1169
creatinine; p < 0 05, Wilcoxon’s test). In the non-sensitive group there seemed to be a negative correlation between the pressor dose (the smallest amount of angiotensin II per kg body weight per min which causes a 20 mm Hg rise in diastolic blood pressure) and urinary 2,3-dinor-TxB,. Our data confirm that observation of Fitzgerald et al by linking increased platelet activation to pregnancy-induced hypertension. However, we also found increased platelet thromboxane formation
patients at risk of pre-eclampsia, even before hypertension developed. This could be an argument for the use of platelet inhibitors such as low-dose aspirin in primigravid women at risk of pregnancy-induced hypertension, even before hypertension is in
apparent. C. VAN GEET B. SPITZ
Department of Obstetrics and Gynaecology, University Hospital of Leuven, Campus Gastuisberg, B-3000 Leuven, Belgium
VERMYLEN F. A. VAN ASSCHE
J.
B. Prostacyclin-thromboxane A2 in normal and hypertensive pregnancy. Doctoral thesis, University of Leaven, 1987: 26. 2. Gant NF, Chand S, Worley RJ, et al. A clinical test useful for predicting the development of acute hypertension in pregnancy. Am J Obstet Gynecol 1974; 120: 1-7. 3. Van Geet C, Arnout J, Eggermont E, et al. Urinary thromboxane B, and 2,3-dinor-thromboxane B; in the neonate born at full-term age. Eicosanoids 1990; 3: 39-43.
1. Spitz
SIR,-Dr Fitzgerald and colleagues report increased excretion of thromboxane B2 (TxB2) metabolites, indicating increased TxA; production, in eight pregnant women with hypertension and albuminuria (pre-eclampsia). They suggest that aspirin should be used to prevent and treat pre-eclampsia. However, as emphasised, aspirin both decreases production of platelet aggregatory and vasoconstrictive thromboxane and reduces the anti-aggregatory and vasodilatory prostacyclin, which is already low in pregnancyinduced hypertension. This may limit the benefit of aspirin in pregnant women: decreased prostacyclin production may reduce responsiveness to pressor agents systemically and in the placental circulation. We have suggested the use of fish oil fatty acids of the n-3 family, especially eicosapentaenoic acid (EPA), to prevent pre-eclampsia.1 Greenland Eskimos are less susceptible than Danes to pre-clampsia and there is a shift in tissue and plasma levels from n-6 to n-3 polyunsaturated fatty acids in Greenlanders due to their high consumption of seafood.2 EPA decreases the formation of TxAj and induces the production of inactive TxA3; it also increases production of prostacyclin 12 and induces the formation of prostacyclin 13, which is as active as prostacyclin 1 Furthermore EPA is effective in hypertension.’ Thus EPA may possess some of the favourable effects of aspirin against pre-eclampsia without the undesirable actions. Gentofte Clinical Chemical Laboratory, DK-2800 Lyngby, Denmark
HANS OLAF BANG
Medi-Lab A/S, Copenhagen
JØRN DYERBERG
Pre-eclampsia and prostaglandins. Lancet 1985; i: 1267. J, Bang HO, Hjøme N. Fatty acid composition of the plasma in Greenland Eskimos. Am J Clin Nutr 1975;: 28: 958-66. 3. Fischer S, Weber PC, Dyerberg J. The prostacyclin/thromboxane balance is favourably shifted in Greenland Eskimos. Prostaglandins 1986; 32: 235-41. 4. Bønaa KH, Bjerve KS, Straume B, Gram IT. Effect of eicosapentaenoic and docosahexaenoic adds on blood pressure in hypertension: a population-based intervention trial from the Tromso study. N Engl J Med 1990; 322: 795-801. 1. Dyerberg J, Bang HO.
2. Dyerberg
Central pontine myelinolysis and changes in serum
SiR,—Your April
7 editorial
on
sodium the management of symptomatic
hyponatraemia advises that the rate of rise of serum sodium should be kept below 0-5 mmol/1 per hour
to avoid central pontine CPM has also been linked to the hyperosmolality of serum found in burns patients,l and one of these patients had a normal serum sodium during the hyperosmolar
myelinolysis (CPM).
