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Biomedical subjects

D J Betteridge

Publications and source records attributed to D J Betteridge.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

Plasma and platelet free catecholamine concentrations in patients with familial hypercholesterolaemia.

1. Plasma and platelet free catecholamine concentrations were measured in 22 normal subjects and in 10 treated and 11 untreated patients with heterozygous familial hypercholesterolaemia. 2. Plasma noradrenaline concentrations were significantly higher in both treated and untreated hypercholesterolaemic patients than in normal subjects. Adrenaline concentrations did not differ. 3. Platelet noradrenaline levels were higher in untreated hypercholesterolaemic patients than in normal subjects. 4. Positive correlations between the plasma noradrenaline concentration and the platelet noradrenaline concentration were observed in both normal subjects and hypercholesterolaemic patients. 5. Combining the data for normal subjects and hypercholesterolaemic patients revealed that the plasma noradrenaline concentration correlated positively with the plasma cholesterol concentration. The platelet noradrenaline concentration was also found to correlate with the plasma cholesterol concentration. 6. Our results suggest that an increased plasma cholesterol concentration may be associated with increased sympathetic nervous system activity as indicated by elevated plasma and platelet noradrenaline levels. Increases in circulating catecholamines may contribute to the platelet hyperaggregability seen in familial hypercholesterolaemia.

Adult↗
PubMed1992

Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome.

OBJECTIVE: The evidence that some women with the polycystic ovary syndrome (PCOS) are hyperinsulinaemic has brought into question their risk of developing early coronary artery disease. We have focused on three cardiac risk factors which have been associated with hyperinsulinaemia by measuring glucose tolerance, fasting serum lipid concentrations and blood pressure in women with PCOS. DESIGN: Comparison of clinical and biochemical measurements in lean and obese women with PCOS and in women with normal ovaries. Determinants of the risk factors for coronary artery disease were assessed by multiple regression analysis. PATIENTS: One hundred and two women with ultrasound diagnosed PCOS and 19 lean women with normal ovaries were studied. Patients were recruited from a reproductive endocrine clinic. MEASUREMENTS: Fasting total cholesterol, triglycerides, high density lipoproteins (HDL), HDL2, glucose tolerance, fasting and stimulated insulin, gonadotrophins, testosterone and androstenedione were measured during a 2-hour oral glucose tolerance test. Recumbent blood pressure was measured automatically. RESULTS: Lean women with PCOS were found to be hyperinsulinaemic and have reduced serum HDL and HDL2 concentrations compared to women with normal ovaries; serum insulin concentrations correlated positively with plasma glucose and blood pressure measurements in multiple regression analysis. Obese women with PCOS were in addition found to have higher systolic blood pressure, serum triglyceride and plasma glucose concentration than lean women with PCOS and controls. CONCLUSIONS: These results support the evidence that hyperinsulinaemic women with PCOS have an increased risk of developing cardiovascular disease and therefore form a population in whom metabolic screening is advisable.

Adult↗
PubMed1992

Fasting lipids and anticardiolipin antibodies as risk factors for vascular disease in systemic lupus erythematosus.

Fasting cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apoprotein AI, and apoprotein B were measured in 64 patients with systemic lupus erythematosus to assess the risk factors for vascular disease. The relation between the lipid profile, steroid treatment, the presence of anticardiolipin antibodies, and the prevalence of vascular disease was examined. Raised concentrations of triglyceride and apoprotein B were seen in those patients treated with more than the equivalent of 10 mg prednisolone a day in the six months before testing. An increase in vascular disease was found only in the subgroup of patients with increased triglycerides who also expressed anticardiolipin antibodies. This study confirms the association between treatment with high doses of steroids in lupus and the development of an atherogenic plasma lipid profile. The presence of anticardiolipin antibodies compounds the risk of developing vascular disease.

Adult↗
PubMed1992

Laboratory facilities for investigating lipid disorders in the United Kingdom: results of the British Hyperlipidaemia Association survey.

