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Biomedical subjects

B Lewis

Publications and source records attributed to B Lewis.

At least 127 records · Page 7Linked to original sources

Intermediate density lipoprotein levels are strong predictors of the extent of aortic atherosclerosis in the St. Thomas's Hospital rabbit strain.

This study assessed nonfasting cholesterol and triglyceride in plasma and in lipoproteins as predictors of the extent of aortic atherosclerosis in 2 similar groups of rabbits from the St. Thomas's Hospital strain; the lipoprotein classes studied in the 2 groups were very low (VLDL), intermediate (IDL), low (LDL), and high density lipoprotein (HDL), and Sf greater than 60 lipoprotein, Sf 12-60 lipoprotein, LDL and HDL, respectively. These rabbits exhibit elevated plasma levels of VLDL, IDL, and LDL, with plasma cholesterol and triglyceride of up to 23 mmol/l and 7 mmol/l, respectively, and with up to 100% of the aortic intima bearing atherosclerosis-like lesions. In group 1 rabbits (n = 25), univariate linear regression showed that cholesterol in plasma, LDL, IDL and in VLDL each were positively associated with the extent of aortic atherosclerosis. In group 2 rabbits (n = 20), cholesterol in plasma, LDL and Sf 12-60, but not in Sf greater than 60 lipoprotein, was consistently positively associated with the extent of aortic atherosclerosis. Neither plasma triglyceride, triglyceride in lipoprotein fractions nor HDL cholesterol was associated consistently with the extent of atherosclerosis. Using step-up multiple linear regression among lipoprotein lipids, IDL and Sf 12-60 lipoprotein cholesterol were the most powerful independent predictors of the extent of aortic atherosclerosis in the 2 groups of rabbits. LDL cholesterol was the only other independent predictor. The results suggest that remnant lipoproteins, whether defined as IDL or Sf 12-60 lipoprotein, play an important causal role in atherosclerosis under conditions where plasma levels of these lipoproteins are elevated.

Animals↗

On lowering lipids in the post-infarction patient.

In patients with coronary heart disease (CHD) elevated serum cholesterol levels, like other classical risk factors, remain predictive of further coronary events. The excess risk attributable to raised cholesterol levels is considerable, and greater than that in subjects without CHD. A recent meta-analysis of all eight qualifying trials of secondary prevention of CHD by cholesterol lowering is reviewed. There were significant reductions in recurrent non-fatal and fatal CHD, with a downward trend in total mortality. Mechanisms underlying the relationship between cholesterol lowering and secondary prevention are reviewed. The implication of this analysis of trials for clinical practice is that hypercholesterolaemia should be sought and effectively treated in patients with CHD, unless contraindications are present.

Humans↗

The pericardial valve in the aortic position ten years later.

To assess the behavior of the pericardial valve at 10 years after implantation, the cases of 240 patients who had undergone aortic valve replacement with the standard Ionescu-Shiley (Shiley, Inc., Irvine, Calif.) bovine pericardial valve between February 1977 and December 1983 were reassessed. Follow-up of the 224 hospital survivors was 99.6% complete. Fifty-seven valve-related events occurred. Fourteen were thrombotic events (1.2%/patient-year), 28 were intrinsic tissue failures (2.4%/patient-year), 13 were cases of prosthetic valve endocarditis (1.1%/patient-year), and 2 were paravalvular leaks (0.17%/patient-year). The linearized rate for death, reoperation, or both resulting from valve-related events was 3.6%/patient-year. Time-related hazard function for the instantaneous risk of death and/or reoperation resulting from valve-related events demonstrated an exponential increase after 80 months. These data, in conjunction with our previous reports on the histologic changes in pericardial collagen and the incidence of calcification (26/28), should be considered regarding new and future generations of pericardial bioprostheses. Although this device provides good hemodynamics and carries a low incidence of thromboembolism, it has a limited durability. New generations of pericardial valves may have improved structural features, but the behavior of glutaraldehyde-fixed, formaldehyde-stored bovine pericardium as currently selected and prepared is unlikely to change.

