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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 19 recordsLinked to original sources

Contact area inside the distal radioulnar joint: effect of axial loading and position of the forearm.

BACKGROUND: A biomechanical study was performed to define the normal profiles of contact area inside the distal radioulnar joint and how these profiles change as a result of damage to the distal radioulnar ligaments. METHODS: Twelve cadaver arms were used and a custom-made jig was designed to allow axial loading of the hand. Tekscan sensor film was used to measure the contact area inside the joint. Measurements were taken with different loads and in different positions of the forearm. The same measurements were taken after dividing either the volar or dorsal distal radioulnar ligament. Finally the measurements were repeated after reconstruction of the divided ligament. FINDINGS: The contact area increases with axial loading of the hand and is greater in supination than pronation. Division of a single distal radioulnar ligament increases the contact area inside the distal radioulnar joint (123% of normal) and reconstruction of the divided distal radioulnar ligament restores the contact patterns towards the normal values (113% of normal). INTERPRETATION: The results show that axial loading of the hand and position of the forearm has a significant effect on the contact area inside the distal radioulnar joint. The study also shows that injury of the distal radioulnar ligament disturbs the normal profiles of contact.

Aged↗

Prevention of type 2 diabetes: a review.

One of the major public health challenges of the 21st century is type 2 diabetes. WHO estimates that by 2025 as many as 200-300 million people worldwide will have developed the disease. A distressing increase in children is perhaps the most alarming sign of something going wrong. Roughly half of the risk of type 2 diabetes can be attributed to environmental exposure and the other half to genetics. Central themes for prevention are the risk factors overweight, sedentary lifestyle, certain dietary components and perinatal factors. Overweight is the most critical risk factor, and should be targeted for prevention of type 2 diabetes especially among children and youths. Ethnicity and perinatal factors are also worth considering. Today we know that prevention helps. In the US Diabetes Prevention Programme for high risk individuals, there was a 58% relative reduction in the progression to diabetes in the lifestyle group compared with the controls. Within the lifestyle group, 50% achieved the goal of more than 7% weight reduction, and 74% maintained at least 150 min of moderately intense activity each week. This review discusses different forms of prevention, and proposes first of all to target people with Impaired Glucose Tolerance with increasing activity and altering dietary factors. And secondly, population-based measures to encourage increased physical activity and decreased consumption of energy-dense foods are important, and may target school children and young people, certain ethnic groups and women with gestational diabetes.

Adult↗

Anti-inflammatory and skin-hydrating properties of a dietary supplement and topical formulations containing oligomeric proanthocyanidins.

BACKGROUND: Anti-inflammatory and skin hydration properties of a dietary supplement and 2 topical formulations (Anthogenol) with oligomeric proanthocyanidins were investigated. METHODS: Forty-two subjects were randomized into 2 groups: one taking the dietary supplement (100 mg/day) and the other without supplement. After 4 weeks, erythema was induced using UV radiation followed by treatment with topical cream or lotion. Erythema was measured for up to 72 h after irradiation. Skin hydration after 1 and 2 weeks of application of the cream and lotion was also measured in separate test fields. RESULTS: Both topical formulations led to a significant suppression of erythema formation and the dietary supplement led to an additional slightly stronger suppression. Thus 72 h after UV exposure and compared to the control fields of patients that had not taken a dietary supplement, erythema was slightly (13.2%) lower in the subjects that had taken a dietary supplement. The cream resulted in a maximal reduction of erythema of 45.9% (p = 0.0015), while the lotion resulted in a maximal reduction of 53.1% (p = 0.0002). Both topical formulations also increased skin hydration (by nearly 20%; p < 0.002 for all combinations of dietary supplementation and topical treatment) and the hydration was higher in the group taking the dietary supplement. CONCLUSION: The regular use of Anthogenol products may help to protect from free-radical-mediated skin inflammation and to increase skin hydration.

Administration, Topical↗

The role of MYH and microsatellite instability in the development of sporadic colorectal cancer.

