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Biomedical subjects

P N Durrington

Publications and source records attributed to P N Durrington.

At least 163 records · Page 9Linked to original sources
PubMed1988

Hypertriglyceridemia and hyperuricemia: effects of two fibric acid derivatives (bezafibrate and fenofibrate) in a double-blind, placebo-controlled trial.

The effects of bezafibrate and fenofibrate on serum lipoproteins and serum urinary uric acid were compared. In a double-blind, placebo-controlled, cross-over study, each drug was administered in random order for 6 weeks followed by a 3-week drug-free phase to ten men with primary hypertriglyceridemia. Serum triglyceride and cholesterol concentrations decreased significantly with both fenofibrate and bezafibrate, although no significant change in serum apolipoprotein B, serum low density lipoprotein (LDL) cholesterol or serum high density lipoprotein (HDL) cholesterol concentrations was apparent. Serum uric acid levels, which were elevated on placebo and bezafibrate, were significantly reduced by 20% by fenofibrate. This was associated with an increase in renal uric acid clearance of 30% during fenofibrate therapy. Because it seems likely that hypertriglyceridemia and hyperuricemia are linked by a common carbohydrate inducibility, we studied the acute hyperuricemic response to orally administered fructose. Fructose (50 g) caused the anticipated rise in serum urate reaching a peak between 60 and 90 minutes, which was quantitatively greater in the men with hypertriglyceridemia than in healthy controls. The serum uric response to fructose was unaffected by bezafibrate, but was converted to normal by fenofibrate. The hyperuricemic action of fenofibrate is of sufficient magnitude to be of therapeutic value in the management of patients whose hypertriglyceridemia is associated with gout.

Bezafibrate↗
PubMed1987

Influence of proteinuria on vascular disease, blood pressure, and lipoproteins in insulin dependent diabetes mellitus.

Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.

Adult↗
PubMed1986

Lipoprotein abnormalities in insulin-dependent diabetes mellitus.

Despite the increased risk of atherosclerosis in diabetes mellitus, levels of serum cholesterol, triglycerides, low-density-lipoprotein (LDL) cholesterol, and high-density-lipoprotein (HDL) cholesterol were similar in 57 men with insulin-dependent diabetes mellitus (IDDM) and 81 non-diabetic controls. However, substantially lower serum levels of apolipoprotein B, the principal apolipoprotein of LDL, and a concomitant increase in the cholesterol-loading of apolipoprotein B were found in IDDM. The likely changes in LDL density and particle size resulting from this compositional abnormality might lead to accelerated atherogenesis analogous to that seen in type III hyperlipoproteinaemia. In addition, there was an increase in the concentration of cholesterol in the smaller, denser, HDL3 subfraction of serum HDL in IDDM.

Adult↗
PubMed1986

Serum and urinary high density lipoproteins in glomerular disease with proteinuria.

The serum lipoprotein concentrations, including high-density lipoprotein (HDL) subfractions and apolipoproteins Al and B were measured in 21 patients (14 male and seven female) with nephrotic range proteinuria (greater than 3g/24hr), well maintained renal function (creatinine clearance greater than 35 mliter/min/1.73m2) and biopsy-proven primary glomerular disease. In these, and in a further five patients (creatinine clearance greater than 15 mliter/min/1.73m2), urinary apolipoprotein Al output was determined. Total HDL cholesterol was similar in patients and controls, but in male patients, HDL2 was low (0.54 +/- 0.10 mmole/liter, mean +/- SEM) compared to controls (0.75 +/- 0.04 mmole/liter, P less than HDL3 was high (0.81 +/- 0.07 in patients and 0.63 +/- 0.02 mmole/liter in controls, P less than 0.01). In women, there was a similar tendency for HDL2 to be lower in patients (0.68 +/- 0.18 mmole/liter) than in controls (0.85 +/- 0.10 mmole/liter). Multiple regression analysis revealed that major determinants of the urinary apolipoprotein Al output were the urinary protein output and selectivity index (multiple r = 0.85). Furthermore, some patients lost apolipoprotein Al into their urine at rates indicating increased production of apolipoprotein Al in the nephrotic syndrome. The serum HDL subfraction concentrations in the nephrotic syndrome could be explained by a combination of increased HDL production and increased urinary loss of low molecular wt HDL.

