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

818 of a

sample not representative practice is unjustified. U.C.H. Alcoholism Outpatient St. Pancras Hospital, London NW1

of the alcoholics

seen

in clinical

IDENTIFICATION OF SICKLE-CELL TRAIT AND HAMOGLOBiN C TRAITS IN CORD BLOOD

(Teaching) Centre, M. M. GLATT

IDENTIFICATION OF SICKLE CELL AND HÆMOGLOBIN C TRAITS IN CORD BLOOD

SIR,-Cellulose-acetate electrophoresis has been proposed initial screening procedure for detecting HbSS in cord blood, with verification of positive samples by citrate/agar-gel electrophoresis.1-1 However, application of this approach to as an

subtypes AS and AC (traits) is limited by the fact that very low concentrations of haemoglobins S and C at birth are not always detectable when cellulose-acetate electrophoresis is done at pH 8.4.2.4.5 Citrate/agar-gel electrophoresis as an initial screen 6-9 for HbSS is also limited because several non-A haemoglobins migrate as HbA on citrate/agar-gel;IQ-I2 and cellulose-acetate electrophoresis is further limited by the fact that certain non-S haemoglobins migrate with HbS at pH 8-40." Microcolumn chromatography has also been recommended for detecting haemoglobin abnormalities in the newborn.13,I4 However, as with the electrophoretic methods, homozygous conditions must be retested in one year to confirm sickle-cell disease (HbSS), HbCC disease, or sickle &bgr;’-thalassaemia; and additional procedures are necessary to distinguish HbS from HbD and HbC from HbE. In our cord-blood screening programme we do cellulose acetate and citrate/agar-gel electrophoresis simultaneously. This screening programme has been introduced in three hospitals in Indiana, and 6072 cord-blood samples have been tested. The specimens are clotted or anticoagulated red blood-cells, and they are tested immediately or stored at 4°C until analysis. The Helena Laboratories electrophoresis system (Beaumont Texas) was used on haemolysates on ’Titan III’ cellulose-acetate plates. The haemolysate is prepared by mixing two drops of unwashed cells with 6 drops of hasmolysate reagent, and electrophoresis is done at 450 V for 15 min in a "tris" boricacid buffer (pH 8.4, ionic strength 0.025). Citrate/agar-gel electrophoresis is done as described previously9 except that the gel is prepared by dissolving 1 g of ’Bacto-Agar’ (Difco Laboratories, Detroit) in 100 ml of sodium-citrate/citric-acid buffer (pH 6-20, ionic strength 0-OS). Of 3511 cord-blood samples from Indiana Blacks 5 were positive for HbSS, 4 for sickle C disease, 38 had Hb F and A plus Barts, 3 had Hb F, A, S, and Barts, 1 had Hb F, A, C, and Bart’s, 4 had Hb F and A plus D or G, and 1 had Hb F and A plus an unidentified haemoglobin. 267 (7-60%) were heterozygous for sickle-cell trait (FAS) and 80 (2.28%) were heterozygous for HbC trait with citrate/agar-gel electrophoresis. Among 2561 cord-blood samples from Whites 2 had sicklecell trait, 2 had HbC trait, 3 had Hb F and A plus Bart’s and 3 had Hb F and A plus D or G. Misdiagnosis of traits by cellulose-acetate electrophoresis during the initial screening procedure is shown in the table: all instances sickle cell and HbAC traits were detected with citrate /agar gel, but with cellulose acetate 14% of sickle-cell traits 1. Schneider, R. G., and others. Br. J. Hœmat. 1974, 28, 515. 2. Serjeant, B. E., and others. Clin. Chem. 1974, 20, 666. 3. Sexauer, C. L., Graham, H. L. Am. J. Dis. Child. 1976, 130, 805. 4. Hicks, E. J., Hughes, B. Clin. Chem. 1975, 21, 1072. 5. Hicks, E. J. Urban Hlth, 1975, 4, 18. 6. Pearson, H. A., and others. J. Am. med. Ass. 1974, 277, 666. 7. Van Baelen, H., Vandepitte, J., Eeckels, R. Ann. Soc. belg. med. trop.

