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Biomedical subjects

B Lewis

Publications and source records attributed to B Lewis.

At least 145 records · Page 8Linked to original sources

Genetic analysis of total cholesterol and triglycerides in a pedigree of St. Thomas rabbits.

A pedigree consisting of 103 New Zealand White hyperlipidemic and normal rabbits was used in a genetic analysis of total cholesterol and triglyceride levels to test for Mendelian control of hyperlipidemia. The founder male of this pedigree was identified through hypercholesterolemia and evidence suggested vertical transmission of a hypercholesterolemic phenotype in this pedigree, although a combined hyperlipidemia phenotype (elevated cholesterol and triglycerides) also occurred in many descendents of the original founders. Segregation analysis of quantitative measures of total cholesterol and triglycerides in this pedigree was employed to test hypotheses about Mendelian control in the presence of substantial inbreeding. A simple Mendelian model was the best explanation for triglycerides in these animals. This best fitting model was essentially co-dominant with genotypic specific variances, where the heterozygote was hypertriglyceridemic and the mutant homozygote showed even more extreme values. The observed distribution of total cholesterol was also compatible with a mixture of distinct genotypic distributions, but there was evidence of non-Mendelian transmission in this pedigree. The observed hypertriglyceridemia in these animals may reflect an abnormality of very low density lipoprotein metabolism described previously. Further studies will be required to elucidate the genetic control of hypercholesterolemia and the associated combined hyperlipidemia in these rabbits.

Animals↗

Late-onset neonatal sepsis due to multiply-resistant coagulase-negative staphylococci.

A cluster of septic episodes that were caused by coagulase-negative staphylococci occurred in eight patients, over a six-month period from August 1, 1984 to January 31, 1985, in a Brisbane neonatal intensive-care unit where sepsis which was due to these organisms previously was uncommon. The organisms were universally-resistant to tobramycin (the aminoglycoside agent that was used at that time) and were variably-resistant to gentamicin, flucloxacillin and cephalothin. All organisms were sensitive to netilmicin, vancomycin, fusidic acid and rifampicin. The affected infants were all of 32 weeks' or less gestation and most of them weighed less than 1500 g at birth. All neonates had been ventilated artificially and had had long intravascular lines. Two infants had ventriculoperitoneal shunts that had been infected with coagulase-negative staphylococci--a potentially-important problem that has not been noted in premature infants in previous reports. Our experience demonstrates that it is important to consider the patterns of resistance to aminoglycoside as well as to beta-lactam antibiotic agents for the empirical therapy of septic episodes and for neurosurgical prophylaxis in nurseries where coagulase-negative staphylococci are emerging as common nosocomial pathogens.

Anti-Bacterial Agents↗

Blood lipid concentrations and other cardiovascular risk factors: distribution, prevalence, and detection in Britain.

To establish the distribution of blood lipid concentrations and the prevalences of other risk factors for cardiovascular disease in Britain 12,092 men and women aged 25-59 in Glasgow, Leicester, London, and Oxford were studied. Subjects were selected by opportunistic case finding, in which patients consulting their general practitioner for any reason were offered a health check by appointment, or random selection from age-sex registers, in which an invitation for a health check was posted. The overall rate of response was 73%, being 91-94% by opportunistic case finding and 36-63% by random selection. At the health check subjects answered a brief questionnaire about risk factors for cardiovascular disease, and their height, weight, and blood pressure were recorded; a blood sample was taken for measuring plasma concentrations of cholesterol, triglyceride, high density lipoprotein cholesterol, and glucose. The mean cholesterol concentrations were 5.9 (SD 1.2) and 5.8 (1.2) mmol/l in men and women, respectively. In London the mean value was 5.5 (1.2) mmol/l for both men and women and was significantly lower than mean values in the three other centres, among which there were no significant differences. In men and women aged 25-29 concentrations were similar but they increased in men until the age of 45-49, after which they showed no further increase; in women concentrations did not increase until the age of 40-44 and by the age of 50-59 values were higher than in men. Mean triglyceride concentrations were significantly higher in men than in women (1.8 (1.4) v 1.3 (0.9) mmol/l, respectively), and trends with age were similar to those for cholesterol concentrations, except that at no age were values higher in women than in men. Mean triglyceride values overall were higher in Glasgow and London than in Oxford and Leicester. Body mass index was higher in Glasgow and London than in the other two centres and correlated with systolic and diastolic blood pressures and triglyceride concentration. In addition, subjects in Glasgow smoked significantly more than those in the other centres. These observations could contribute to the higher rate of coronary heart disease in Glasgow. Plasma lipid concentrations and the prevalences of other risk factors for cardiovascular disease were similar in subjects selected by opportunistic case finding and by random selection. In Britain cholesterol values have changed little during the past 12 years despite dietary recommendations and health education.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Effective lipid lowering diets including lean meat.

