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GROWTH-HORMONE RESPONSE TO BROMOCRIPTINE IN PARKINSONISM
194 than for other women. Lehfeldt et al.’ suggested that this is because the antifertility effect of the i.u.c.D. is due to enzymatic or chemical action, possibly flowing retrogradely from the endometrium outwards. Hence the antifertility effect is greatest in the endometrium, weaker in the tubes, and absent beyond that. We suggested2 that the chemical action might be due to a substance resembling prostaglandins which is secreted abundantly from the endometrium, causing contractions and preventing implantation. Prostaglandin is also secreted from the fallopian tubes in less amounts. However, the non-contractile ovaries produce far less. Alternatively, we thought that the l.U.C.D. might alter the ratio of the prostaglandins secreted, so that tubal peristalsis is reversed and the ovum is carried the
opposite way.2 Although we agree with Mr Weekes and Dr Sutherst regarding the role of pelvic inflammatory disease, we would like to point out that this complication decreases with time from as high as 7-7/100 women during the first 15 days ofi.u.c.D. protection, to 0-9/100 women in the fourth to sixth years.3 Mishell et al.4 have shown that even when bacteria are introduced by I.U.C.D. insertion into the normally sterile uterus, the uterus becomes sterile once again within 30 days. Also it is generally agreed that pelvic infection which occurs later than the first month after I.U.C.D. insertion is usually due to venereal or intercourse-related causes.4-6 We believe that I.U.C.D. wearers are exposed to a greater risk of pelvic inflammatory disease because of more frequent and prolonged bleeding, which breaks down the normal cervical defences against the ascent of bacteria. Broadgreen Hospital, Liverpool. Department of Obstetrics and Gynæcology, University of Liverpool,
Liverpool.
SAMIA T. A. SAAFAN D. H. DARWISH
POSTOPERATIVE FEEDING AND METABOLISM
SIR,-We have applied the principles stated in your editorial’ to the management of an infant with intractable diarrhoea. The term intractable diarrhoea is applied by us to persistent diarrhoea in small infants associated with total sugar intolerance and poor absorption of protein and fat. These infants, if they are to survive, require prolonged parenteral nutrition. Intractable diarrhoea is a not infrequent problem in Malaysia. The infant, a male aged 1 month and weighing 2.5 kg was maintained for 1 week on ’Intralipid’ (4 g/kg), L-aminoacid (as ’Sohamin’) (550 mg nitrogen/kg), and 5% glucose. Volume requirements were based on 150 ml/kg. Over this period of 7 days, the infant received 80 cal/kg/day. The solutions were administered via peripheral veins. Morbidity was low compared with that noted in infants receiving aminoacid and 10% glucose solutions. During the period of 7 days the baby gained 300 g in weight. No cedema was noted, and protein, electrolyte, and acid-base studies during this period ranged as follows: plasma sodium 131-139, potassium 4.1-5.2, chloride 90-100, and serum-bicarbonate 22 mmol/1; blood-glucose 40 mg/dl; blood pH 7-33-7-40; serum total proteins 6.8and albumin
3.6 g/dl. We believe that this regimen requires further study, and we embarking on detailed metabolic studies of infants with intractable diarrhoea who are on this type of parenteral nutrition. are
Department of Pædiatrics, University Hospital, Kuala Lumpur, Malaysia. 1. 2.
N. IYNGKARAN M. J. ROBINSON
Lehfeldt, H., Tietze, C., Garstein, F. Am. J. Obstet. Gyn. 1970, 108, 1005. Darwish, D. H., Saafan, S. T. A. Brit. med. J. 1975, iv, 143. 3. Tietze, C. Stud. Family Plann. 1970, 55, 1. 4. Mishell, D. R., Bell, J. H., Good, R. G., Moyer, D. L. Am. J. Obstet. Gyn. 1966, 96, 119. 5. Kleinman, R. L. (editor) Intrauterine Contraception; p. 399. International Planned Parenthood Federation, London, 1972. 6. Statham, R., Morton, R. S. Br. med. J. 1968, iv, 623. 7. Lancet, 1975, ii, 263.
