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Biomedical subjects

H A Neil

Publications and source records attributed to H A Neil.

At least 37 records · Page 2Linked to original sources
PubMed1998

Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23)

OBJECTIVE: To evaluate baseline risk factors for coronary artery disease in patients with type 2 diabetes mellitus. DESIGN: A stepwise selection procedure, adjusting for age and sex, was used in 2693 subjects with complete data to determine which risk factors for coronary artery disease should be included in a Cox proportional hazards model. SUBJECTS: 3055 white patients (mean age 52) with recently diagnosed type 2 diabetes mellitus and without evidence of disease related to atheroma. Median duration of follow up was 7.9 years. 335 patients developed coronary artery disease within 10 years. OUTCOME MEASURES: Angina with confirmatory abnormal electrocardiogram; non-fatal and fatal myocardial infarction. RESULTS: Coronary artery disease was significantly associated with increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, and increased triglyceride concentration, haemoglobin A1c, systolic blood pressure, fasting plasma glucose concentration, and a history of smoking. The estimated hazard ratios for the upper third relative to the lower third were 2.26 (95% confidence interval 1.70 to 3.00) for low density lipoprotein cholesterol, 0.55 (0.41 to 0.73) for high density lipoprotein cholesterol, 1.52 (1.15 to 2.01) for haemoglobin A1c, and 1.82 (1.34 to 2.47) for systolic blood pressure. The estimated hazard ratio for smokers was 1.41 (1.06 to 1.88). CONCLUSION: A quintet of potentially modifiable risk factors for coronary artery disease exists in patients with type 2 diabetes mellitus. These risk factors are increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, raised blood pressure, hyperglycaemia, and smoking.

Adult↗
PubMed1998

Coronary event and case fatality rates in an English population: results of the Oxford myocardial infarction incidence study. The Oxford Myocardial Infarction Incidence Study Group.

OBJECTIVES: To determine coronary event and case fatality rates in an English population aged less than 80 years in Oxfordshire, and to compare these rates with those reported by the UK monitoring trends and determinants of cardiovascular disease (MONICA) centres in Scotland and Northern Ireland and those ascertained in Oxfordshire in 1966-67. DESIGN: A population wide surveillance study conducted in 1994-95 using prospective and retrospective case ascertainment. SETTING: A resident population in Oxfordshire of 568,800. SUBJECTS: Patients with suspected myocardial infarction or coronary death. OUTCOME MEASURES: A diagnosis of definite or possible myocardial infarction or coronary death using WHO MONICA diagnostic criteria based on symptoms, electrocardiograms, cardiac enzymes, necropsy findings, and past medical history. RESULTS: The annual rate for a first or recurrent coronary event per 100,000 population aged less than 65 years in 1994-95 was 273 for men and 66 for women after age adjustment to a standard world population. Rates in the age group 65-79 years were 1350 for men and 677 for women. Between 1966-67 and 1994-95, the age standardised event rate in the age group 30-69 years decreased significantly by 33% (95% confidence interval (CI) 44 to 21) in men, and there was a non-significant reduction of 8% (95% CI -33 to 17) in women. The age standardised 28 day case fatality rates also decreased significantly by 28% (95% CI 41 to 15) in men and by 32% (95% CI 55 to 9) in women. CONCLUSIONS: The coronary event rate in Oxfordshire was much lower than rates reported by MONICA centres in Glasgow and Belfast, and similar to rates reported by MONICA centres in France and northern Italy. The substantially lower event rate accounts for lower coronary heart disease mortality in Oxfordshire than in Scotland and Northern Ireland. The reduced coronary mortality in this region is attributable to declines in coronary event and case fatality rates.

Adult↗
PubMed1997

Serum Lp(a) lipoprotein concentration is not associated with clinical and angiographic outcome five years after coronary artery bypass graft surgery.