Adolescent↗

Prevention of coronary heart disease: putting theory into practice.

The two main approaches to delivering preventive care for coronary heart disease, ie to reducing its causal risk factors, depend upon an understanding of the major causes of this disorder. One is population based and involves educating the public in healthier behaviour and making changes in the environment to facilitate this. In the other, persons at high risk are identified and provided with individual counselling and ongoing care; the diagnostic and therapeutic components of this approach must proceed in parallel, and resources will be needed to permit this. Both strategies are necessary: they are complementary; they are not competitive either conceptually or for funding. Personal risk varies widely. Hence a system of priorities is required for phasing the provision of care according to need. High risk is mot often due to the presence of multiple risk factors but also results from single, pronounced risk factors. Those in greater need include persons with coronary disease, those with multiple sources of risk, and those with severe hypercholesterolaemia, hypertension, or diabetes. So-called selective testing differs little, in practice, from such a prioritized system of comprehensive risk factor control.

Coronary Disease↗

Genetic epidemiology of differences in low-density lipoprotein (LDL) cholesterol concentration: possible involvement of variation at the apolipoprotein B gene locus in LDL kinetics.

Circulating levels of low-density lipoprotein (LDL) vary considerably within and between populations, paralleled by differing coronary heart disease (CHD) mortality rates. We have previously shown that variation in the apolipoprotein (apo) B gene as associated with certain restriction fragment length polymorphisms (RFLPs) influences the metabolism of LDL in the U.K. population. To investigate a possible genetic contribution to variation in LDL levels in differing populations we have extended this original study. RFLPs of the apo B gene were determined in samples of individuals from the United Kingdom, Finland, Italy, Spain, and Africa. Significant associations of LDL fractional catabolic rate with the apo B EcoRI and XbaI RFLP genotypes were detected only in the two North European populations. In the African population sample, the XbaI RFLP displayed a significant association with LDL apo B synthesis. The data suggest that variation in the apo B gene influences the metabolism of LDL and that it is different in individuals of different ethnic background.

Adult↗

Muscle strength as a predictor of bone mineral density in young women.

It is widely accepted that physical activity is beneficial to bone. However, the specific relationships of muscle strength to bone mineral density (BMD) are poorly understood. We examined strength and BMD in 59 women aged 18-31 years who ranged in exercise patterns from sedentary to active. Mineral density of the right proximal femur (hip) and spine (L2-4) was evaluated by dual-energy x-ray absorptiometry. BMD at the midradius was measured by single-photon absorptiometry. Dynamic strength (one repetition maximum) was measured for the following muscle groups: back, elbow flexors (biceps), leg extensors (quadriceps), and the hip flexors, extensors, adductors, and abductors. Isometric grip strength was assessed by dynamometry. Mineral density at the hip correlated independently with muscle strength and body weight, but not with age. Specifically, femoral neck BMD was significantly correlated with back strength and weight, whereas trochanter and overall hip mineral density were significantly related to biceps, back, and hip adductor strength. Hip mineral density was not related to strength of the quadriceps groups or to that of the hip flexors, extensors, or abductors. In addition, muscle strength was an independent predictor of lumbar spine and midradius mineral density. In stepwise multiple regression analysis, biceps strength proved the most robust predictor of hip BMD and grip strength best predicted bone density at the lumbar spine and radius. We conclude that muscle strength is an independent predictor of bone mineral density, accounting for 15-20% of the total variance in bone density of young women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Metabolic studies on the hypolipidaemic effect of guar gum.