In three of the cases of CPM reported by Boon et al,2 one bone marrow graft and two developing after liver transplantations, the rises in serum sodium were 03, 025, and 0-15 mmol/1 per hour, well within the recommended safety limit. Treated hypernatraemia was a feature in every case but was not commented upon. The rapid rises in serum sodium and osmolality which may develop after the surgical clipping of some anterior communicating and anterior cerebral artery aneurysms because of transient postoperative diabetes insipidus or during a positive water deprivation test for cranial diabetes insipidus are not associated with osmotic demyelination syndromes, despite rates of change in serum sodium of 2-4 mmol/1 per hour. For example, if a 70 kg male reaches the 4% loss of body weight termination point in the water deprivation test for cranial diabetes insipidus,3 his serum sodium will have risen by about 9 mmol/1 over 2-4 hours. This is a much greater rate than that considered safe in the treatment of hyponatraemia. Thus in CPM, the rate of change in osmolality, the length of time that this rate change persists,4and the clinical condition of the patient are all important factors.
episode. after
a
Department of Chemical Pathology, Beaumont Hospital, Dublin 9, Ireland
W. P. TORMEY
1. McKee
AC, Winkelman MD, Banker B. Central pontine myelinolysis in severely burned patients: relationship to hyperosmolality. Neurology 1988; 38: 1211-17. 2. Boon AP, Carey MP, Salmon MV. Central pontine myelinolysis not associated with rapid correction of hyponatraemia. Lancet 1988; ii: 458. 3. Ismail AAA. Disorders of the antidiuretic hormone. In: Biochemical investigations in endocrinology: methods and interpretations. London: Academic Press, 1981: 132-42. 4. Laureno R, Karp BI. Pontine and extrapontine myelinolysis following rapid correction of hyponatraemia. Lancet 1988; i: 1439-41.
Thalassaemia in the Maldives SIRS,—The Maldive islands in the Indian Ocean has a population of about 143 000, which is probably of Indonesian/ Sri Lankan origin, with a more recent admixture from Arabia and East Africa. Until recently the islands were highly malarial. 0-thalassaemia, Hb S, and HbE are all known to occur but there have been no population surveys. The islands are now malaria-free, and clean water, extended immunisation, and oral rehydration policies are conscientiously implemented. Infant mortality was 60 per 1000 in 1985. It is at this stage in a country’s development that inherited disease may emerge as a health issue-vulnerable infants who would previously have died of infections now survive-and haemoglobin disorders are often the first to manifest. By 1987 it was clear that thalassaemia was important in the Maldives, and the government contacted the World Health Organisation for advice. One of us (B. M.) visited the main island, Male, at the end of 1988 and, with local staff, started to estimate the heterozygote frequency, to evaluate the implications for families, and to see how this country, with limited resources, might cope. This collaboration continued during a 3-month student elective period (by N. H.). Definitive laboratory methods’ were not yet available in the Maldives, and the diagnosis of thalassaemia major or intermedia had to be based on anaemia with characteristic physical findings, transfusion dependency, family history, blood films, and starch gel electrophoresis. B. M. examined most of the affected children attending the Central Hospital, Male. Heterozygote frequency was estimated from the homozygote birth-rate with the HardyWeinberg equation. N. H. brought with him the requirements for a one-tube osmotic fragility test, a primary screen for thalassaemia and HbE traits,2 and this was applied to 477 blood samples. 55 children with a known major haemoglobinopathy live in Male, and 40 were examined: 35 had (&bgr;-thalassaemia major (on the above criteria), 3 had thalassaemia intermedia (confirmed by glass slide electrophoresis in 2), and 2 had HbS/&bgr;-thalassaemia. Most children were transfused every 4-6 weeks, the haemoglobin usually being kept above 9 g/dl, and these children had a tolerable quality of life. However, in poorer families the Hb often fell to 5-6 g/dl, and these children were chronically sick. The hospital has a blood bank and
creatinine; p < 0 05, Wilcoxon’s test). In the non-sensitive group there seemed to be a negative correlation between the pressor dose (the smallest amount of angiotensin II per kg body weight per min which causes a 20 mm Hg rise in diastolic blood pressure) and urinary 2,3-dinor-TxB,. Our data confirm that observation of Fitzgerald et al by linking increased platelet activation to pregnancy-induced hypertension. However, we also found increased platelet thromboxane formation
patients at risk of pre-eclampsia, even before hypertension developed. This could be an argument for the use of platelet inhibitors such as low-dose aspirin in primigravid women at risk of pregnancy-induced hypertension, even before hypertension is in
apparent. C. VAN GEET B. SPITZ
Department of Obstetrics and Gynaecology, University Hospital of Leuven, Campus Gastuisberg, B-3000 Leuven, Belgium
VERMYLEN F. A. VAN ASSCHE
J.
