Massive hypertriglyceridemia associated with atenolol.
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Biomedical subjects
Publications and source records attributed to H C Seftel.
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Total cholesterol and triglyceride concentrations in 127 samples of capillary and venous blood were measured with the portable Reflotron 'dry chemistry' reflectometer and compared with serum levels measured in the laboratory using wet chemistry methods. Results were grouped into low, middle and high ranges. Levels measured with the Reflotron correlated closely with those measured by wet chemistry methods. Reflotron values for both lipid fractions were, however, consistently higher than wet chemistry levels but the differences were small except at high levels. It is concluded that the Reflotron is a satisfactory instrument for providing clinically useful measurements of cholesterol and triglyceride nearer to the patient.
The mechanism of early morning bronchospasm in asthma was investigated by analyzing circadian variations in the plasma levels of cortisol, ACTH, epinephrine, and norepinephrine, as well as in the serum neutrophil chemotactic activity and heart rate in asthmatic patients with (n = 6) and without (n = 7) "morning dipping" and normal subjects. Findings suggested that an exaggerated nocturnal nadir in plasma cortisol levels may precipitate "morning dipping" in some patients with asthma.
Serum magnesium, calcium, sodium and potassium, and erythrocyte magnesium, sodium and potassium levels were measured in a selected group of 296 urbanised black male labourers in Johannesburg. Of these, 214 subjects were normotensive and 82 were hypertensive. The aim of the study was to examine the relationship between serum and erythrocyte electrolytes, specifically magnesium and calcium, and blood pressure in this population sample. The results showed a significant decrease in serum magnesium, calcium and potassium in the hypertensive subjects. Red blood cell magnesium was significantly lowered and red blood cell sodium was significantly raised in this group. A significant inverse correlation was found between serum magnesium and blood pressure, erythrocyte magnesium and blood pressure, serum calcium and blood pressure, and serum potassium and blood pressure. A positive correlation was observed between erythrocyte sodium and blood pressure. Of all the electrolytes assessed, magnesium (serum and erythrocyte) correlated most closely with blood pressure. The data reported here suggest that body magnesium and its interactions with calcium, sodium and potassium may, in certain groups of individuals, play an important role in the development and maintenance of high blood pressure.
Beta-cell reserve was investigated in 15 patients with proven idiopathic haemochromatosis (IHC) (7 normoglycaemic haemochromatotic patients, 4 non-insulin-requiring diabetics and 4 insulin-requiring diabetics) by measuring the response of plasma C-peptide, insulin and glucose to a 2 mg intravenous bolus of glucagon, and compared with that in 5 lean normal subjects. The corresponding C-peptide/insulin molar ratios were also calculated. Despite the significant fasting hyperglycaemia in the insulin-requiring haemochromatotic diabetics, mean fasting C-peptide concentrations were similar in all four groups. However, after glucagon stimulation the C-peptide response was significantly reduced in the insulin-requiring group over the whole period of observation. A trend in insulin response to glucagon was noted, with the highest values in the non-diabetic haemochromatotic patients, followed by the controls and then by the non-insulin-requiring diabetics, although there were no significant differences. In contrast, C-peptide/insulin molar ratios after glucagon were significantly reduced in the normoglycaemic IHC group. These results suggest the presence of at least two abnormalities of insulin metabolism in IHC--a progressive reduction in beta-cell function and a diminished rate of removal of insulin by the liver.
Ischaemic heart disease risk factors, with particular reference to familial hypercholesterolaemia, were studied in 47 male and 6 female Afrikaners, aged 55 years and under, admitted to hospital for coronary bypass surgery. The outstanding feature in this group with severe coronary atherosclerosis demonstrated angiographically was that about half had severe hypercholesterolaemia (greater than or equal to 8.5 mmol/l), and that of the severely hypercholesterolaemic patients about half again had familial hypercholesterolaemia (FH). This yielded an overall prevalence of FH in the 53 cases of 1 in 4 (26.7%) and strongly supports the contention that FH is a major risk factor for severe coronary artery disease in young Afrikaners. The only other risk factor of importance was cigarette smoking, about 80% of the patients being current or ex-smokers.
