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Biomedical subjects

J C Gibson

Publications and source records attributed to J C Gibson.

47 records · Page 3Linked to original sources

High-density lipoprotein in chronic renal failure and after renal transplantation.

Serum high-density-lipoprotein (HDL) cholesterol and apoprotein (apo) A concentrations were significantly reduced at the time of renal transplantation in 26 patients with chronic renal failure. In a prospective evaluation the behaviour of HDL concentrations after grafting was found to depend on renal function. Graft function was sustained in 19 patients, in whom HDL-cholesterol and apo A concentrations increased to lie within normal limits by six months after the operation. Successful transplantation also restored to normal the lipid and protein content of HDL as expressed by the ratio of HDL cholesterol to apo A. When transplant function was not sustained (seven patients), however, no changes in HDL were observed up to the time of the graft loss. Such changes in HDL with successful kidney grafting augur well in a population with many risk factors for coronary heart disease.

Adult↗

High density and low density lipoproteins in chronic renal failure before and after renal transplantation.

The hyperlipoproteinaemia accompanying chronic renal failure and renal transplantation has been re-examined in terms of the apoprotein (apo A and apo B) moieties of the high density (HDL) and low density (LDL) lipoproteins. Hypertriglyceridaemia is prevalent in chronic uraemia and is not corrected by haemodialysis or renal transplantation. Hypercholesterolaemia is characteristic only of renal allograft recipients. Apo A levels are reduced in undialyzed uraemic and remain low during haemodialysis, as well as in patients with renal allografts of less than six months duration. In renal transplant recipients of greater than one year duration, apo A levels are normalized. The normalization of apo A level is related to the stability of graft function, as determined by sequential analysis of 15 renal transplant recipients. Apo B levels are normal transplant recipients. Apo B levels are normal in uraemic and dialyzed patients, but are elevated in long term transplant recipients. Unlike apo A levels, this alteration does not appear to reflect the restoration of kidney function.

Apolipoproteins↗

Coronary artery disease in young Australian women.

Over a 12-year period, from 1965 to 1977, 43 women under 46 years of age were documented with angiographic evidence of coronary atherosclerosis at St Vincent's Hospital, Sydney. Twenty-five of the women were able to be followed up at a mean interval of 31 months. This group of young women with coronary artery disease was compared with an age-matched control group of 660 "healthy" women drawn from the general population. Hyperlipidaemia was present in 72% of patients and in 13% of controls. Seventy-three percent of patients were regular cigarette smokers compared with 21% of controls. Only one patient out of 43 showed neither hyperlipikaemia, nor hypertension, nor smoked cigarettes, and multiple risk factors were commonly present. The level of high density or alpha-lipoprotein was significantly reduced in young women with coronary artery disease. These results highlight the presence of classical risk factors in these young women, as well as the importance of alpha-lipoproteins.

Apolipoproteins↗

The effects of plasma exchange on cholesterol metabolism.

Four patients heterozygous for familial hypercholesterolaemia were treated by repeated plasma exchange with or without lipid-lowering drugs. Repeated plasma exchange without drug therapy in 3 patients was associated with a significant 18--28% decrement in plasma cholesterol level, comparing control with plateau values observed 3 weeks after exchange. Further decrements in plateau values followed the addition of lipid-lowering drugs used in combination, clofibrate--nicotinic acid or clofibrate--nicotinic acid--cholestyramine (range of total decrement 39--50%). Plasma exchange was associated with an increased excretion of endogenous faecal steroids, but this increase was completely abolished by the subsequent administration of clofibrate--nicotinic acid. This therapy prevented any increase in bile acid excretion with concomitant use of cholestyramine resin. Plasma exchange with drug therapy was associated with a sustained rise in plasma cholesterol specific radioactivity. In a fourth patient, clofibrate--nicotinic acid was administered prior to plasma exchange and led to a 24% fall in plasma cholesterol. Subsequent plasma exchange in this patient produced no sustained change in plasma cholesterol plateau level. In two patients, withdrawal of drugs allowed plasma cholesterol to return to pre-exchange control levels. These observations suggest that plasma exchange probably produced an increase in endogenous cholesterol synthesis and a mobilisation of tissue cholesterol. In relation to plateau cholesterol values 3 weeks after an exchange, the data suggested that the reduction in plasma cholesterol level with plasma exchange and drug therapy could have been achieved by intensive drug therapy alone.

Adult↗

The influence of a wide range of absorbed cholesterol on plasma cholesterol levels in man.