B. Prostacyclin-thromboxane A2 in normal and hypertensive pregnancy. Doctoral thesis, University of Leaven, 1987: 26. 2. Gant NF, Chand S, Worley RJ, et al. A clinical test useful for predicting the development of acute hypertension in pregnancy. Am J Obstet Gynecol 1974; 120: 1-7. 3. Van Geet C, Arnout J, Eggermont E, et al. Urinary thromboxane B, and 2,3-dinor-thromboxane B; in the neonate born at full-term age. Eicosanoids 1990; 3: 39-43.
1. Spitz
SIR,-Dr Fitzgerald and colleagues report increased excretion of thromboxane B2 (TxB2) metabolites, indicating increased TxA; production, in eight pregnant women with hypertension and albuminuria (pre-eclampsia). They suggest that aspirin should be used to prevent and treat pre-eclampsia. However, as emphasised, aspirin both decreases production of platelet aggregatory and vasoconstrictive thromboxane and reduces the anti-aggregatory and vasodilatory prostacyclin, which is already low in pregnancyinduced hypertension. This may limit the benefit of aspirin in pregnant women: decreased prostacyclin production may reduce responsiveness to pressor agents systemically and in the placental circulation. We have suggested the use of fish oil fatty acids of the n-3 family, especially eicosapentaenoic acid (EPA), to prevent pre-eclampsia.1 Greenland Eskimos are less susceptible than Danes to pre-clampsia and there is a shift in tissue and plasma levels from n-6 to n-3 polyunsaturated fatty acids in Greenlanders due to their high consumption of seafood.2 EPA decreases the formation of TxAj and induces the production of inactive TxA3; it also increases production of prostacyclin 12 and induces the formation of prostacyclin 13, which is as active as prostacyclin 1 Furthermore EPA is effective in hypertension.’ Thus EPA may possess some of the favourable effects of aspirin against pre-eclampsia without the undesirable actions. Gentofte Clinical Chemical Laboratory, DK-2800 Lyngby, Denmark
HANS OLAF BANG
Medi-Lab A/S, Copenhagen
JØRN DYERBERG
Pre-eclampsia and prostaglandins. Lancet 1985; i: 1267. J, Bang HO, Hjøme N. Fatty acid composition of the plasma in Greenland Eskimos. Am J Clin Nutr 1975;: 28: 958-66. 3. Fischer S, Weber PC, Dyerberg J. The prostacyclin/thromboxane balance is favourably shifted in Greenland Eskimos. Prostaglandins 1986; 32: 235-41. 4. Bønaa KH, Bjerve KS, Straume B, Gram IT. Effect of eicosapentaenoic and docosahexaenoic adds on blood pressure in hypertension: a population-based intervention trial from the Tromso study. N Engl J Med 1990; 322: 795-801. 1. Dyerberg J, Bang HO.
2. Dyerberg
Central pontine myelinolysis and changes in serum
SiR,—Your April
7 editorial
on
sodium the management of symptomatic
hyponatraemia advises that the rate of rise of serum sodium should be kept below 0-5 mmol/1 per hour
to avoid central pontine CPM has also been linked to the hyperosmolality of serum found in burns patients,l and one of these patients had a normal serum sodium during the hyperosmolar
myelinolysis (CPM).
