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Biomedical subjects

C Walton

Publications and source records attributed to C Walton.

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

Survey of diabetic retinopathy screening services in England and Wales.

A postal survey of diabetologists was conducted regarding the provision of diabetic retinopathy screening services in England and Wales. About 2.5 million people had no existing or planned screening service. For the rest, the perceived percentage of patients with diabetes screened varied from less than 25% to more than 90%. Multiple modes of screening were used in most units. Lack of funding was identified as the major reason for non-provision of an adequate screening service. About 18% of the units had to use research or charitable funds for screening. Only 50% of the units using optometrists for screening had standard protocols for referral. The average wait before an ophthalmologist's opinion on sight threatening retinopathy detected by screening was unacceptably high in some units. We would suggest that establishment of identical screening protocols and provision of adequate funding on a national basis ought to be the priority if incidence of blindness from diabetic retinopathy is to be reduced according to the St Vincent Declaration.

Diabetic Retinopathy↗
PubMed1998

The effect of menopause on serum uric acid levels in non-obese healthy women.

Elevated circulating serum uric acid concentrations may be linked with an increased risk of coronary heart disease (CHD). We measured serum uric acid levels in 50 premenopausal and 88 postmenopausal non-obese white women who underwent an intravenous glucose tolerance test. The uric acid concentration was significantly higher in postmenopausal versus premenopausal women. Adjustment of the data to take into account a number of confounding variables, including the age and body mass index (BMI), revealed a highly significant independent difference between the groups. BMI was found to be a significant independent predictor of the uric acid concentration, but this was confined to premenopausal women. Postmenopausal women were found to be more insulin-resistant, and significant correlations were observed between components of the insulin resistance syndrome and uric acid in both groups. We conclude that increases in serum acid in postmenopausal women may result from changes in metabolism as a consequence of the menopause, and may be associated with the increased risk of CHD seen in these women.

Adult↗
PubMed1998

MR imaging and CT of orbital infections and complications in acute rhinosinusitis.

The acute onset of orbital and periorbital inflammation presents the clinician with a diagnostic and therapeutic dilemma, the consequence of which may be very serious. The progression from the initial stage of cellulitis to orbital abscess, cavernous sinus thrombosis, brain abscess, meningitis, or visual loss may be quite rapid at times. CT, ultrasonography, and MR imaging play an important role in clinical management of these patients. Indeed, it is the information obtained through orbital imaging that directs the clinician to use the correct therapeutic modality.

Abscess↗
PubMed1998

Associations of smoking, alcohol and physical activity with risk factors for coronary heart disease and diabetes in the first follow-up cohort of the Heart Disease and Diabetes Risk Indicators in a Screened Cohort study (HDDRISC-1).

OBJECTIVES: To investigate the associations between risk factors for cardiovascular disease and cigarette smoking, alcohol intake, and physical activity in a group of predominantly healthy men. DESIGN: Cohort study with baseline characterisation, clinical follow-up, and identification of predictors of coronary artery disease and diabetes. SETTING: University hospital metabolic day ward. SUBJECTS: Participants in a company health programme (n=742). MAIN OUTCOME MEASURES: Routine haematology and biochemistry, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol (on a subset of 522 subjects), and glucose and insulin levels during a 3 h oral glucose tolerance test (OGTT). RESULTS: Independent associations with previous cigarette smoking included high uric acid and low HDL cholesterol, and with current cigarette smoking, high haemoglobin and white cell count and low OGTT insulin. Increasing alcohol intake was associated with increasing blood pressure, uric acid, HDL cholesterol and fasting glucose. The moderate range of exercise intensity in this cohort was associated with decreasing systolic blood pressure, fasting insulin and OGTT glucose and insulin. Factor analysis distinguished principal factors comprising features of the metabolic syndrome with low physical activity, and high white cell count, high haemoglobin concentration and low HDL cholesterol with increasing previous and current cigarette smoking and alcohol intake. CONCLUSIONS: Some characteristics of the metabolic syndrome were seen with previous but not current smoking habit. Regular alcohol consumption was associated with mainly unfavourable metabolic characteristics, although there was an independent beneficial association with HDL cholesterol. The improved metabolic syndrome profile seen with increasing exercise is consistent with even moderate degrees of physical activity having beneficial effects on metabolism.

Adult↗
PubMed1998

Factors of the metabolic syndrome: baseline interrelationships in the first follow-up cohort of the HDDRISC Study (HDDRISC-1). Heart Disease and Diabetes Risk Indicators in a Screened Cohort.

