CORTICOSTEROID THERAPY FOR MALE AUTOIMMUNE INFERTILITY

815 We

collected, preserved, and stored

serum

of five

M.S.

and five

non-demyelinating neurological patients, using Carp’s method.2 Each specimen was injected intraperitoneally into 5 non-infected, inbred C3H/He, weanling, female mice. Peripheral blood was taken from the mice at 11 A.M., 1 week and 3 weeks after injections. P.M.N. counts were done on the mouse peripheral-blood smears by an independent "blind"

patients

observer. The table shows that there was no statistical difference in the P.M.N. counts of M.S. compared with non-M.S. injected mice at 1 week or 3 weeks. We therefore failed to reproduce Carp’s experiment even though we took care to eliminate many of the variables which may influence P.M.N. counts in mice.] Others have also failed to reproduce this experiment. 4,5 Our results confirm the difficulties in experimental work where many biological variables may influence results. Department of Neurology, Groote Schuur Hospital, Cape Town, South Africa

BRYAN M. KIES FRANCES AMES

FAMILIAL SUSCEPTIBILITY TO LUNG CANCER

AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE

SIR,-Professor Cohen and her colleagues (Sept. 10, p. 523) have shed new insight on the aetiology of lung cancer and chronic obstructive pulmonary disease (C.O.P.D.). Pulmonaryfunction studies on first-degree relatives of lung cancer and C.O.P.D. probands and controls purport to correlate a common familial predisposing factor to both diseases. Indeed Cohen et al. suggest that detection of lung-cancer susceptibility might in part be accomplished through the recognition of impaired forced expiration. We have observedacommon thread in the two diseases in a study of 12 families prone to lung cancer (defined as two, or more first-degree relatives with histologically verified bronchogenic carcinoma). There were 29 verified lung-cancer patients in these pedigrees. Cancer at all anatomic sites showed a significant excess in first-degree relatives when compared with second and third degree relatives (P<005). In the 12 families, the frequency of C.O.P.D. exhibited a positive association with increasing genetic relationship (co-ancestry) to lungcancer probands. These frequencies (9% of first-degree and 3% of second-degree relatives) were based upon medical history and are probably underestimates, pulmonary-function studies not being done. However, Kueppers et al. found a high correlation between medical history of C.O.P.D. and data from pulmonary-function studies. An analysis of the variation in age of onset of lung cancer among and within our families showed a lack of correlation among siblings of the same family (intra-class correlation, 29.9%). Moreover, the age of lung-cancer onset in our families did not differ significantly from population expectations. This contrasts with a pattern witnessed in families prone to cancer of other anatomic sites-namely, that virtually all histological varieties of familial cancer occur at an earlier age than in the general population.s The interaction of genetic and environmental factors in inducing a lesion with such a strong exogenous component (such as lung cancer) may be such that prolonged exposure to carcinogens is required before its phenotypic expression. Therefore, it is conceivable that environmental factors are obscuring the significance of genetic factors. 3.Russell, E

S., Newfeld, E. F., Higgins, C. T. Proc. Soc. exp. Biol. Med. 1951, 78, 761. 4.Brown, P., Gajdusek, D.C.Nature, 1974, 247, 217. 5 Madden, D. L., Kreslewicz, A., Gravell, M., Sever, J. L. Neurology, 1977, 27, 371. 6. Lynch, H. T., Guirgis, H. A., Harris, R. E., Swartz, M. J. in Proceedings, Tobacco and Health Institute, Lexington, Kentucky (in the press). 7. Kueppers, F., Miller, R. D., Gordon, H., Hepper, N. G., Offord, K. Am. J. Med. 1977, 63, 336. 8.Lynch, H.T.Cancer Genetics; p. 639. Springfield, Illinois, 1976.

The observations of Cohen at al. and our findings6 clearly show the importance of careful evaluation of associated pulmonarv disease in the study of families prone to lung cancer. Department of Preventive Medicine/Public Health, Creighton University School of Medicine, Omaha, Nebraska 68178, U.S.A.

