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Biomedical subjects

D J Betteridge

Publications and source records attributed to D J Betteridge.

At least 91 records · Page 5Linked to original sources
PubMed1991

Effects of pravastatin and cholestyramine on gonadal and adrenal steroid production in familial hypercholesterolaemia.

1. Adrenal and gonadal steroids are derived from cholesterol, which may be derived from plasma lipoproteins or de novo synthesis. 2. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate limiting enzyme in cholesterol synthesis, may therefore affect steroidogenesis when used as lipid-lowering agents in hypercholesterolaemia. 3. We have assessed gonadal and adrenal function in subjects with heterozygous familial hypercholesterolaemia (FH) before and after 12 weeks treatment with pravastatin, an HMG CoA reductase inhibitor, or cholestyramine as a control in maximal recommended doses. 4. No changes in measured plasma cortisol responses to tetracosactrin injection were seen in 11 patients on cholestyramine or 12 on pravastatin. 5. No changes were seen in testosterone, sex hormone binding globulin, androstenedione, dehydroepiandrosterone sulphate, oestradiol or 17 alpha-hydroxyprogesterone. 6. Gonadotrophin levels were unaffected in 10 male subjects on cholestyramine and 7 on pravastatin. 7. Measurements on a subset of subjects continuing to 24 weeks treatment also showed no changes. 8. No adverse effect on adrenal or gonadal function could be demonstrated in patients with familial hypercholesterolaemia on maximal recommended doses of pravastatin.

Adrenal Glands↗
PubMed1990

Abnormalities of blood rheology in familial hypercholesterolaemia: effects of treatment.

Whole blood and plasma viscosity, red cell aggregability and deformability, and plasma fibrinogen have been compared between 20 patients with heterozygous familial hypercholesterolaemia (FH), without clinical arterial disease, and 20 age- and sex-matched controls. Plasma fibrinogen was elevated in FH, associated with increased whole blood viscosity at low shear rate, plasma viscosity and red cell aggregation. At high shear rate blood viscosity was not elevated, and red cell deformability was normal. The effect of 12 weeks double blind treatment with cholestyramine 16-24 g/day, pravastatin 20 mg b.i.d. or placebo on blood rheology was studied in 17 FH patients. Mean plasma cholesterol fell significantly by 24.7% with pravastatin and 21.5% with cholestyramine, the latter also causing a significant 42% rise in triglyceride. Pravastatin, but not cholestyramine, caused a significant fall in plasma viscosity and fibrinogen, but no change was seen in whole blood rheology. This suggests that the rheological abnormalities in FH are at least partly related to the plasma lipid levels and hence reversible with treatment.

Adult↗
PubMed1990

Lipids and thrombosis.

There is extensive evidence of important interactions between plasma lipoproteins and platelet function. Some population groups, particularly hypercholesterolaemic patients, have strong evidence of abnormal platelet function which is mediated by the binding of lipoproteins, especially oxidized LDL, to surface receptors. Additionally, abnormal plasma lipid levels precipitate membrane composition changes by increasing the cholesterol:phospholipid ratio. The resulting changes in microviscosity seem to affect transmembrane signalling and might in some cases influence receptor binding. This not only has important therapeutic implications with regard to lipid-lowering drug therapy but also with regard to the potential beneficial effects of dietary therapy.

Blood Platelets↗
PubMed1990

Effects of aspirin upon the flushing reaction induced by niceritrol.

The usefulness of niceritrol as a lipid-lowering agent is limited by a prostaglandin-mediated flushing reaction after each dose occurring in the early stages of treatment. We have tested the effect of premedication with aspirin on the reaction to 250 mg niceritrol in 30 healthy male volunteers using both subjective and observed assessments of severity. Both 300 mg and 600 mg of aspirin significantly reduced the severity of flushing when compared with placebo. No significant difference was seen between the two dose levels. Prior dosing with aspirin may increase acceptability of niceritrol and hence improve compliance.

Adolescent↗
PubMed1990

Withdrawal phenomena after atenolol and bopindolol: hormonal changes in normal volunteers.

