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Biomedical subjects

N E Miller

Publications and source records attributed to N E Miller.

At least 91 records · Page 5Linked to original sources
PubMed1988

Associations of alcohol consumption with plasma high density lipoprotein cholesterol and its major subfractions: the Caerphilly and Speedwell Collaborative Heart Disease Studies.

In surveys of 4860 middle-aged men in Caerphilly (South Wales) and Speedwell (Bristol) alcohol consumption has been related to high density lipoprotein (HDL) cholesterol and its major subfractions, HDL2 and HDL3, measured in a single fasting blood sample. The results confirm that high density lipoprotein cholesterol concentration increases as the amount of alcohol regularly consumed increases. The relationship appears to be linear and is independent of age, smoking habit, body mass index, low density lipoprotein cholesterol and plasma total triglyceride. This rise in HDL cholesterol is not mediated through either HDL2 cholesterol or HDL3 cholesterol alone. Both subclasses increase significantly and by similar amounts with increasing alcohol intake.

Alcohol Drinking↗
PubMed1988

Effects of cimetidine and ranitidine on plasma high-density lipoprotein subclasses in humans.

The effects of cimetidine (400 mg b.d.) and ranitidine (150 mg b.d.) on high-density lipoprotein (HDL) subclasses and other plasma lipoproteins were studied in 18 men and 15 women with reflux oesophagitis and/or duodenitis. Serum testosterone and sex hormone binding globulin (SHBG) concentrations were also measured. Treatment with either drug was continued for 12 weeks. Ranitidine had no significant effect on any measured variable in either men or women. Cimetidine had no effect in men, but in women it raised the cholesterol concentration in the HDL2 subclass by 15% after 8 weeks, and by 48% after 12 weeks. In females, cimetidine also reduced the concentrations of SHBG (by 24% at 12 weeks) and of total testosterone (by 25% at 12 weeks). The significance of these latter changes is uncertain, however, as estimates of the biologically active free testosterone concentration were unchanged.

Adult↗
PubMed1988

DNA polymorphisms of the apolipoprotein AII and AI-CIII-AIV genes: a study in men selected for differences in high-density-lipoprotein cholesterol concentration.

We have investigated the frequencies of RFLPs of the apolipoprotein (apo) AII gene and of the apo AI-CIII-AIV gene cluster in 109 men, selected from a random sample of 1,910 men aged 45-59 years, to cover a wide range of plasma high-density-lipoprotein (HDL)-cholesterol concentration. There was no significant difference in apo AI or apo AII RFLP allele frequency between groups of individuals with high and low HDL-cholesterol concentration. However, the apo AI PstI RFLP showed an association with genetic variation determining the plasma concentration of apo AI in this sample. Genetic variation in the apo AI-CIII-AIV gene region, as defined by haplotypes, accounted for 16% of the phenotypic variance in the apo AI concentration and for 8% of the phenotypic variance in HDL-cholesterol concentration. There was no significant association between alleles of the apo AII MspI RFLP and genetic variation determining apo AII or HDL concentration. The data demonstrate that genetic variation in the apo AI-CIII-AIV gene cluster is involved in determining the serum concentration of apo AI in this sample of clinically well individuals.

Alleles↗
PubMed1987

Effects of adrenoceptor-blocking drugs on plasma lipoprotein concentrations.

Evidence from numerous clinical trials has indicated that beta-adrenoceptor blocking agents without intrinsic sympathomimetic activity increase plasma triglycerides and decrease high density lipoprotein cholesterol in patients with hypertension or coronary artery disease. There appears to be little or no difference between the nonselective and cardioselective drugs in this regard. In contrast, beta blockers with intrinsic sympathomimetic activity and alpha 1 blockers appear not to have these effects. The changes induced by adrenoceptor-blocking agents in lipid and lipoprotein metabolism and their possible significance in relation to the pathogenesis of coronary artery disease are discussed.

Adrenergic alpha-Antagonists↗
PubMed1987

Knowledge-based indexing of the medical literature: the Indexing Aid Project.

