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-
817 effusions. Of the 53 minoxidil-treated patients with pericardial effusions 17 had no evidence of renal impairment or other known cause of pericarditis. 3 of these 17 had tamponade which was successfully treated by pericardectomy and in 2 the minoxidil was continued without recurrence of effusion. In 5 of the 17, effusions disappeared spontaneously without treatment while minoxidil was continued. Dr Martin suggests that effusions developing in minoxidil-treated patients with normal renal function may be part of the general fluid retention which occurs with this drug. The incidence may be less if fluid weight gain is prevented. Asymptomatic pericardial effusions may develop in patients treated with minoxidil, and only a proportion of these will have clinically detectable pericarditis. This may explain why so few cases have been reported. Echocardiography should be a routine part of the follow-up of patients on minoxidil until more is known about this complication. Pericardial effusion with tamponade is a well-known complication in patients on dialysis, but minoxidil therapy almost certainly increases the incidence, and the suggestion that minoxidil is preferable to bilateral nephrectomy for refractory hypertension in patients on dialysis2 seems to deserve closer examination. When pericardial effusion develops in a patient with normal renal function who is receiving minoxidil it may not be necessary to stop the drug, but the patient should be observed closely while excessive fluid retention is controlled. Department of Medicine, Toronto Western Hospital, Toronto, Ontario, Canada
ANNA MARQUEZ-JULIO P. ROBERT ULDALL
HÆMOPERITONEUM IN A TRANSSEXUAL
SIR,-Long-term therapy with sex steroids is associated with liver damage. Dr Westaby and his colleagues (Aug. 6, p. 261) found a high frequency of abnormal liver scans in female transsexuals taking 17 Ot-alkylated steroids while others3.4have described hepatic peliosis and neoplasia in females taking oral contraceptives. These patients often present as surgical emergencies with haemorrhage into the liver, peritoneal cavity, or both. A 69-year-old patient with Klinefelter’s syndrome was admitted to the Radcliffe Infirmary with severe abdominal pain and ansmia. For 20 years he had lived as a female, receiving stilboestrol implants every 6 months until 1975, when suppression of male secondary sex characteristics was continued with ethinyloestradiol (0.55 mg daily). There was no history of trauma. On admission he had right-upper-quadrant peritonitis, and a liver scan showed medial displacement of the right hepatic lobe. Coeliac angiography revealed zones of dilated hepatic vasculature but no evidence of tumour. At laparotomy a hsmoperitoneum was released and a large subcapsular hxmatoma adjacent to the right lobe of the liver was drained. This case is an indication that the use of long-term sex steroid therapy to induce gender change artificially has the risk of converting psychosexual problems into organic disease. Nuffield Department of Surgery, Radcliffe Infirmary, Oxford
J. I. BELL M. C. BISHOP B. J. BRITTON
SEX AND HISTOCOMPATIBILITY TESTING
SIR,-The
sex
difference in
histocompatibility matching
found by Dr Opelz and Professor Terasaki (Aug. 27, p. 419)
may indeed be due to the "less outspoken" character of female antigens, as Dr Ounsted and Dr Taylor suggest (Sept. 10, p. 2. Pettinger, W. A., Mitchell, H. C. New Engl. J. Med. 1973, 289, 167. 3 Chnstopherson, W. M., Mays, E. T. J. natn. Cancer Inst. 1977, 58, 167. 4 McAvoy, J. M., Tompkins, R. K., Longmire, W. P. Archs Surg. 1976, 761.
563). It might also, however, be in some manner connected with the fact that the female mammal is adapted to life with a
half-foreign fetus on board.
Since both this effect, and the fact that in mammals the female is homozygotic with respect to sex chromosomes, have been looked at by gerontologists as possible causes of the inherently lower age-specific mortality in females, it might be of interest to look at the histocompatibility of birds, where there is no close fetal connection and the female is heterozygotic. Any light on the feminine advantages conferred by like sex chromatin and higher autoimmune tolerance would be of great incidental interest to gerontology since in birds there is some evidence1,2 that the longevity/sex correlation may be reversed in favour of the male. Institute for Higher Studies, 2311 Garden Street, Santa Barbara, California 93108, U.S.A.
