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Biomedical subjects

A F Winder

Publications and source records attributed to A F Winder.

At least 55 records · Page 3Linked to original sources
PubMed1994

Unrecognized dyslipoproteinemia in United Kingdom families recruited to a genetic register because of unexplained coronary heart disease.

A register was built up of DNA from United Kingdom families with premature coronary heart disease and no perceived risk associations in the expectation that obscure causal factors could be defined through future genetic analysis. Referrals came from interested, predominantly cardiologic units in southern England. For inclusion, probands had documented coronary heart disease before age 55 years that was regarded as unexplained, in families with at least two living affected first-degree and two other members, in most families over two generations. Referred probands and family members completed a questionnaire on general health and habits and were examined for body mass index, blood pressure, resting electrocardiogram, and lipoprotein profile. Data are presented on 276 living members from 26 families, representing 75.4% of all members age 15 years and older. The striking observation was the extent of dyslipoproteinemia that was not identified by the referring units as relevant to the expression of accelerated coronary heart disease. This was expressed as hypercholesterolemia, reduced levels of high-density lipoprotein, or both, in comparison with profiles recorded over the same period and for a similar but unselected general British population. Further genetic analysis for a major occult risk factor in these families is inappropriate. Present concerns with potential adverse associations with low cholesterol, or with lipid-lowering treatment, should be addressed in the knowledge that uncontrolled dyslipoproteinemia also has severe adverse associations. These associations are still not widely appreciated in the management of patients and families with premature coronary heart disease.

Adult↗
PubMed1993

Brisk walking and serum lipoprotein variables in formerly sedentary men aged 42-59 years.

1. The purpose of this study was to examine the influence of brisk walking on serum lipoprotein variables. 2. Seventy-two apparently healthy but physically inactive men (aged 42-59 years) were recruited. These men were normotensive non-smokers without a history of dyslipidaemia. Subjects were randomly allocated on a 2 to 1 basis into either a walking group (n = 48) or a control group (n = 24). Walkers followed a self-monitored programme of brisk walking for 1 year, whereas control subjects maintained their habitual lifestyle. 3. Treadmill walking tests were conducted to examine changes in fitness. Concentrations of serum lipids and lipoproteins were determined in fasting subjects. The amount of body fat was measured by body density. Circumferences at the waist and hip and skinfold thicknesses were used to determine the distribution of body fat. Dietary intakes were assessed by weighed food inventories. 4. Seven subjects (six walkers and one control subject) dropped out during the study. Walkers did an average of 28 (SEM 1.4; n = 42) min of brisk walking/day. This improved endurance fitness but did not influence serum concentrations of total cholesterol, high-density lipoprotein cholesterol, triacylglycerol, apolipoprotein A-1, apolipoprotein B or lipoprotein (a). Neither body mass nor the amount of body fat changed, relative to control subjects. 5. These data suggest that brisk walking does not modify lipoprotein metabolism in normolipidaemic middle-aged men.

Adult↗
PubMed1993

Hypoalphalipoproteinaemia and polymorphisms associated with reduced expression of the apolipoprotein A-I gene and resolution of disputed paternity in a large English family.

A Pst-I RFLP polymorphism adjacent to the 3' end of the apolipoprotein A-I gene is reported to associate with hypoalphalipoproteinaemia with dominant inheritance in families identified through accelerated coronary heart disease. This association was not apparent in a large English family identified through voluntary health screening, and with no evident premature coronary disease. Any association could, however, be masked by sex, or by further undetermined variation affecting Pst-I restriction sites. Analysis of this and other polymorphisms present also led to resolution both of disputed paternity and of a long-standing family feud.

Adolescent↗
PubMed1993

Management of hyperlipidaemia: guidelines of the British Hyperlipidaemia Association.

There is considerable evidence to suggest that the identification and treatment of dyslipidaemia will reduce the risk of premature CHD, i.e. before the age of 65. Diagnosis of the cause of raised plasma lipid levels will enable appropriate decisions to be taken with regard to management. The cornerstone of treatment is nutritional counselling and attention to other major risk factors for CHD, particularly smoking and hypertension. For a small percentage of patients with severe hyperlipidaemia drug therapy is indicated. Appropriate drug choices need to be made based on the particular lipid abnormality to be treated. In general those patients with clinical vascular disease are treated more aggressively than those where the aim is primary prevention. More research is needed to determine individual risk more precisely and to allow proper targeting of therapy. Genetic factors, qualitative changes in lipoproteins, lipoprotein (a), fibrinogen, and other coagulation and thrombotic factors are likely to be important in individual risk assessment. There is no doubt that more information is needed from prospective studies of lipid-lowering therapy in terms of risk benefit for affected individuals. Hopefully the major studies currently underway will fill some of the gaps in our knowledge. Until then aggressive therapy with drugs should be reserved for those at highest risk where the benefit is likely to be greatest.