HENRY T. LYNCH HODA A. GUIRGIS RANDALL E. HARRIS

CONTRIBUTIONS AND EDITORIAL PRIVILEGE interested in the report by Dr Howe and his colleagues (Sept. 17, p. 578) on artificial sweeteners and human bladder cancer and your editorial comment on it in the same issue. Valuable though both accounts are, I wish to make a few remarks, not on the oncological/epidemiological problem of the saccharin-cancer relationship but on the more general issue of scientific communication and editorial privilege. A group of scientists has submitted a paper to your journal; you have studied it, accepted it, and published it. You do not agree with it and in your editorial you state that "The Lancet is publishing the work so that data on which the claimed association is based are available for independent assessment by a wider audience. Under such scrutiny certain weaknesses in the study can hardly be overlooked". Perfectly fair. But you then plunge into a full page of commentary questioning the method and conclusions of your contributors and politely but thoroughly tearing apart the whole paper. Disquieting questions on the extent of editorial privilege and editorial power thus loom into the picture. Were the contributors informed that they would be subjected to such editorial mauling? If the paper was published "so that data ... are available for independent assessment by a wider audience" does not your attack prejudge the issue for that wider audience? Should you not have asked for and published the authors’ comments or rebuttal in the same issue? Publishing other signed contributions presenting opposing views would be perfectly acceptable, but does not an unsigned editorial influence the "independent assessment" that you are seeking? Some journals do publish original contributions together with several papers from referees and editors, agreeing or disagreeing with the work. Current Anthropology does this admirably, but then its contributors know and agree with the system. This is not established practice in The Lancet, and picking on one group of authors smacks of unfairness, for which your journal is not known. And to clarify my "independence" as far as the subject matter of the controversy is concerned, I do not know Dr Howe and his colleagues, I take saccharin, and I smoke, and, like you, until more convincing data are presented I do not believe that artificial sweeteners create bladder cancer. But that is not the issue.

SIR,-I

was

5 Chemin de Tavernay, 1218 Geneva, Switzerland

*** Dr Howe and his do.-ED. L.

S. W. A. GUNN

colleagues

were

told what

we

planned to

CORTICOSTEROID THERAPY FOR MALE AUTOIMMUNE INFERTILITY

SiR,—Shulman* has described the successful treatment of male autoimmune infertility with a high dose of methylprednisolone (’Medrol’). We wish to report a similar success. A young couple with two years’ primary infertility came to us to be tested for anti-sperm antibodies. Gynaecological findings were negative except for persistent poor post-coital tests. In the husband’s past history there was an operation for inguinal hernia, three years before. The husband had a normal sperm-count but on examination the sperm showed asthenozoospermia, necrospermia, and a marked tail-to-tail autoagglu1.

Shulman, S. Lancet, 1976, ii, 1243.

816 MONOAMINE-OXIDASE INHIBITORS AND CAVIAR

tination. The titres of spermagglutinating antibodies in his serum and seminal plasma were 1/160 and 1/32, respectively in Kisbrick testing.2 The serum also had spermatotoxic activity (60% at the 1/5 dilution) as evaluated by the Hamerlinck modified technique.2 The patient took 2 mg dexamethasone acetate daily for three months and then decreasing doses for three months. Blood and sperm were sampled one month before therapy began, at the second and the fifth month of treatment, and two months after treatment ended.