Ischaemic heart disease (IHD) risk factors, with particular reference to familial hypercholesterolaemia (FH), were studied in 39 male and 12 female Afrikaners aged 55 years or under in an intensive care unit immediately after an acute myocardial infarction and in the survivors at about 3 months after the infarct. Two major risk factors were found. Firstly, about three-quarters of both male and female patients smoked more than 15 cigarettes daily. Secondly, 51% of males and 37% of females had serum cholesterol values of greater than or equal to 7.0 mmol/l and about 20% of both men and women had levels of greater than or equal to 8.5 mmol/l. Three male and 2 female patients--1:10 of the whole sample--had FH diagnosed by rigorous criteria, a prevalence similar to the figure of 1:8 predicted from the frequency of FH heterozygotes in the Afrikaans-speaking population. None of the other IHD risk factors such as hypertension, diabetes and hyperuricaemia appeared to be important. The role of obesity appeared to be indirect by virtue of its frequent association with and possible contribution to hypercholesterolaemia. Many of the patients had a history of previous IHD episodes.
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Free fatty acids (FFA) are believed to play a role in the genesis of the fat embolism syndrome (FES). Levels of plasma FFA, glucose, insulin, and the stress hormones cortisol, growth hormone, prolactin, glucagon, and catecholamines were measured on admission to hospital in: a) 14 patients with long bone fractures at risk of developing FES, b) 14 patients with soft-tissue injuries of comparable severity, and c) 20 healthy fasting subjects. The findings were similar in both groups of injured patients and in keeping with the hormonal and substrate responses to the stress of trauma; plasma FFA levels were raised but in neither group was the rise pronounced. Plasma FFA levels of the fracture patients were only moderately higher than the values of the healthy fasting subjects. These findings suggest that mobilized FFA from peripheral adipose tissue are not important in the genesis of the FES, but do not exclude a role for FFA derived mainly from hydrolysis of triglyceride emboli in the lung.
The effect of low density lipoproteins on esterification of cholesterol was studied in lymphocytes from patients with familial hypercholesterolaemia; results were compared with those obtained using cells from normal individuals. Freshly isolated lymphocytes were maintained in lipoprotein-deficient medium for 48 h and the rate of formation of [3H] cholesteryl oleate from [3H] oleate was then determined in the presence or absence of low density lipoproteins. In the absence of low density lipoproteins, incorporation of [3H] oleate was higher in heterozygote and homozygote cells than in normal lymphocytes. Incorporation in the presence of low density lipoproteins was increased relative to that measured in their absence for all of the subjects studied; heterozygotes and homozygotes showed marked changes in some cases but not in others.
The aim of this study was to assess the acute effects of clonidine, an alpha 2-adrenergic agonist, on hormonal responses to graded exercise in 8 healthy young men. After fasting overnight, each subject was tested on 2 mornings, 1 week apart. On one occasion he was given 200 micrograms clonidine orally and on the other identical placebo tablets, the order being randomized in a double-blind fashion over the 2 days. Thereafter each subject performed 2 successive treadmill runs, equivalent to 60 and 100%, respectively, of maximal aerobic power. Clonidine pretreatment blunted the maximal increase in plasma catecholamines by more than 60% of the control response (p less than 0.01), without significantly altering the rise of plasma cortisol or ACTH. Furthermore, clonidine significantly reduced the exercise-induced maximal rise in plasma glucose, without modifying the slight decline in mean plasma insulin or increase in pancreatic glucagon levels. The drug did not affect the maximal increments in plasma growth hormone or prolactin occurring after exercise. It was concluded that a single dose of clonidine suppressed peripheral sympathetic responses, without altering central (pituitary) alpha-adrenergic-mediated hormonal responses, to short-term exercise in healthy men.