The hypolipidaemic effect of guar gum (30 g/day) was examined in a double blind placebo-controlled crossover study in 9 patients with primary hyperlipidaemia. The treatment periods were of six weeks duration. Cholesterol levels in low density lipoprotein (LDL) were decreased by 11.5% and in intermediate density lipoprotein (IDL) by 10.7%. Plasma cholesterol levels were reduced by 9.6% (P less than 0.05). Kinetic studies using autologous 125I-labelled LDL showed a decrease of 21.6% in plasma LDL apo B pool size (P less than 0.05) that resulted from a 39.1% increase in its fractional rate of catabolism. The kinetic effects of guar gum on LDL metabolism appear similar to that of bile acid binding resins in that LDL apo B fractional catabolism is greatly increased while there is a slight increase in production rate.

Aged↗

Effect on plasma lipids and lipoproteins of postmenopausal oestrogen therapy with added dydrogesterone.

In a prospective, randomized, cross-over study, 14 postmenopausal women completed 9 months of treatment with conjugated equine oestrogens, 1.25 mg daily. Seven women added dydrogesterone 20 mg daily for 12 days during months 2, 3 and 4, and then 10 mg daily for an identical time in months 5, 6 and 7. The other seven women added the two dydrogesterone doses in reverse sequence. No dydrogesterone was taken during months 8 and 9. Lipids and lipoproteins were measured before treatment and at the end of months 4, 7 and 9. Lipids were also estimated in an untreated (reference) group of eight postmenopausal women on two occasions 6 months apart; these showed significant changes in HDL2- and HDL3-cholesterol. In the treatment group, HDL-cholesterol and apolipoprotein (apo) A1 were significantly higher and LDL-cholesterol and apo B were significantly lower at months 4, 7 and 9 compared with baseline values. Triglyceride levels were increased significantly over baseline values, but remained within the normal range. No significant differences between the two dydrogesterone doses were observed on any lipid and lipoprotein fraction, nor were there any differences between the oestrogen-only and oestrogen/dydrogesterone treatment phases. Dydrogesterone appears to cause little, if any, lipid and lipoprotein changes and assessment in a larger population of postmenopausal women is warranted.

Dydrogesterone↗

Diet and exercise as regulators of lipid risk factors.

Comparisons of different countries have shown that populations with a low dietary intake of saturated fat also have a low mortality from coronary heart disease. Controlled-feeding experiments have shown that the potential for altering plasma cholesterol levels and, consequently, altering the risk of coronary heart disease by dietary modification is great. However, in practice the influence of dietary advice to the general population on plasma cholesterol levels has been less pronounced. Several investigators have shown that by decreasing the intake of saturated fats and dietary cholesterol and increasing the intake of polyunsaturated fats and foods providing soluble fibre, plasma cholesterol levels can be reduced by up to 29% and low density lipoprotein (LDL)-cholesterol by over 33%. In most studies, levels of high density lipoprotein (HDL)-cholesterol are not materially altered by modern lipid-lowering diets; generally, plasma levels are maintained, or increased after correction of overweight is is achieved. It has been calculated that the risk of fatal coronary heart disease is 32% lower in subjects consuming such a diet than in those following a typical American diet, and life expectancy is 5 years greater in the former group. Life expectancy is also 2 to 3 years longer in populations habitually following low fat diets than in Western populations. Frequent exercise has been inversely related to risk of coronary heart disease. Physically active individuals have a more favourable lipoprotein profile than sedentary individuals but the extent of a direct effect of exercise on lipoprotein levels is not known.

Cholesterol↗

Top management program: management development in New Zealand's health services.

This article describes New Zealand's program for developing managers in health services, called the National Management Development Program (NMDP), run by a newly established unit of the Department of Health. This is a set of programs for training various groups of individuals in health administration: those with no experience who wish to enter the field, those in a particular area of health, and those who are already managers in the health field. The Top Management Program, designed for professionals already heading health agencies, offers continuing education as a sustained approach to improving individual management ability.

Education, Continuing↗

Effects of exercise and fat ingestion on high density lipoprotein production by peripheral tissues.

