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Biomedical subjects

G R Thompson

Publications and source records attributed to G R Thompson.

At least 163 records · Page 9Linked to original sources
PubMed1982

Renal failure in familial lecithin: cholesterol acyltransferase deficiency.

Familial lecithin cholesterol acyltransferase (LCAT) deficiency is a rare inherited enzyme deficiency characterized by widespread disturbance of lipid metabolism and infiltration of many organs, including kidneys by lipids; usually it results in death from renal failure in the fourth or fifth decades. We have described a new family with LCAT deficiency and have studied three sisters with characteristic corneal opacities and no detectable plasma LCAT activity, together with eight obligate heterozygotes who have reduced LCAT activity but are phenotypically normal. All three sisters had the typical lipid abnormalities including large molecular weight particles in the low density lipoprotein (LDL) fraction of plasma previously described only in LCAT deficient patients with renal disease. However, only the youngest sister had proteinuria and renal failure. Renal biopsies from two of the sisters were infiltrated with lipid but the biopsy from the youngest contained electron dense deposits indistinguishable from those seen in immune complex disease. These findings cast doubt on the concept that large molecular weight LDL particles are the sole determinants of renal failure in LCAT deficiency.

Adult↗
PubMed1981

Contrasting patterns of coronary atherosclerosis in normocholesterolaemic smokers and patients with familial hypercholesterolaemia.

An angiographic comparison was made of the extent and severity of coronary artery disease in 25 patients with heterozygous familial hypercholesterolaemia and 25 normocholesterolaemic patients with coronary artery disease in whom heavy cigarette consumption was the chief risk factor. The patients with familial hypercholesterolaemia were younger and included a much higher proportion of women than the smokers. Significantly more patients with familial hypercholesterolaemia had disease of the main stem of the left coronary artery (eight v none, p less than 0.05) and triple-vessel disease (18 v four, p less than 0.05). Disease affecting only distal vessels occurred in five smokers, whereas all the patients with familial hypercholesterolaemia showed a combination of proximal and distal lesions. These findings suggest that cigarette smoking and familial hypercholesterolaemia predispose to different patterns of coronary atheroma. Early coronary angiography with a view to coronary artery bypass surgery seems desirable in symptomatic patients with familial hypercholesterolaemia because of the common association of this disorder with life-threatening left main-stem disease.

Adult↗
PubMed1981

Superiority of partial ileal bypass over cholestyramine reducing cholesterol in familial hypercholesterolaemia.

Low density lipoprotein (LDL) turnover studies were conducted on three occasions in each of six patients with heterozygous familial hypercholesterolaemia (FH)-on diet, after 1 month on cholestyramine 16 g/day, and 2 months after partial ileal bypass. Partial ileal bypass lowered total and LDL cholesterol levels and increased the fractional catabolic rate of LDL to a greater extent than did cholestyramine; this difference presumably reflects the greater increase in bile acid excretion induced by the surgical procedure. Studies in two other heterozygotes showed that partial ileal bypass specifically enhanced receptor-mediated catabolism of LDL. The findings support the concept that therapeutic stimulation of bile acid synthesis increases the rate of receptor-mediated uptake and degradation of LDL by the liver.

Adult↗
PubMed1981

Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo.

The role of low density lipoprotein (LDL) receptors in the pathogenesis of hereditary and acquired forms of hypercholesterolemia has been investigated in vivo by simultaneously determining total and receptor-independent LDL catabolism with 125I-labeled LDL and 131I-labeled LDL coupled with cyclohexanedione. Receptor-mediated catabolism of LDL, determined as the difference between the turnover of 125I and 131I, was found to be virtually absent in two homozygotes with familial hypercholesterolemia and markedly reduced in a hypothyroid patient. Treatment of the latter with L-thyroxine markedly stimulated receptor-mediated catabolism and reduced LDL levels as did cholestyramine administration in a control subject. Reduction of LDL levels by plasma exchange in a control subject and homozygote had no such effect. These results demonstrate the existence of an intrinsic and almost total defect of receptor-mediated LDL catabolism in homozygous familial hypercholesterolemia and demontrate an analogous but reversible abnormality in hypothyroidism.

Biological Transport↗
PubMed1980

Serum lipids and high density lipoprotein cholesterol in peripheral vascular disease.

Serum lipids and high density lipoprotein (HDL) cholesterol concentrations were measured in 32 patients with peripheral vascular diseases (PVD) and 38 control subjects. Hypertriglyceridaemia (> 1.8 mmol/l) was significantly more common in PVD patients of both sexes than among controls but mean serum triglyceride levels were significantly higher only among males. Hypercholesterolaemia (> 7 mmol/l) was not more common in PVD patients nor did mean serum total cholesterol or HDL cholesterol levels differ significantly from control subjects. The HDL ratio, however, was significantly reduced in both males and females with PVD. These results suggest that expressing the amount of cholesterol carried in HDL in relative terms is a better index of vascular risk than is its absolute concentration. The HDL cholesterol level and the HDL ratio were both significantly lower in controls who smoked than in non-smokers; this may explain the reduced HDL ratio in PVD patients, most of whom were smokers.

Cholesterol↗
PubMed1980

Congenital dyserythropoietic anaemia (CDA) with severe gout, rare Kell phenotype and erythrocyte, granulocyte and platelet membrane reduplication: a new variant of CDA type II.

