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Biomedical subjects

D J Betteridge

Publications and source records attributed to D J Betteridge.

At least 73 records · Page 4Linked to original sources
PubMed1993

The influence of aspirin on plasma and platelet catecholamine levels, and platelet function in normal man.

The aim of the study was to determine whether aspirin influences sympathoadrenal output in normal human subjects. Plasma and platelet adrenaline and noradrenaline levels were measured before and after chronic administration of oral aspirin (300 mg per day for 7 days). Catecholamine concentrations measured immediately following aspirin did not differ from control (pre-treatment) values. Platelet noradrenaline and plasma adrenaline levels were, however, significantly increased 2 weeks after cessation of treatment. Platelet TxB2 generation was significantly reduced following aspirin treatment indicating that platelet cyclooxygenase had been inhibited. Catecholamine concentrations did not correlate with TxB2 generation. In vitro platelet aggregation induced by ADP, adrenaline and collagen was reduced after aspirin providing additional confirmation of cyclooxygenase inhibition. However, the in vivo markers of platelet function, beta-TG and PF4 were unaffected. These data do not provide convincing evidence for an action of aspirin on sympathoadrenal outflow, either directly or via a prostaglandin (thromboxane) mediated effect, although this does not exclude a later, delayed effect. There was no evidence for interactions between thromboxane, catecholamine levels in plasma and platelets, and platelet function.

Adenosine Diphosphate↗
PubMed1993

Altered cellular signalling and decreased platelet sensitivity to adenosine in insulin-dependent diabetic patients with proliferative retinopathy.

Platelets from patients with insulin-dependent diabetes with proliferative retinopathy showed the same reactivity to ADP as those from control subjects. Responsiveness of platelets to the aggregation inhibitor adenosine and to the analogue N-ethylcarboxamidoadenosine was decreased in diabetes. In contrast, responsiveness to the anti-aggregatory effects of prostaglandin I2 was not significantly altered in diabetes. Platelets from diabetic patients exhibited decreased formation of cyclic AMP in response to N-ethylcarboxamidoadenosine compared with those from control subjects. In contrast, when adenylyl cyclase was stimulated by prostaglandin I2 or by forskolin, no differences in cyclic AMP formation were observed between control and diabetic platelets. Diabetes was associated with an apparent loss of high-affinity binding of [3H]N-ethylcarboxamidoadenosine to platelet membranes. Possible mechanisms that could contribute to this diabetes-induced change in signalling through the platelet A2 adenosine receptor are discussed.

Adenosine↗
PubMed1993

Decreased sensitivity to adenosine in platelets from patients with familial hypercholesterolaemia--a change reversed by cholestyramine treatment.

Platelet-rich plasma was obtained from patients with untreated heterozygous familial hypercholesterolaemia (FH), from FH patients treated with cholestyramine and from control subjects. Responsiveness of platelets to the aggregation inhibitors adenosine, its analogue N-ethylcarboxamidoadenosine (NECA) and prostaglandin I2 was decreased in FH. Patients on cholestyramine therapy showed normal responsiveness to adenosine and NECA. There were only minor changes in the binding of [3H]NECA to high-affinity binding sites on platelet membranes from untreated FH or cholestyramine-treated FH patients. The initial rate of cyclic AMP formation in response to a high concentration of NECA was severely decreased in platelets from FH patients. By contrast, the rate of cyclic AMP formation in response to forskolin or a high concentration of prostaglandin I2 was unchanged. These data point to a defect in the coupling of the platelet A2 adenosine receptor to adenylyl cyclase in untreated FH patients.

Adenosine↗
PubMed1993

Management of hyperlipidaemia: guidelines of the British Hyperlipidaemia Association.

There is considerable evidence to suggest that the identification and treatment of dyslipidaemia will reduce the risk of premature CHD, i.e. before the age of 65. Diagnosis of the cause of raised plasma lipid levels will enable appropriate decisions to be taken with regard to management. The cornerstone of treatment is nutritional counselling and attention to other major risk factors for CHD, particularly smoking and hypertension. For a small percentage of patients with severe hyperlipidaemia drug therapy is indicated. Appropriate drug choices need to be made based on the particular lipid abnormality to be treated. In general those patients with clinical vascular disease are treated more aggressively than those where the aim is primary prevention. More research is needed to determine individual risk more precisely and to allow proper targeting of therapy. Genetic factors, qualitative changes in lipoproteins, lipoprotein (a), fibrinogen, and other coagulation and thrombotic factors are likely to be important in individual risk assessment. There is no doubt that more information is needed from prospective studies of lipid-lowering therapy in terms of risk benefit for affected individuals. Hopefully the major studies currently underway will fill some of the gaps in our knowledge. Until then aggressive therapy with drugs should be reserved for those at highest risk where the benefit is likely to be greatest.

Cholesterol, Dietary↗
PubMed1993

Ciprofibrate--a profile.

The cornerstone of management in hyperlipidaemia is dietary and lifestyle therapy. Nonetheless, a proportion of patients will require drug therapy. Of the currently available choices, statins are of obvious value for raised cholesterol and low dose resins have a place in treating moderate hypercholesterolaemia. There is also an important role for the fibrates, particularly for modifying the hypertriglyceridaemic state and hence influencing low density lipoprotein (LDL) metabolism. Ciprofibrate is a compound newly introduced into the United Kingdom which shares many pharmacokinetic properties with other fibrates. Time to maximum serum concentration is about one hour and the long elimination half life (80 hours) permits once daily dosing. After a 12 week treatment period in Type II patients, LDL cholesterol was reduced by 24%. More recent work has shown a fall among Type IIa patients of 29% in LDL cholesterol with an increase in HDL cholesterol when ciprofibrate was given at 200 mg/day. A triglyceride reduction of 42% was recorded in Type IIb patients. Favourable effects have been described at 5 years of follow up for patients with Type IIa, Type IIb and Type IV patterns. Effects on clotting parameters are favourable and there is no significant long-term effect on biliary cholesterol saturation. In addition, no structural changes were observed in a small number of biopsies from treated patient liver. Side effects and contraindications are as for other fibrates. Ciprofibrate seems to be a valuable addition to drug therapy for the management of a variety of dyslipidaemias.

Clofibric Acid↗
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↗