considerable experience of the procedureWe have therefore used this method to test the activity of zidovudine in doubling concentrations ranging from 0.01 J1g/ml to 20 j.lg/ml against Mycopbs7m fermentans (incognitus and PG18 strains), M pneumoniae, M horrrinis, and Ureaplasma urealytictan. The question of cidal or static activity did not arise for the latter three microorganisms because none of these was inhibited by the concentrations of zidovudine tested. The growth of both strains of Mfermentans was inhibited only by 20 J1.g/ml of zidovudine, but successful subculture showed that the organisms had not been killed. Why our findings do not accord with those of the French group is uncertain but we are confident of our results. We think that the failure of zidovudine to affect mycoplasma growth means that inhibition by this drug is not a factor that needs to be considered in

687

attempts to recover mycoplasmas from HIV-positive patients with or without AIDS. The use of zidovudine is very unlikely to be the cause of the difficulties encountered in mycoplasma isolation. The fact that HIV-positive patients may be receiving antibiotics that are inhibitory to mycoplasmas should be noted and the possible inhibitory activity of other antiretroviral drugs should also be

considered. Division of Sexually Transmitted Diseases, Clinical Research Centre, Harrow, Middlesex HA1 3UJ, UK

D. TAYLOR-ROBINSON P. M. FURR

1. Editorial. Mycoplasma and AIDS: what connection? Lancet 1991; 337: 20-22. 2. Taylor-Robmson D. Mycoplasmas of various hosts and their antibiotic sensitivities.

Postgrad Med J 1967; 43: 100-04. 3. Taylor-Robinson D, Furr PM. The static effect of rosaramicin on Ureaplasma urealyticum and the development of antibiotic resistance. J Antimicrob Chemother 1982; 10: 185-91.

Ear malformation in baby born to mother using tretinoin cream SiR,—The teratogenic potential of vitamin A (retinol) and its congeners (tretinate, etretinate, isotretinoin, tretinoin) is well known. Tretinoin (all-trans-retinoic acid) is used for topical treatment of acne, and the use of retinoids on the skin with the hope of cutaneous rejuvenation has attracted great public interest. However, there are no adequate studies in pregnant women who have used gels, creams, or lotions containing tretinoin. Reproduction studies in rats and rabbits have not detected any important defect. We have seen a baby girl with crumpled hypoplastic ear and atresia of the external auditory meatus on the right side. She was bom at 41 weeks’ gestation to non-consanguineous healthy parents. At birth she weighed 2620 g ( < 3th centile) and length was 49 cm (25th centile) and head circumference 32-5 cm (3th centile). The eyes were normal, microbiological screens were negative, cerebral computed tomography showed no defect, and the halyotype was 46,XX. The mother had used ’Retin-A’ (tretinoin) cream 0-05% during the month before her last menstruation and during the first Iweeks of pregnancy. It is difficult to establish if the association between topical tretinoin and the ear malformation in this case is causal or fortuitous. Nonetheless, the mother used tretinoin cream in a critical period, the baby was small for dates, and the pattern of ear malformation was identical to that caused by vitamin A congeners. In Italy, product information on tretinoin cream does not mention the risk of teratogenicity, whereas in the USA the Physicians’ Desk Reference warns women to use the drug during pregnancy only if absolutely necessary. We thank Dr Edward J. Lammer for support. Centre for Human Genetics, Galliera Hospital, 16128 Genoa, Italy

GIANNI CAMERA

Department of Paediatrics, Savona

PAOLA PREGLIASCO

higher frequency

of side-effects with ACE

Heart failure can be regarded as a malignant disease and should be treated as such. Resources should be sought for basic investigations, including echocardiography, in all patients with heart failure, to confirm the diagnosis (as is required by doctors for most other malignant diseases) and to assess prognosis. Ignoring the possibility of syncope will not prevent it from happening. Good medical supervision can reduce the frequency of this complication and prevent its more severe sequelae. Your editorial, although rightly encouraging a more widespread use of ACE inhibitors, does both doctors and ACE inhibitors a disservice by failing to emphasise the importance of objectively establishing the presence of and cause of heart failure. Simple guidelines for the safe institution of ACE inhibitor therapy have been issued by the British Heart Foundation (Factfile, 1989) and should be adhered to in all patients receiving diuretic therapy. Department of Medicine (Cardiology), Royal Postgraduate Medical School, Hammersmith Hospital, London W12 0NN, UK