OBJECTIVE: To examine the association between serum Lp(a) lipoprotein concentration and clinical and angiographic outcomes five years after coronary artery bypass graft (CABG) surgery. SETTING: A regional cardiothoracic centre, Freeman Hospital, and the University Clinical Investigation Unit, Royal Victoria Infirmary, Newcastle upon Tyne. PATIENTS AND DESIGN: 353 consecutive patients (56 female, 297 male, mean age 57-2 years) undergoing first time CABG surgery for stable angina were studied prospectively. MAIN OUTCOME MEASURES: Late cardiac death (beyond 30 days) and non-fatal myocardial infarction; prevalence of angina five years after surgery in 291 (94%) survivors and vein graft patency (evaluated by patient) in 118 survivors five years after surgery. Serum Lp(a) concentration and lipid profiles were measured before operation, and 3, 6, 12, and 60 months after surgery. Lipid profiles were also measured 24 months after surgery. RESULTS: Weighted Lp(a) concentration (by tertile) was not associated with late cardiac death or with the combination of late cardiac death and non-fatal myocardial infarction, with the presence of angina, or with vein graft occlusion. The association remained non-significant if analysis was restricted to the upper tertile of LDL cholesterol (> 4.1 mmol/l) or to patients under the age of 55 years at the time of surgery. CONCLUSIONS: Serum Lp(a) concentration did not predict late cardiac death, the combination of late cardiac death and non-fatal myocardial infarction, or the prevalence of angina or vein graft occlusion five years after CABG surgery.

Angina Pectoris↗
PubMed1997

Approach to maintaining comparability of biochemical data during long-term clinical trials.

Our objective was to design a structured approach to maintaining comparability of biochemical data during a long clinical trial. Maintaining the comparability of clinical and biochemical data obtained in long-term studies is essential, even though analytical methods in the laboratory may be changed, conventions on specimen handling and storage revised, calibration procedures updated, quality-control systems replaced, and secular changes may occur. The United Kingdom Prospective Diabetes Study (UKPDS), a large randomized control trial investigating therapy for type 2 diabetes, was the setting for the study. Data were collected from 5102 subjects randomized since 1977. Our techniques included quality control, external quality assurance, direct comparison of laboratory methods when updating assays and statistical techniques for the detection of unsuspected changes in assay bias, laboratory comparisons of new with old assay methodologies, the realigning of data to current methods, the use of a suitable reference population for long-term monitoring, and rules to aid decision-making about clinical vs statistical significance. Procedures by which comparability of data is assured should be specified for all long-term trials and, where possible, comparison with reference methods should be detailed to allow results from different laboratories to be compared.

Diabetes Mellitus, Type 2↗
PubMed1995

Randomised trial of lipid lowering dietary advice in general practice: the effects on serum lipids, lipoproteins, and antioxidants.

OBJECTIVE: To determine the relative efficacy in general practice of dietary advice given by a dietitian, a practice nurse, or a diet leaflet alone in reducing total and low density lipoprotein cholesterol concentration. DESIGN: Randomised six month parallel trial. SETTING: A general practice in Oxfordshire. SUBJECTS: 2004 subjects aged 35-64 years were screened for hypercholesterolaemia; 163 men and 146 women with a repeat total cholesterol concentration of 6.0-8.5 mmol/l entered the trial. INTERVENTIONS: Individual advice provided by a dietitian using a diet history, a practice nurse using a structured food frequency questionnaire, or a detailed diet leaflet sent by post. All three groups were advised to limit the energy provided by fat to 30% or less and to increase carbohydrate and dietary fibre. MAIN OUTCOME MEASURES: Concentrations of total cholesterol and low density and high density lipoprotein cholesterol after six months; antioxidant concentration and body mass index. RESULTS: No significant differences were found at the end of the trial between groups in mean concentrations of lipids, lipoproteins, and antioxidants or body mass index. After data were pooled from the three groups, the mean total cholesterol concentration fell by 1.9% (0.13 mmol/l, 95% confidence interval 0.06 to 0.22, P < 0.001) to 7.00 mmol/l, and low density lipoprotein cholesterol also fell. The total carotenoid concentration increased by 53 nmol/l (95% confidence interval 3.0 to 103, P = 0.039). CONCLUSIONS: Dietary advice is equally effective when given by a dietitian, a practice nurse, or a diet leaflet alone but results in only a small reduction in total and low density lipoprotein cholesterol. To obtain a better response more intensive intervention than is normally available in primary care is probably necessary.

