50 CIGARETTE SMOKING AND RISK OF RETINOPATHY

it may be an idiosynwith the XYY sex-chromosome complement, a possibility suggested by the raised levels of prolactin found in others who have not been treated with lactogenic drugs. We would be interested to hear of any patients with this chromosome abnormality who experience the same side-effect on phenothiazine treatment or who are found to have raised prolactin levels when not on any drug therapy. Men with a 47,XYY karyotype at maximum security hospitals are above average height and are admitted in greater than expected numbers. The possibility that prolactin secretion is abnormal in these patients is therefore of interest since it is a hormone known to stimulate growth in some species and its secretion may be related to behaviour. are

given simultaneously. Alternatively,

crasy in

(3.8%). In contrast to the results of Paetkau et al. we found in non-smokers a strong relationship between proliferative retinopathy and duration of diabetes. Among non-smokers who had had diabetes for fifteen years or more, 15% had proliferative lesions (10 of 66). In long-duration cases who were smokers this rate was 9% (3 of 33). Among the 447 nonsmokers there were 166 former smokers. Rates of retinopathy (24-1%) and proliferative retinopathy (3-0%) were the same as in those who had never smoked. Mean duration of known diabetes was seven years in both of these subgroups. More data are needed but our results lend no support to the hypothesis that smoking is a risk factor for diabetic retinopathy. Diabetics should not smoke, because they are already at risk of coronary and peripheral vascular disease. Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, U.S.A.

KELLY M. WEST JUDY A. STOBER

PROLACTIN SECRETION IN XYY MALES the clinical examination of patients with a at a maximum security hospital, a 27-yearold man was found to have marked gynxcomastial and galactorrhoea. He had been aware of breast enlargement for about two years and during that time he was treated with fortnightly injections of 50 mg fluphenazine decanoate. Intermittent lactation had been occurring for several months. Mild gynscomastia had been noted when the patient had been treated with cestrogens 7 years earlier, but it was not known if this had persisted when treatment was discontinued after about a year. He refuses to provide further blood-samples. Gynaecomastia was not noted in any others with the same karyotype but in three, aged 23, 29, and 43 years, who had not received any drugs, the prolactin levels were 394, 745, and 426 mU/1, respectively, all of which are abnormally high. Several factors such as exercise,2 sleep,3 stress,2 and even venepuncture may raise circulating prolactin levels, but in blood-samples obtained in an identical manner, under similar conditions, from men at the same institution who only had one Y chromosome the prolactin levels were normal. ’Most males with a 47,XYY karyotype are free from physical abnormality, and the patient reported here is the first we have seen with any breast enlargement. We believe that the gynaecomastia and the lactation are complications of treatment with fluphenazine, but the severity seems disproportional to the dose of the drug and raises the possibility of an increased sensitivity. This could be related to the previous oestrogen administration since phenothiazine-stimulated prolactin secretion is augmented by aestrogens,4 but usually when the drugs

SIR,-During

47,XYY karyotype

Price, W. H., Brunton, M , Buckton, K. E., Jacobs, P. A. Clin Genet. 1976, 9, 389. 2. Noel, G. L., Sug, H. K., Stone, J G., Franz, A. G. J. clin. Endocr. Metab 1.

1972, 35, 840. 3. Sassin, J. F., Frantz,

A.

G., Weitz, E. D., Kapen, S. Science, 1972, 177,

1205. 4.

Buckman, M. T., Peake, G. T. J. clin. Endocr. Metab 1973, 37, 977.

men

We thank Dr E. A. Cameron of the regional hormone laboratory for estimations of prolactin and the consultant psychiatrists in charge of the patients at the security hospitals for kind cooperation.

Department of Medicine and M.R.C. Clinical and Population

Cytogenetics Unit, Western General Hospital, Edinburgh EH4 2XU

W. H. PRICE W. B. RENTON W. A. CAMPBELL

PROPRANOLOL THERAPY FOR SECONDARY HYPERPARATHYROIDISM IN URÆMIA

SiR,—The description by Dr Caro and Dr Besarab (April 15, p. 827) of a patient in whom propranolol decreased both raised

raised plasma-parathyroid-horreport the preliminary results of two studies on the interference of antihypertensive drugs with the hormonal control of calcium-phosphate homoeostasis in ursemic patients. In a first study, thirteen hoemodialysed patients were successively treated for 6-week periods with equally antihypertensive regimens of metoprolol, methyldopa, and clonidine. P.T.H. and plasma concentrations of calcitonin, calcium, and phosphate were measured before the first dialysis in the sixth week of each period of treatment. Throughout the study other theraa