GROWTH-HORMONE RESPONSE TO BROMOCRIPTINE IN PARKINSONISM
SIR,-Dopaminergic mechanisms play a major role in hypothalamic function’ and are important regulators of growth hormone (G.H.) secretion.2 Oral levodopa given to parkinsonian patients causes a significant rise in G.H. concentrations after acute3 and chronic4 administration. Untreated parkinsonian patients have defective basal G.H. levels’ and impaired G.H. release with insulin-induced hypoglycaemia,6 possibly related to central dopamine deficiency. Levodopa increases G.H. levels in healthy people7 but in acromegaly it leads to a paradoxical reduction.8 Bromocriptine lowers G.H. levels in acromegalics9 10 and increases G.H. levels in normals." Little is known about the effects of bromocriptine on G.H. levels in parkinsonism. Debono et al.’ found an increase in G.H. concentrations in two out of seven patients after a single oral dose of 2’S5 mg bromocriptine. We report our findings in patients on maximum tolerated therapy. Nine patients with Parkinson’s disease who entered a therapeutic trial of bromocriptine" were studied. Patients were fasted overnight and confined to bed for 24 h to allow maximum resting conditions. Baseline evaluation was performed before therapy and again when the patient had received maximum tolerated dosage for at least 6 weeks. Bromocriptine (mean total dose 40 mg daily) was administered in three equally divided doses. Blood-samples for G.H. measurement were taken at 9 A.M. (fasting, 2 h after drug), noon (3 h after breakfast, 5 h after drug), and 5.30 P.M. (30 min before supper, 30 min and 41 h after drug), and a mean of the three values in each of the 2-day study periods was calculated. The average mean G.H. concentration before therapy was 19 mU/i (range 1’0-4-3) and during treatment was 3.1 mU/1 (range 1.8-5.0). The standard deviation of the differences was 179; p<0’10. There was no significant difference between levels at different times of the day. The basal G.H. levels are low and consistent with the previous observations in parkinsonism. However, compared with levodopa, the increase in G.H. after bromocriptine is modest and less than would be expected in normals." It has been suggested 14 that bromcriptine requires the presence of dopamine before a favourable therapeutic response can be obtained in parkinsonism, and it is possible that adequate hypothalamic dopamine concentrations are necessary for G. H. response to
bromocriptine. We thank Sandoz Products Ltd for supplies ot- bromocriptine.
K. M. SHAW A. J. LEES S. HAYES Departments of Neurology and Endocrinology, University College Hospital, London WC1E 6AU.
E. J. Ross G. M. STERN B. D. THOMPSON
Fuxe, K., Hökfelt, T. in Hypothalamus (edited by L. Martini, M. Motta, and F. Fraschini); p. 123. New York, 1969. 2. Martin, J. B., N. Engl. J. med. 1973, 288, 1384. 3. Boyd, A. E., Lebovitz, H. E., Pfeiffer, J. B. New Engl. J. Med. 1970, 283,
1.
1425.
Sirtori, C. R., Bolme, P., Azarnoff, D. C. ibid. 1972, 287, 729. Mena, I., Cotzias, E. C., Brown, F. C., Papavasilou, P. S., Miller, S. T. ibid. 1973, 288, 320. 6. Boyd, A. E., Lebovitz, H. E., Feldman, J. M. J. clin. Endocr. Metab. 1971, 33, 829. 7. Cavagnini, F., Peracchi, M., Scotti, G., Raggi, V., Pontivoli, A. E., Bana, R. J. Endocr. 1972, 54, 425. 8. Liuzzi, A., Chiodini, P. G., Botalia, L., Crennascoli, G., Silvestrini, F. J.J clin. Endocr. Metab. 1972, 35, 941. 9. Liuzzi, A., Chiodini, P. G., Botalia, L., Crennascoli, G., Muller, E. E., Silverstrini, F. J. clin. Endocr. Metab. 1974, 38, 109. 10. Thorner, M. O., Chait, A., Aitken, M., Benker, G., Bloom, S. R., Mortimer. C. H., Sanders, P., Stuart Mason, A., Besser, G. M. Brt. med.J. 1975. i, 299. 11. Camanni, F., Massara, F., Belforte, L., Molinatti, G. M. J. clin. Endocr Metab. 1975, 40, 363. 12. Debono, A. G., Donaldson, I., Marsden, C. D., Parkes, J. D. Lancet, 1975 ii, 987. 13. Lees, A. J., Shaw, K. M., Stern, G. M. Lancet, 1975, ii, 709. 14. Lieberman, A., Zolfaghari, M., Boal, D., Hassouri, H., Vogel, B. Vth International Symposium on Parkinson’s Disease, Vienna, 1975; abstr. 46 4. 5.