In three of the cases of CPM reported by Boon et al,2 one bone marrow graft and two developing after liver transplantations, the rises in serum sodium were 03, 025, and 0-15 mmol/1 per hour, well within the recommended safety limit. Treated hypernatraemia was a feature in every case but was not commented upon. The rapid rises in serum sodium and osmolality which may develop after the surgical clipping of some anterior communicating and anterior cerebral artery aneurysms because of transient postoperative diabetes insipidus or during a positive water deprivation test for cranial diabetes insipidus are not associated with osmotic demyelination syndromes, despite rates of change in serum sodium of 2-4 mmol/1 per hour. For example, if a 70 kg male reaches the 4% loss of body weight termination point in the water deprivation test for cranial diabetes insipidus,3 his serum sodium will have risen by about 9 mmol/1 over 2-4 hours. This is a much greater rate than that considered safe in the treatment of hyponatraemia. Thus in CPM, the rate of change in osmolality, the length of time that this rate change persists,4and the clinical condition of the patient are all important factors.
episode. after
a
Department of Chemical Pathology, Beaumont Hospital, Dublin 9, Ireland
W. P. TORMEY
1. McKee
AC, Winkelman MD, Banker B. Central pontine myelinolysis in severely burned patients: relationship to hyperosmolality. Neurology 1988; 38: 1211-17. 2. Boon AP, Carey MP, Salmon MV. Central pontine myelinolysis not associated with rapid correction of hyponatraemia. Lancet 1988; ii: 458. 3. Ismail AAA. Disorders of the antidiuretic hormone. In: Biochemical investigations in endocrinology: methods and interpretations. London: Academic Press, 1981: 132-42. 4. Laureno R, Karp BI. Pontine and extrapontine myelinolysis following rapid correction of hyponatraemia. Lancet 1988; i: 1439-41.
Thalassaemia in the Maldives SIRS,—The Maldive islands in the Indian Ocean has a population of about 143 000, which is probably of Indonesian/ Sri Lankan origin, with a more recent admixture from Arabia and East Africa. Until recently the islands were highly malarial. 0-thalassaemia, Hb S, and HbE are all known to occur but there have been no population surveys. The islands are now malaria-free, and clean water, extended immunisation, and oral rehydration policies are conscientiously implemented. Infant mortality was 60 per 1000 in 1985. It is at this stage in a country’s development that inherited disease may emerge as a health issue-vulnerable infants who would previously have died of infections now survive-and haemoglobin disorders are often the first to manifest. By 1987 it was clear that thalassaemia was important in the Maldives, and the government contacted the World Health Organisation for advice. One of us (B. M.) visited the main island, Male, at the end of 1988 and, with local staff, started to estimate the heterozygote frequency, to evaluate the implications for families, and to see how this country, with limited resources, might cope. This collaboration continued during a 3-month student elective period (by N. H.). Definitive laboratory methods’ were not yet available in the Maldives, and the diagnosis of thalassaemia major or intermedia had to be based on anaemia with characteristic physical findings, transfusion dependency, family history, blood films, and starch gel electrophoresis. B. M. examined most of the affected children attending the Central Hospital, Male. Heterozygote frequency was estimated from the homozygote birth-rate with the HardyWeinberg equation. N. H. brought with him the requirements for a one-tube osmotic fragility test, a primary screen for thalassaemia and HbE traits,2 and this was applied to 477 blood samples. 55 children with a known major haemoglobinopathy live in Male, and 40 were examined: 35 had (&bgr;-thalassaemia major (on the above criteria), 3 had thalassaemia intermedia (confirmed by glass slide electrophoresis in 2), and 2 had HbS/&bgr;-thalassaemia. Most children were transfused every 4-6 weeks, the haemoglobin usually being kept above 9 g/dl, and these children had a tolerable quality of life. However, in poorer families the Hb often fell to 5-6 g/dl, and these children were chronically sick. The hospital has a blood bank and
