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Biomedical subjects

A F Winder

Publications and source records attributed to A F Winder.

At least 19 recordsLinked to original sources
PubMed1998

Changing patterns of referral to UK lipid clinics - a ten-year perspective.

OBJECTIVE: To review changing attitudes of British physicians to the significance of lipids and associated cardiovascular risks over the last decade. METHODS: Analysis of annual trends in referrals to specialist UK lipid clinics as recorded in the UK lipid clinics programme computerised database, with data on source, clinical and metabolic status of up to 12932 patients referred from 1986-1995. - RESULTS: Over the decade the proportion of referrals from hospital teams rather than GP s, and with clinical vascular disease has increased. The predominantly male patients have been referred at lower initial cholesterol levels but increasing BMI, with less emphasis on rare disorders. Recorded reductions in total cholesterol on treatment have also fallen from some 20% to 13%. Alcohol and smoking habits have been in accord with national trends. CONCLUSIONS: These changes suggest that awarerness of the significance of cholesterol and particularly of the opportunities available in secondary prevention, and awareness that lipid problems are seen to apply to a much wider patient base than the rare genetic disorders have all increased. However the increasing proportion of cases found at first referral to have lipaemia secondary to other undiagnosed metabolic disturbance suggests that appreciation of such wider influences on lipids remains incomplete.

Adult↗
PubMed1998

Lipids and stroke: neglect of a useful preventive measure?

The epidemiological studies linking lipid variables and stroke are reviewed. These studies indicate that serum total cholesterol (TC) levels are associated positively with thrombotic and negatively with haemorrhagic strokes. Relationships for other lipid fractions are not as clearly defined. The results of trials with lipid lowering drugs suggest that only statins effectively reduce the incidence of stroke. Differences between trial results may be due to variation in the extent of reduction of TC levels. Possible underlying mechanisms for benefit and the apparent superiority of statins are also discussed. The reduction in the risk of thrombotic stroke with statins is most evident through meta-analyses (p < 0.001) and less impressive in individual trials (p < 0.03). This difference is largely attributable to the small number of events in trials primarily aimed at evaluating ischaemic heart disease (IHD) reduction. This also means that benefit may be limited to those with established IHD. IHD and thrombotic stroke share common risk factors and patients with one condition are at high risk of developing the other. Therefore, one additional reason for using statins in these patients is that these drugs can effectively prevent IHD-related events including deaths.

Arteriosclerosis↗
PubMed1998

Usual care dietary practice, achievement and implications for medication in the management of hypercholesterolaemia. Data from the U.K. Lipid Clinics Programme.

AIMS: To evaluate long-term responses to cholesterol-lowering diets in usual care and their associations with responses to lipid medication. METHODS: Analysis of paired data from the U.K. Lipid Clinics Programme computerized database for lipid responses, and associations of weight loss with later response to medication, plus analysis of a questionnaire on clinic dietary practice. RESULTS: Cholesterol, predominantly as low density lipoprotein was reduced in 60% of 2508 patients entered, and maintained long-term. Moderate 5-7% average responses incorporated reductions of at least 0.6 mmol x (-1) in 40% of patients, consistent with a 25% fall in the risk of cardiac events if maintained for 2 years. Responses to medication were greater for up to 2194 patients who previously lost weight on diet, an effect not apparent for 291 patients on statins alone. Physicians worked with dieticians in most clinics, and with individually tailored diets but with incomplete appreciation of the differences between available dietary protocols. CONCLUSIONS: Usual care dietary advice can be effective in lipid management, weight loss is important and associates with greater responses to lipid medication although statin monotherapy may not be affected. However, average responses are modest and physicians are not well informed of the dietary principles involved.

Adult↗
PubMed1998

Corneal arcus, case finding and definition of individual clinical risk in heterozygous familial hypercholesterolaemia.