Aged↗
PubMed1986

Serum apolipoproteins AI and B and lipoproteins in middle aged men with and without previous myocardial infarction.

The serum high density lipoprotein (HDL) subfractions, HDL2, and HDL3, and serum apolipoprotein AI and B (apo AI and B) were evaluated as potential indicators of the risk of ischaemic heart disease in men aged less than 60 years who had previously had a myocardial infarction and in controls with a similar socioeconomic background who had no history of myocardial ischaemia. Discriminant analysis confirmed that the combination of serum cholesterol, triglycerides, and total HDL cholesterol distinguished poorly between patients and controls. The best single discriminating variable was apo B. Stepwise discriminant analysis showed that this discrimination could be improved to a small extent by combining apo B with apo AI and parental history, but nothing was gained by measurement of serum cholesterol triglycerides, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, HDL cholesterol, HDL2 or HDL3 cholesterol. Significantly more patients than controls with type IV hyperlipoproteinaemia had raised concentrations of serum apolipoprotein B, but the frequency of raised apolipoprotein B concentrations was no greater in patients with type IV hyperlipoproteinaemia than in those with normal serum lipids. The value of apo B as an indicator of cardiovascular risk should be assessed in prospective studies.

Apolipoprotein A-I↗
PubMed1985

Double-blind, placebo-controlled, cross-over trial of probucol in heterozygous familial hypercholesterolaemia.

Ten patients with heterozygous familial hypercholesterolaemia (FH) were given probucol 500 mg b.d. or placebo for 3 months in a randomised order in a double-blind cross-over trial. There was a 14% decrease in serum cholesterol concentration due to a reduction in both low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol. The subfraction of HDL most affected was HDL2. Reductions in serum LDL cholesterol concentration exceeding 20% were obtained in 3 (30%) of the patients. The magnitude of the change in LDL cholesterol concentration was related to the level of serum HDL2 cholesterol without therapy and to the magnitude of its decrease on probucol. Intravenous intralipid tolerance was unaffected by probucol administration. Serum apolipoprotein B concentration decreased less with probucol than did that of serum LDL cholesterol.

Adolescent↗
PubMed1985

Short-term effects of beta-adrenoceptor blocking drugs with and without cardioselectivity and intrinsic sympathomimetic activity on lipoprotein metabolism in hypertriglyceridaemic patients and in normal men.

In six patients with hypertriglyceridaemia presenting whilst receiving treatment with beta-adrenoreceptor blocking drugs (mean serum triglycerides 31.2 mmol/l) the half-life (t1/2) of an intravenously administered triglyceride emulsion was 32.8 +/- 7.9 min (mean +/- SEM) on beta-blocker and 22.8 +/- 4.8 min after stopping beta-blocker treatment. In three of these patients subsequent administration of a beta-blocker with intrinsic sympathomimetic activity had no effect on t1/2. In a cross-over trial of placebo, atenolol (beta 1-blocker), propranolol (beta 1- and beta 2-blocker) and pindolol (beta 1- and beta 2-blocker with intrinsic sympathomimetic activity) in 11 normal men t1/2 was 11.8 +/- 0.9, 12.6 +/- 1.1, 14.3 +/- 1.7 and 12.4 +/- 1.1 min respectively. None of the apparent differences achieved statistical significance, but in two men marked increases in t1/2 occurred on propranolol. The concentrations of serum triglycerides and very low density lipoprotein cholesterol in the normal men were, however, increased by beta-blockade, most markedly by pindolol. Serum high density lipoprotein (HDL) cholesterol concentration decreased in normal men on beta-blockers, most clearly on atenolol and propranolol. This decrease was due to a reduction in cholesterol in the HDL2 subfraction. No statistically significant effects on serum low density lipoprotein cholesterol or apolipoprotein B concentrations occurred in the normal men. The doses of atenolol and propranolol used in this study were equipotent as judged by the heart rate response to exercise.

Adrenergic beta-Antagonists↗
PubMed1984

Clinical aspects of hyperlipidaemia.

Disagreement about the epidemiological aspects of hyperlipidaemia has meant that many onlookers have become disenchanted with its clinical importance. This is unfortunate because new insights into the metabolism of the hyperlipidaemias have established clearer indications for treatment.

