Two cases of adrenocortical carcinoma presenting as Conn's syndrome.
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Adenocarcinoma↗
Biomedical subjects
R F Bing
Publications and source records attributed to R F Bing.
Human erythrocyte membrane fluidity and calcium pump activity in primary combined hyperlipidaemia.
1. Human erythrocyte membrane cholesterol, fluidity and basal and calmodulin-stimulated calcium pump (Ca(2+)-Mg(2+)-ATPase) activities were compared in 24 patients with primary combined hyperlipidaemia and 20 age-matched normolipidaemic control subjects. 2. There was no correlation between serum and membrane cholesterol. Despite the differences in serum cholesterol levels between the two groups, membrane cholesterol levels were similar. 3. 1,6-Diphenyl-1,3,5-hexatriene anisotropy was lower in the hyperlipidaemic group, suggesting increased fluidity in the hydrocarbon core of the phospholipid membrane bilayer. 4. Basal calcium pump activity was lower in the hyperlipidaemic group with increased membrane fluidity. 5. These results suggest that membrane adaptive mechanisms can maintain membrane cholesterol within a narrow range, that serum triacylglycerol is more important than serum cholesterol in determining membrane fluidity and that increased membrane fluidity reduces basal calcium pump activity.
Adult↗
Human red cell membrane fluidity and calcium pump activity in normolipidaemic type II diabetic subjects.
Red cell membrane cholesterol, 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[(4-trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) anisotropies and basal and calmodulin-stimulated calcium pump activities were compared in 16 normolipidaemic Type 2 (non-insulin-dependent) diabetic patients and 20 normolipidaemic control subjects using the Mann-Whitney U-test. Serum cholesterol, membrane cholesterol, and membrane DPH and TMA-DPH anisotropies were similar in the two groups but both basal and calmodulin-stimulated calcium pump activities were reduced in the diabetic group: basal activity (median (inter-quartile range), mumol mg-1 h-1) 1.66 (1.18-1.97) vs 2.09 (1.90-2.50), p < 0.005 and calmodulin-stimulated activity 4.19 (3.07-5.48) vs 5.53 (4.70-6.88), p < 0.006. Although there were no correlations between glycaemic control and membrane anisotropy and between glycaemic control and calcium pump activity, the reduction in calcium pump activity is most likely due to a direct effect of diabetes on the calcium pump protein itself.
Adult↗
Treatment of familial hypercholesterolaemia. United Kingdom lipid clinics study of pravastatin and cholestyramine.
OBJECTIVE: To compare the efficacy and safety of cholestyramine, an anion exchange resin, and pravastatin, a new hydrophilic specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in the treatment of heterozygous familial hypercholesterolaemia. DESIGN: Double blind, double dummy, placebo controlled study with three parallel groups. SETTING: Six specialist lipid clinics in the United Kingdom. PATIENTS: 128 patients aged 18-70 with heterozygous familial hypercholesterolaemia diagnosed on strict biochemical and clinical findings. MAIN OUTCOME MEASURES: Total plasma cholesterol, triglyceride, and lipoprotein subfractions and biochemical and haematological safety parameters. RESULTS: Pravastatin (40 mg/day) led to a 25% reduction in total plasma cholesterol concentration and a reduction in low density lipoprotein cholesterol concentration of 30%. Cholestyramine (24 g/day) led to similar reductions in concentrations of total cholesterol (23%) and low density lipoprotein cholesterol (31%). No consistent changes occurred in high density lipoprotein cholesterol values with either compound. Plasma triglyceride concentrations showed a small rise (18%) on resin therapy. No serious adverse drug reactions occurred during the study. CONCLUSIONS: Pravastatin seems to be a highly effective, well tolerated drug for severe hypercholesterolaemia. Patients chosen for this study were recruited on the basis that they could tolerate a full dose of cholestyramine, and in this situation cholestyramine was also highly effective in lowering plasma low density lipoprotein cholesterol concentrations.
Adolescent↗
Erythrocyte calcium-stimulated, magnesium-activated adenosine 5'-triphosphatase activity in essential hypertension.