opposite way.2 Although we agree with Mr Weekes and Dr Sutherst regarding the role of pelvic inflammatory disease, we would like to point out that this complication decreases with time from as high as 7-7/100 women during the first 15 days ofi.u.c.D. protection, to 0-9/100 women in the fourth to sixth years.3 Mishell et al.4 have shown that even when bacteria are introduced by I.U.C.D. insertion into the normally sterile uterus, the uterus becomes sterile once again within 30 days. Also it is generally agreed that pelvic infection which occurs later than the first month after I.U.C.D. insertion is usually due to venereal or intercourse-related causes.4-6 We believe that I.U.C.D. wearers are exposed to a greater risk of pelvic inflammatory disease because of more frequent and prolonged bleeding, which breaks down the normal cervical defences against the ascent of bacteria. Broadgreen Hospital, Liverpool. Department of Obstetrics and Gynæcology, University of Liverpool,
Liverpool.
SAMIA T. A. SAAFAN D. H. DARWISH
POSTOPERATIVE FEEDING AND METABOLISM
SIR,-We have applied the principles stated in your editorial’ to the management of an infant with intractable diarrhoea. The term intractable diarrhoea is applied by us to persistent diarrhoea in small infants associated with total sugar intolerance and poor absorption of protein and fat. These infants, if they are to survive, require prolonged parenteral nutrition. Intractable diarrhoea is a not infrequent problem in Malaysia. The infant, a male aged 1 month and weighing 2.5 kg was maintained for 1 week on ’Intralipid’ (4 g/kg), L-aminoacid (as ’Sohamin’) (550 mg nitrogen/kg), and 5% glucose. Volume requirements were based on 150 ml/kg. Over this period of 7 days, the infant received 80 cal/kg/day. The solutions were administered via peripheral veins. Morbidity was low compared with that noted in infants receiving aminoacid and 10% glucose solutions. During the period of 7 days the baby gained 300 g in weight. No cedema was noted, and protein, electrolyte, and acid-base studies during this period ranged as follows: plasma sodium 131-139, potassium 4.1-5.2, chloride 90-100, and serum-bicarbonate 22 mmol/1; blood-glucose 40 mg/dl; blood pH 7-33-7-40; serum total proteins 6.8and albumin
3.6 g/dl. We believe that this regimen requires further study, and we embarking on detailed metabolic studies of infants with intractable diarrhoea who are on this type of parenteral nutrition. are
Department of Pædiatrics, University Hospital, Kuala Lumpur, Malaysia. 1. 2.
N. IYNGKARAN M. J. ROBINSON
Lehfeldt, H., Tietze, C., Garstein, F. Am. J. Obstet. Gyn. 1970, 108, 1005. Darwish, D. H., Saafan, S. T. A. Brit. med. J. 1975, iv, 143. 3. Tietze, C. Stud. Family Plann. 1970, 55, 1. 4. Mishell, D. R., Bell, J. H., Good, R. G., Moyer, D. L. Am. J. Obstet. Gyn. 1966, 96, 119. 5. Kleinman, R. L. (editor) Intrauterine Contraception; p. 399. International Planned Parenthood Federation, London, 1972. 6. Statham, R., Morton, R. S. Br. med. J. 1968, iv, 623. 7. Lancet, 1975, ii, 263.