Premature corneal arcus may identify individuals with hyperlipidaemia and increased cardiovascular risk. We have attempted to quantitate relationships through determination of graded prevalence of corneal arcus with age for 81 males and 73 females suffering from heterozygous familial hypercholesterolaemia (HFH) at presentation, and for 280 male and 353 female unselected patients (age range 16-76 years) attending a country general practice. Some degree of arcus affected 50% of HFH patients by age 31-35 years, and 50% of practice patients by age 41-45 years. Complete full ring arcus affected 50% of the familial hypercholesterolaemia (FH) group by age 50 years, with only 5% similarly affected in the non-FH group. Arcus grade with age was advanced by some 5 years in males versus females. Premature arcus potentially alerting to HFH can be broadly defined for males and females combined, as heavy full ring by age 50 years, or any degree of arcus by age 30-35 years. Arcus grade was not related to the presence of coronary disease. Accelerated development of corneal arcus with age is an indicator of HFH, but premature arcus is not an additional marker of premature coronary disease for individual cases of HFH.

Adolescent↗
PubMed1996

Lipid screening in an elderly population: difficulty in interpretation and in detection of occult metabolic disease.

AIMS: To determine lipid profiles and associations with other metabolic disease in a representative British elderly population. METHODS: Part of a prevalence survey of dementia in all 75+ year olds conducted from the large general practice serving the town and surrounding area of Melton Mowbray, Leicestershire (the M-old study). Patients (n = 224) aged from 75 to 98 years, and representative of the overall population, also provided pre-prandial blood samples on which various age and nutrition related analytes were determined. These included documented medical history, thyroid stimulating hormone (TSH), glucose, immunoglobulins, and lipid profile in plasma. RESULTS: Cholesterol and lipid variables showed wide scatter, with some negative trends but no significant associations with age for total cholesterol, high density lipoprotein (HDL) cholesterol, the ratio of total to HDL cholesterol or triglycerides. Women had significantly higher concentrations of total and HDL cholesterol at all ages. Serum TSH was above 6.0 mU/1 in 10/205 patients, random glucose was above 11.2 mmol/l in nine of 207 patients, borderline dysglobulinaemia was present in four of 210 patients, all without correlation with cholesterol concentrations. CONCLUSION: This British data is consistent with an inverse correlation between survival and cholesterol, but wide scatter restricts reliance on single result lipid data in individual patient management. Random lipid screening is also unhelpful, inefficient and without added value in revealing other age related and unrecognised occult metabolic disease.

Aged↗
PubMed1996

The pathology of cornea in Tangier disease (familial high density lipoprotein deficiency).

AIMS: To clarify the underlying causes of corneal opacification in Tangier disease. METHODS: Both corneas were removed at death from a 62 year old man with Tangier disease, and were examined by direct and transmission electron microscopy, histochemistry, biochemical analysis by thin-layer and gas-liquid chromatography after extraction, and by differential scanning calorimetry. RESULTS: Membranous inclusions in the stroma were seen on transmission electron microscopy. Direct analysis confirmed enrichment with phospholipids and cholesterol, with acyl patterns and proportions as ester broadly similar to those of normal cornea. Tangier cornea showed major thermotropic phase transitions in the range 28-37 degrees C, peak 30-33 degrees C, extending above profiles of normal clear cornea and without the complexity of those seen with cornea with heavy arcus involvement. CONCLUSIONS: Lipid accumulation underlies corneal opacification in Tangier disease. The excess material is mainly phospholipid and cholesterol esters. As at other sites which are below body core temperature, notably tonsil, accumulation may be enhanced by local impaired mobilisation of material as the phase transitions of the excess lipid present extend above ambient corneal temperatures.

Calorimetry, Differential Scanning↗
PubMed1995

A trinucleotide deletion together with a base duplication event at codon 439 in the human tyrosinase gene identifies a mutational hotspot.

Molecular analysis of the human tyrosinase gene in two patients suffering from a temperature-sensitive form of albinism has identified a thymine triplet deletion at codon 439 which is accompanied by a duplication of the immediately preceding cytosine residue. This results in a two base pair frame shift leading to premature termination at codon 448, giving a truncated protein. Its relationship to other mutations in tyrosinase and the possible cause are discussed. The temperature-sensitive phenotype is due to the guanine to adenine mutation at codon 422, known to generate a temperature-sensitive enzyme. The CTTT at F439 in tyrosinase is also present at F508 in CFTR, the main mutation causing cystic fibrosis.