OBJECTIVE: The aim of this study was to investigate the basis of reduced erythrocyte calcium-stimulated, magnesium-activated adenosine 5' triphosphatase (Ca2+, Mg(2+)-ATPase) activity in essential hypertension. DESIGN: Experiments were performed to establish whether the reduced erythrocyte Ca2+, Mg(2+)-ATPase activity in patients with essential hypertension, when compared with age- and sex-matched normotensive control subjects, was due to changes in enzyme properties or to an altered membrane environment. METHODS: Erythrocyte membrane Ca2+, Mg(2+)-ATPase activity was determined by measuring ATP-dependent 45Ca2+ uptake in inside-out vesicles and calcium-dependent gamma-32P ATP hydrolysis in ghost membranes, prepared from the same sample of blood. Calcium-dependent gamma-32P ATP hydrolysis activity was also measured in detergent extracts of erythrocyte membranes. RESULTS: In the absence and presence of calmodulin, both ATP-dependent Ca2+ uptake and calcium-dependent ATP hydrolysis activities of erythrocyte membranes prepared from patients with essential hypertension were significantly reduced when compared with normotensive subjects. No difference in calmodulin affinity was observed between hypertensive and normotensive subjects, although the calcium dependence of calmodulin-independent Ca2+ uptake activity in inside-out vesicles was altered. No significant difference in calcium-dependent ATP hydrolysis activity was observed between hypertensive and normotensive preparations after detergent solubilization of erythrocyte membrane proteins. CONCLUSIONS: These results suggest that the number of Ca2+, Mg(2+)-ATPase units is similar in erythrocytes of hypertensive and normotensive subjects and that the reduced activity in the intact erythrocyte membrane of hypertensive patients is due to an altered membrane environment.
Ca(2+) Mg(2+)-ATPase↗
Reversal of experimental renovascular hypertension.
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Animals↗
Effect of temperature on the erythrocyte membrane Ca2(+)-ATPase activity in hypertension.
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Animals↗
Erythrocyte membrane calcium adenosine 5'-triphosphatase activity in the spontaneously hypertensive rat.
1. Ca2+-adenosine 5'-triphosphatase (Ca2+-Mg2+-ATPase) activity was studied simultaneously in calmodulin-deficient erythrocyte ghost membranes and inside-out vesicles (IOVs) from 12-week-old female spontaneously hypertensive rats (SHR) and their matched controls: [Wistar-Kyoto normotensive rats (WKY)], and in detergent extracts of ghost membranes. 2. Both adenosine 5'-triphosphate (ATP)-dependent Ca2+ uptake by IOVs and Ca2+-dependent ATP hydrolysis activity of ghost membranes were reduced significantly in the SHR compared with WKY, when either the calmodulin-independent or calmodulin-stimulated activities were compared. 3. The ratios between Ca2+ uptake and ATP hydrolysis activities in the SHR remained approximately 1.0, showing a proportional reduction in both activities. 4. No difference in affinity for calmodulin was observed between SHR and WKY. 5. No significant difference in Ca2+-dependent ATP hydrolysis activity was observed between SHR and WKY after detergent solubilization of erythrocyte ghost membranes. 6. These results suggest that the number of Ca2+-Mg2+-ATPase units are similar in SHR and WKY and that the reduced activity in the intact SHR membrane is due to altered membrane environment.
Animals↗
Renal vasodepressor mechanism: characterization by chemical medullectomy.
The features of hypertension produced in the rat by chemical medullectomy with 2-bromoethylamine hydrobromide are described. This procedure partially prevents the fall in blood pressure that occurs when the constriction is removed from the renal artery of rats with two-kidney one-clip Goldblatt hypertension. In normal rats, chemical medullectomy causes a moderate but consistent blood pressure elevation that is dose related and associated with elevation of peripheral resistance; the venous side of the circulation is normal. The hypertension is not associated with sodium retention or with activation of the renin angiotensin system. Although vasopressin levels are elevated, the rise is only modest, and blood pressure is not reduced by a vascular AVP antagonist. It is concluded that chemical medullectomy removes the source of a humoral substance that has been shown by other workers to carry out a vasodepressor role. The chemical medullectomy model therefore offers new insights into the renomedullary vasodepressor system.
Animals↗
Acute inotropic effects of intravenous nifedipine and its vehicle compared with saline: a double-blind study of systolic time intervals in normal subjects.
1. The inotropic effects of intravenous nifedipine and its vehicle were studied noninvasively in a double-blind placebo controlled crossover fashion using systolic time intervals in 12 normal subjects. 2. Nifedipine caused vasodilation, a fall in systolic and diastolic blood pressure, and increased heart rate. The vehicle alone caused vasodilation and decreased systolic blood pressure, without a change in heart rate. 3. Nifedipine increased left ventricular ejection time (LVET) and decreased pre-ejection period (PEP) and the ratio PEP/LVET, whereas the vehicle alone had the opposite effect. Neither treatment affected the total duration of electromechanical systole. 4. These results suggest that the vehicle has a negative inotropic effect, which is overcome by the indirect positive inotropic effect of nifedipine when they are administered together systemically.