SIR,-A 65-year-old woman had been taking ’Parstelin’ tablets (tranylcypromine 10 mg, trifluoperazine 1 mg), one three times daily for a depressive illness for 4 years with apparent therapeutic benefit. Her physical health was good and in 1976 her blood-pressure was 130/80 mm Hg. On Jan. 1, 1977, she took her third parstelin tablet of the day at 6.45 P.M. At 7.30 P.M. she had three or four heaped tablespoonsful of Iranian caviar. At 8.10 she had a "bursting" headache, nausea, and palpitations and felt very hot. One of us (P.I.) was called to see her and arrived at 8.15. He found the patient very distressed and anxious. She felt that her body was going to explode and that she was going to die. Her face was bright red. The upper chest was "goose pimpled" and she was sweating profusely. The conjunctive were suffused. Her pulse-rate was 84/min with frequent ectopic beats. Blood-pressure was 210/120 mm Hg. In the ambulance she improved, and by the time she reached hospital her blood-pressure was 120/50 mm Hg pulse 84/min, and there was no sweating, and the headache had nearly gone. She had fully recovered the next day and her blood-pressure was 130/80 mm Hg. A few years previously she had taken some soup with cheese in it and had had a similar but more severe and prolonged attack. Russian (not Iranian) caviar was obtained from a delicatessen in Oxford. Extracts were analysed by thin-layer chromatography, paper chromatography, and spectrophotofluorimetry. Tyramine was identified by all three methods, and the caviar analysed contained 0.68 mg/g. We calculated that the patient ate about 60 mg of tyramine, certainly enough to produce hypertension in a patient on M.A.o. inhibitors.’ Because of the flushing the caviar was also analysed for histamine, but none was identified. To the long list of foodstuffs!,2 containing amines which might produce hypertensive reactions in patients taking M.A.o. inhibitors should be added Iranian and Russian caviar. Wheatley,

EFFECT OF DEXAMETHASONE THERAPY ON

PATIENT’S

SPERM

P. ISAAC

Oxfordshire

M.R.C. Unit and University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford OX2 6HE

B. MITCHELL D. G. GRAHAME-SMITH

PERICARDIAL EFFUSIONS ASSOCIATED WITH MINOXIDIL

*

Mean values from 5 sperm examinations.

t 2 mg/day dexamethasone. :B: Decreasing doses of dexamethasone. The patient’s wife became pregnant during the fifth month of his treatment. At this time the titre of serum spermagglutinins was reduced and seminal plasma agglutinins and serum spermatotoxins had virtually disappeared (see figure). The sperm had normal morphological and behavioural features (see

table). In samples taken two months after treatment, serum spermatotoxic activity had reappeared but spermagglutinating antibodies remained in low titre. Sperm auto-agglutination was again observed morphologically despite the absence of agglutinating antibodies in the seminal plasma. Inserm U

23,

Hôpital Saint-Antoine, 75571 Paris Cédex 12, France

M. DE ALMEIDA

Laboratoire d’Histologie, Centre Hospitalier du Kremlin-Bicêtre, 94270 Le Kremlin, France

J. C. SOUFIR

SIR,-Dr Dargie and his colleagues (Sept. 10, p. 515) have demonstrated the efficacy of monoxidil in resistant hypertension. We have also been impressed with the value of this drug in refractory hypertension, but have had problems with pericardial effusions.3 Of 18 patients treated by us for refractory hypertension, 7 (39%) had pericardial effusions. Of these 7 patients, 4 had terminal renal failure and were on dialysis, 1 had moderate renal insufficiency, and 2 had normal renal function. All were symptom-free except for 1 patient whose hypotension during hsemodialysis may have reflected a degree of tamponade. Pericardial friction rubs were heard in only 4 but echocardiography was diagnostic in all 7. In the 2 patients with normal renal function, the pericardial effusion re? ’ved in 1 within 2 weeks of the drug being stopped while the other patier.t has remained symptom-free while continuing to receive minoxidil, and the effusion has persisted. Dr William B. Martin (personal communication) has reviewed the worldwide incidence of pericardial effusion in 1760 patients whose course on minoxidil therapy had been reported to Upjohn (Kalamazoo, Michigan) up to June, 1977. 53 cases of pericardial effusion were reported (3%). Fatal tamponade developed in 7 of 18 haemodialysis patients who had 1. 2

Massey Stewart, M. Adverse Drug Reaction Bull. 1976, 58, 200. Marley, E. in Drug Interactions (edited by D. G. Grahame-Smith); p. 171

3.

Marquez-Julio, A., From, plant Ass. (in the press).

London, 1977. 2. Rose, N. R., Hjort, T., Rümke, Immun. 1976, 23, 175.

Ph., Harper, M. J. K., Vyazov, O. Clin. exp.

G. L. A.,

Uldall,

P. R. Proc. Eur.

Dialysis Trans-