PubMed Health⌕ Search

Biomedical subjects

H Mather

Publications and source records attributed to H Mather.

15 recordsLinked to original sources
PubMed2001

An attempt to identify the evolutionary origin of a novel serotype of Salmonella enterica isolated from harbour porpoises.

The isolation since 1991 of a new serotype of Salmonella enterica (antigenic formula 4,12:a:-) from harbour porpoises (Phocoena phocoena) at post-mortem examination raised the question of its evolutionary origin. Representative strains of S. enterica serotype 4,12:a:- and strains of eight other serotypes of serogroup 04 with phase-1 flagellar antigen H 'a' were examined by EcoRI ribotyping, IS200 fingerprinting and PCR-based profiling. Statistical analysis of results of multiple typing showed that strains of Salmonella serotype 4,12:a:- were genetically distant from those of antigenically similar salmonella serotypes, none of which seemed likely to be the progenitor of the 'porpoise' serotype.

Animals↗
PubMed2000

Family outbreak of dysentery caused by a rhamnose non-fermenting, ONPG-negative strain of Shigella sonnei phage type 6.

Three members of a Scottish family, with no history of foreign travel but who had recently visited Bristol, were infected by a strain of Shigella sonnei of phage type 6 (PT 6) that did not ferment rhamnose and was negative for o-nitrophenyl-beta-D-galactopyranoside (ONPG). The incident exposed limitations associated with commercial systems for the identification of strains of S. sonnei with atypical biochemical properties.

Adult↗
PubMed1998

Cardiovascular outcomes in type 2 diabetes. A double-blind placebo-controlled study of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study.

OBJECTIVE: To determine whether serum lipid intervention, in addition to conventional diabetes treatment, could alter cardiovascular outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS: There were 164 type 2 diabetic subjects (117 men, 47 women) without a history of clinical cardiovascular disease randomized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospectively for a minimum of 3 years. Serial biochemical and noninvasive vascular assessments, carotid and femoral artery B-mode ultrasound measurements, and those pertaining to coronary heart disease (CHD)--clinical history, the World Health Organization (WHO) cardiovascular questionnaire, and resting and exercise electrocardiogram (ECG)--were recorded. RESULTS: Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride (-32 vs. 4%, P = 0.001), total cholesterol (-7 vs. -0.3%, P = 0.004), and total-to-HDL cholesterol ratio (-12 vs. -0.0%, P = 0.001), and an increase in HDL cholesterol (6 vs. -2%, P = 0.02) as compared with placebo. There was a trend toward a greater reduction of fibrinogen (-18 vs. -6%, P = 0.08) at 3 years. No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease. In those treated with bezafibrate, there was a significant reduction (P = 0.01, log-rank test) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infarction. CONCLUSIONS: Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease, although the lower rate of "definite CHD events" in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease.

Adult↗
PubMed1996

Relative fasting hypoinsulinaemia and ultrasonically measured early arterial disease in type 2 diabetes. The SENDCAP Study Group, St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention Study.

Macrovasular disease is the most important cause of morbidity and mortality in Type 2 (non-insulin-dependent) diabetes. Dyslipidaemia and hyperinsulinaemia have been proposed as aetiological factors. This paper describes the interrelationships between fasting serum insulin, serum lipids, and the extent of ultrasonically measured early arterial disease in Type 2 diabetic subjects screened for entry into a prospective study set up to ascertain whether improving serum lipids can alter the progress of arterial disease in Type 2 diabetes. Measurements were made of the initima media thickness (IMT) in the carotid artery, and an arterial ultrasound score (AUS) based on appearances of both carotid and femoral arteries was calculated for 192 established Type 2 diabetic subjects, males and females, mean age 51 (range 35-66) years, median duration of diabetes 3.5 years, with no known cardiovascular disease. Multiple regression analysis showed that carotid IMT increased with age and was inversely related to serum insulin (variance accounted for, R2, = 8.8%, p = 0.0002). AUS increased with age and was related inversely to serum insulin, or to C-peptide when this was substituted in the model. In addition to age and serum insulin, AUS was positively associated with non-HDL cholesterol and negatively with HDL 3 cholesterol (R2 = 26%, p = 0.0001). Early thickening and damage to the arterial wall in Type 2 diabetes may be related to relative fasting hypoinsulinaemia.

