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Vasopressin in edematous disorders
628
~&cose IeveIsin ~ai%~~ children da&g quinine tberspy for malaria. In a study of Q$ Maiawian children with cerebral malaria, we found that 19 (20 %) had pre-treatment hypaglycaemia (blood glucose C 2.2 nlmol/l). These children were significantly more likely to die or develop neurological sequelae than those without hypodycaemia despite adequate correction of blood glucose by infusion of 50% dextrose. Elevated alanine and lactate levels in association with hypoglycaemia suggest that impaired hepatic ~u~neogenesis may ~n~bute to the fall in bfood glucose. Insulin tevels were appropriately iow in h~ogly~emic patients. The infusion of quinine was followed by increased piasma insulin concentrations, but a regular infusion of 5 % dextrose was sufficient to prevent quinine-induced hypoglycaemia in these patients. M.E. Molyneux (1)
LiverpoolSchoolof Tropical Medicine, LiverpoolL3 SQA, UK
Vmoprwah in edematous disorders.
Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis and nephrotic syndrome. In recent years the use of a sensitive ~dio~munoas~y for plasma vasopressin has implicated the role of non-osmotic vas~pressin in the water retention of these edematous disorders. In experimental studies and studies in humans it has been found that the non-osmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the non-osmotic release of vasopressin (carotid and aortic baroreceptors) and activation of the renin-~giotensin system (renal baroreceptors and ~ta~drener~c receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial vasodilation. In this context, neither total extracellular fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated either by a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g., high output cardiac failure, cirrhosis, pregnancy, sepsis, afteriovenous tistulae and pharmacological vasodilatom). With a decrease in effective arterial blood volume (EABV), initiated by either a fall in cardiac output or @pheral arterial v~o~Iation, the acute response involves vaso~nst~ction mediated by angiaiensin, r&Be
(1) N. En@. J. Med. (1988) 319, 1040.
sympathetic mediators and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and afdosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation, limits the distal tubular delivery of sodium and water thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated gtomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium siti water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation. R.W.Schrier (2) Universityof ColoradoSchoolof Medicine, Denver CO 80262,USA Growth factors in Breast cancer. Several oncogenes seem to encode certain growth factors that may play a part in regulating cell growth in turnours. To assess ;Hhether such factors are synthesised endogenously by t~mour cells the amounts of messenger RNA for several growth factors known to be synthesised by cancer celts of the breast in vitro were examined in biopsy specimens from 52 malignant and 15 non-~~~i~g~ant : urnours of the breast and four samples of normal hleast. Transforming growth factor be?a messenger RN.4 was significantly more abundant in breast cancers (32 of 42-76%-having appreciable amounts) than non-malignant breast tissue (5 of 13-38 %-having simular amounts). Transcripts for both transforming growth factor alpha and its receptor, epidermal growth E;ictor receptor, were found more commonly in carcinonas that were negative for oestrogen receptor (64 % an* 87 %, respectively) than in those that were positive (27 % and 30 %, respectively). Insulin-like growth factor II messenger RNA was present in all I5 samples of non-malignant tissue but was found (in ~Rside~bly lower arnoun~~ in only 11 of 21 (52 %) carcinomas. Epidermal growth factor receptor was also found in all non-malignant breast tissues, compared with 19 of 45 (42 %) carcinomas. Platelet derived growth factor A and B chain transcripts coexisted in all normal and benign tissue and most carcinomas. This differing pattern of expression growth factors in tissue from maiignant tumours compared with benign tumours and normal breast tissue suggests that some growth factors, particularly transforming growth factors alpha and beta, may have an important role in controlling growth of human breast cancer, patiicular!y those that are hormone indeptndent. W.C.Coombes(3) Si Georges Hospital Medical School,
London SW17 ORE, UK
(2) N. EngL J. Med. (1988) 319. 1065. (3) Br. Med. J. (1988) 2%. 1621.