GROWTH-HORMONE RESPONSE TO BROMOCRIPTINE IN PARKINSONISM
SIR,-Dopaminergic mechanisms play a major role in hypothalamic function’ and are important regulators of growth hormone (G.H.) secretion.2 Oral levodopa given to parkinsonian patients causes a significant rise in G.H. concentrations after acute3 and chronic4 administration. Untreated parkinsonian patients have defective basal G.H. levels’ and impaired G.H. release with insulin-induced hypoglycaemia,6 possibly related to central dopamine deficiency. Levodopa increases G.H. levels in healthy people7 but in acromegaly it leads to a paradoxical reduction.8 Bromocriptine lowers G.H. levels in acromegalics9 10 and increases G.H. levels in normals." Little is known about the effects of bromocriptine on G.H. levels in parkinsonism. Debono et al.’ found an increase in G.H. concentrations in two out of seven patients after a single oral dose of 2’S5 mg bromocriptine. We report our findings in patients on maximum tolerated therapy. Nine patients with Parkinson’s disease who entered a therapeutic trial of bromocriptine" were studied. Patients were fasted overnight and confined to bed for 24 h to allow maximum resting conditions. Baseline evaluation was performed before therapy and again when the patient had received maximum tolerated dosage for at least 6 weeks. Bromocriptine (mean total dose 40 mg daily) was administered in three equally divided doses. Blood-samples for G.H. measurement were taken at 9 A.M. (fasting, 2 h after drug), noon (3 h after breakfast, 5 h after drug), and 5.30 P.M. (30 min before supper, 30 min and 41 h after drug), and a mean of the three values in each of the 2-day study periods was calculated. The average mean G.H. concentration before therapy was 19 mU/i (range 1’0-4-3) and during treatment was 3.1 mU/1 (range 1.8-5.0). The standard deviation of the differences was 179; p<0’10. There was no significant difference between levels at different times of the day. The basal G.H. levels are low and consistent with the previous observations in parkinsonism. However, compared with levodopa, the increase in G.H. after bromocriptine is modest and less than would be expected in normals." It has been suggested 14 that bromcriptine requires the presence of dopamine before a favourable therapeutic response can be obtained in parkinsonism, and it is possible that adequate hypothalamic dopamine concentrations are necessary for G. H. response to
bromocriptine. We thank Sandoz Products Ltd for supplies ot- bromocriptine.
K. M. SHAW A. J. LEES S. HAYES Departments of Neurology and Endocrinology, University College Hospital, London WC1E 6AU.
E. J. Ross G. M. STERN B. D. THOMPSON
Fuxe, K., Hökfelt, T. in Hypothalamus (edited by L. Martini, M. Motta, and F. Fraschini); p. 123. New York, 1969. 2. Martin, J. B., N. Engl. J. med. 1973, 288, 1384. 3. Boyd, A. E., Lebovitz, H. E., Pfeiffer, J. B. New Engl. J. Med. 1970, 283,
1.
1425.
Sirtori, C. R., Bolme, P., Azarnoff, D. C. ibid. 1972, 287, 729. Mena, I., Cotzias, E. C., Brown, F. C., Papavasilou, P. S., Miller, S. T. ibid. 1973, 288, 320. 6. Boyd, A. E., Lebovitz, H. E., Feldman, J. M. J. clin. Endocr. Metab. 1971, 33, 829. 7. Cavagnini, F., Peracchi, M., Scotti, G., Raggi, V., Pontivoli, A. E., Bana, R. J. Endocr. 1972, 54, 425. 8. Liuzzi, A., Chiodini, P. G., Botalia, L., Crennascoli, G., Silvestrini, F. J.J clin. Endocr. Metab. 1972, 35, 941. 9. Liuzzi, A., Chiodini, P. G., Botalia, L., Crennascoli, G., Muller, E. E., Silverstrini, F. J. clin. Endocr. Metab. 1974, 38, 109. 10. Thorner, M. O., Chait, A., Aitken, M., Benker, G., Bloom, S. R., Mortimer. C. H., Sanders, P., Stuart Mason, A., Besser, G. M. Brt. med.J. 1975. i, 299. 11. Camanni, F., Massara, F., Belforte, L., Molinatti, G. M. J. clin. Endocr Metab. 1975, 40, 363. 12. Debono, A. G., Donaldson, I., Marsden, C. D., Parkes, J. D. Lancet, 1975 ii, 987. 13. Lees, A. J., Shaw, K. M., Stern, G. M. Lancet, 1975, ii, 709. 14. Lieberman, A., Zolfaghari, M., Boal, D., Hassouri, H., Vogel, B. Vth International Symposium on Parkinson’s Disease, Vienna, 1975; abstr. 46 4. 5.