This article describes the Indexing Aid Project for conducting research in the areas of knowledge representation and indexing for information retrieval in order to develop interactive knowledge-based systems for computer-assisted indexing of the periodical medical literature. The system uses an experimental frame-based knowledge representation language, FrameKit, implemented in Franz Lisp. The initial prototype is designed to interact with trained MEDLINE indexers who will be prompted to enter subject terms as slot values in filling in document-specific frame data structures that are derived from the knowledge-base frames. In addition, the automatic application of rules associated with the knowledge-base frames produces a set of Medical Subject Heading (MeSH) keyword indices to the document. Important features of the system are representation of explicit relationships through slots which express the relations; slot values, restrictions, and rules made available by inheritance through "is-a" hierarchies; slot values denoted by functions that retrieve values from other slots; and restrictions on slot values displayable during data entry.

Abstracting and Indexing↗
PubMed1987

Sex, plasma lipoproteins, and atherosclerosis: prevailing assumptions and outstanding questions.

We review the hypothesis that the incidence of coronary heart disease (CHD) is higher in men than in women due to differences in plasma lipoprotein risk factors between the sexes. Men and women appear to be equally susceptible to the effects of lipoprotein risk factors for CHD, and the difference between the sexes in lipoprotein risk factors for CHD appears to be consistent with their being, at least in part, responsible for the sex difference in CHD. This is apparent both when men and women of equal age are compared, and when age-related variations in the sex differences in plasma lipoproteins and CHD are considered. Differences between the sexes in lipoprotein concentrations are still present when sex differences in adiposity, cigarette smoking, physical activity, and diet are taken into account. Evidence relating these sex differences in CHD and lipoproteins to the effects of sex hormones is critically examined. It is commonly accepted that androgens induce changes in lipoprotein concentrations that would predispose towards CHD, whereas estrogens are held to have opposite effects. However, much of the evidence for this comes from studies of changes associated with administration of synthetic gonadal steroids or with changes in gonadal function. Studies of differences in lipoprotein metabolism in normal men and women are extremely limited. In males high-density lipoprotein (HDL) cholesterol levels fall at puberty, correlating with the rise in plasma testosterone concentrations. In females, HDL levels do not change at puberty, despite the rise in estrogen concentrations. Evidence for lipoprotein changes during the menopause, when estrogen levels decline, is equivocal. Similarly, the evidence for an increase in CHD incidence at the menopause is inconclusive. National mortality data indicate that the decreasing sex difference in CHD after 50 years of age is due to a declining rate of increase in men rather than to an acceleration in CHD incidence in women. In men the age-related increase in low-density lipoprotein (LDL) concentrations diminishes beyond 50 years of age, whereas in women the rate of increase remains unchanged. Studies of the effects of gonadectomy are of doubtful relevance in assessing the roles of sex hormones in CHD, and have not been performed with sufficient rigor to provide definitive conclusions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Double-blind trial of the long-term effects of acebutolol and propranolol on serum lipoproteins in patients with stable angina pectoris.

In order to evaluate the long-term effects of propranolol and acebutolol on serum lipoprotein lipids, a double-blind clinical trial was carried out. Fifteen patients with stable angina pectoris, aged 32 to 79 years (mean = 53), were randomized to propranolol (80 to 160 mg/day) or acebutolol (400 mg/day) treatment groups, and followed for approximately 1 year (mean = 371 days). Blood was collected on the day treatment was begun, after approximately 5 months (mean = 158 days), and on completion of the trial. Very low-density lipoproteins (VLDL) (alpha less than 1.006), low-density lipoproteins (LDL) (1.006 to 1.063), and high-density lipoproteins (HDL) (1.063 to 1.125 [HDL2] and 1.125 to 1.21 [HDL3]) were isolated by sequential preparative ultracentrifugation, and their cholesterol and triglyceride quantified by enzymic procedures. After 1 year propranolol had raised the mean VLDL triglyceride concentration by 79% (p less than 0.005) and had lowered total HDL cholesterol by 24% (p less than 0.005). As LDL cholesterol was unchanged, the LDL cholesterol/HDL cholesterol ratio was increased by 26% (p less than 0.005). Mean values at 5 months were intermediate between those at baseline and those at 1 year. In contrast to these changes, acebutolol had no significant effect on any measured lipoprotein lipid.