Syndromes of risk factor disturbance may contribute to the development of coronary heart disease and non-insulin-dependent diabetes mellitus, but their definition and quantification remain problematic. Using factor analysis, constellations of risk factor variables that could indicate distinct syndromes of metabolic disturbance were explored in the baseline data of the first follow-up cohort of 742 men from the Heart Disease and Diabetes Risk Indicators in a Screened Cohort (HDDRISC) study. The primary analysis considered 16 intercorrelated variables measured in more than 90% of cohort participants. A missing-values estimation routine was used to ensure inclusion of all participants in the analysis. Subanalyses were undertaken, including a repeat of the primary analysis on the 522 individuals who had received measurement of HDL cholesterol, an oblique rather than orthogonal factor rotation procedure performed on primary and HDL subset analyses, a repeat of these two primary and HDL subset analyses using only those participants with complete measurements, and a repeat of these six analyses including only the seven variables conventionally associated with the metabolic syndrome. The principal factor that emerged in all analyses undertaken comprised oral glucose tolerance test insulin and glucose response, serum uric acid, and body mass index. Fasting serum triglyceride concentration was included in this factor in 11 of the 12 analyses undertaken, fasting plasma insulin in 8, fasting plasma glucose in 5, and mean arterial pressure in 3. HDL cholesterol factored in isolation from insulin in all analyses undertaken. These findings provide strong support for a core metabolic cluster, which is unlikely to include blood pressure and does not include HDL. The factor scores relating to this cluster will provide a means of assessing its quantitative importance in prospective analysis of the development of CHD and diabetes in this cohort.

Adult↗
PubMed1998

Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk.

In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insulin, and insulin sensitivity. We therefore considered that alterations in plasma leptin concentrations could constitute an additional component of a metabolic syndrome of cardiovascular risk. To explore this hypothesis, we employed factor analysis, a multivariate statistical technique that allows reduction of large numbers of highly intercorrelated variables to composite, biologically meaningful factors. Seventy-four men [age, 48.4+/-1.3 years (mean+/-SEM); body mass index (BMI), 25.6+/-0.3 kg/m2] who were free of coronary heart disease and diabetes underwent anthropometric measurements (subscapular-to-triceps [S:T] and subscapular-to-biceps [S:B] skinfold thickness ratios, measurement of fasting plasma leptin, and an intravenous glucose tolerance test (IVGTT) for assessment of insulin sensitivity. Plasma leptin concentrations were correlated with BMI (r=0.57, P<0.001), S:T (r=0.34, P=0.003), S:B (r=0.37, P<0.001), systolic and diastolic blood pressures (both r=0.24, P=0.044), fasting triglycerides (r=0.31, P=0.007), serum uric acid (r=0.35, P=0.003), fasting glucose (r=0.32, P=0.003) and insulin (r=0.33, P=0.004), and IVGTT insulin (r=0.63, P<0.001). A negative correlation was observed between leptin and insulin sensitivity (r=-0.32, P=0.006). No significant correlations emerged between plasma leptin concentrations and age, high density lipoprotein cholesterol, or IVGTT glucose. In multivariate regression analyses, BMI (standardized coefficient [SC]=0.40, P=0.001), fasting insulin (SC=0.23, P=0.036), and IVGTT insulin (SC=0.51, P<0.001) emerged as independent predictors of plasma leptin concentrations (R2=0.56, P<0.001). After adjustment for BMI, only IVGTT insulin emerged as a significant predictor of plasma leptin concentrations (SC=0.56, P<0.001, R2=0.45, P<0.001). Factor analysis of plasma leptin concentrations and the variables that are considered relevant to the insulin resistance syndrome revealed a clustering of plasma leptin concentrations with a factor dominated by insulin resistance and high IVGTT insulin, separate from a high IVGTT glucose/central obesity factor and a high triglyceride/low high density lipoprotein cholesterol factor. Together, these factors accounted for 55.9% of the total variance in the dataset. In conclusion, interindividual variations in plasma leptin concentrations are strongly related to the principal components of the insulin resistance syndrome. Further studies are needed to determine whether the insulin-leptin axis plays a coordinating role in this syndrome and whether plasma leptin concentrations could provide an additional measure of cardiovascular risk.

Blood Pressure↗
PubMed1998

The use of microsatellites to study gene flow in natural populations of Anopheles malaria vectors in Africa: potential and pitfalls.