Antioxidants↗
PubMed1995

Patients undergoing coronary artery bypass graft surgery are at high risk of impaired glucose tolerance and diabetes mellitus during the first postoperative year.

This study demonstrates that patients who have undergone coronary artery bypass graft (CABG) surgery have a high prevalence of abnormal glucose tolerance 3 months and 1 year later. Although only 6% were known to have diabetes mellitus (DM) preoperatively, a further 4% were classified DM at two oral glucose tolerance tests (OGTTs) over the subsequent year and a further 18% were classified as having impaired glucose tolerance (IGT) at 12 months. Reproducibility of the 120-minute plasma glucose level in the 75-g OGTT was estimated from a repeat test performed within 10 days. The coefficient of variation (CV) of 120-minute glucose was between 14% and 18%. The observed changes in class of glucose tolerance observed at OGTTs repeated 6 and 12 months after surgery differed from the predicted changes based purely on the estimated variability of 120-minute glucose measurement. There was evidence of regression to the mean for the IGT group. However, there was also evidence of deteriorating glucose tolerance in some subjects. Between 4% and 9% of those with IGT 3 months after CABG surgery developed DM by 12 months, and 26 (13%) of those with initially normal glucose tolerance (NGT) developed IGT. Insulin and glucose responses in the OGTT and estimates of insulin resistance and beta-cell function from fasting samples show that insulin resistance was the principal abnormality in IGT subjects, whereas in DM subjects, both insulin resistance and beta-cell dysfunction contributed. Analysis of preoperative patient characteristics showed that the presence of either a systolic blood pressure of 140 mm Hg or body mass index (BMI) of more than 25 kg/m2 identified 51% of the subjects who would at 1 year after surgery include all those who would be classified DM and 67% of those who would have IGT. Further analyses including insulin levels identified groups at particularly high risk of DM, but no combination of readily available preoperative measures identified all those destined to be classified IGT.

Blood Glucose↗
PubMed1995

Assessing the impact of blood sample type on the estimated prevalence of impaired glucose tolerance and diabetes mellitus in epidemiological surveys.

In a prospective study of 353 patients who had undergone coronary artery bypass graft surgery a 75 g oral glucose tolerance test was performed at 3 months and 12 months after surgery. Venous whole blood glucose and venous plasma glucose samples were assayed on a bench-top analyser. The World Health Organization diagnostic criteria for impaired glucose tolerance and diabetes mellitus were applied to venous whole blood glucose and venous plasma glucose measurements. The difference between the plasma and whole blood concentration of glucose was 0.79-0.86 mmol l-1 at a plasma glucose of 7.8 mmol l-1 and 1.22-1.24 mmol l-1 at a plasma glucose of 11.1 mmol l-1 (compared to 1.1 mmol l-1 by World Health Organization criteria at both cut-points). Despite this, in our subject population with a high prevalence of impaired glucose tolerance (20.3% at 3 months, 15.3% at 12 months) and diabetes mellitus (10.1% at 3 months and 12 months), there was no significant difference in the proportion classified impaired glucose tolerance or having diabetes mellitus using venous whole blood glucose compared to venous plasma glucose. We conclude that despite the minor anomaly between WHO diagnostic criteria based on venous whole blood glucose and venous plasma glucose measurements, these criteria are robust and give broadly comparable population prevalence of diabetes mellitus and impaired glucose tolerance irrespective of blood sample choice.

Autoanalysis↗
PubMed1994

Segregation analysis of NIDDM in Caucasian families.