Cholesterol, Dietary↗
PubMed1990

Receptor-mediated endocytosis of low-density lipoprotein by cultured human glomerular cells.

Lipoproteins might be involved in the pathogenesis of glomerular damage. Uptake of low-density lipoprotein (LDL) by cultured human glomerular cells has been studied using LDL, labelled with the fluorescent probe 1,1'-dioctadecyl-3,3,3'3'-tetramethyl-indocarbocyanine perchlorate (diI). Cells have been characterised using phase-contrast microscopy, monoclonal antibodies and lectins. Differentiated glomerular epithelial cells, epithelial-like cells and mesangial cells all took up diI-LDL. Uptake was specific for LDL, of high affinity and inhibited by excess unlabelled LDL, heparin and preloading the cells with cholesterol. Binding of diI-LDL to the cell surface was restricted to discrete areas which were arranged in linear arrays on mesangial cells. Endocytosis of surface-bound diI-LDL occurred within 3 min and breakdown of internalised diI-LDL within 30 min. These results indicate that cultured human glomerular cells take up LDL by receptor-mediated endocytosis.

Cells, Cultured↗
PubMed1988

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↗
PubMed1988

Role of duodenal bile crystal analysis in the investigation of 'idiopathic' pancreatitis.

Duodenal bile crystal analysis for the detection of gallstones was assessed in 26 patients with acute pancreatitis of known aetiology (11 attributable to gallstones and 15 to alcohol) and in 37 patients without a history of acute pancreatitis (21 with gallstones and 16 without). The sensitivity was 64-67 per cent and the specificity was 94-100 per cent in these groups. Analysis of duodenal bile from 14 patients with 'idiopathic' pancreatitis revealed calcium bilirubinate crystals (but not cholesterol crystals) in 5 patients (36 per cent). Gallstones were confirmed at cholecystectomy in three of these patients and also in one other patient who had a gallstone on a 'late' ultrasound examination but was negative for crystals. Thus 29 per cent of the original 'idiopathic' group had gallstones confirmed. Gallstone analysis showed that pigment stones were present in 7 of 31 (23 per cent) non-pancreatitis controls compared with 9 of 13 (69 per cent) pancreatitis patients (P = 0.0048). These results suggest that duodenal bile crystal analysis (involving both calcium bilirubinate and cholesterol crystals) may be a useful technique for the investigation of patients with 'idiopathic' pancreatitis.

Acute Disease↗
PubMed1988

Clinical and laboratory responses to niceritrol in the treatment of hypercholesterolaemia.

Twenty-five hypercholesterolaemic patients from three centres in the UK were investigated in an open study of the efficacy and side effects of niceritrol. Five patients dropped out of the study at an early stage and had insufficient data for analysis. There were 13 males and 7 females (mean age 49.2 years, range 18-69). Fourteen patients had heterozygous familial hypercholesterolaemia, and six polygenic hypercholesterolaemia. Niceritrol was started at a dose of 750 mg/day and this was increased at weekly intervals over 4 weeks to the maximum tolerated dosage up to 3 g/day. This was then maintained for a further 8 weeks. There were statistically significant decreases in total plasma cholesterol, total triglyceride, LDL cholesterol and VLDL triglyceride; HDL cholesterol remained unchanged after 12 weeks of treatment (Wilcoxon matched pairs, signed ranks test). The 14 patients with familial hypercholesterolaemia showed a 13.9% fall in total cholesterol and a 19.8% fall in LDL cholesterol. All patients reported flushing and some had gastrointestinal symptoms but 19 would have been prepared to continue with the therapy at doses up to 3 g/day. Thus niceritrol has been found to be beneficial in the treatment of both familial and polygenic hypercholesterolaemia.

Adolescent↗
PubMed1988

Surface tension properties of human urine: relationship with bile salt concentration.