Adult↗
Dietary changes in membrane lipids and leucocyte calcium.
It has been postulated that changes in the fatty acid component of cell membrane phospholipids play an important role in cell membrane ion handling. To test this hypothesis, we have administered the polyunsaturated fatty acid linoleic acid (as 4 g daily of safflower oil) to 25 normotensive volunteers in a double-blind crossover trial for 4 weeks. There was a significant decrease in leucocyte ionised calcium at the end of active treatment compared with the end of placebo period. There was no difference in subjects with and without a family history of hypertension and there was no significant effect upon blood pressure. It is concluded that cell membrane fatty acids play a role in the regulation of intracellular calcium in the leucocyte, and perhaps therefore in other tissues.
Adult↗
The haemodynamic effects of intravenous nifedipine in normotensive and hypertensive subjects.
The antihypertensive effects of intravenous nifedipine, given by bolus and 2 hour infusion, were studied at two dose levels in seven hypertensive (mean BP 178/114 mmHg) and five age-matched normotensive controls (mean BP 128/81 mmHg). Nifedipine significantly reduced systolic and diastolic blood pressure in the hypertensive patients by approximately 20%, but not in the normotensive controls. Similar changes in heart rate and forearm blood flow were seen after bolus injection in both groups, but these were not sustained during infusion. Intravenous nifedipine may be a useful acute treatment for hypertensive emergencies.
Adult↗
Nifedipine infusion in acute myocardial infarction: experience in twelve patients.
Studies of nifedipine have not shown that it reduces myocardial infarct size in humans. These studies did not consider the pharmacokinetics and dynamics of nifedipine. Oral doses of nifedipine cause high plasma concentrations and possibly harmful hemodynamic changes. Intravenous nifedipine infusion can rapidly achieve and maintain a steady concentration without repeated hemodynamic upsets. We studied 24-h intravenous nifedipine infusion in 12 patients with acute myocardial infarct, starting within 6 (mean 4.0 +/- 0.7) h of onset of pain, to determine its safety, pharmacokinetics, and dynamics. An intravenous nifedipine bolus of 15 micrograms/kg was followed by an infusion of 0.9 mg/h for 24 h. After the bolus, pulse rate rose 12.5 +/- 8.0 p less than 0.01) and blood pressure fell (systolic by 20 +/- 34, p less than 0.05, and diastolic by 7.5 +/- 15.6, p less than 0.05). There were similar but lesser changes during the infusion. Myocardial oxygen requirements, as measured by the rate-pressure product, did not increase. The mean nifedipine concentration at steady state was 17.2 +/- 4.2 ng/ml and mean elimination T 1/2 3.57 +/- 2.70 h. Nifedipine was discontinued in 3 patients because of hypotension (SBP less than 90), rapid atrial fibrillation, and complete heart block in one patient each. Seven patients developed thrombophlebitis. Large studies of this preparation examining infarct size limitation and mortality are feasible, although in view of the problems of thrombophlebitis in peripheral veins, shorter infusion times or infusion via central lines would be more acceptable.
Administration, Oral↗
Haemodynamic consequences of experimental papillary necrosis in the rat.
Experimental renal papillary necrosis induced by 2-bromoethylamine hydrobromide (BEA) results in hypertension in the rat. The haemodynamics of this increase in blood pressure were investigated with radiolabelled microspheres, thus enabling individual organ blood flows to be evaluated. Total peripheral resistance was raised in BEA-treated rats (3.6 +/- 0.3 mmHg ml-1 min X 100 g) compared with control rats (2.87 +/- SEM 0.2, P less than 0.05) whilst cardiac index remained similar (39.9 +/- 3.6 vs 39.2 +/- 3.1 ml min-1 100 g-1). Heart and brain from BEA rats demonstrated a significant rise in vascular resistance with a normal blood flow. In the kidneys vascular resistance increased still further and here there was a reduction in renal blood flow despite an increase in kidney size. These findings are compatible with a loss of renomedullary vasodepressor mechanisms acting directly or indirectly on the resistance vessels.
Animals↗
Membrane handling of calcium in essential hypertension.