mone

plasma-calcium and (P.T.H.) prompts us to

a

peutic measures were kept constant. Variance analysis showed no significant differences between the three treatments except that the predialysis plasma-calcium was lower after metoprolol (8-5 ±0-2 mg/dl) than after clonidine (9-2±0-2). Because a higher P.T.H. was not observed after metoprolol despite the fall in plasma-calcium, metoprolol could have had a greater suppressive effect or a lower stimulating effect on P.T.H. secretion than clonidine. Because the study produced no denmuve conclusion about the absolute effect of these antihypertensive drugs on the hormonal control of calcium phosphate homceostasis, we began a second study to evaluate the acute effects of propranolol and metoprolol on P.T. H. and plasma-calcitonin. Propranolol (blocking &bgr;I and 32 receptors) was given intravenously (priming dose 1 mg given over 5 min and 1 p.g/kg/min given over 85 min) to nine uraemic patients not yet on dialysis and metoprolol (blocking only 31 receptors) was given intravenously (priming dose 1.2mg given over 5 min and 1.2 ug/ kg/min given over 85 min) 15 days later to six of these patients. Venous blood was taken before and 15, 30, 60, and 90 min after starting the injection. P.T.H. and plasma concentrations of total and ionised calcium, phosphate, and calcitonin were measured. The antibody used for P.T.H. was specific for the fragment 1-34 and the native human molecule. There was no significant change at any time in phosphate or total ionised calcium. The significant decrease in heart-rate was of the same magnitude with both drugs, suggesting equally effective 31 receptor blockade. P.T.H. decreased significantly (by 36%) at 30 min with propranolol but did not decrease with metoprolol. Calcitonin also decreased significantly at 60 min after propranolol (by 40%) but did not change after metoprolol. It appears, therefore, that propranolol acutely suppresses

51 P.T.H. and calcitonin secretion in ursemic patients. Further studies are needed to assess their long-term effects on the secretion of these hormones and on renal osteodystrophy. The contrast between the significant effect of propranolol and the non-significant effect of metoprolol on P.T.H. and plasma-calcitonin supports the idea that P.T.H. and calcitonin secretion is modulated by specific &bgr;2 receptors. Our results thus accord with those of Aurbach et al.’1 A. FOURNIER B. COEVOET J. F. DE FREMONT J. GUERIS G. CAILLENS Service d’Hémodialyse du C.H.U., C. DESPLAN Amiens Hôpital Nord, C. CALMETTE 8000 Amiens, France M. S. MOUKHTAR et I.N.S.E.R.M. U 18 et U 113, Paris

Platelet-count

ASPIRIN FOR THE TREATMENT OF RECURRENT TOXÆMIA woman was seen in 1976 at the SacraMedical Center in her 29th week of pregnancy. She had

SIR,-A 31-year-old mento

hypertension (180/110 mm Hg), thrombocytopenia (pla000/jjd), and was delivered by cassarean section at approximately the 30th week. The infant weighted 870 g and died after 4 days with ascites, thrombocytopenia, and renal failure (mirror syndrome).2 The patient’s first pregnancy, managed elsewhere, had run a similar course. Between pregnancies her platelet-counts were normal, as were all other laboratory tests and physical findings. In the 15th week of gestation of her third pregnancy, her platelet-count was 59 000/ul and her hxmatocrit was 40%. Bone-marrow and peripheral-blood smear suggested peripheral consumption of platelets. There was no other laboratory suggestion of microangiopathic anxmia or consumption coagulopathy throughout her pregancy. She was treated with heparin 5000 units three times a day for 4 weeks with no appreciable effect on platelet-count. At the 22nd week, aspirin 600 mg three times a day was started, with gradual improve-’ ment in platelet-count (figure). The aspirin was discontinued in the 32nd week because of the fear of creating a closed fetal ductus. She then began to severe

during pregnancy.