AIMS: To determine the availability of facilities for the investigation of hyperlipidaemia in the United Kingdom. METHODS: A questionnaire was sent to all health districts in the United Kingdom. RESULTS: The response rate was 81%. All laboratories used enzymatic techniques to measure serum triglyceride and cholesterol concentrations, although there were differences in standardisation procedures. Reference ranges for serum lipids were quoted by 58% of laboratories while 50% quoted "desirable limits". Almost half specified that fasting blood samples were required. High density lipoprotein cholesterol concentrations were estimated by 75% and apolipoproteins AI and B by 14% of laboratories; there were differences in specimen type and considerable diversity in procedures used for measurement. CONCLUSIONS: Many laboratories were unaware of current recommendations for screening for hypercholesterolaemia in the community. The present survey indicated an urgent need for the introduction of better reference methods, standardisation, and quality assurance procedures before apolipoproteins become a routine part of coronary heart disease risk assessment.

Apolipoproteins↗
PubMed1992

Carnitine deficiency associated with long-term pivampicillin treatment: the effect of a replacement therapy regime.

A 51 year old female developed a skeletal muscle myopathy after 3 months of pivampicillin therapy. Pivampicillin can cause carnitine deficiency due to the pivalic acid side group. Plasma carnitine content and the patients symptoms failed to improve significantly on discontinuing the drug. Oral carnitine replacement therapy was administered for 6 weeks but the patient's plasma carnitine levels responded only slowly to this treatment. It is suggested that pivampicillin inhibits uptake of carnitine from the gut and may either directly or indirectly depress endogenous carnitine synthesis. In such cases a more aggressive carnitine replacement regime is indicated and pivampicillin should be avoided in patients requiring long-term antibiotic administration.

Carnitine↗
PubMed1992

Hypertension and insulin resistance.

Insulin resistance and hyperinsulinemia is now recognized in non-insulin-dependent diabetes, essential hypertension, obesity, atherosclerotic heart disease, dyslipidemia, heart failure, and in heavy smokers. Several mechanisms have been proposed to explain hyperinsulinemia, insulin resistance and its relationship to hypertension; reduced sodium excretion, activation of the sympathetic nervous system, increased activity of the sodium/hydrogen pump, and stimulation of cellular growth. Some of the nonpharmacological methods to control hyperinsulinemia are of benefit in the management of hypertension, most notably weight loss, exercise program, and reduced salt intake. High-fiber and reduced-protein diets also reduce hyperinsulinemia. Thiazide diuretics can result in insulin resistance, and insulin secretion may be inhibited, possibly associated with concomitant hypokalemia. beta-Blockers result in some reduction of glucose tolerance and mask some of the features of hypoglycemia. Angiotensin-converting enzyme (ACE) inhibitors and alpha-receptor blockers do not effect insulin resistance; probably the same is true for calcium antagonists. Although the effect on risk factors should not be discounted, it is the effect of treatment on hard end points, cerebrovascular accidents, myocardial infarction, or death that is most important. Evidence in hypertension is at present restricted to diuretics and beta-blocking drugs.

Animals↗
PubMed1991

Blood rheology and fibrinogen in children with familial hypercholesterolaemia.

Whole blood and plasma viscosity, red cell aggregability and deformability, and plasma fibrinogen have been compared between 16 children aged between 6 and 18 years with heterozygous familial hypercholesterolaemia (FH) and 16 controls individually matched for age and sex. Mean (SD) plasma cholesterol was 7.19 (1.23) mmol/l in the patients and 4.31 (0.84) mmol/l in the controls. This was due to a similar difference in low density lipoprotein (LDL) cholesterol, while triglycerides and high density lipoprotein (HDL) cholesterol were similar between groups. No differences were seen in any of the rheological parameters between the two groups. This suggests that the rheological abnormalities seen in adults with FH are not a direct consequence of their hyperlipidaemia, and may instead be a reflection of their more extensive atherosclerosis.

Adolescent↗
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↗