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Biomedical subjects

G R Thompson

Publications and source records attributed to G R Thompson.

At least 109 records · Page 6Linked to original sources
PubMed1989

Restriction fragment length polymorphisms in the apo B gene in relation to coronary artery disease.

We have determined the frequencies of the alleles at the EcoRI (E), XbaI (X) and PvuII (P) polymorphic restriction sites in the apo B gene in 124 white men with coronary artery disease (CAD) and in 146 white men free from CAD. The frequencies of the E- (restriction site absent) and X- alleles were both significantly higher in normocholesterolaemic men with CAD than in those without CAD, but the frequency of the P+ allele (restriction site present) was similar in the 2 groups. The frequency of the E- allele was significantly higher in CAD men with hypertriglyceridaemia than in normal men without hypertriglyceridaemia. In the normocholesterolaemic men without CAD, the mean serum cholesterol concentration was higher in those with genotype X++ than in those with genotype X--. Mean serum LDL-apo B and LDL-cholesterol concentrations did not differ significantly between men with different XbaI or EcoRI genotypes. Serum apo A-I levels differed significantly between normal men with different XbaI genotypes. Serum HDL-cholesterol levels differed significantly between CAD men with different XbaI genotypes. These results suggest that in white men the E- and X- alleles are in linkage disequilibrium with a nearby allele that is causally related to CAD. It is also possible that the amino acid substitution at position 4154 in apo B, brought about by the nucleotide change responsible for the EcoRI polymorphism, has a direct effect on the atherogenicity of LDL.

Adult↗
PubMed1989

Apolipoprotein A-I gene polymorphisms: frequency in patients with coronary artery disease and healthy controls and association with serum apo A-I and HDL-cholesterol concentration.

We have investigated the association between serum high density lipoprotein-cholesterol (HDL-C) and apo A-I concentration and the PstI and XmnI restriction fragment length polymorphisms of the apolipoprotein AI-CIII-AIV multigene complex. Two groups of subjects were examined. The first comprised 174 unrelated male patients under 60 years of age with angiographic evidence of coronary artery disease (CAD). Of this group 34 were non-North European. The second group consisted of 104 unrelated healthy male North European subjects aged under 60 and free from demonstrable CAD, who attended a health screening clinic in London. For the PstI polymorphism, the frequency of the rarer P2 allele was 0.12 in both the North European and non-North European patients and this was higher than in the control group (P2 frequency 0.06, P less than 0.05). Healthy individuals with the genotype P1P2 had higher levels of apo A-I but similar levels of HDL-C compared to those with the genotype P1P1. However, CAD patients with the genotype P1P2 had lower serum levels of apo A-I and significantly lower serum levels of HDL-C compared to those with the genotype P1P1 (0.85 mmol/l vs. 1.0 mmol/l, P less than 0.05). The allele frequencies of the XmnI polymorphisms were not significantly different in the control group and the group of North European patients, although within the sample of non-North European patients, the frequency of the X2 allele was significantly higher than that found in the North European controls (0.26 vs. 0.09). Patients with the genotype X1X2 had a higher mean serum concentration of HDL-C and apo A-I compared with patients with the genotype X1X1 (1.14 and 0.93 mmol/l for HDL-C, P less than 0.05; 147 and 123 mg/dl for apo A-I, P less than 0.05). Associations between HDL-C and apo A-I levels and PstI and XmnI genotype were similar in patients taking and not taking beta-blockers. The data show that genetic variation in the apo AI-CIII-AIV gene cluster is associated with coronary artery disease although only weakly, and suggest that the mechanism of this association may operate through an effect in determining the serum concentration of apo A-I and HDL-cholesterol.

Adult↗
PubMed1989

Effect of enprostil on glucose and lipid metabolism in type 2 diabetes.