We evaluated beta-cell secretory capacity over 60 minutes in response to oral glucose (75 g) followed 30 minutes later by the intravenous injection of tolbutamide 0,5 g and glucagon 1 mg (combined) in 10 black and 8 white obese non-diabetic female volunteers. Thirty minutes after oral glucose administration both insulin and C-peptide levels were significantly higher in the white group. The levels of both substances after tolbutamide-glucagon stimulation were likewise higher in the white group at all times, being significantly so 30 minutes after the injection. Hepatic extraction of insulin, calculated as the C-peptide: insulin molar ratio, was similar in both groups. These results indicate that the beta-cell secretory capacity of black obese subjects is less than that of whites. In response to insulin-induced hypoglycaemia in 6 of the black and 5 of the white subjects, the pancreatic glucagon rise was lower in the black group, despite greater falls in plasma glucose levels. In view of this finding it is possible that blacks may be at risk of slower recovery from insulin-induced hypoglycaemia.
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This study was designed to assess whether transcendental meditation (TM) could influence various endocrine responses in 10 experienced male meditators. Nine matched subjects, uninformed of the TM procedure, acted as controls. Meditators successfully practised their technique for 40 min in the morning while controls relaxed for this period. No significant differences emerged between these 2 groups with respect to carbohydrate metabolism (plasma glucose, insulin and pancreatic glucagon concentrations), pituitary hormones (growth hormone and prolactin) or the 'stress' hormones, cortisol and total catecholamines-although meditators tended to have higher mean catecholamine levels. Plasma free fatty acids were significantly elevated in meditators 40 min after completing the period of TM. No clear evidence was thus obtained that any of the stress, or stress-related, hormones were suppressed during or after meditation in the particular setting examined.
The aim of this study was to assess whether the potent calcium antagonist nifedipine was capable of modifying the hormonal response to graded exercise in 7 healthy young men. After fasting overnight, each subject came to the laboratory on 2 consecutive mornings. On one day he was given 10 mg of nifedipine sublingually and on the other an identical placebo capsule; the order was randomised in a double-blind fashion over the 2 days. Thereafter each subject performed 2 successive short treadmill runs, equivalent to 60 and 100%, respectively, of maximal aerobic power. While significantly blunting the rise in mean systolic blood pressure and inducing a greater fall in diastolic blood pressure during and after exercise compared with the placebo, nifedipine did not impair the brisk response to pituitary-adrenal hormones (ACTH, cortisol and total catecholamines). Nifedipine also did not modify the effects of short-term exercise in raising mean plasma glucose levels, stimulating pancreatic glucagon secretion and producing a delayed increase in plasma insulin concentrations. Nor did the drug blunt the significant rise of growth hormone and prolactin levels occurring during and after the treadmill run. It was concluded that, apart from inducing significant changes in blood pressure, a single dose of nifedipine does not appear to suppress the counterregulatory hormonal responses to short-term physical activity in healthy men.
The role of the alpha-adrenergic system in the pathogenesis of asthma is investigated. We administered 150 micrograms oral clonidine to a group of patients with relatively mild asthma and a group of non-asthmatic subjects, and compared their responses by measuring plasma levels of growth hormone (GH), immunoreactive insulin, potassium and glucose. There was no significant difference between the groups in respect of any of these variables, nor was there a significant difference in the blood pressure responses. However, 3 of the asthmatic subjects demonstrated marked hyper-responsiveness of the plasma GH levels after clonidine. It is possible that increased alpha-adrenergic responses may be more frequently demonstrable in a group of severe asthmatics or by means of an alpha-agonist which is more potent and less selective than clonidine. Alternatively, the 3 hyper-responsive individuals may represent a subgroup of asthmatics in whom alpha-adrenergic overactivity is an important pathogenetic mechanism.