The potential of microsatellites as population genetic markers in the malarial vectors Anopheles gambiae and Anopheles arabiensis was assessed using 4 loci. Substantial genetic divergence was found not only between these species but also between the Mopti and Forest chromosomal forms of An. gambiae, demonstrating that microsatellites do have the power to detect barriers to gene flow in these mosquitoes. However, application and interpretation of microsatellites was not necessarily straightforward. Despite the use of semiautomated fluorescent technology that enabled fragment sizes to be determined precisely, some difficulty was encountered in allele classification. Sequence analysis revealed insertions/deletions and base changes in the flanking regions of the microsatellite as the probable cause of this problem. The implications of this and other potential pitfalls in the use of microsatellites to study vector populations are discussed.

Africa, Western↗
PubMed1997

Evaluation of the European Spine Phantom in a multi-centre clinical trial.

The European Spine Phantom (ESP) has recently been developed as a universal standard for instruments measuring bone density. The ESP is composed of three semi-anthropomorphic hydroxyapatite vertebrae of varying densities surrounded by soft tissue equivalent plastic designed to resemble human bone and soft tissue when scanned on bone densitometers. In multi-centre studies it is particularly important to verify that each participating bone densitometer is performing in a stable and linear fashion. The aim of this study was to evaluate the ESP within the context of a multi-centre clinical trial. Eighteen centres in the UK and Canada with dual-energy X-ray absorptiometry (DXA) instruments (Lunar DPX, DPX-alpha and DPX-L) participated in the study. The ESP was scanned 10 times on each instrument without repositioning using standardized protocols. The precision of the bone mineral density (BMD) measurements (LI-3) expressed as a coefficient of variation ranged from 0.4% to 1.1% (mean 0.7%). The mean BMD of each instrument was expressed as a percentage difference from the overall mean and ranged from -1.33% to 1.33%. Linear regression analysis showed that all instruments behaved in a linear fashion across the range of densities with correlation coefficients all > or = 0.999 and standard errors of the estimate < 1.5% of the mean BMD ESP value. The data from this study demonstrate that the ESP is a useful phantom for assessing the linearity, stability and differences between DXA instruments from one manufacturer.

Absorptiometry, Photon↗
PubMed1997

Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure.

OBJECTIVES: We attempted to assess insulin sensitivity in patients with chronic heart failure (CHF) and its relation to disease severity. BACKGROUND: Peripheral muscular changes influence the progression of heart failure. This effect may be due to chronic disturbances of insulin and glucose metabolism that affect the energy status of skeletal and myocardial muscle. METHODS: We investigated insulin sensitivity in 79 men-38 patients with CHF, 21 patients with angiographic evidence of coronary artery disease without CHF and 20 healthy control subjects-and assessed its relation to disease severity, etiology and hormonal status (all subjects had a similar age and body mass index). Insulin sensitivity was estimated by minimal modeling analysis of the glucose and insulin and profiles during a 0.5 g/kg body weight intravenous glucose tolerance test. RESULTS: Compared with control subjects, patients with CHF had similar mean fasting glucose but increased insulin levels (67 vs. 29 pmol/liter, p < 0.002) and a 58% reduced mean insulin sensitivity (2.01 vs. 4.84 min-1/pmol/ml x 10(5), p < 0.0001). Peak oxygen consumption (VO2) (r = 0.63), fasting triglycerides (r = -0.62) and age (r = -0.46, all p < 0.001) predicted insulin sensitivity independently. Rest norepinephrine and epinephrine levels, left ventricular ejection fraction and heart failure etiology were not related to insulin sensitivity. Patients with coronary artery disease but no CHF had an intermediate mean insulin sensitivity (3.30 min-1/pmol/ml x 10(5) [-32%, p = 0.042 vs. control subjects; +113%, p = 0.0023 vs. patients with CHF due to ischemic heart disease]). In multivariate analyses of all 79 subjects, age (p = 0.0006), triglycerides (p = 0.0023), fasting insulin (p = 0.0037) and the presence of CHF (p = 0.018) were independent predictors of impaired insulin sensitivity (adjusted joint R2 = 0.53, p < 0.0001). CONCLUSIONS: CHF is associated with marked insulin resistance, characterized by both fasting and stimulated hyperinsulinemia. Advanced heart failure (in terms of reduced peak VO2) is related to increased insulin resistance, but this is not directly mediated through ventricular dysfunction or increased catecholamine levels.