Enprostil, a dehydro-prostaglandin E2 analogue, has been tested as treatment for peptic ulcer. Its effect on blood glucose and lipid metabolism in Type 2 diabetes was assessed in a randomized, double-blind trial. Fifteen patients on sulphonylurea therapy received, in addition, enprostil 35 micrograms or placebo thrice daily for two weeks, with a 2-week wash-out before crossover. Data from 12 patients were analysed. After a 530 Cal test breakfast at the end of active treatment, plasma glucose rose from a fasting concentration similar to that after the last placebo dose (10.5 +/- 0.8 (+/- SE) and 10.6 +/- 1.1 mmol l-1 respectively) to 1, 2 and 3 h concentrations which were 1.5 to 2.1 mmol l-1 lower than on placebo (2 h concentration 14.6 +/- 0.9 vs 16.4 +/- 1.3 mmol l-1, p less than 0.05). Serum fructosamine concentrations at the end of active treatment and placebo were 3.66 +/- 0.22 and 3.78 +/- 0.24 respectively (p = 0.051). No changes in fasting or post-prandial insulin concentrations were observed. After 2 weeks of enprostil, fasting serum triglyceride (1.76 +/- 0.18 mmol l-1) and total cholesterol (6.27 +/- 0.29 mmol l-1) concentrations were lower than after placebo (2.14 +/- 0.25 and 7.35 +/- 0.46 mmol l-1, p = 0.031 and p = 0.002, respectively), the latter effect being primarily due to reduced LDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Lipid related consequences of intestinal malabsorption.

The small intestine plays a key role in lipid metabolism by absorbing fat and synthesising apoproteins. Fat malabsorption secondary to intestinal disease results in abnormalities of lipoprotein concentration and composition and can lead to deficiency of essential fatty acids and fat-soluble vitamins. Malabsorption of fat can be induced by administration of neomycin and malabsorption of bile acids by administration of anion-exchange resins or by creating a partial ileal bypass. These induced forms of malabsorption are useful in the treatment of hyperlipidaemic patients liable to atherosclerosis.

Animals↗
PubMed1989

Current management of hyperlipidaemia.

Hyperlipidaemia is a major cause of coronary heart disease (CHD) and is especially prevalent in Britain. Prior to lipid-lowering therapy it is necessary to define the type of lipoprotein abnormality present and whether it is primary or secondary. Diet forms the initial treatment but additional drug therapy may be necessary in patients with established CHD or considered to be at high risk of developing CHD or rarely, in the case of severe hypertriglyceridaemia, acute pancreatitis.

Humans↗
PubMed1989

Reappraisal of partial ileal bypass for the treatment of familial hypercholesterolemia.

Eleven patients with heterozygous familial hypercholesterolemia (type IIa) were treated by partial ileal bypass. Postoperatively, mean total cholesterol levels fell by 26% at 1 month, and then rose steadily to 20% below preoperative levels of 20-24 months. The rise in cholesterol levels was due in part to an increase in high density lipoprotein (HDL) cholesterol with a resultant improvement in the HDL:LDL ratio (LDL, low density lipoprotein). Five patients had refractory hypercholesterolemia and were treated with lovastatin. One of them was treated with a combination of lovastatin and LDL-apheresis. All patients experienced diarrhea which improved with time, but two patients required reversal of their bypass for intractable gas bloat syndrome. Each received lovastatin to control recrudescence of hypercholesterolamia following reversal. Ten patients are alive and well, but one patient died after a myocardial infarction 55 months postoperatively. The advent of lovastatin and other HMG COA reductase inhibitors is likely to decrease the use of partial ileal bypass to treat familial hypercholesterolemia.

Adult↗
PubMed1988

Clinical consequences of hyperlipidaemia.

Hyperlipidaemia is a common and important clinical entity which frequently has a genetic basis. The chief features of severe hypertriglyceridaemia are eruptive xanthomata and acute pancreatitis, whereas most forms of hypercholesterolaemia are associated with premature coronary heart disease. This applies especially to familial hypercholesterolaemia, which is also characterized by tendon xanthomata. Better recognition of hyperlipidaemia allied to recent improvements in treatment should help reduce the frequency of its disabling and sometimes fatal consequences.

Humans↗
PubMed1988

High prevalence of hypertriglyceridaemia and apolipoprotein abnormalities in coronary artery disease.

Serum lipids and apolipoproteins A-I and B were measured in 174 men aged less than 60 with angiographically confirmed coronary artery disease and in 572 healthy control men. Two thirds of the patients had raised age-corrected values of fasting serum cholesterol and/or triglyceride and/or a low high density lipoprotein (HDL) cholesterol compared with the controls. Eighteen (30%) of the 61 normolipidaemic patients had a concentration of serum apolipoprotein A-I below the 5th percentile of 233 controls. In normolipidaemic patients on beta blockers the relative prevalence of serum low density lipoprotein (LDL)-apolipoprotein B values above the 95th percentile of 339 controls was significantly increased. Discriminant function analysis showed that a raised concentration of serum triglyceride was the best discriminant between patients and controls, with raised LDL-apolipoprotein B and reduced apolipoprotein A-I coming second only to triglyceride in analyses where each was separately compared with all the lipid variables. These associations were highly significant and were independent of other influences, including beta blockade. These findings re-emphasise the importance of hypertriglyceridaemia as a risk factor and confirm that apolipoprotein abnormalities occur frequently in coronary disease, even in normolipidaemic patients.