The peripheral production of high density lipoprotein (HDL) cholesterol and of the subclasses HDL2 and HDL3 was assessed by measurement of the arteriovenous fluxes across the human forearm, at rest and after 20 min isometric exercise in the forearm. Eight subjects were studied twice--fasting and after a high-fat meal--and one other subject was studied only after fat loading. In the fasted state the net fluxes of HDL2 and HDL3 cholesterol were slightly negative in the resting forearm, but they became positive during exercise, indicating greater production during short-term muscular activity. The effect of exercise, particularly that on HDL3 cholesterol, was greatly increased by a high-fat meal; the difference in HDL3 cholesterol arteriovenous flux between rest and exercise was significant (-0.06 [SEM 0.05] vs 0.51 [0.17] mumol/100 ml forearm/min). By contrast, there was no peripheral production of HDL2 or HDL3 cholesterol during exercise in two patients with lipoprotein lipase deficiency. These findings suggest that formation of HDL3 during lipolysis by lipoprotein lipase in the muscle capillary bed is influenced by the supply of chylomicrons and other lipoprotein substrates for this enzyme. Muscle blood flow may therefore be an important determinant of HDL production by this mechanism. The effect of exercise in raising HDL cholesterol, and the inverse relation between exercise and coronary heart disease, may be partly the result of this process.

Adult↗

Primary prevention of atherosclerosis by lovastatin in a genetically hyperlipidaemic rabbit strain.

Lovastatin, a lipid-lowering drug which inhibits cholesterol synthesis, was administered to genetically hyperlipidaemic rabbits from the age of 2 months. Twenty rabbits were selected with similar plasma cholesterol levels and divided into matched treatment and control groups. The treated animals showed a 60% decrease in plasma cholesterol due to reduced levels of low density lipoprotein (LDL) and intermediate density lipoprotein (IDL). Levels of other lipoproteins remained unchanged. In untreated animals cholesterol levels in plasma, LDL and IDL increased with age. The area of aortic atherosclerosis-like lesions was quantified after 2-10.5 months of treatment. At each time point the extent of arterial disease was profoundly less in treated than in untreated animals. The findings demonstrate that primary prevention of arterial lesions resembling human atherosclerosis (increased amounts of fibrous tissue, smooth muscle cell proliferation, foam cell formation and necrosis at the base of the plaques) results from early effective reduction of elevated plasma lipids by lovastatin in this rabbit strain.

Animals↗

Nephropathy in cadmium workers: assessment of risk from airborne occupational exposure to cadmium.

To assess the quantitative relation between exposure to airborne cadmium and various markers of renal tubular and glomerular function, 45 male workers employed at a plant that recovers cadmium from industrial waste and 32 male hospital workers of similar age and geographical location were examined. Cumulative external exposure to airborne cadmium (dose) was estimated from historical air sampling data, adjusted for respirator use. Increasing cadmium dose was associated with multiple renal tubular functional abnormalities, including reduced reabsorption of beta-2-microglobulin (beta-2), retinol binding protein (RBP), calcium, and phosphate. Serum creatinine concentration also increased with cadmium dose, suggesting impaired glomerular function. Mean systolic and diastolic blood pressures were higher in the cadmium workers than in the unexposed (134 v 120 mm Hg and 80 v 73 mm Hg respectively), but only systolic blood pressure was significantly associated with cadmium dose in multivariate analyses. Cadmium dose remained the most important predictor of serum creatinine concentration after controlling for age, blood pressure, body size, and other extraneous factors. Logistic regression to model the probability (prevalence) of various renal abnormalities with increasing dose of cadmium was used. The probability of multiple tubular abnormalities and raised serum creatinine concentration increased sharply at cumulative cadmium exposures exceeding 300 mg/m3 days, corresponding to working for 4.3 years at the current permissible United States exposure limit for cadmium dust.

Air Pollutants, Occupational↗