Adult↗
PubMed1995

Increased secretion of 32,33 split proinsulin after intravenous glucose in glucose-tolerant first-degree relatives of patients with non-insulin dependent diabetes of European, but not Asian, origin.

OBJECTIVE: The aetiology of non-insulin dependent diabetes is unknown, but defective insulin secretion is a feature. The disease also has a strong genetic basis and first-degree relatives of patients have an increased risk of future diabetes. To investigate whether beta-cell dysfunction is an early feature of the disease, we studied insulin secretion in healthy first-degree relatives of patients with non-insulin dependent diabetes. DESIGN: Each subject underwent a 1-hour intravenous glucose tolerance test (0.3 g/kg). PATIENTS: Seventeen first-degree relatives of patients (10 of European and 7 of Asian (Indian subcontinent) origin) with normal glucose tolerance were compared with 17 matched control subjects with no family history of diabetes. MEASUREMENTS: Plasma immunoreactive insulin (IRI) was measured by radioimmunoassay, and specific insulin, intact and 32,33 split proinsulin were measured by specific immunoradiometric assays (IRMA) for the 1st phase (0-10 minutes) and 2nd phase (10-60 minutes) responses. Glucose and intermediary metabolites were measured enzymatically. RESULTS: Fasting concentrations of IRI, IRMA insulin, intact and 32,33 split proinsulin were similar in relatives and controls in each group. Fasting glucose levels were similar in European relatives and controls but lower in Asian relatives compared to their controls (mean +/- SE 4.9 +/- 0.2 vs 5.5 +/- 0.2 mmol/l, P < 0.05). Following intravenous glucose, European relatives had similar IRI and glucose levels to their controls. Secretion of 32,33 split proinsulin was increased in European relatives compared to their controls, significantly so for 2nd phase secretion (1st phase median (range): 71 (7-352) vs 55 (17-118) pmol/l min, NS; 2nd phase: 433 (115-1459) vs 234 (55-745) pmol/l min, P < 0.05). Secretion of IRMA insulin and intact proinsulin were similar in European relatives and controls (IRMA insulin: 1st phase 2757 (700-10,969) vs 2830 (632-4682) pmol/l min; 2nd phase 6387 (3006-15,865) vs 5284 (2060-18,605) pmol/l min; intact proinsulin: 1st phase 31 (13-113) vs 32 (16-72) pmol/l min; 2nd phase: 174 (87-737) vs 159 (97-298) pmol/l min). European relatives had a greater percentage of proinsulin-like molecules (intact + 32,33 split proinsulin) to total insulin (sum of IRMA insulin + intact + 32,33 split proinsulin) during the 2nd phase of secretion (9.1 (5.0-11.8) vs 5.9 (4.3-12.6)%, P < 0.05). In contrast, Asian relatives had similar secretion of IRI, IRMA insulin, intact and 32,33 split proinsulin to their controls. Glucose disappearance (KG) was similar in relatives and controls within each ethnic group (Europeans: relatives 725 +/- 101 vs controls 668 +/- 47/min; Asian: relatives 610 +/- 97 vs controls 783 +/- 936/min). Asian relatives had higher fasting circulating glycerol (65 +/- 7 vs 44 +/- 4 mumol/l, P < 0.05), non-esterified fatty acid (569 +/- 59 vs 375 +/- 64 mumol/l, P < 0.05) and 3-hydroxybutyrate levels (147 (44-187) vs 35 (21-57) mumol/l, P < 0.01) than their controls and this persisted following intravenous glucose. This difference was not observed in the European group. CONCLUSION: First-degree relatives of European patients with NIDDM possess early signs of beta-cell dysfunction, with increased and disproportionate secretion of 32,33 split proinsulin after intravenous glucose, whilst glucose tolerance is still normal.

Adult↗
PubMed1995

Atherosclerosis risk factors: variation in healthy hospital workers and members of local communities asymptomatic for vascular disease. Implications for normal controls.