The influence of absorbed dietary cholesterol on plasma cholesterol concentration was studied in two populations, one Seventh Day Adventist (SDA) vegetarian and one nonvegetarian, representing a broad range of plasma cholesterol values and dietary cholesterol intakes. As a group, the SDA vegetarians had significantly lower levels of plasma cholesterol and triglycerides than did the nonvegetarians. This hypolipidemic pattern in the SDA vegetarians was apparently closely related to dietary habits, sinceanother group of SDA who were nonvegetarian had significantly higher plasma cholesterol and triglyceride levels than their vegetarian counterparts. Both the dietary intake of cholesterol and the percentage absorption of cholesterol were lower in vegetarians than in nonvegetarians. The mass of cholesterol absorbed increased linearly with the mass of cholesterol ingested in all groups, but no relationship could be demonstrated between absorbed cholesterol and plasma cholesterol concentration.

Absorption↗

Haematological and biochemical abnormalities associated with intralipid hyperalimentation.

Haematological and biochemical parameters were monitored in six patients during Intralipid hyperalimentation. A mild anaemia was consistently observed, accompanied by morphological changes in red cells, granulocytes, and platelets. All patients demonstrated an abnormally high percentage of plasma cholesterol in the unesterified form and altered plasma cholesterol esterification, but red cells were not uniformly enriched in cholesterol. These findings stress the need for careful monitoring during Intralipid therapy.

Adult↗

The effect of metoprolol and atenolol on plasma high density lipoprotein levels in man.

1. The effects of two beta-adrenoreceptor blocking drugs, metoprolol and atenolol, on plasma lipoproteins were studied in thirty-four patients using a single-blind cross-over design, with a 10-day placebo washout period between drugs. 2. Compared with placebo values, neither metoprolol nor atenolol influenced total plasma cholesterol levels, while total plasma triglycerides increased slightly. 3. Low density lipoprotein protein level remained unaltered, while high density lipoprotein (HDL) cholesterol and protein were significantly reduced by both beta-adrenoreceptor blockers. 4. The ratio of total cholesterol to HDL cholesterol was increased by both drugs. 5. The data suggest that patients taking these drugs over many years may be exposing themselves to increased vascular risk, despite other anticipated benefits from such therapy.

Atenolol↗

Apo E-containing lipoproteins in low or high density lipoprotein deficiency.

Apolipoprotein (apo) E-containing subfractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and high density lipoprotein (HDL) have been described in normolipidemic and hyperlipidemic subjects. These lipoproteins exist, however, in the presence of large amounts of apo A-I- and apo B-containing lipoproteins so that it has been difficult to assess the independence of these apo E-containing subclasses from the major lipoprotein classes. The present study has approached this question by taking advantage of three hypolipidemic states in which one or more of the major apolipoproteins is deficient or absent. After separating lipoproteins from whole plasma by molecular sieve chromatography followed by radioimmunoassay of column fractions, we found that two subjects with abetalipoproteinemia had no apo E-containing lipoproteins the size of VLDL or IDL and all the plasma apo E was in a fraction of large HDL. Two subjects with Tangier disease and two with familial apo A-I/C-III deficiency had extremely low levels of HDL cholesterol and of apo A-I-containing lipoproteins. In spite of the absence of classical HDL, a major fraction of apo E-containing lipoproteins was reproducibly observed at the elution volume characteristic of large HDL and was identical to that found in normal subjects. These data thus suggest the existence of apo E-containing lipoproteins that are the size of HDL and are not dependent upon the presence of either apo B or apo A-I. While studies in normal subjects indicate that apo E is associated with other apolipoproteins in HDL, further investigations will be needed to determine the full composition of these apo E-containing lipoproteins in the lipoprotein-deficient patients described in this report.

Abetalipoproteinemia↗

Plasma lipoprotein distribution of apolipoprotein E in familial hypercholesterolemia.

Although familial hypercholesterolemia (FH) has been well characterized in terms of the etiology of the major lipoprotein abnormality, that of low density lipoproteins (LDL), less information is available on changes in other lipoproteins which could influence the atherogenic process in this disorder. The present study has focused on such potential abnormalities by studying in detail the lipoprotein association of apolipoprotein E (apo E) in a large group of subjects homozygous for FH. Total plasma apo E levels in homozygous subjects were significantly elevated (p less than 0.001) relative to heterozygous subjects which were, in turn, significantly greater (p less than 0.001) than controls (137.6 micrograms/ml, 69.4 micrograms/ml, 46.5 micrograms/ml respectively). After separation of plasma lipoproteins by 4% agarose chromatography, an increased mass of apo E in lipoproteins of intermediate size was present; this may reflect the absence of LDL receptors that normally mediate their clearance. Homozygous FH subjects also demonstrated an increased mass of apo E-enriched high density lipoproteins (HDL) of large size, but a reduction in HDL cholesterol and apo A-I. The increase in the potentially atherogenic remnant lipoproteins and the decrease in HDL are associated with an increased risk for atherosclerosis, even in the absence of the LDL elevation, which is characteristic of FH. The increase in apo E-enriched HDL could reflect a compensatory mechanism that permits reverse cholesterol transport in the absence of LDL receptors.

Apolipoprotein C-III↗