1. In order to observe and compare the withdrawal phenomena which follow treatment with the beta-adrenoceptor blocking drugs, bopindolol (with partial agonist activity PAA) and atenolol (without PAA), two groups of six normal volunteers were studied before, during and after 16 days drug administration. 2. Measurements of plasma levels of cortisol, prolactin, insulin, noradrenaline, adrenaline, glucose and potassium were made during a pre-treatment baseline period, on maximum dose and for 21 days after drug withdrawal. Isoprenaline infusions were given to determine sensitivity of heart rate responses and haemodynamic changes measured in response to physiological manoeuvres. 3. Following atenolol withdrawal the results show hormonal evidence of adrenergic overactivity in the form of elevation of plasma cortisol, insulin and glucose levels. After bopindolol withdrawal there was, in contrast, an overshoot of plasma prolactin and a persistent elevation of plasma potassium and adrenaline post-isoprenaline. 4. The hormonal changes which follow withdrawal of atenolol and bopindolol are associated with haemodynamic changes reported elsewhere (Walden et al., 1990). 5. These observations provide confirmatory evidence of a post beta-adrenoceptor blockade withdrawal syndrome which differs between the two drugs studied and this may reflect the properties of the drugs, in particular the PAA of bopindolol.

Adrenergic beta-Antagonists↗
PubMed1989

Lipids, lipoproteins, and coronary heart disease: implications for antihypertensive therapy.

There is now considerable evidence that treatment of abnormalities of lipids and lipoproteins reduces the incidence of coronary heart disease (CHD). Treatment of hypertension, another major cardiovascular risk factor, has not been shown to have the same impact on CHD. Possible explanations for this are that cardiovascular risk factors may occur in combination in an individual or that therapy for hypertension has adversely affected one or several of the other risk factors for CHD, thereby offsetting the benefit gained by lowering blood pressure. This article reviews the relationship between lipids, lipoproteins, and coronary heart disease, and the impact of cholesterol lowering on CHD. The evidence that antihypertensive drugs are associated with lipid and lipoprotein abnormalities is introduced by a critical appraisal of the several studies for such evidence. Implications for the treatment of the hypertensive patient are discussed.

Antihypertensive Agents↗
PubMed1989

Platelet efflux of noradrenaline in patients with type 1 diabetes mellitus.

1. Endogenous noradrenaline release from washed platelets incubated under resting conditions and in the presence of thrombin was examined in 14 normal subjects and 10 subjects with type 1 (insulin-dependent) diabetes. 2. Irreversible aggregation of platelets from both normal and diabetic subjects was induced by thrombin (0.3 unit/ml). Platelets from diabetic subjects were more sensitive than platelets from normal subjects, extents of aggregation being 89% and 76%, respectively (P less than 0.002). 3. Stimulation with thrombin (0.3 unit/ml) elicited marked platelet release of noradrenaline to the incubation medium in both normal and diabetic subjects. Supernatant noradrenaline concentrations obtained under thrombin-stimulated conditions did not significantly differ between normal and diabetic subjects. However, under resting conditions noradrenaline levels were significantly greater (+93%, P less than 0.02) for diabetic than normal subjects. 4. Measurement of platelet noradrenaline contents after thrombin stimulation revealed no difference between normal and diabetic subjects. Under resting conditions, however, platelet noradrenaline levels were significantly lower (-46%, P less than 0.02) for diabetic than normal subjects. Thus, in the diabetic subjects increased resting platelet efflux of noradrenaline is mirrored by a decreased platelet noradrenaline content. 5. A consequence of increases in resting catecholamine efflux may be enhanced platelet activity resulting in increased platelet aggregation.

Adult↗
PubMed1989

Diabetes, lipoprotein metabolism and atherosclerosis.

As diabetologists in the United Kingdom we care for our patients against a background of one the highest population rates of coronary heart disease (CHD) in the world. As emerging evidence serves to confirm the pivotal role of blood cholesterol and particularly low density lipoprotein (LDL) cholesterol in the development of atherosclerosis-related disease, it is timely to consider the importance of lipid and lipoprotein disorders in diabetes. Although specific microvascular disease contributes significantly, atherosclerosis remains the most important cause of morbidity and mortality in long-standing diabetes. From epidemiological studies of different populations, particularly the Japanese, it is clear that premature CHD is not an inevitable consequence of diabetes. This provides encouragement for prevention especially given the recent impetus in the understanding of the role of blood lipids in the pathogenesis of atherosclerosis. In this short review I will highlight some recent developments in the cholesterol/heart disease story, how the diabetic state may influence lipid and lipoprotein metabolism and how hyperlipoproteinaemia in the diabetic should be managed.

Cholesterol↗
PubMed1989

Effects of noradrenaline infusion on platelet catecholamine levels and platelet aggregation.