The plasma lipid and lipoprotein responses to two modified isoenergetic diets including meat were studied in 15 free living men with hyperlipidaemia (mean plasma cholesterol and triglyceride concentrations 8.1 and 3.4 mmol/l). A reference diet (diet A, 42% energy from fat, ratio of polyunsaturated to saturated fatty acids (P:S ratio) 0.2) was compared with a fat reduced diet (diet B, 35% energy from fat, P:S ratio 0.5) and with a further fat modified diet supplemented with fibre (diet C, 27% energy from fat, P:S ratio 1.0). Daily intake of meat and meat products (180 g/day) was the same in each dietary period; that in diet A had a fat content typical of the average British diet, whereas that in diets B and C was based on very lean meat and meat products. During consumption of diet B the plasma cholesterol concentration fell by 8.6% and low density lipoprotein cholesterol by 11%. During consumption of diet C plasma cholesterol fell by 18.5% and low density lipoprotein cholesterol by 23.8%. Triglyceride and high density lipoprotein cholesterol concentrations and body weight did not change appreciably during the study. A modified diet including a moderate amount of lean meat and meat products is compatible with a reduced lipoprotein mediated risk of atherosclerotic heart disease.

Cholesterol↗

Modified plasma-derived lipoproteins in human atherosclerotic plaques.

Low density lipoproteins extracted from surgical specimens of human atherosclerotic plaques (A-LDL) showed altered electrophoretic mobility indicating a greater negative charge than that of plasma LDL (P-LDL). A-LDL but not P-LDL showed high affinity binding/degradation by human monocyte-derived macrophages; this was inhibited by acetylated LDL but not by native P-LDL. Following injection of 125I-labelled autologous P-LDL prior to reconstructive arterial surgery, polyacrylamide and agarose gel electrophoresis of A-LDL extracted from arterial intima showed that the A-LDL and its apolipoprotein B moiety were derived from P-LDL; the electrophoretic mobility of the product A-LDL was greater than that of native P-LDL. The compositions of arterial intermediate density lipoprotein (A-IDL) and A-LDL differed from those obtained from human plasma intermediate density lipoprotein (P-IDL) and P-LDL. A-IDL showed a reduced triglyceride content and increased esterified and unesterified cholesterol. Although the total cholesterol content of A-LDL was similar to that of P-LDL, there was an increase in unesterified cholesterol and a decrease of cholesteryl ester. These studies indicate that LDL extracted from human atherosclerotic plaque is derived from and modified from P-LDL in vivo. Compared with native P-LDL, A-LDL showed differences in charge and composition, associated with its high affinity binding by the acetyl LDL receptor of human macrophages.

Arteriosclerosis↗

The fractional catabolic rate of low density lipoprotein in normal individuals is influenced by variation in the apolipoprotein B gene: a preliminary study.

In a random sample of 22 normolipidaemic male Caucasian individuals, 35-49 years old, homozygosity for the X2 allele (cutting site) of the XbaI RFLP of the apo B gene was associated with higher mean total cholesterol and LDL-cholesterol concentration. These individuals also had significantly lower LDL fractional catabolic rate (P less than 0.03) and a lower degradation of LDL by mononuclear cells in vitro. We propose that the XbaI polymorphism is associated with amino acid changes in the apo B protein which influences LDL binding to the LDL-receptor. This modulates catabolism of this lipoprotein and so contributes to variability of plasma cholesterol levels.