Biallelic germline mutations in MYH are associated with colorectal neoplasms, which develop through a pathway involving somatic inactivation of APC. In this study, we investigated the incidence of the common MYH mutations in an Australian cohort of sporadic colorectal cancers, the clinicopathological features of MYH cancers, and determined whether inactivation of mismatch repair and base excision repair (BER) were mutually exclusive. The MYH gene was sequenced from lymphocyte DNA of 872 colorectal cancer patients and 478 controls. Two compound heterozygotes were identified in the cancer population and all three cancers from these individuals displayed a prominent infiltration of intraepithelial lymphocytes. In total, 11 heterozygotes were found in the cancer group and five in the control group. One tumour from an individual with biallelic germline mutation of MYH also demonstrated microsatellite instability (MSI) as a result of biallelic hypermethylation of the MLH1 promoter. Although MYH-associated cancers are rare in a sporadic colorectal population, this study shows that these tumours can develop through either a chromosomal or MSI pathway. Tumours arising in the setting of BER or mismatch repair deficiency may share a biological characteristic, which promotes lymphocytic infiltration.

Adaptor Proteins, Signal Transducing↗

Evaluation of models to predict BRCA germline mutations.

The selection of candidates for BRCA germline mutation testing is an important clinical issue yet it remains a significant challenge. A number of risk prediction models have been developed to assist in pretest counselling. We have evaluated the performance and the inter-rater reliability of four of these models (BRCAPRO, Manchester, Penn and the Myriad-Frank). The four risk assessment models were applied to 380 pedigrees of families who had undergone BRCA1/2 mutation analysis. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operator characteristic (ROC) curve were calculated for each model. Using a greater than 10% probability threshold, the likelihood that a BRCA test result was positive in a mutation carrier compared to the likelihood that the same result would be expected in an individual without a BRCA mutation was 2.10 (95% confidence interval (CI) 1.66-2.67) for Penn, 1.74 (95% CI 1.48-2.04) for Myriad, 1.35 (95% CI 1.19-1.53) for Manchester and 1.68 (95% CI 1.39-2.03) for BRCAPRO. Application of these models, therefore, did not rule in BRCA mutation carrier status. Similar trends were observed for separate BRCA1/2 performance measures except BRCA2 assessment in the Penn model where the positive likelihood ratio was 5.93. The area under the ROC curve for each model was close to 0.75. In conclusion, the four models had very little impact on the pre-test probability of disease; there were significant clinical barriers to using some models and risk estimates varied between experts. Use of models for predicting BRCA mutation status is not currently justified for populations such as that evaluated in the current study.

Area Under Curve↗

Ethnicity recording in general practice computer systems.

BACKGROUND: Ethnicity data in general practice (GP) computerized medical records can be utilized to audit equity in health care. METHODS: We evaluated a patient profiling project targeted to improve ethnicity recording. RESULTS: Data extracted from 16 practices showed an increase in ethnicity recording from <1% before the intervention to 48% after. Recorded codes could be mapped onto the basic national statistics six-category ethnicity classification headings, and their proportions were similar to the 2001 census values. CONCLUSION: Recording of data using multiple coding hierarchies has reduced the utility of data as clinically important ethnic subgroups cannot be identified. Practitioners should be encouraged to use the single recommended ethnicity coding hierarchy.

Adult↗

Effects of age and resistance exercise on skeletal muscle interstitial prostaglandin F(2alpha).

Prostaglandin (PG) F2alpha has been shown to contribute to the anabolic events in skeletal muscle. We measured the skeletal muscle interstitial concentration of PGF2alpha at rest and following a standard bout of resistance exercise in eight young (27+/-2 year) and eight old (75+/-4 year) men. Interstitial PGF2alpha concentration was determined from microdialysate samples obtained from two microdialysis probes placed in the vastus lateralis. Microdialysates were collected 1h pre- and 5-6, 8-9, and 24-25 h postexercise. The exercise bout consisted of 4 exercises (3 sets of 8 replications at 80% 1 RM per exercise) emphasizing the quadriceps. Interstitial PGF2alpha levels were not different (P>0.05) between young and old at rest (1.50+/-0.35 vs. 1.52+/-0.30 ng ml-1) or at any time point following the resistance exercise bout. For the young and old combined there was a change (P<0.05) in PGF2alpha levels at 5-6 h (93%) and 8-9 h (95%), which had returned to preexercise levels by 24-25 h. These results show that PGF2alpha is increased in skeletal muscle following a standard bout of resistance exercise and aging does not alter interstitial levels of this PG at rest or after exercise. These data, coupled with previous findings, suggest that the anabolic factor PGF2alpha should be considered when discussing the complex processes that regulate muscle mass in young and old individuals.