Non-insulin-dependent diabetes mellitus (NIDDM) has a substantial genetic component, but the mode of inheritance and the molecular basis are unknown. We have undertaken segregation analysis of NIDDM after studying 247 subjects in 59 Caucasian nuclear pedigrees ascertained without regard to family history of the disorder. The analyses were performed using POINTER and COMDS, which are computer programs which apply statistical models to the data. POINTER analysis was performed defining the phenotype as a presence or absence of hyperglycaemia. Among single locus hypothesis, the analyses rejected a recessive model and favoured a dominant model, but could not statistically show that this fitted better than a mixed model (a single locus against a polygenic background) or a polygenic model. COMDS analysis assumed a continuum of hyperglycaemia from normality to NIDDM, classified family members into a series of diathesis classes with increasing plasma glucose levels and compared the distribution with that found by screening the normal population. This analysis improved the likelihood of a dominant single locus model and suggested a gene frequency of 7.4%. It raised the possibility of a second locus, but cannot identify or exclude a polygenic model. In conclusion, two types of segregation analyses rejected a recessive model and favoured a dominant model of inheritance, although they could not statistically show that this fitted better than the polygenic model. The results raised the possibility of a common dominant gene with incomplete penetrance, but genetic analysis of NIDDM needs to take into account the likelihood of polygenic inheritance with genetic heterogeneity.

Adult↗
PubMed1994

Simvastatin in non-insulin-dependent diabetes mellitus: effect on serum lipids, lipoproteins and haemostatic measures.

The clinical efficacy of the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase inhibitor simvastatin in the treatment of hypercholesterolaemia in non-insulin-dependent diabetes (NIDDM), was examined in a double-blind placebo-controlled study of 6 months in 70 patients with NIDDM (age 25-70 years), of whom 57 were randomised to placebo (29 patients) or simvastatin for 6 months, following a 3-month run-in on diet. Patients were hypercholesterolaemic (7.8 (7.6-8.0) (mean (95% confidence intervals)) mmol/l simvastatin vs. 8.0 (7.7-8.5) mmol/l placebo) and mildly hypertriglyceridaemic (2.6 (2.2-3.0) simvastatin vs. 2.9 (2.3-3.5) placebo). Other lipid measures and estimates of glycaemic control and haemostasis were similar in both groups. There were no significant changes in lipids, haemostatic factors, or measures of glycaemic control in the placebo treatment group. Conversely by the end of 24 weeks, simvastatin produced a 28% reduction in cholesterol (to 5.6 (5.0-6.2) mmol/l (P < 0.001)), a 38% reduction in LDL cholesterol (from 5.5 (5.4-5.6) mmol/l to 3.4 (2.8-4.0) mmol/l, P < 0.001), a 15% reduction in triglyceride (to 2.2 (1.8-2.6) mmol/l, P < 0.05, and a 9% rise in HDL (from 1.16 (1.07-1.25) to 1.23 (1.14-1.32) mmol/l, P < 0.05). Improvements in apolipoprotein B (apo B) (-28%, P < 0.001), the LDL cholesterol to apo B ratio (-20%, P < 0.001), and apo A1 (+15%, P < 0.001) were recorded. There were no effects upon fibrinogen, factor VII activity, factor VIII activity, or measures of glycaemic control (fasting glucose, insulin, C-peptide, or HbA1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Coronary artery disease is associated with increased lipoprotein(a) concentrations independent of the size of circulating apolipoprotein(a) isoforms.

Lipoprotein(a) [Lp(a)] concentration and apolipoprotein(a) [apo(a)] isoforms (identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE] and Western blotting) were determined in a group of 508 asymptomatic Caucasian members of the community and in 318 Caucasian patients with angiographically defined coronary artery disease (CAD). Conventional risk factors for CAD were also measured. Lp(a) concentration was almost twice as high in subjects with CAD (geometric mean, 152 mg/L [geometric SD, 10 to 1398 mg/L]) as in asymptomatic control subjects (geometric mean, 84 mg/L [geometric SD, 21 to 334 mg/L]). Asymptomatic women had higher concentrations of Lp(a) than asymptomatic men. Patients with CAD were older and were more likely to have smoked and to have a first-degree relative with premature CAD (< 55 years of age), and a higher proportion were male. Patients with CAD had higher concentrations of Lp(a) independently of the number of isoform bands expressed. When apo(a) isoforms were allocated to 1 of 10 classes on the basis of their molecular size (Rf versus apoB in SDS-PAGE), patients with CAD did not express an excess of low-molecular-mass (higher concentration) isoforms but did express a higher proportion of double-band phenotypes with fewer "null" phenotypes. The relationship between the two isoform bands in a double-band phenotype was the same in both populations. Isoform mobility was defined as a continuous variable equal to the mobility of a single isoform band (single-band phenotypes) or the mean of the two isoforms in a double-band phenotype. Two variables, isoform mobility and the number of isoform bands expressed, were used to summarize the large range of isoform patterns (at least 45) that could be identified. Isoform mobility, the number of isoform bands expressed, and the presence of CAD were the three most important independent predictors of Lp(a) concentration (descending order). Only sex and LDL cholesterol were additional independent predictors of Lp(a) concentration in step-wise regression models including a wide range of demographic factors and lipid and glycemic risk factors. We conclude that Lp(a) concentration is associated with CAD independently of the isoform pattern expressed. The apo(a) gene locus exerts a strong control over circulating Lp(a) concentration, and a better understanding of the control of expression of the apo(a) gene will be essential to understand the relationship between Lp(a) and CAD.