Adult↗
PubMed1982

Serum high density lipoprotein cholesterol subfractions in type I (insulin-dependent) diabetes mellitus.

The concentration of cholesterol in serum high density lipoproteins (HDL) and their subfractions (HDL2 and HDL3) was determined in men and women with type I diabetes treated with insulin and in non-diabetic men and women matched for age, weight and serum cholesterol, but not for triglyceride-rich lipoproteins which were higher in the diabetic patients. In none of the patients was the diabetes badly controlled as assessed by measurement of the percentage of haemoglobin in the glycosylated state (HbA1). Regardless of their diabetic control, significantly increased serum HDL3 cholesterol concentration was found in male diabetic patients compared to non-diabetic controls, and in both male and female diabetics the ratio of HDL2 to HDL3 cholesterol was significantly reduced. In patients with well-controlled diabetes (HbA1 less than or equal to 9%) serum HDL3 cholesterol was significantly increased in both men and women, whereas in those with less well-controlled diabetes (HbA greater than 9%) it was similar to that of non-diabetic controls. In only one group of patients, the less well controlled men, was there a significant reduction in serum HDL2 cholesterol. On the basis of current theory, the results of this study would support the view that HDL3 does not contribute to the inverse relationship between total serum HDL and the risk of ischaemic heart disease.

Adult↗
PubMed1982

The assessment of Achilles tendon size in primary hypercholesterolaemia by computed tomography.

The Achilles tendons of 43 men and women were examined by conventional radiography and by computed tomography (CT). Eleven subjects were normolipidaemic and 32 had familial hypercholesterolaemia, of whom 19 were considered to have polygenic hypercholesterolaemia and 13 monogenic. Achilles tendon xanthomata were identifiable by both radiography and CT. In assessing the size of xanthomata, CT had advantages since the junction between muscle and tendon was easily identified and all the dimensions and the cross-sectional area of the tendon could be measured. The area of Achilles tendons was closely correlated with body height in normolipidaemic men and women and patients with polygenic hypercholesterolaemia. In monogenic hypercholesterolaemia this relationship was lost. The tendons of the normolipidaemic group and of patients with polygenic hypercholesterolaemia were indistinguishable, whereas those of patients with monogenic hypercholesterolaemia were significantly larger. Neither the maximum nor the average CT attenuation values of the tendons differed significantly between the 3 groups. Of the patients with monogenic hypercholesterolaemia, those whose Achilles tendons were less than 200 mm2 in area had received treatment longer than those with larger tendons. CT shows promise as a means of assessing the therapeutic response of patients with monogenic familial hypercholesterolaemia.

Achilles Tendon↗
PubMed1982

Effects of insulin and glucose on very low density lipoprotein triglyceride secretion by cultured rat hepatocytes.

The effect of insulin on hepatic triglyceride synthesis and secretion is controversial. Previously, we have described a cell culture system of adult rat hepatocytes that synthesize and secrete very low density lipoprotein (VLDL) triglycerides with small and irreproducible effects of insulin on triglyceride metabolism. To study the primary effects of insulin on hepatic triglyceride metabolism a method was developed utilizing fibronectin-coated culture dishes that allowed adhesion, spreading, and maintenance of hepatocytes for 2-3 d in the absence of serum and insulin. This culture system allowed mass measurements of both cellular and secreted VLDL triglycerides for long time periods after the addition of physiological concentrations of insulin to hormone-free culture medium. In the absence of insulin and after an initial 4 h in culture, the medium was replenished and triglyceride mass was measured at the end of 18-h incubations. VLDL triglyceride accumulated in the culture medium at a linear rate over this time-course with increasing accumulation as the medium glucose concentration was raised from 2.5 to 25 mM glucose (1.77+/-0.24 to 3.09+/-0.76 mug triglyceride/mg cell protein per h). There was no apparent significant lipolysis or hepatocellular reuptake of secreted VLDL triglycerides. In the absence of insulin cellular triglyceride levels were unchanged between 3 and 24 h in culture while insulin (50-500 muU/ml) significantly increased cellular triglyceride content at all glucose concentrations tested (0-25 mM). The addition of insulin to the culture medium progressively reduced the rate of VLDL triglyceride secretion accompanied by an increase in cellular triglyceride at insulin concentrations > 50 muU/ml. Most or all of the observed increase in cell triglyceride content could in all experiments be accounted for by the insulin-induced inhibition of VLDL secretion. Incorporation of [2-(3)H]glycerol into cellular and VLDL triglycerides as a function of insulin concentration was also measured. Glycerol incorporation data at 20-22 h after plating of the cells closely paralleled the insulin-induced changes in cellular and VLDL triglyceride as determined by mass analysis. The observed effects of insulin occurred at concentrations close to the physiological range and suggest that the direct hepatic effect is to suppress VLDL secretion although the net effect in vivo will clearly reflect many additional accompanying changes.