Noradrenaline infusions were administered to 10 normal subjects through stepped doses and continued at 60 ng/kg per min for 2 h. Plasma noradrenaline rose from 1.7 +/- 0.3 to 7.7 +/- 0.7 pmol/ml and platelet noradrenaline rose from 2.1 +/- 0.2 to 2.6 +/- 0.2 pmol/mg protein. There was no change in plasma or platelet adrenaline. Platelet aggregation studies using ADP, adrenaline, collagen and thrombin as aggregants showed no overall change during the course of the infusion. Blood was sampled from a heated hand vein (hot box at 60 degrees C) to test the degree of arterialization. Plasma noradrenaline and blood pO2 and pCO2 showed intermediate levels at this sampling site compared with venous and true arterial values. Changes in platelet noradrenaline content can occur over 2 h when plasma levels are considerably increased by noradrenaline infusion. No change in platelet sensitivity to aggregation was observed. The heated hand vein did not provide true arterial levels of noradrenaline.

Adult↗
PubMed1989

A log-dose-response study of xipamide and its effect on metabolic parameters.

An extended dose-response study with xipamide, using seven doublings of the dose, from 0.3125 to 40 mg/day at 4-week intervals, was carried out in 12 hypertensive patients. Blood pressure showed a progressive decline with doses from 5 to 20 mg, and 40 mg xipamide produced no greater fall. Some subjects showed a maximum fall in blood pressure with a single dose increase but most showed a declining blood pressure over two or more dose increases. Plasma urea increased with doses of 5-40 mg to a similar extent, but there was no fall in the mean potassium level except with the 40-mg dose. Urinary calcium was reduced (from 4.2 to 1.7 mmol/24 h) on the 40-mg dose and the corrected plasma calcium level rose from 2.28 to 2.32 mmol/l. Triglycerides, very-low-density lipoprotein cholesterol and plasma aldosterone increased at the maximum dose; the cholesterol ratio, however, was unchanged.

Blood Pressure↗
PubMed1989

Platelet noradrenaline release in patients with familial hypercholesterolaemia.

We have examined resting and thrombin (0.3 units ml-1) induced release of noradrenaline by washed platelets from 15 normal subjects and eight patients with heterozygous familial hypercholesterolaemia. Platelets from both normal and hypercholesterolaemic subjects showed irreversible aggregation with 0.3 units ml-1 thrombin. Extents of aggregation were 76.3% and 90.8% respectively, platelets from hypercholesterolaemic patients being significantly more sensitive (P less than 0.002). Under resting conditions platelet noradrenaline release was 136% greater (P less than 0.02) in hypercholesterolaemic patients than in normal subjects. Thrombin-stimulated release of noradrenaline was also higher (73%, P less than 0.05) in hypercholesterolaemics than in normals. The differences between resting and thrombin-stimulated release were greater for hypercholesterolaemic patients than normal subjects (P less than 0.05). Under resting conditions total platelet noradrenaline levels (sum of supernatant and platelet pellet concentrations) were similar in preparations from the two groups. However, following thrombin stimulation total noradrenaline concentrations were substantially greater (86%) in platelets from hypercholesterolaemics than normals (P less than 0.02). In hypercholesterolaemic patients thrombin stimulation was associated with an 101% increase (over resting levels) in total platelet noradrenaline (P less than 0.01), no increases being observed with normal subjects. We suggest that platelet membranes may be more permeable in patients with familial hypercholesterolaemia leading to increased non-specific release of catecholamines. Platelets from patients with familial hypercholesterolaemia may also be more responsive to stimulation with respect to catecholamine release. The results obtained on calculation of total platelet noradrenaline levels may indicate that abnormalities of platelet dense granules occur in familial hypercholesterolaemia. In this context the relative proportions of free and conjugated catecholamine may be of relevance.

Adolescent↗
PubMed1989

Lipoproteins and coronary heart disease.

With increasing acknowledgement of the multiple risk factor approach to the prevention of coronary heart disease (CHD), physicians treating hypertension have turned their attention to the presence of other CHD risk factors, particularly dyslipidaemia, in their patients. There appears to be a 'clustering' of lipid abnormalities within the hypertensive population and furthermore, some antihypertensive agents may have adverse effects on plasma lipid and lipoprotein concentrations. In this article lipoprotein metabolism is reviewed and the evidence linking individual lipoproteins to the atherosclerotic process discussed. Finally, some guidelines are given for the dietary and, where necessary, the pharmacological modification of plasma lipoprotein concentrations.

Animals↗