Acebutolol↗
PubMed1987

On the associations of body cholesterol pool size with age, HDL cholesterol and plasma total cholesterol concentration in humans.

Data from 17 subjects, in whom cholesterol kinetics had been measured by two-pool analysis of medium-term plasma cholesterol specific activity-time curves, were examined by multiple linear regression to explore the determinants of the size of the slowly exchanging cholesterol pool (MBmin) in humans. Pool size was independently and positively related to body weight (regression coefficient, 0.94 g per kg; P = 0.05) and age (1.77 g per year; P = 0.02). After allowance for these effects, MBmin retained a significant negative association with the plasma high density lipoprotein (HDL) cholesterol concentration (-0.56 g per mg/dl; P = 0.03), but was unrelated to plasma total cholesterol. This result is consistent with published data on the composition of those human tissues whose cholesterol is known to be largely a component of the slowly exchanging pool. It differs, however, from that of a recent study of cholesterol turnover [Blum et al, J. Lipid Res., 1985; 26: 1079-1088] in which pool size, measured by three-pool analysis of long-term decay curves, was unrelated to HDL and directly related to plasma total cholesterol. On the basis of other published data, it is considered that this discrepancy is unlikely to be a consequence of the difference between our respective studies in the duration and method of analysis of the specific activity decay curves. Differences in the variances of HDL cholesterol and plasma total cholesterol concentration that were examined, and in the biochemical-genetic factors underlying these variances, provide a more likely explanation. The overall weight of evidence favours the view that the pool of slowly exchangeable cholesterol in many human tissues expands during ageing at a rate which is increased in the presence of severe hypercholesterolemia, and which under some, but not all, circumstances also varies inversely with HDL cholesterol. The critical components of HDL metabolism which affect this process remain to be identified.

Adult↗
PubMed1987

High-density lipoprotein: a major risk factor for coronary atherosclerosis.

The high-density lipoproteins (HDL) are a polydisperse family of lipid--protein complexes whose principal functions in lipid transport are: (1) to act as a reservoir of C apoproteins required for triglyceride transport; (2) to act as a 'scavenger' of surplus cholesterol and phospholipid liberated from lipolysed triglyceride-rich lipoproteins; and (3) to transport surplus cholesterol from peripheral tissues to the liver for excretion and catabolism (reverse cholesterol transport), both directly and indirectly via other lipoproteins and the lipid transfer protein. The concentration of HDL cholesterol (mostly cholesteryl ester) has been found to be a strong risk factor for coronary atherosclerosis, and its clinical complications in most industrialized communities have been studied. The association with disease risk is independent of other lipoproteins and risk factors, has been found in both sexes, and persists following reduction of plasma lipids by diet and certain drugs. It is not yet clear whether or not certain HDL subclasses and/or apoproteins are better predictors of risk than HDL cholesterol. Indirect evidence from clinical studies and data from animal experiments suggests that certain pharmacologically induced increases in HDL cholesterol concentration are associated with a reduction of atherogenesis. However, the mechanism of the link between HDL and atherogenesis is not yet clear: although the original suggestion that it reflects the function of HDL in reverse cholesterol transport remains plausible, alternative mechanisms are possible. These include effects of HDL on platelet function and prostacyclin synthesis. Alternatively, the association might be indirect, reflecting an atherogenic effect of triglyceride-rich lipoproteins and/or their remnants, the plasma concentrations of which are correlated with HDL cholesterol.

Apolipoprotein A-I↗
PubMed1987

Mental health services use by elderly adults in a primary care setting.