Adult↗
PubMed1988

Detection of alcohol-induced fatty liver by computerized tomography.

Computerized tomographic (CT) scanning of the liver was undertaken in 17 occasional and 19 heavy drinkers undergoing health screening. The median attenuation value of the liver (CT number) in occasional drinkers with normal liver function tests was 54.4 compared with 25.9 in the heavy drinkers (P less than 0.001). Fourteen of the heavy drinkers had a CT number below the lowest value observed in occasional drinkers with normal liver function, indicating reduced liver density due to fatty change. Serum gamma-glutamyl transpeptidase was normal in 36% of these individuals. A rise in CT number was observed in 4 out of 5 heavy drinkers who underwent a second scan after decreasing their alcohol consumption. These findings suggest that CT scanning provides a noninvasive and convenient method of screening for a fatty liver, which occurred to a variable degree in over 70% of the men who admitted to regularly taking 8 or more alcoholic drinks per day.

Fatty Liver, Alcoholic↗
PubMed1988

Normal and pathological lipoprotein metabolism.

Lipids are transported in plasma as lipoproteins, and an increase in 1 or more classes of lipoprotein underlies all forms of hyperlipidaemia. Physiological influences on lipoprotein metabolism are age, gender, bodyweight, diet and exercise. Pathological influences include genetic abnormalities, endocrine dysfunction, renal impairment and iatrogenic effects. Three inherited forms of hyperlipidaemia which predispose to atherosclerosis are familial hypercholesterolaemia (FH), type III hyperlipoproteinaemia and familial combined hyperlipidaemia (FCH), each of which has its own distinctive metabolism defect. In FH, deficiency of low density lipoprotein (LDL) receptors results in the accumulation in plasma of LDL-cholesterol because of a reduction in the receptor-mediated component of LDL catabolism. In type III hyperlipoproteinaemia, the presence of an abnormal apo E isoform (apo E2) in remnant particles leads to their accumulation in plasma, through nonrecognition by remnant receptors and a consequent reduced rate of hepatic uptake. In contrast, there is no primary catabolic defect in FCH, in which increased levels of very low density lipoprotein (VLDL) and LDL are largely the result of increased synthesis.

Arteriosclerosis↗
PubMed1988

Behavior of human apolipoprotein A-I: phospholipid and apoHDL:phospholipid complexes in vitro and after injection into rabbits.

Apolipoprotein A-I was purified from human high density lipoprotein and complexed with polyunsaturated phosphatidylcholine (PC) in deoxycholate (Lipostabil); the bile salt was removed subsequently by dialysis. The behavior of the resultant apoA-I/PC complexes was compared with that of Lipostabil in vitro and after injection into rabbits. In vivo apoA-I/PC complexes had the density of HDL throughout but had both alpha and pre beta electrophoretic mobility, the latter probably reflecting dissociation of apoA-I from PC. Lipostabil initially behaved like LDL but gradually acquired the density of HDL after incubation with plasma and in vivo. Both preparations increased plasma total phospholipids in normolipidemic rabbits to a similar extent, but, increments in HDL phospholipid were greater after apoA-I/PC complexes were injected. ApoHDL/PC complexes, prepared in a similar manner, appeared to promote efflux of cholesterol from perfused rabbit aortas in the presence of lecithin:cholesterol acyltransferase (LCAT) activity, consistent with a stimulatory effect on cholesterol mobilization. Injection of apoHDL/PC complexes into hyperlipidemic rabbits decreased plasma cholesterol but increased HDL cholesterol, whereas Lipostabil decreased both. These findings suggest that human apoA-I/PC complexes resemble HDL in their behavior more closely than does Lipostabil, and show that both types of liposome undergo modification upon interaction with plasma. It remains to be shown whether they possess any therapeutic potential.

Animals↗