MANAGEMENT OF ALCOHOLISM
SiR,-The finding by workers at the Institute of Psychiatry, London, referred to in your editorial (Sept. 3, p. 488), that in randomised samples of alcoholics "advice" alone did not lead results than "treatment" is very surprising. Most of the alcoholics I saw in clinics and hospitals and on domiciliary visits could not have been safely left with advice. Even in the absence of definite physical or mental complications, many had abnormal liver-function tests; there were those who were very depressed and talked of suicide or who were misusing other drugs and those who drove cars while affected by alcohol; some alcoholics lived on their own and could not look after themselves ; and there were wives who planned to leave home because their husbands had so often broken their promises to keep off drink. In practice, since alcoholics were often not willing to have treatment (or treatment was not available) many did get advice only-and they turned up again and again, often requiring admission elsewhere while in a much worse condition, and sometimes when action was delayed the patient died. There must, therefore be some striking difference between the "alcoholics" Dr Edwards and his colleagues studiedand those seen by me over the years. Among the criteria for inclusion in this study were "that a referring agent considered the patient to have a drinking problem ... [and] the psychiatrist’s confirmation that a drinking problem existed". The term "drinking problem" is even more ambiguous than "alcoholic". "Problem drinkers" probably include some with minor alcohol problems, and many problem drinkers will respond to informed, sympathetic advice. But the situation is surely very different for the addict with psychological and/or physical dependence on alcohol. The drinkers all attended a family clinic with .their wives, spending three hours in assessment; and there seems to have been no great discrepancy at assessment or during follow-up between the independent evidence of husband and wife. This is strange, because when a drinker and his wife are interviewed independently their stories as a rule are so different that one often wonders whether the two are talking about the same person. Again this suggests that the research sample contained more early problem drinkers than would be found in clinical practice. Informed advice such as that given to the untreated group in this study may often be sufficient for problem drinkers (especially when coupled with a recommendation that they join Alcoholics Anonymous), but for the many who require treatment there is still a woeful lack of community and inpatient services. No-one doubts the overriding importance of preventionor research, but to ask, as you do, for a radical recasting of the services for alcoholism in the light of a study to worse
Eisner, E. Expl Geront. 1967, 2, 187. Cherkin, A., Eckhardt, M J. J. Geront 1977, 32, 38. 3. Edwards, G., and others J. Stud. Alcohol, 1977, 38, 1004. 4. Glatt, M. M. Alcoholism: a Social Disease; p. 193. London, 1976. 1. 2.
111,
ALEX COMFORT
t
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-
817 effusions. Of the 53 minoxidil-treated patients with pericardial effusions 17 had no evidence of renal impairment or other known cause of pericarditis. 3 of these 17 had tamponade which was successfully treated by pericardectomy and in 2 the minoxidil was continued without recurrence of effusion. In 5 of the 17, effusions disappeared spontaneously without treatment while minoxidil was continued. Dr Martin suggests that effusions developing in minoxidil-treated patients with normal renal function may be part of the general fluid retention which occurs with this drug. The incidence may be less if fluid weight gain is prevented. Asymptomatic pericardial effusions may develop in patients treated with minoxidil, and only a proportion of these will have clinically detectable pericarditis. This may explain why so few cases have been reported. Echocardiography should be a routine part of the follow-up of patients on minoxidil until more is known about this complication. Pericardial effusion with tamponade is a well-known complication in patients on dialysis, but minoxidil therapy almost certainly increases the incidence, and the suggestion that minoxidil is preferable to bilateral nephrectomy for refractory hypertension in patients on dialysis2 seems to deserve closer examination. When pericardial effusion develops in a patient with normal renal function who is receiving minoxidil it may not be necessary to stop the drug, but the patient should be observed closely while excessive fluid retention is controlled. Department of Medicine, Toronto Western Hospital, Toronto, Ontario, Canada
ANNA MARQUEZ-JULIO P. ROBERT ULDALL
HÆMOPERITONEUM IN A TRANSSEXUAL
SIR,-Long-term therapy with sex steroids is associated with liver damage. Dr Westaby and his colleagues (Aug. 6, p. 261) found a high frequency of abnormal liver scans in female transsexuals taking 17 Ot-alkylated steroids while others3.4have described hepatic peliosis and neoplasia in females taking oral contraceptives. These patients often present as surgical emergencies with haemorrhage into the liver, peritoneal cavity, or both. A 69-year-old patient with Klinefelter’s syndrome was admitted to the Radcliffe Infirmary with severe abdominal pain and ansmia. For 20 years he had lived as a female, receiving stilboestrol implants every 6 months until 1975, when suppression of male secondary sex characteristics was continued with ethinyloestradiol (0.55 mg daily). There was no history of trauma. On admission he had right-upper-quadrant peritonitis, and a liver scan showed medial displacement of the right hepatic lobe. Coeliac angiography revealed zones of dilated hepatic vasculature but no evidence of tumour. At laparotomy a hsmoperitoneum was released and a large subcapsular hxmatoma adjacent to the right lobe of the liver was drained. This case is an indication that the use of long-term sex steroid therapy to induce gender change artificially has the risk of converting psychosexual problems into organic disease. Nuffield Department of Surgery, Radcliffe Infirmary, Oxford
J. I. BELL M. C. BISHOP B. J. BRITTON
SEX AND HISTOCOMPATIBILITY TESTING
SIR,-The
sex
difference in
histocompatibility matching
found by Dr Opelz and Professor Terasaki (Aug. 27, p. 419)
may indeed be due to the "less outspoken" character of female antigens, as Dr Ounsted and Dr Taylor suggest (Sept. 10, p. 2. Pettinger, W. A., Mitchell, H. C. New Engl. J. Med. 1973, 289, 167. 3 Chnstopherson, W. M., Mays, E. T. J. natn. Cancer Inst. 1977, 58, 167. 4 McAvoy, J. M., Tompkins, R. K., Longmire, W. P. Archs Surg. 1976, 761.