Apolipoproteins A↗
PubMed1994

A meta-analysis of the effect of garlic on blood pressure.

OBJECTIVE: To undertake a systematic review, including meta-analysis, of published and unpublished randomized controlled trials of garlic preparations to determine the effect of garlic on blood pressure relative to placebo and other antihypertensive agents. DATA IDENTIFICATION: Studies were identified by a search of Medline and the Alternative Medicine electronic databases, from references listed in primary and review articles, and through direct contact with garlic manufacturers. STUDY SELECTION: Only randomized controlled trials of garlic preparations that were at least 4 weeks in duration were deemed eligible for inclusion in the review. DATA EXTRACTION: Data were extracted from the published reports by the two authors independently, with disagreements resolved by discussion. RESULTS: Eight trials were identified (all using the same dried garlic powder preparation (Kwai) with data from 415 subjects included in the analyses. Only three of the trials were specifically conducted in hypertensive subjects, and many had other methodological shortcomings. Of the seven trials that compared the effect of garlic with that of placebo, three showed a significant reduction in systolic blood pressure (SBP) and four in diastolic blood pressure (DBP). The overall pooled mean difference in the absolute change (from baseline to final measurement) of SBP was greater in the subjects who were treated with garlic then in those treated with placebo. For DBP the corresponding reduction in the garlic-treated subjects was slightly smaller. CONCLUSIONS: The results suggest that this garlic powder preparation may be of some clinical use in subjects with mild hypertension. However, there is still insufficient evidence to recommend it as a routine clinical therapy for the treatment of hypertensive subjects. More-rigorously designed and analysed trials are needed.

Blood Pressure↗
PubMed1993

Association between impaired glucose tolerance and circulating concentration of Lp(a) lipoprotein in relation to coronary heart disease.

OBJECTIVE: To examine whether impaired glucose tolerance and raised Lp(a) lipoprotein concentrations are associated in subjects with coronary artery disease. DESIGN: Study of two subject populations, one with and one without symptomatic coronary artery disease. Case-control analysis of patients with impaired glucose tolerance and normal glucose tolerance performed in each subject population independently. SETTING: A general practice and a hospital ward in Newcastle upon Tyne. SUBJECTS: 517 apparently healthy subjects, 13 with impaired glucose tolerance, and 245 patients who had undergone coronary artery bypass graft surgery 12 months before, 51 with impaired glucose tolerance. MAIN OUTCOME MEASURES: Serum Lp(a) lipoprotein concentration, plasma glucose concentration before and after oral challenge with 75 g glucose monohydrate, and Lp(a) lipoprotein isoforms. RESULTS: In both the asymptomatic subjects and the subjects with coronary artery disease there was no significant difference between subjects with impaired glucose tolerance and subjects with normal and body mass index in serum Lp(a) lipoprotein concentrations (geometric mean 61 (geometric SD 4) mg/l v 83 (5) mg/l for asymptomatic subjects, 175 (3) v 197 (2) for subjects with heart disease), nor was there any difference in the proportion of subjects who had Lp(a) lipoprotein concentrations > 300 mg/l (31% v 23% for asymptomatic subjects, 37% v 37% for subjects with heart disease). For both subject groups there was no significant correlation between Lp(a) lipoprotein concentration and plasma glucose concentration after a glucose tolerance test, nor did Lp(a) lipoprotein concentration vary by quintile of glucose concentration after the test. Examination of Lp(a) lipoprotein isoforms in the subjects with coronary artery disease revealed an inverse relation between isoform size and plasma Lp(a) lipoprotein concentration, but there was no evidence that impaired glucose tolerance was associated with particular Lp(a) lipoprotein isoforms. CONCLUSION: Raised Lp(a) lipoprotein concentrations are not responsible for the association between impaired glucose tolerance and coronary artery disease.