Albumins↗
PubMed1982

High-density lipoprotein cholesterol: methods and clinical significance.

The known limitations and advantages of methods for determining serum high-density lipoprotein (HDL) cholesterol concentration are reviewed with special emphasis on the applicability of each method to clinical medicine. The evidence for and against the relevance of serum HDL cholesterol to the prediction of the likelihood of an individual man or woman developing clinically evident ischemic heart disease is discussed. The possibility that HDL subfractions may be more relevant to this issue is also discussed. Information about serum HDL cholesterol concentration in diseases other than ischemic heart disease is reviewed. The effect of diet, body-weight, exercise, cigarette-smoking, alcohol intake, and hyperlipoproteinemia and the effect of modification of these factors on serum HDL cholesterol levels is discussed. Finally, a practical approach to the patient with a low concentration of serum HDL cholesterol is suggested.

Chemical Phenomena↗
PubMed1980

Serum high density lipoprotein cholesterol in diabetes mellitus: an analysis of factors which influence its concentration.

The study assesses whether diabetes has an effect on serum high density lipoprotein (HDL) cholesterol concentration independent of other factors known to influence serum HDL cholesterol concentration. Concentrations of serum HDL cholesterol, serum cholesterol, serum M particles and blood sugar, and the proportion of haemoglobin in the form of HbA1 were measured in a diabetic and a non-diabetic polulation. Relative body weight, alcohol and cigarette consumption, age, a clinical estimate of diabetic control and duration of disbetes were also recorded. The diabetic patients were divided into those in whom insulin treatment was clinically indicated and those in whom it was not. Serum HDL cholesterol concentration was significantly higher in diabetic men treated with insulin than in normal men and also higher in diabetic women treated with insulin than in normal women. In the diabetic men and women not treated with insulin, serum HDL cholesterol concentration was not significantly different from normal. There were differences between the diabetic and non-diabetic populations in terms of factors known to influence serum HDL cholesterol and also in the degree of correlation between these and the serum HDL cholesterol. Multivariate analysis revealed that in both male and female diabetic patients treated with insulin, diabetes was a highly significant influence on serum HDL cholesterol concentration, but in the non-insulin-treated diabetic patients the influence was absent in women and only marginal in men. The proportion of HbA1 influenced serum HDL cholesterol concentration negatively in insulin-treated diabetes but not in diabetes treated without insulin.

Alcohol Drinking↗
PubMed1980

The effects of treatment with insulin on serum high-density-lipoprotein cholesterol in rats with streptozotocin-induced diabetes.

1. No significant difference in serum high-density-lipoprotein (HDL) cholesterol was observed when control rats were compared with rats with streptozotocin-induced diabetes of 14 days duration. Blood glucose and serum cholesterol and triglyceride concentrations were significantly higher in the diabetic group. 2. In a second experiment rats with streptozotocin-induced diabetes of 8 days duration were given long-acting porcine insulin (1 unit/day or 3 units/day subcutaneously for 14 days) and were compared with a control group. Blood glucose and serum cholesterol and triglyceride concentrations did not differ significantly with the two doses of insulin and there was no significant difference between serum high-density-lipoprotein cholesterol in control rats and either of the two groups of rats given insulin. 3. When the rats given insulin were grouped according to their blood glucose concentrations, those with blood glucose in the range 20-30 mmol/l were found to have significantly higher serum high-density-lipoprotein cholesterol concentrations than those with higher or lower blood glucose levels or than controls. There was thus a statistically significant curvilinear relationship between blood glucose and serum high-density-lipoprotein cholesterol concentrations.

Animals↗