Blood Glucose↗
PubMed1997

Spontaneous recovery of chemotherapy-induced primary ovarian failure: implications for management.

A 14-year-old female patient presented with a swelling, which was excised, over the left forearm. Histology revealed a poorly differentiated rhabdomyosarcoma and she was treated with multiple chemotherapy for 2 years, including cyclophosphamide, cisplatin and vincristine. She developed secondary amenorrhoea shortly after commencing treatment which persisted on its completion. Biochemical investigations were consistent with ovarian failure, which was assumed to be chemotherapy-induced and permanent. She was given hormone replacement with a conjugated equine oestrogen/norgestrel combination, resulting in regular withdrawal bleeding. At 22 years of age; she presented with amenorrhoea for 3 months. Investigations revealed FSH 2.7 IU/l, LH > 50 IU/l and oestradiol > 1320 pmol/l. A pregnancy test was positive and subsequent ultrasound scanning confirmed the presence of a foetus of 18 weeks gestation. The patient initially considered a termination as she had been unprepared for this event but later elected to continue the pregnancy which proceeded uneventfully and resulted in the birth of a normal infant. Ovarian function should be reassessed periodically in patients with chemotherapy-induced gonadal damage and/or the oral contraceptive pill should be used as hormone replacement unless fertility is desired.

Adolescent↗
PubMed1997

Selection of antigens for use in a virus-vectored immunocontraceptive vaccine: PH-20 as a case study.

The European wild rabbit (Oryctolagus cuniculus) has become the major agricultural and environmental pest species in Australia. Current methods of rabbit control are lethal procedures which are increasingly questioned for their overall efficiency, applicability, specificity, cost and humaneness. New initiatives are required. One such initiative is virus-vectored immunocontraception. In this approach, the lagomorph-specific myxoma virus will be genetically engineered to include genes encoding components of rabbit gametes which can induce an immune response that causes infertility. Central to such a strategy is the ability to identify antigens capable of inducing an immunocontraceptive response. A strategy for identifying such antigens has been described previously. A case study of one sperm antigen, PH-20, is reported here. The issues involved in developing this antigen to the stage where it could be considered as a candidate for insertion into a recombinant myxoma virus with the ultimate goal of testing for immunocontraceptive efficacy are discussed. Techniques for inserting genes into myxoma virus have been described previously. The knowledge gained from research with this particular antigen are broadly applicable to other antigens used for both immunocontraceptive vaccines in general and, specifically, for virus-vectored immunocontraception.

Animals↗
PubMed1996

Crystal structures of MS2 capsids with mutations in the subunit FG loop.

The loop between the F and G beta strands (FG loop) of the bacteriophage MS2 coat protein subunit forms inter-subunit contacts around the 5-fold and 3-fold (quasi 6-fold) axes of the T=3 protein shell. In capsids, the loop is found in two very different conformations, one in B subunits, which form the 5-fold contact, and one in A and C subunits, which form the quasi 6-fold contact. One proline residue, Pro78, is strictly conserved in the coat protein of all related bacteriophages, and in the case of MS2 this proline residue is preceded by a cis peptide bond in the B subunit. In order to probe the role of the FG loop in capsid assembly, we have determined the crystal structures of two MS2 capsids, formed by coat proteins with mutations at two positions in the FG loop, P78N or E76D. These mutants show conformational changes in the FG loops that explain the reduced temperature stability of the capsids. The P78N mutant has a normal trans peptide bond at position 78.

Capsid↗
PubMed1996

Recurrent hypoglycaemia associated with first and second trimester insulin sensitivity in a patient with insulin-dependent diabetes.

A 35-year-old insulin-dependent diabetic woman presented at 8 weeks gestation with multiple severe hypoglycaemic episodes occurring during the day and night without warning. Her pre-pregnancy insulin dosage of 45 units daily was progressively reduced by 73% to 12 units daily by week 17 because of multiple hypoglycaemic episodes. Investigation showed no pathological cause for the hypoglycaemia. Insulin dosage increased to 16 units daily by week 19 and then increased sharply to 60 units daily at 23 weeks and finally to 72 units at week 37. Following delivery her insulin dosage returned to pre-pregnancy values. Insulin-dependent diabetic women may rarely develop exaggerated insulin sensitivity in the first trimester of pregnancy resulting in severe hypoglycaemia, but spontaneous improvement occurs with increasing insulin resistance in the second and third trimesters.

Adult↗