A 43-year-old man with lifelong anaemia showed features which indicate him to have a previously undescribed variant of congenital dyserythropoietic anaemia (CDA), type II. The main clinical features--of which the first two are unique or very unusual in CDA--have been severe tophaceous gout, massive splenomegaly, gall stones mecessitating cholecystectomy and haemosiderosis affecting the liver and probably the heart. At age 41 he sustained a spontaneous retinal detachment. In the peripheral blood there were large numbers of nucleated red blood cells and marked macrocytosis; otherwise the picture was typical of CDA type II. The bone marrow contained many bi- and multi-nucleated erythrocyte precursors. There were increased levels of a number of red cell enzymes and a slightly raised level of HbF. Uncharacteristically, the red cells failed to lyse with acidified normal serum. The cells were strongly agglutinated by anti-i and were of the rare Kpb-negative phenotype. Plasma lipid analysis showed very low levels of cholesterol and vitamin E. Lipid peroxidation was markedly increased. Ultrastructural studies showed reduplication of the erythrocyte, granulocyte, and platelet cell membranes.

Adult↗
PubMed1980

Effect of lipoprotein concentration and lecithin: cholesterol acyltransferase activity on cholesterol esterification in human plasma after plasma exchange.

The rate of cholesterol esterification in plasma, plasma lecithin cholesterol acyltransferase (LCAT) activity and plasma lipoprotein levels have been measured in five subjects who underwent therapeutic plasma exchange to reduce their plasma cholesterol concentration. In the week following the exchange the cholesterol esterification rate and the plasma triglyceride concentration returned rapidly in parallel to pre-exchange levels, while high density lipoprotein (HDL) cholesterol and LCAT activity returned to normal more slowly but also in parallel. The data suggest that the rate-limiting factor for cholesterol esterification in plasma is unlikely to be solely the enzyme levels, but is probably a combination of factors, including the enzyme level and either substrate availabiltiy or product removal. Plasma very low density lipoprotein (VLDL) may either provide substrates for the reaction or provide a means of removing one of the products from the site of reaction.

Adult↗
PubMed1980

Assessment of long-term plasma exchange for familial hypercholesterolaemia.

The effectiveness of repeated plasma exchange with 2 to 4 litres of plasma protein fraction as long-term treatment for familial hypercholesterolaemia has been evaluated in six severely affected patients receiving conventional cholesterol lowering treatment. Cell-separator mediated exchange at monthly intervals for one to two years reduced mean serum cholesterol levels from 18.5 mmol/l (715 mg/dl) to 12.4 mmol/l (480 mg/dl) in two female homozygotes but failed to influence xanthomata or prevent a two- to threefold increase in their left ventricular aortic systolic pressure gradients. More effective reduction of mean serum cholesterol levels from 15.7 mmol/l (608 mg/dl) to 8.6 mmol/l (333 mg/dl) in two male homozygotes by plasma exchange at fortnightly intervals for two to three years was accompanied by resolution of xanthomata and by stabilisation of aortocoronary lesions. In two male heterozygotes with angina, coronary angiographic appearances were unaltered or improved after one to two years of thrice-monthly plasma exchange, which reduced mean serum cholesterol levels from 6.4 mmol/l (248 mg/dl) to 4.7 mmol/l (182 mg/dl). We conclude that plasma exchange every one to two weeks, combined with oral nicotinic acid and/or cholestyramine, retards the rate of progression of atheroma in homozygotes and possibly induces regression in heterozygotes.

Adult↗
PubMed1980

Cadiovascular complications of homozygous familial hypercholesterolaemia.

Seven patients with homozygous familial hypercholesterolaemia, two female and five male, aged 12 to 25 years, underwent clinical and angiographic assessment to define the associated cardiovascular abnormalities. Four patients had angina, two of whom also had syncope on exertion. All had an ejection systolic murmur but no ejection click and a loud aortic second sound. All but one had a systolic gradient between the left ventricle and aorta, ranging from 20 to 80 mmHg at the time of presentation. Angiography showed a characteristic narrowing of the aortic root in all and five of the seven patients had coronary ostial stenosis. One patient died after an aortocoronary bypass and aortic valvotomy and two others underwent aortocoronary bypass and aortic valve replacement, one of whom also died after operation. The survivor and three other patients are now undergoing regular plasma exchange and remain well. The seventh patient died suddenly before the latter form of treatment could be started. These findings confirm that premature, severe atheroma of the aortic valve and root is a characteristic feature of homozygous familial hypercholesterolaemia and carries a high mortality.

Adolescent↗
PubMed1980

Uptake and cellular degradation of low-density lipoprotein.

In vitro data suggest that low-density lipoprotein (LDL) is bound to specific receptors located in pits on the surface of fibroblasts by a high-affinity process and subsequently undergoes catabolism in lysosomes. This binding seems to be mediated by ionic interaction between LDL and its receptor, the latter being totally or partially absent from the fibroblasts of patients with familial hypercholesterolaemia (FH). In vivo data suggest that LDL is also catabolised by a concentration-dependent, low-affinity pathway which is probably mainly located in the liver. LDL catabolism is reduced in FH and after saturated fat feeding, whereas polyunsaturated fat has the reverse effect. Hypocatabolism of LDL alters LDL composition, accelerates atherosclerosis and may lead to premature death from coronary heart disease.

Cells, Cultured↗
PubMed1980

Effect of jogging on serum low density lipoprotein cholesterol.

The effects of jogging on serum lipids were assessed in 16 normolipidemic males who ran an average of 5.8 miles (9.3 kilometres) per week for 6 weeks. There was no change in serum triglyceride concentration or clearance nor in HDL-cholesterol, but both total and LDL-cholesterol concentrations decreased significantly, by 5.7 and 8.3% respectively. Individual decreases in LDL-cholesterol were correlated with the distance run and it seems probable tht a stimulatory effect of exercise on LDL catabolism was responsible. These findings suggest a possible explanation for the known protective effect of exercise against coronary heart disease, even when taken in amounts insufficient to raise HDL-cholesterol.

Adult↗