Adult↗

The load-bearing characteristics of the forearm: pattern of axial and bending force transmitted through ulna and radius.

A biomechanical study was performed on 12 cadaveric arms to define the normal profiles of force transmission through the ulna and radius and demonstrate the effect on these of simulated injury of the distal radioulnar joint (DRUJ). Strain gauges were used to measure the axial and bending forces transmitted through each bone. Axial force transmitted through the ulna is, broadly, reciprocal to that seen in the radius, with the greatest force seen in supination. In all 12 arms, axial loading of the hand created an anterior bending force (to create a posterior convexity) in the distal radius. Axial loading of the hand created an anterior bending force in the distal ulna for half the specimens and a posterior bending force in the remaining half. Division and division with reconstruction of either the volar or the dorsal distal radioulnar ligament (DRUL) had no significant effect on force transmission through the ulna and radius, while excision of the ulnar head significantly disrupted the profiles of the axial and bending forces.

Aged↗

A multi-analytical platform approach to the metabonomic analysis of plasma from normal and Zucker (fa/fa) obese rats.

Plasma obtained from 20 week old normal Wistar-derived and Zucker (fa/fa) rats was analysed using a number of different analytical methodologies to obtain global metabolite profiles as part of metabonomic investigations of animal models of diabetes. Samples were analysed without sample pre-treatment using 1H NMR spectroscopy, after acetonitrile solvent protein precipitation by ultra-performance liquid chromatography-MS (UPLC-MS) and after acetonitrile protein precipitation and derivatisation for capillary gas chromatography-MS (GC-MS). Subsequent data analysis using principal components analysis revealed that all three analytical platforms readily detected differences between the plasma metabolite profiles of the two strains of rat. There was only limited overlap between the metabolites detected by the different methodologies and the combination of all three methods of metabolite profiling therefore provided a much more comprehensive profile than would have been provided by their use individually.

Animals↗

Remote ischaemic preconditioning of the hind limb reduces experimental liver warm ischaemia-reperfusion injury.

BACKGROUND: Direct ischaemic preconditioning of the liver reduces ischaemia-reperfusion injury (IRI). Remote ischaemic preconditioning (RIPC) of a limb has been shown to reduce IRI to the heart. This study determined the effect of brief remote ischaemia to the limb in reducing early liver warm IRI. METHODS: Twenty-eight male rabbits were allocated to four groups: sham operated, RIPC alone, IRI alone, and RIPC plus IRI. RIPC was induced in the leg with a tourniquet, before liver IRI, by three alternate cycles of 10 min ischaemia followed by 10 min reperfusion. Liver IRI was produced by total inflow occlusion for 25 min. Markers of liver injury and systemic and hepatic haemodynamics were measured for 2 h after reperfusion. RESULTS: At 2 h, IRI alone was associated with increased serum levels of aminotransferases, and reduced mean arterial blood pressure, hepatic blood flow and peripheral oxygen saturation. There was significant improvement in these variables in animals that had RIPC before liver IRI, and hepatic venous nitrate/nitrite levels were also significantly higher. CONCLUSION: In this experimental model RIPC appeared to reduce liver IRI.

Animals↗

Toll-like receptor expression in chronic hepatitis C: correlation with pro-inflammatory cytokine levels and liver injury.

BACKGROUND/AIMS: Toll-like receptors (TLR's) are critical receptors that promote innate immune responses to pathogen-associated molecular patterns. Activation of TLR's leads to production of pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha. This study investigates whether peripheral blood monocyte expression of TLR's is disturbed in patients with chronic hepatitis C and whether levels of expression of these molecules are significantly correlated with hepatitis C virus (HCV) genotype, viral load, hepatic necroinflammatory activity, histological stage and circulating TNF-alpha concentrations. METHODS: In 18 non-cirrhotic patients with biopsy-proven, virologically-confirmed chronic hepatitis C and 32 controls, we measured expression of TLR2 and TLR4 on peripheral blood monocytes. HCV genotype, viral load, serum alanine aminotransferase (ALT) levels, histological stage of disease and circulating TNF-alpha and endotoxin levels were also determined. RESULTS: Peripheral blood monocyte expression of TLR2 and TLR4 were significantly increased in patients with chronic hepatitis C compared to controls, irrespective of HCV genotype or histological stage of disease. Circulating levels of TNF-alpha were also significantly increased in patients with chronic hepatitis C. In both the overall study cohort and patients with chronic hepatitis C, monocyte expression of TLR2, but not of TLR4, correlated significantly with serum TNF-alpha levels. In patients with chronic hepatitis C, monocyte expression of TLR2, but not of TLR4, also correlated significantly with serum ALT levels. Expression of TLR's was not significantly correlated with viral load. CONCLUSIONS: Up-regulation of peripheral blood monocyte expression of TLR2 and TLR4 occurs in patients with chronic hepatitis C. Increased monocyte expression of TLR2, but not of TLR4, correlates significantly with both increased circulating TNF-alpha levels and hepatic necroinflammatory activity in this disorder.