Adult↗

Use of percutaneous gastrostomy in the intensive care patient.

We evaluated the use of percutaneous endoscopic gastrostomy in 30 ICU patients. There was a 14% incidence of minor complications, no major complications, and no mortality. We conclude that percutaneous endoscopic gastrostomy is a useful alternative to operative gastrostomy in the ICU patient.

Aged↗

Isolated tricuspid valve prolapse.

Tricuspid valve prolapse is commonly associated with mitral valve prolapse or other heart abnormalities and is rarely found as an isolated finding. A patient with isolated tricuspid valve prolapse is described which was discovered on routine examination of an asymptomatic pilot.

Adult↗

Gemfibrozil in the treatment of resistant familial hypercholesterolaemia and type III hyperlipoproteinaemia.

The efficacy of gemfibrozil in the treatment of resistant familial hypercholesterolaemia and type III hyperlipoproteinaemia was evaluated in 26 individuals over a mean period of 16 months. In the untreated state both disorders are associated with a high frequency of coronary heart disease. In the former, gemfibrozil with a bile acid sequestrant reduced plasma cholesterol by 32%, an incremental decrease of 17% compared with sequestrant therapy alone. In type III, plasma cholesterol was reduced by 40% and plasma triglyceride by 70%, while high-density lipoprotein cholesterol increased by 45%. In none of the patients studied did clinical or biochemical side effects occur.

Cholesterol↗

Effect of tamoxifen on oestrogen binding, lipid and lipoprotein concentrations and blood clotting parameters in premenopausal women with breast pain.

As part of a controlled trial of the use of tamoxifen for the treatment of mastalgia, some of the metabolic and haematological effects of this agent were measured. A panel of haemostatic variables including prothrombin time, kaolin cephalin clotting time, fibrinogen, euglobulin lysis time, factor VII, factor VIII, protein C and anti-thrombin III were determined. In addition, levels of sex hormone-binding globulin and both total and free oestradiol were estimated. No alteration in clotting function was found during the administration of tamoxifen, although hepatic function did alter during this period with an increase in concentration of sex hormone-binding globulin. There was a significant increase in total oestradiol and free oestradiol although the percentage of biologically available free oestradiol fell slightly during the course of tamoxifen treatment. There was a slight reduction in low-density lipoprotein cholesterol with an increase in HDL2, a subclass of high-density lipoprotein (HDL) cholesterol, consistent with an oestrogen-agonist effect. These data suggest that tamoxifen administration does not adversely influence haemostatic mechanisms or lipoprotein metabolism in the short term.

Adult↗

Population and individual strategies for the prevention of coronary heart disease. Policy of the European Atherosclerosis Society.

Coronary heart disease (CHD) risk factors affect a large proportion of European adult populations; hence most CHD results from the exposure of many people to moderately elevated risk factor levels. The population strategy is directed to improving the health-related behaviour of the entire population, by means of mass education and administrative measures aimed at nutrition, smoking and exercise; these measures are reviewed in some detail. This approach is inadequate for minimising risk in the minority in whom pronounced risk factor levels are present (e.g. major forms of hyperlipidaemia); such persons require individual therapy in a clinical setting, i.e. an individual strategy. The European Atherosclerosis Society (EAS) endorses both strategies and regards them as complementary. It advocates a case-finding approach to identifying those people requiring individual care. Although lipid risk factors, like blood pressure, are continuous variables, the EAS has defined action limits for plasma cholesterol, triglyceride and HDL-cholesterol concentrations; the interpretation of these is influenced by the presence and extent of other risk factors and of cardiovascular disease, and by age and sex. Recently the EAS has produced guidelines on the recognition and treatment of hyperlipidaemia. These provide sufficient step by step detail to permit the effective, safe management of most hyperlipidaemic patients by the non-specialised physician, with advice on dietary and drug therapies, and the investigation and management of all major forms of hyperlipidaemia. The main features of these guidelines are described in this paper.

Coronary Disease↗