~&cose IeveIsin ~ai%~~ children da&g quinine tberspy for malaria. In a study of Q$ Maiawian children with cerebral malaria, we found that 19 (20 %) had pre-treatment hypaglycaemia (blood glucose C 2.2 nlmol/l). These children were significantly more likely to die or develop neurological sequelae than those without hypodycaemia despite adequate correction of blood glucose by infusion of 50% dextrose. Elevated alanine and lactate levels in association with hypoglycaemia suggest that impaired hepatic ~u~neogenesis may ~n~bute to the fall in bfood glucose. Insulin tevels were appropriately iow in h~ogly~emic patients. The infusion of quinine was followed by increased piasma insulin concentrations, but a regular infusion of 5 % dextrose was sufficient to prevent quinine-induced hypoglycaemia in these patients. M.E. Molyneux (1)
LiverpoolSchoolof Tropical Medicine, LiverpoolL3 SQA, UK
Vmoprwah in edematous disorders.
Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis and nephrotic syndrome. In recent years the use of a sensitive ~dio~munoas~y for plasma vasopressin has implicated the role of non-osmotic vas~pressin in the water retention of these edematous disorders. In experimental studies and studies in humans it has been found that the non-osmotic release of vasopressin is consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the non-osmotic release of vasopressin (carotid and aortic baroreceptors) and activation of the renin-~giotensin system (renal baroreceptors and ~ta~drener~c receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial vasodilation. In this context, neither total extracellular fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated either by a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g., high output cardiac failure, cirrhosis, pregnancy, sepsis, afteriovenous tistulae and pharmacological vasodilatom). With a decrease in effective arterial blood volume (EABV), initiated by either a fall in cardiac output or @pheral arterial v~o~Iation, the acute response involves vaso~nst~ction mediated by angiaiensin, r&Be
(1) N. En@. J. Med. (1988) 319, 1040.
sympathetic mediators and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and afdosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation, limits the distal tubular delivery of sodium and water thus maximizing the water-retaining effect of vasopressin and impairing the normal escape from the sodium-retaining effects of aldosterone. The elevated gtomerular filtration rate and filtered sodium load in pregnancy allows increased distal sodium siti water delivery in spite of a decrease in EABV, thus limiting edema formation during gestation. R.W.Schrier (2) Universityof ColoradoSchoolof Medicine, Denver CO 80262,USA Growth factors in Breast cancer. Several oncogenes seem to encode certain growth factors that may play a part in regulating cell growth in turnours. To assess ;Hhether such factors are synthesised endogenously by t~mour cells the amounts of messenger RNA for several growth factors known to be synthesised by cancer celts of the breast in vitro were examined in biopsy specimens from 52 malignant and 15 non-~~~i~g~ant : urnours of the breast and four samples of normal hleast. Transforming growth factor be?a messenger RN.4 was significantly more abundant in breast cancers (32 of 42-76%-having appreciable amounts) than non-malignant breast tissue (5 of 13-38 %-having simular amounts). Transcripts for both transforming growth factor alpha and its receptor, epidermal growth E;ictor receptor, were found more commonly in carcinonas that were negative for oestrogen receptor (64 % an* 87 %, respectively) than in those that were positive (27 % and 30 %, respectively). Insulin-like growth factor II messenger RNA was present in all I5 samples of non-malignant tissue but was found (in ~Rside~bly lower arnoun~~ in only 11 of 21 (52 %) carcinomas. Epidermal growth factor receptor was also found in all non-malignant breast tissues, compared with 19 of 45 (42 %) carcinomas. Platelet derived growth factor A and B chain transcripts coexisted in all normal and benign tissue and most carcinomas. This differing pattern of expression growth factors in tissue from maiignant tumours compared with benign tumours and normal breast tissue suggests that some growth factors, particularly transforming growth factors alpha and beta, may have an important role in controlling growth of human breast cancer, patiicular!y those that are hormone indeptndent. W.C.Coombes(3) Si Georges Hospital Medical School,
London SW17 ORE, UK
(2) N. EngL J. Med. (1988) 319. 1065. (3) Br. Med. J. (1988) 2%. 1621.