Blood Glucose↗
PubMed1992

Biometry and auto-fluorescence of the anterior ocular segment in diabetics with and without autonomic neuropathy: a case control study.

The biometry and auto-fluorescence of the anterior ocular segment were examined in a case control study of two populations of diabetics. Cases, with diabetic autonomic neuropathy, and controls without neuropathy (forty in each group) were selected from a community based diabetic population and matched individually for age, sex, and type of diabetes. Scheimpflug and auto-fluorescence anterior segment photography were performed and analysed by digital image analysis in a masked fashion. There were differences between the groups in axial lens thickness, front radius of curvature of the lens, anterior chamber depth and lenticular auto-fluorescence. These findings are discussed in the context of the known association between autonomic neuropathy and narrow angle glaucoma, and possible common mechanisms of tissue damage in diabetes.

Aged↗
PubMed1992

Autofluorescence of the crystalline lens in early and late onset diabetes.

Blue/green autofluorescence (excitation around 420 to 430 nm, emission around 520 nm) of the crystalline lens has been studied by an in vivo photographic method in two populations of diabetics and controls. The populations consisted of a geographically based survivor group of 161 mixed early and late onset diabetics (and 133 non-diabetic controls) and a second group of 104 early onset insulin dependent diabetics (and 138 non-diabetic controls), the latter all with non-cataractous lenses. Powerful associations (p less than 10(-6) were found between the presence of diabetes and increased lenticular autofluorescence in both populations. Among the mixed diabetics diabetic type was a significant factor after accounting for the effects of age and diabetic duration. In the early onset group (clear lenses) a powerful association existed between autofluorescence and diabetic duration (p = 0.000011) after allowing for the effect of age, while in a subgroup of late onset diabetics with clear lenses this effect was modest (p = 0.015). In the early onset diabetic group diabetic retinopathy (p = 0.0064) was associated with increased lenticular autofluorescence after allowing for the effects of age and diabetic duration. In addition a powerful interaction between diabetic duration and the presence of diabetic retinopathy (p less than 10(-6) was found in this subgroup. Among the geographically based population of diabetics, increased nuclear brunescence was powerfully associated (p less than 10(-6) with increased autofluorescence after allowing for the effects of age, diabetic duration, and type of diabetes. This association was not found in the non-diabetic population. Non-enzymatic glycosylation of lens proteins should be considered as a possible mechanism of production of the fluorogen with emission around 520 nm.

Adolescent↗
PubMed1992

Biometry of the crystalline lens in late onset diabetes: the importance of diabetic type.

Lenticular and anterior chamber biometry were studied in non-cataractous eyes by means of Scheimpflug photography and digital image analysis. The study population consisted of 91 late onset diabetic subjects and 115 non-diabetic controls. Anteroposterior axial lens thickness, cortical thickness, nuclear thickness, anterior clear zone thickness, anterior chamber depth, and anterior and posterior lenticular curvatures were assessed. Age played an important role in determining lens biometry in all subjects, and small but significant differences were found between late onset diabetics and non-diabetics. In the late onset diabetic subgroup, apart from age, diabetic retinopathy was the only significant parameter found which determined lens biometry. These biometric findings in late onset diabetes are in marked contrast to the large overall effect of diabetes and the powerful effect of diabetic duration which we previously reported in early onset diabetes. Further analysis of the data from our previous study has been provided, which clearly demonstrates differences between the impact of early and late onset diabetes on the biometry of the anterior ocular segment.

Adult↗