The major risk factors for atherosclerosis were measured in 100 middle-aged members of the local community aged between 40 and 66 attending hospital for minor operations, hernia repair, varicose veins or endoscopy, and their healthy accompanying spouses. Levels in this group were compared with those measured in 75 age- and sex-matched hospital workers. Ten of the 12 risk factors measured were more unfavourable in the local population (P = 0.039). Levels of total cholesterol (P = 0.0013), low-density lipoprotein (LDL) cholesterol (P = 0.0002) and body mass index (P = 0.0074) were higher in members of the local community. There was no difference in levels of triglycerides, high-density lipoprotein cholesterol, von Willebrand factor (vWf, an index of damage to the endothelial cell), fibrinogen, glucose, systolic and diastolic blood pressure, waist-to-hip ratio or the proportion of smokers. We also found systolic blood pressure (P = 0.014) and vWf (P = 0.021) to be higher, while high-density lipoprotein (P = 0.022) was lower in the 35 smokers, but we could not identify any factor that correlated with age. However, systolic (P = 0.028) and diastolic (P = 0.0072) blood pressures, triglycerides (P = 0.029) and waist-to-hip ratio (P < 0.0001) were all lower, while high-density lipoprotein was higher (P < 0.0001) in the 80 women compared to the men. We conclude that precise definition of the identity of the control group is necessary in studies of risk factors for atherosclerosis, or in frank disease, if mis-interpretation is to be avoided.

Aged↗
PubMed1994

Insulin sensitivity in non-diabetic relatives of patients with non-insulin-dependent diabetes from two ethnic groups.

OBJECTIVE: Non-insulin-dependent diabetes is a heterogeneous disorder, the basis of which may differ in different ethnic groups. In order to investigate early metabolic abnormalities occurring during the development of the condition we assessed insulin secretion and insulin action in subjects predisposed to the later development of non-insulin-dependent diabetes from two different ethnic groups. DESIGN: Subjects were studied on two separate occasions by an oral glucose tolerance test and a short insulin tolerance test. PATIENTS: Twenty-four glucose-tolerant first-degree relatives of patients with non-insulin-dependent diabetes (12 of European and 12 of Asian origin) were compared with 24 ethnically matched control subjects with no family history of diabetes. MEASUREMENTS: Insulin, proinsulin, glucose and intermediary metabolites were measured during a 75-g oral glucose tolerance test. Insulin sensitivity was assessed using a 15-minute insulin tolerance test (0.05 units/kg). RESULTS: Asian relatives compared to Asian controls had significantly higher fasting levels of immunoreactive insulin (83 +/- 17 vs 40 +/- 6 pmol/l, P < 0.05), which were not due to increased proinsulin. Blood glycerol concentrations were elevated (83 +/- 9 vs 51 +/- 4 mumol/l, P < 0.005), but fasting glucose and non-esterified fatty acid (NEFA) concentrations were similar. Relatives of European origin did not differ from their European controls in any of these measurements. The glucose response to oral glucose was similar in relatives and controls, irrespective of ethnic group. The insulin responses were non-significantly greater in relatives from both ethnic groups. Proinsulin levels were not significantly different. Asian relatives had higher circulating glycerol and NEFA levels after oral glucose than Asian controls, but these differences were not observed in the European group. Insulin sensitivity was reduced in the Asian relatives compared to their controls (183 +/- 7 vs 139 +/- 12 mumol/l/min, P < 0.01) but there was no difference in insulin sensitivity between the European relatives and European controls (167 +/- 11 vs 160 +/- 11 mumol/l/min). CONCLUSIONS: First-degree relatives of non-insulin-dependent diabetic patients of Asian, but not of European, origin are insulin insensitive in terms of both glucose metabolism and lipolysis, and have true hyperinsulinaemia. This suggests that insulin insensitivity may be an early abnormality in the development of non-insulin-dependent diabetes in the Asian population.

Adult↗
PubMed1994

Genetic analysis of glucokinase and the chromosome 20 diabetes susceptibility locus in families with type 2 diabetes.