This study examined the use of general health, mental health, and other medical specialty services by elderly persons 65 and older with mental disorders and compares them with adults 45 to 64 and 18 to 44. Data were collected at the Bunker Hill Health Center (BHHC), a Boston neighborhood health center providing a broad range of ambulatory medical and specialty mental health services. Results show that the 5-year rate of mental disorder diagnoses for elderly individuals is not significantly different from persons 45 to 64, although it is higher than the rate for young adults 18 to 44. Not only were elderly adults less likely to see a mental health specialist, but when they did, their use of mental health specialty services was usually lower.

Adult↗
PubMed1987

Studies with doxazosin on the saturable binding of 125I-LDL by liver in normocholesterolemic mice.

Tissue culture studies have provided evidence that alpha 1-adrenergic receptor inhibition with doxazosin increases the number of low-density lipoprotein (LDL) receptors in human fibroblasts. A similar effect occurring in vivo might explain the reduction of plasma LDL concentration observed in some clinical trials of prazosin. In order to examine this question further, mice were given doxazosin 100 or 400 micrograms/kg/day by i.p. injection for 4 days, after which they were killed, blood was collected and livers were excised. Binding of 125I-labelled human LDL to tissue homogenates, over the concentration range 30-120 micrograms LDL protein/ml, was measured at 37 degrees C in the absence and presence of excess unlabelled LDL. Woolf plots of the results for saturable binding were found to be compatible with a single class of binding site. In control animals Bmax for this receptor was 867 +/- 117 ng LDL protein/mg tissue protein, and the equilibrium dissociation constant was 32.7 +/- 6.6 micrograms LDL protein/ml (mean +/- SD, n = 5). Doxazosin treatment had no effect on either parameter of 125I-LDL binding. A trend towards a decrease in liver triglyceride concentration with increasing doses of doxazosin was recorded, but there was no evidence for effects on liver cholesterol or serum lipid concentrations.

Adrenergic alpha-Antagonists↗
PubMed1986

Association between dietary fat intake and plasma factor VII coagulant activity--a predictor of cardiovascular mortality.

Repeated measurements were made in 8 adults of factor VII coagulant activity (VIIc) and fibrinogen concentration (two haemostatic variables associated with cardiovascular mortality), together with factor VII concentration, factor X, prothrombin, and serum cholesterol and triglyceride concentrations, while the usual diet was recorded by precise weighing over 12-14 days. In 6 subjects measurements were continued while low-fat and high-fat diets were taken for a further 2 and 3 weeks respectively. Plasma VIIc was related positively and independently to fat and protein intake, whereas factor VII concentration was associated only with protein consumption. In a second study, consumption of 50% extra energy for one day increased VIIc significantly when taken mainly as fat but not when taken mostly as carbohydrate. The character of the VIIc response to fat intake suggested an association with post-prandial lipaemia. A high fat intake may lead not only to coronary atheroma but also to fibrin deposition and thrombus formation through direct activation of the coagulation system.

Adult↗
PubMed1986

Failure to replicate visceral learning in the acute curarized rat preparation.

An attempt was made to replicate a series of experiments reported to demonstrate robust visceral learning (autonomic instrumental learning) in rats during acute (2-4 hr) pharmacological paralysis. The results of exploratory procedures involving more than 2,000 animals are described, and six complete experiments, representing systematic observations on an additional 500 animals, are presented. In the first three experiments, which closely followed the original procedures, the characteristics of the preparation were reproduced with the exception of initial heart rhythm and visceral learning. In the second three, the respiration procedure was modified to satisfactorily reproduce the heart rhythm, and the PaO2, PaCO2, and pH were verified to be within the range of freely moving, normally behaving animals; nevertheless, visceral learning was not observed in these experiments either. After more than 2,500 rats were studied, it is concluded that the original visceral learning experiments are not replicable and that the existence of visceral learning remains unproven; however, neither the original experiments nor the replication attempt included the necessary controls to support a general negative conclusion about visceral learning. Because continuing and extensive citation of the original experiments indicates their widely perceived significance, specific requirements for critically testing the visceral learning hypothesis are given, and the limited theoretical implications and practical value of neuromuscular blockade are discussed.

Animals↗