Several abnormalities have been described in the blood-cell handling of calcium in patients with hypertension and rats with genetic hypertension. We have suggested elsewhere that the multiple abnormalities of monovalent and divalent ion handling by blood cells in hypertension, which are loosely and variably associated with blood pressure, reflect a global variability of cell membrane lipids. In the light of this suggestion we tested the relevance of decreased membrane binding of calcium by examining basal and maximal calcium binding in hypertensive patients and in normotensive subjects with and without a family history of hypertension. Calcium binding was reduced to a similar degree in both hypertensive subjects and those with a family history of hypertension. To examine the role of membrane lipids we examined calcium binding in relation to erythrocyte membrane composition, and found a negative correlation between the palmitic:linoleic acid ratio and calcium binding. This is consistent with the observation of a reduction in the unsaturated fatty acid, linoleic acid, in the erythrocyte membrane of hypertensive subjects, and this may therefore be of functional significance. In further studies, although there was no net difference in leucocyte cytosolic calcium between essential hypertensive subjects and normotensive controls, there was a positive relationship between leucocyte calcium and membrane palmitic:linoleic acid ratio only in normotensives. To test further the role of membrane lipids in calcium handling we administered linoleic acid (4 g daily safflower seed oil) to 13 normotensive volunteers in a double-blind crossover trial. Four weeks of administration of the linoleic acid produced a significant decrease in leucocyte calcium (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Pharmacokinetics and pharmacodynamics of nifedipine infusion in normal volunteers.
Two studies of the pharmacokinetics and pharmacodynamics of intravenous nifedipine infusion were performed: the first, a randomised double-blind crossover study of nifedipine and its vehicle in eight subjects, the second a dose ranging study in nine subjects. Nifedipine pharmacokinetics did not vary with dose or duration of infusion up to 8 h, and are similar to those reported for other nifedipine preparations. Nifedipine increased heart rate and forearm blood flow and decreased blood pressure after bolus injection but not during prolonged infusion. The vehicle decreased blood pressure and increased forearm blood flow after bolus injection but not during prolonged infusion. It did not affect heart rate. The vehicle's haemodynamic activity has not been previously recognised and is of potential importance in the study of this and similar preparations of calcium antagonists.
Adult↗
Reversal of renovascular hypertension: role of the renal medulla.
The fall in blood pressure, which occurs when renovascular hypertension is corrected surgically, offers a means of elucidating the factors responsible for blood pressure control. When Goldblatt two-kidney, one-clip hypertension in the rat is reversed by unclipping the renal artery, or by removal of the ischaemic kidney, restoration of normal blood pressure is due to a fall in peripheral resistance. This is associated with sodium retention and cannot be modified by inhibition of the renin-angiotensin system. The fall is, however, partially inhibited by chemical removal of the renal medulla by means of 2-bromo-ethylamine hydrobromide. When normal rats are chemically medullectomized, moderate hypertension is produced, which cannot be attributed to the renin-angiotensin system or sodium retention. It is concluded that a renomedullary vasodepressor system is ablated by chemical medullectomy: further, this system plays a role in the surgical correction of Goldblatt hypertension.
Animals↗
Effect of cold pressor test-induced stress on leukocyte sodium transport and norepinephrine.
The effects of stress on leukocyte membrane sodium efflux rate constant and plasma norepinephrine levels were studied before and during cold pressor test in normotensive subjects with and without a family history of hypertension. After 20 minutes of supine rest, no significant differences in total, ouabain-resistant or ouabain-sensitive sodium efflux rate constants were apparent between the two groups. In normotensive subjects with no family history, there was no significant change in any efflux rate constant during cold pressor test, although there was a highly significant negative correlation between change in total efflux rate constant and change in norepinephrine levels (r = -0.82, p less than 0.01, n = 12). During cold pressor test in subjects with a family history of hypertension, there was a significant rise in the ouabain-resistant efflux rate constant (1.5 +/- 0.1 vs 1.0 +/- 0.1 hr-1; p less than 0.01, n = 10); this level was also significantly higher than that in control subjects (p less than 0.002). In this group, the ouabain-sensitive efflux rate constant fell slightly but not significantly (1.8 +/- 0.2 vs 2.1 +/- 0.2 hr-1; n = 10). These results suggest that stress in the form of a cold stimulus produces qualitative differences in leukocyte cation transport in normotensive offspring of hypertensive patients as compared with subjects without such a family history.
Adult↗