Mutations of the glucokinase gene (chromosome 7p) have been shown to cause some cases of familial maturity onset diabetes of youth (MODY) but few, if any, cases of late onset familial Type 2 diabetes. A further single large pedigree with MODY has shown linkage to a marker for the adenosine deaminase gene (ADA, chromosome 20q), although the diabetes susceptibility gene at this locus has not been identified. We have studied members of 19 families with familial Type 2 diabetes (including 10 European families, 6 families from the Indian subcontinent, and 3 families of Afro-Caribbean origin), 2 of which were of MODY type (and both European), with a glucokinase marker and a marker linked to ADA, to examine whether glucokinase, or the unknown defect on chromosome 20, are implicated in diabetes in our pedigrees. Several models were constructed for standard two-point linkage analysis. Glucokinase is not the cause of diabetes in all of these families but was excluded in only one MODY family. It was possible to exclude both loci in the second MODY pedigree. No evidence was found of linkage to either marker in this multi-ethnic population under the models used. At least one further locus is involved in determining susceptibility to MODY.

Adult↗
PubMed1994

Retinal blood flow changes during pregnancy in women with diabetes.

PURPOSE: To study retinal blood flow (RBF) during pregnancy in subjects with and without diabetes and to relate the changes to progression in diabetic retinopathy. METHODS: RBF in a major temporal retinal vein was measured, where possible, during all three trimesters (T1 to T3) and the postpartum period (PP) using laser Doppler velocimetry (measuring velocity [V]) and monochromatic fundus photographs (measuring diameter [D]). RESULTS: In the subjects without diabetes (n = 19), no significant change in RBF was demonstrated. V was significantly greater in T3 than in PP (P = 0.01). D was significantly smaller in T1 to T3 than in PP (P < or = 0.01). RBF in the subjects with diabetes was significantly higher in T2 and T3 than in PP (P < 0.05). V increased from T1 to T2 (P = 0.04) and decreased from T2 to PP (P = 0.001) and from T3 to PP (P = 0.002). The only significant change in D was a smaller value in T1 than in PP (P = 0.003). However, it was only those subjects whose DR progressed (n = 11) who had a significant increase in RBF during pregnancy (P = 0.0001). CONCLUSIONS: These data suggest that the hyperdynamic circulation present in pregnancy led to compensatory retinal vessel constriction (autoregulation) in the group without diabetes; this was largely absent in the patients with diabetes, with resultant increase in retinal blood flow associated with worsening retinopathy. This finding lends further support to the hypothesis that increased retinal blood flow is a pathogenic mechanism for diabetic retinopathy.

Adult↗
PubMed1981

Twice-daily insulin regimens in management of severe diabetes.

Diurnal glucose profiles have been compared in ten insulin dependent diabetics receiving, firstly, a twice-daily soluble insulin (SI): isophane insulin (NPHI) insulin (30% SI, 70% NPHI). For each patient the two regimens gave similar profiles though nocturnal blood glucose control was better on Mixtard. HbA1 values were similar on the two regimens. The findings show that, using highly purified formulations, small changes in insulin proportions in twice-daily SI: NPHI regimens may be irrelevant to diabetic control; they also suggest that highly purified NPHI may have a substantially shorter duration of action than its older counterpart and that the convenient regimen of twice-daily Mixtard is usually as good as any more complicated 'tailormade' regimen of highly purified insulins.

Adolescent↗
PubMedDate not supplied

A genetic analysis of type 2 (non-insulin-dependent) diabetes mellitus in Punjabi Sikhs and British Caucasoid patients.

A genetic analysis of diabetic and non-diabetic Punjabi Sikhs (n = 164) was made for markers of non-insulin-dependent diabetes mellitus using insulin receptor, insulin, and HLA-D alpha chain gene probes. Additionally British Caucasoids (n = 163) were studied using the insulin receptor probe. Insulin receptor gene restriction fragment length polymorphisms were defined using Southern blot techniques and the restriction enzyme Bgl II and BAm Hl. In Punjabi Sikhs and British Caucasoids neither of the restriction fragment length polymorphisms distinguished non-insulin-dependent diabetes mellitus subjects from controls. In the Sikhs no association with non-insulin-dependent diabetes mellitus was seen with the hypervariable region of the insulin gene or with HLA-DR/DQ/DX alpha chain restriction fragment length polymorphisms. We therefore conclude that despite the high prevalence of non-insulin-dependent diabetes mellitus in Asians we were unable to find any genetic markers for this disease using the available cloned gene probes.

Diabetes Mellitus, Type 2↗