The surface tension of urine has been simply and rapidly measured using two methods, the DuNouy ring detachment method and the Wilhelmy blade immersion method. The methods agree, the correlation coefficient, r, was 0.992. The effect of ageing of the surface, of storage, of temperature, pH, dilution and albumin on urine surface tension are described. Volume corrected 24 hour urine surface tensions from 6 volunteers over 12 or more days showed variations between individuals of mean surface tensions of 6 mN/m (S.D. +/- 2.16 mN/m). This suggests individual variation in excretion of surface active agents, probably bile salts. This was confirmed by further studies which showed that: 1. Surface tension of urines and rediluted extracts were not significantly different when amphiphilic and hydrophobic solutes including bile salts were extracted from urine and subsequently rediluted in water of the same volume. 2. Bile salt concentration in urine measured by RIA and by enzymatic spectrofluorometric methods correlated well with urine surface tension, r = -0.91, and r = -0.60. 3. Molecular surface area for urinary surfactant was 79 A2 similar to pure conjugated bile salt solutions calculated from dilution studies. We conclude that the main determinant of urine surface tension is bile salt concentration.

Adult↗
PubMed1985

Thermal transition studies of a mature xanthelasma by differential scanning calorimetry.

A large xanthelasma which had been present for at least 5 years was removed surgically from a normolipaemic female age 54 years, and examined in the fresh state by differential scanning calorimetry. Thermal transitions recorded over the range 30-40 degrees C suggest that the lipid present, predominantly esterified cholesterol, is not bound to protein or other tissue components, and that the chronicity of mature xanthelasmata as with ectopic lipid deposits at other sites is enhanced by chemical modification of lipid and effects on component phase behaviour, which are significant at local skin temperature.

Calorimetry, Differential Scanning↗
PubMed1985

Direct and maternal aspects of the risk of cataract with partial disorders of galactose metabolism.

Partial deficiencies of the enzymes of galactose metabolism can be associated with cataract, both directly and through maternal effects during pregnancy on enzymatically normal children. However, the associations are modest, variable and not obviously expressing cause and effect. We have recorded ophthalmological and biochemical observations including oral galactose tolerance on families with established enzyme deficiencies and/or cataracts, including possible effects during pregnancy. With the partial disorders a simple relationship between the extent of biochemical abnormality and the risk of cataract is not apparent and the association may be substantially coincidental. Cataract is common, and the attractive possibility that expression is significantly due to heterozygous or lesser deficiency of the enzymes of galactose metabolism, amenable to early dietary control of children or mothers at risk, is on present evidence not well supported.

Adolescent↗
PubMed1985

Familial lecithin:cholesterol acyltransferase deficiency. Biochemistry of the cornea.

Opacification of the cornea from lipid accumulation is an early and characteristic feature of familial lecithin:cholesterol acyltransferase (LCAT) deficiency. Visual impairment in a female age 48 years led to keratoplasty and the first detailed analysis of cornea in this disorder. Multilaminar figures were present, and total lipid extracts were enriched with phospholipid and cholesterol; cholesteryl esters were reduced, and accounted for about 12% of the cholesterol. Linoleate C18:2 was the predominant residue in the cholesteryl ester fatty acid fraction, with a C18:1/18:2 ratio of 1:6.5. This ratio differs from that in normal cornea, and from that in plasma and in other tissue deposits in LCAT deficiency. Various disorders of the HDL/LCAT system in plasma can lead to corneal lipid accumulation and opacification. These disorders may share general defects of lipid clearance from the cornea, but this study of LCAT cornea indicates that the character of the accumulating lipid is significantly influenced by active local metabolism, irrespective of the defect in the HDL/LCAT system also present.

Chromatography, Gas↗
PubMed1984

Ocular effects of acute hyperglycaemia.

Intraocular pressure and levels of glucose in plasma were recorded during a standard glucose tolerance test for 54 patients with chronic simple or low-tension glaucoma, and osmolality in plasma was also recorded for 12 patients. Significant correlations between the rates of change of these variables were not obtained, but the overall response of intraocular pressure correlated with the overall increase of plasma glucose, which also correlated with the increase of osmolality. These results show that the changes in refraction associated with acute hyperglycaemia arise from adjustments in fluid balance between intraocular compartments.

Aged↗