JOHN G. F. CLELAND

JGF, Dargie HJ, McAlpine H, et al. Severe hypotension after first dose of enalapril in heart failure. Br Med J 1985; 291: 1309-12. SOLVD Investigators Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325:

1. Cleland 2

293-302.

SIR,-Your suggestion that concern about side-effects has discouraged the use of ACE inhibitors in congestive heart failure prompted us to audit our practice in a district general hospital. Inpatients discharged between April and August, 1991, with a primary or secondary diagnosis of congestive heart failure were included, all now having at least six months’ follow-up. Demographic data were obtained from the case notes and cardiomegaly was assessed on chest radiograph. Echocardiogram results were included when available. 40 patients were identified, 2 of whom were excluded due to incomplete information in the case notes. In 3 cases, only acute anteroposterior chest radiographs were available, but 21 (60%) of the remaining 35 had cardiomegaly, a proportion similar to that in SOLVD (56%).1 Mean left-ventricular ejection fraction on echocardiography in 12 patients was 43% (25% in

SOLVD).

20 patients had been tried on an ACE inhibitor or were currently taking one. Of the 18 who had not, 5 had relative contraindications: aortic stenosis (2 patients, gradients 30 and 80 mm Hg), hypotension (2, systolic blood pressure 85 and 90 mm Hg), or severe renal impairment (1, creatinine 386 (miol/1), and 2 patients had severe disabling disease (cerebrovascular accidents with dense hemiplegia). Of the remainder, 7 were 80 years old or more and had mild disease, and another 2 had heart failure after myocardial infarction, and its chronicity was unconfirmed. We thus found that ACE inhibitor treatment had been used in more than half the patients, and where it had not there was often a sound reason. In SOLVD, 45% of patients were excluded because of "cardiovascular problems", "contraindications", or "lifethreatening illness".

ACE inhibitors and heart failure SiR,—The frequency of syncope after the first dose of an ACE inhibitor has fallen strikingly over the past decade. One of the implications of your Feb 1 editorial (p 278) was that since the frequency of syncope after the first dose of an ACE inhibitor was now as low as 0’5-2’2%, it could effectively be ignored. Since syncope after the first dose of an ACE inhibitor is not infrequently associated with cardiac, renal, and neurological complications,l and is occasionally fatal, even if the frequency of syncope were 0’ 1 % it would still be of considerable concern. You fail to point out that more than 85% of patients who qualified for entrance to the SOLVD study were excluded from randomisation for various reasons.2 The low frequency of reported syncope may be attributable not only to earlier institution of the ACE inhibitor but also to careful patient selection and good medical management. Additionally, the patients reported in the SOLVD study were fairly young, but most of those with heart failure are elderly and have a

inhibitors, including

syncope.

JOHN Y. YIANNAKOU Barnet General Hospital, Barnet EN5 3DJ, UK

KENNETH E. GRAY ROBERT J. D. WINTER

Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293-302

1. SOLVD

SIR,-We strongly support the appropriate use of ACE inhibitors in the treatment of heart failure. However, extrapolation from selected trials to clinical practice may mislead. Ischaemic heart disease commonly underlies heart failure. The benefits of or harm from ACE inhibition may depend in individual patients on the critical balance between the ischaemic problem (extent of coronary artery narrowing and risk of vessel occlusion) and the need to preserve remaining ventricular function.1 A serious omission in your Feb 1 editorial was comment on the CONSENSUS II trial, not yet published in full. This placebo

In-vitro activity of zidovudine against Mycoplasma.

686 We had planned a case-control study and we interviewed 13 men, from the same clinical practice as the men with KS, who were known to have had sex...
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