563). It might also, however, be in some manner connected with the fact that the female mammal is adapted to life with a
half-foreign fetus on board.
Since both this effect, and the fact that in mammals the female is homozygotic with respect to sex chromosomes, have been looked at by gerontologists as possible causes of the inherently lower age-specific mortality in females, it might be of interest to look at the histocompatibility of birds, where there is no close fetal connection and the female is heterozygotic. Any light on the feminine advantages conferred by like sex chromatin and higher autoimmune tolerance would be of great incidental interest to gerontology since in birds there is some evidence1,2 that the longevity/sex correlation may be reversed in favour of the male. Institute for Higher Studies, 2311 Garden Street, Santa Barbara, California 93108, U.S.A.
MANAGEMENT OF ALCOHOLISM
SiR,-The finding by workers at the Institute of Psychiatry, London, referred to in your editorial (Sept. 3, p. 488), that in randomised samples of alcoholics "advice" alone did not lead results than "treatment" is very surprising. Most of the alcoholics I saw in clinics and hospitals and on domiciliary visits could not have been safely left with advice. Even in the absence of definite physical or mental complications, many had abnormal liver-function tests; there were those who were very depressed and talked of suicide or who were misusing other drugs and those who drove cars while affected by alcohol; some alcoholics lived on their own and could not look after themselves ; and there were wives who planned to leave home because their husbands had so often broken their promises to keep off drink. In practice, since alcoholics were often not willing to have treatment (or treatment was not available) many did get advice only-and they turned up again and again, often requiring admission elsewhere while in a much worse condition, and sometimes when action was delayed the patient died. There must, therefore be some striking difference between the "alcoholics" Dr Edwards and his colleagues studiedand those seen by me over the years. Among the criteria for inclusion in this study were "that a referring agent considered the patient to have a drinking problem ... [and] the psychiatrist’s confirmation that a drinking problem existed". The term "drinking problem" is even more ambiguous than "alcoholic". "Problem drinkers" probably include some with minor alcohol problems, and many problem drinkers will respond to informed, sympathetic advice. But the situation is surely very different for the addict with psychological and/or physical dependence on alcohol. The drinkers all attended a family clinic with .their wives, spending three hours in assessment; and there seems to have been no great discrepancy at assessment or during follow-up between the independent evidence of husband and wife. This is strange, because when a drinker and his wife are interviewed independently their stories as a rule are so different that one often wonders whether the two are talking about the same person. Again this suggests that the research sample contained more early problem drinkers than would be found in clinical practice. Informed advice such as that given to the untreated group in this study may often be sufficient for problem drinkers (especially when coupled with a recommendation that they join Alcoholics Anonymous), but for the many who require treatment there is still a woeful lack of community and inpatient services. No-one doubts the overriding importance of preventionor research, but to ask, as you do, for a radical recasting of the services for alcoholism in the light of a study to worse
Eisner, E. Expl Geront. 1967, 2, 187. Cherkin, A., Eckhardt, M J. J. Geront 1977, 32, 38. 3. Edwards, G., and others J. Stud. Alcohol, 1977, 38, 1004. 4. Glatt, M. M. Alcoholism: a Social Disease; p. 193. London, 1976. 1. 2.
111,
ALEX COMFORT
t