Adolescent↗
PubMed1995

Limited discriminant value of lipoprotein AI, lipoprotein Lp(a) and other lipoprotein particles in patients with and without early onset ischaemic heart disease.

AIMS: To assess whether the ability of lipoprotein related variables to discriminate between individuals with or without premature clinical ischaemic heart disease (IHD) was improved using data on high density lipoprotein-lipoprotein AI (HDL-LpAI) fractions, alone or in combination with data on Lp(a). METHODS: Lipid and apolipoprotein concentrations were measured in 26 middle-aged men (mean age 50.3 years) with early onset IHD and coronary artery bypass grafting prior to sampling, and in 26 matched lipaemic and 26 normolipaemic asymptomatic controls. RESULTS: Triglyceride and Lp(a) concentrations were higher, while HDL cholesterol and apolipoprotein A-I (apoA-I) concentrations were lower in patients than in controls. LpAI concentrations were also lower in IHD patients and were correlated with HDL and apoA-I in both IHD and control groups. Lp(a) was not correlated with any other lipid or apolipoprotein measured in either patients or controls. Univariate discriminant function analysis showed that the proportion correctly classified as patients or controls was marginally greater using LpAI concentrations as the discriminator, which was not increased in combination with Lp(a). Serum triglycerides, HDL cholesterol, apoA-I and Lp(a) alone all had similar, but weaker, discriminant power, which increased in various combinations with LpAI. CONCLUSIONS: LpAI particle measurement may be useful in research to define mechanisms of cardiovascular protection by HDL but the discriminating power for IHD was only marginally superior to measuring total apoA-I or Lp(a) concentrations. Little further advantage arose through combining LpAI data with other variables.

Adult↗
PubMed1995

A common variant in the gene for lipoprotein lipase (Asp9-->Asn). Functional implications and prevalence in normal and hyperlipidemic subjects.

Subjects with combined hyperlipidemia (CHL) were screened for mutations in the lipoprotein lipase (LPL) gene by single-strand conformational polymorphism, and a previously reported G-->A DNA sequence change in exon 2, causing substitution of Asp by Asn at position 9, was identified in 2 individuals. Because this substitution destroys a recognition site for Taq I, pooling of DNA samples, amplification, and digest with Taq I allowed the rapid screening of 1563 healthy individuals and patients of Dutch, Swedish, English, and Scottish origin. In the general populations of all four countries, healthy carriers of the mutation were detected at a frequency of 1.6% to 4.4% (mean, 3.0%; 95% confidence interval, 2.0% to 4.0%). The frequency of carriers was roughly twice as high (range, 4.0% to 9.8%) in selected patients with CHL or type IV hyperlipoproteinemia or in subjects with angiographically assessed atherosclerosis; the frequency was consistently higher in each patient group compared with its matched control group. In 773 healthy men from two general practices in the United Kingdom, 25 carriers and 2 homozygotes for the mutation were identified. In these 27, plasma triglyceride but not plasma cholesterol levels were significantly higher than in noncarriers (2.25 versus 1.82 mmol/L, P < .02), and this difference was maintained in three subsequent annual measurements. Postheparin LPL activity data were available for some carriers and for 7 of 9 individuals from the patient groups, and 6 of 6 individuals from the control groups had LPL activity that was lower than the respective group mean. In vitro mutagenesis and transient expression in COS cells showed that compared with the LPL-Asp9 construct, LPL-Asn9 activity and mass were reduced by 20% to 30% in the culture media. Overall however, LPL-Asn9 had only slightly reduced specific activity (by 18%). Thus, although the precise mechanism of the effect is unclear, the data strongly suggest that the LPL-Asn9 variant is associated with and may play a direct role in predisposing carriers to develop hypertriglyceridemia.

Adult↗