Arrows represent dexamethasone 12 mg.

normotensive with sedation and bedrest. However,

at

her 33rd

hypertension (160/100 mm Hg) appeared, and platelet-count decreased to 50 000/1 and her haematocrit

week,

severe

her increased. The ultrasonic B scans had shown normal fetal growth and amniotic fluid up to the 28th week, but with the toxxmia fetal growth apparently ceased and amniotic fluid dis-

appeared.

again given aspirin and her platelet-count returned normal in the 34th week. Twice she was given dexamethasone to mature fetal lungs. The non-stress fetal heartrate test pattern showed variable decelerations, and we were unable to obtain further amniotic fluid for analysis. She was delivered by caesarean section of a 1410 g growth-retarded male fetus (placental weight 305 g) who showed no respiratory distress. The baby’s platelet-count was 180 000/1 and he did well. Post partum, the patient’s platelet-count remained normal, as did her blood-pressure. She showed a marked haemodilution in the post-partum period with a 30% fall in haematocrit. This case demonstrates the thrombocytopenia seen with some cases of recurrent toxxmia, as well as the possible beneficial effects of aspirin therapy. Aspirin may benefit thrombocvtopenia in children with the haemolytic ursemic syndrome.3 It She

was

to near

G. D., and others, Calc. Tissue Res. 1977, suppl. 22, 117. R., Cotton, D., Haesslein, H. Am J. Obstet. Gynec. in the 3. Arenson, E., August, C. J. Pediat. 1975, 86, 957.

1. Aurbach, 2. Goodlin,

press

aspinn.

may also ameliorate this type of recurrent toxasmia, which may be related to the post-partum haemolytic renal failure syndrome.

telet-count 40

experience painful uterine contractions and for the first time in this pregnancy, had mildly increased blood-pressure (150/88 to 150/92 mm Hg). She was admitted to hospital and became

,

ASA=

Sacramento Medical Center, Sacramento, California 95817, U.S.A. Glenn Memorial Hospital Willows, California

R. C. GOODLIN H. O. HAESSLEIN

J. FLEMING

COBALT IN URÆMIC CARDIOMYOPATHY

SIR,-Two years agol we presented a case with progressive renal failure and heart enlargement in association with a high serum concentration of cobalt. After kidney transplantation the heart size became normal as did the serum-cobalt, and urinary cobalt excretion was high. Among possible ursemic toxins to the heart (i.e., toxins producing uraemic cardiomyopathy with or without pericardial effusion) we have paid special attention to trace elements such as cobalt. Cobalt excretion depends on renal function. Cobalt is toxic to the myocardium. 1-4 Although the setiology of Quebec beer drinkers’ cardiomyopathy is considered multicausal, cobalt is thought to be the prime factor, and this has been supported by experimental evidence.5,6 Mohiuddin et al. have described an animal model for cobalt-induced cardiac disease which possesses the features of the disease as it occurs in man. We have now studied the cobalt concentration in the myocardium in four cases with progressive renal failure. At necropsy in all cases the myocardium was stiff and hypertrophied, especially the wall of the left ventricle and the septum which showed the features of a hypertrophic non-obstructive cardiomyopathy. The concentrations of cobalt in uraemic and normal heart tissue, measured by neutron-activation analysis, are presented in the table. All patients had high cobalt concentrations in the myocardium ranging from 3 to 23 times (mean 10 times) over the upper limit of normal concentrations as determined in the twenty normal controls presented by Wester.8 None of the patients had received treatment with cobalt, which we consider contraindicated in renal failure. 1. Lins, L. E., Pehrsson, K. Lancet, 1976, i, 1191. 2. Lamarche, M. Arnould, P., Koracev, V. Koracev, R. Biol. c. r. 1957, 157, 1415. 3. Jalavisto, E., Makkonen, E., Makkonen, H., Pallasvua, M. R. Ann. Acad.

Sci. fenn. 1965, 115, 1. 4. Semenova, L. A., Martyniuk, R. A., Martsinovich, V. P. Cor Vasa, 1975, 17, 145. 5. Sullivan, J., Woodbury, J., Degan, J. J. Lab. clin. Med. 1967, 70, 814. 6. Sullivan, J., Parker, M., Carson, S. B. ibid. 1968, 71, 813. 7. Mohiuddin, S., Taskar, P. K., Rheault, M., Roy, P-E., Chenard, J., Mosin, Y. Am Heart J. 1970, 80, 532. 8. Wester, P. O. Acta med. scand. 1965, suppl. 439.

Propranolol therapy for secondary hyperparathyroidism in uraemia.

50 CIGARETTE SMOKING AND RISK OF RETINOPATHY it may be an idiosynwith the XYY sex-chromosome complement, a possibility suggested by the raised levels...
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