1969, 49, 157. 8. Pearson, H. A., O’Brien, R. T. Am. J. Dis. Child. 1976, 130, 799. 9. O’Brien, R. T., McIntosh, S., Aspnes, G. J., Pearson, H. A. J. Pediat. 1976, 89, 205. 10. Schneider, R. G. C.D.C. Manual, Laboratory Methods of Hemoglobinopathy Detection; course 8983-C, p. 18. Atlanta, Georgia, 1973. 11. Hicks, E. J., Griep, J. A., Nordschow, C. D. Am. J. clin. Path. 1973, 60, 434. 12. Hicks, E. J., Griep, J. A., Nordschow, C. D. Lab. Med. 1974, 5, 6. 13. Powars, D., Schroeder, W. A., White, L. Pediatrics, 1975, 55, 630. 14. Schroeder, W. A., and others. J. Lab. clin. Med. 1975, 86, 528.

and 12% of HbC traits were missed. If cellulose acetate had been used alone we would have misdiagnosed 48 heterozygous conditions. However, when a more concentrated haemolysate is used or if the infant is re-tested in three or six months, cellulose-acetate (or starch-gel) electrophoresis confirms our initial results with citrate agar. The advantages of analysing cord-blood hxmolysates by both citrate/agar-gel and cellulose-acetate electrophoresis are:

(1.) The haemolysate prepared for cellulose acetate can be used for citrate/agar-gel electrophoresis at an additional cost of$1 per specimen4 (the combined cost for the two procedures being$2-50). (2.)

70-100

gel in 2 h. (3.) With

haemotysates

the

may be

grouped and

run on

,

I

citrate-agar

improved sensitivity of citrate/agar-gel electrophoresis

very low levels of Hb S and C at birth are detectable in traits.2-5 (4.) Hb Barts can be detected by cellulose-acetate electrophoresis,

permitting

identification of x-thalasssemias; this is

not

possible

on

citrate/agar gel. Non-S variants migrating with HbS on cellulose acetate are up by citrate/agar-gel electrophoresis, the roles being reversed for non-A variants.

(5.) picked

EDWARD J. HICKS WEI P. LOH ROBERT HAMILTON ROSIE HORTON

Department of Clinical Pathology Indiana University Medical Center, Indianapolis, Indiana 46202, U.S.A.

OF WATER WORMS AND OTHER WORMS worms coming from the cold water tap of a hospitall and the investigation of the reservoir in the roof spaces intrigued us. We were, however, jolted mid-sentence by the statement that an identical worm was found in an alveolus in a necropsy specimen. Tubifex, with dimensions of 1 cm in length and 1 mm in width, is too large to fit neatly into an alveolus. The accompanying figure, moreover, showed a section of lung tissue with what seems to be a nematode larva similar in appearance to a microfilaria. Judging from the size of the adjacent alveolar cells the dimensions of the worm would closely match those of the microfilaria of Wuchereria bancrofti or of Brugia spp. infecting man (approximately 275 (un x 7 fJ.l11). Although microfilariae are not usually found free in alveoli they do have a preference for the capillary bed of the lung, from which they could be easily freed into adjacent spaces during manipulations at necropsy.

SIR,-The description of Tubifex

U.S. Naval Medical Research Unit 2, Jakarta Detachment, Box 2 A.P.O. San Francisco, California 96356, U.S.A.

D. T. DENNIS PURNOMO

Department of Parasitology and General Pathology,

University of Indonesia School of Medicine Jakarta, Indonesia

***This letter has been shown

to

FELIX PARTONO

Dr

Tabaqchali,

whose

reply

follows.-ED. L. are not surprised that Dr Dennis and his colthink that the worm in the lung tissue was a microfilaria leagues of Wuchereria bancrofti or of Brugia spp., since filariasis is endemic in Indonesia. A similar diagnosis occurred to us, but we ruled it out because the specimen was normal lung tissue from a routine necropsy on a patient who had not travelled to

SIR,-We

1.

Tabaqchali, S., Stevens, J. K., Gazidis, C. Lancet, 1977, ii, 84.

I

Management of alcoholism.

817 effusions. Of the 53 minoxidil-treated patients with pericardial effusions 17 had no evidence of renal impairment or other known cause of pericard...
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