Adolescent↗

Structured patient education: the diabetes X-PERT Programme makes a difference.

AIMS: To develop a patient-centred, group-based self-management programme (X-PERT), based on theories of empowerment and discovery learning, and to assess the effectiveness of the programme on clinical, lifestyle and psychosocial outcomes. METHODS: Adults with Type 2 diabetes (n = 314), living in Burnley, Pendle or Rossendale, Lancashire, UK were randomized to either individual appointments (control group) (n = 157) or the X-PERT Programme (n = 157). X-PERT patients were invited to attend six 2-h group sessions of self-management education. Outcomes were assessed at baseline, 4 and 14 months. RESULTS: One hundred and forty-nine participants (95%) attended the X-PERT Programme, with 128 (82%) attending four or more sessions. By 14 months the X-PERT group compared with the control group showed significant improvements in the mean HbA1c (- 0.6% vs. + 0.1%, repeated measures anova, P < 0.001). The number needed to treat (NNT) for preventing diabetes medication increase was 4 [95% confidence interval (CI) 3, 7] and NNT for reducing diabetes medication was 7 (95% CI 5, 11). Statistically significant improvements were also shown in the X-PERT patients compared with the control patients for body weight, body mass index (BMI), waist circumference, total cholesterol, self-empowerment, diabetes knowledge, physical activity levels, foot care, fruit and vegetable intake, enjoyment of food and treatment satisfaction. CONCLUSIONS: Participation in the X-PERT Programme by adults with Type 2 diabetes was shown at 14 months to have led to improved glycaemic control, reduced total cholesterol level, body weight, BMI and waist circumference, reduced requirement for diabetes medication, increased consumption of fruit and vegetables, enjoyment of food, knowledge of diabetes, self-empowerment, self-management skills and treatment satisfaction.

Aged↗

The Canadian National Outcomes Measurement Study in Schizophrenia: overview of the patient sample and methodology.

OBJECTIVE: The Canadian National Outcomes Measurement Study in Schizophrenia (CNOMSS) is a prospective survey of routine clinical practice. METHOD: Patients with schizophrenia or a related disorder were consecutively enrolled from all regions of Canada. Both academic and community psychiatric clinics were included and patients were followed up for 2 years. Clinical and functional status, quality of life, medication and economic costs were assessed at enrollment and monitored throughout the follow-up period. RESULTS: Patients attending an academic clinic tended to be younger and more severely ill than those from community clinics. Both types of sites prescribed atypical neuroleptics to more than three-quarters of the patients. The majority of those enrolled were unemployed and living in poverty. Poor clinical status was associated with poverty. CONCLUSION: The CNOMSS provides demographic, clinical and treatment-related information about a large Canada-wide sample of psychiatric patients. The following three articles in this issue of Acta Psychiatrica Scandinavica explore issues related to medication, quality of life and resource utilization.

Academic Medical Centers↗

Medication decisions and clinical outcomes in the Canadian National Outcomes Measurement Study in Schizophrenia.

OBJECTIVE: To evaluate over a 2-year period, patients from academic/non-academic centres, from each region of Canada, to determine whether location or other variables such as medication type, gender or income was associated with outcome as defined by non-hospitalization and persistence on original treatment. METHOD: A total of 448 patients were recruited from academic and non-academic centres across all provinces of Canada and followed up for 2 years. RESULTS: Patients from British Columbia had significantly lower rates of hospitalization than patients from other provinces. Male patients showed greater symptomatic improvement at 2 years from initial assessment compared to females. Patients on clozapine, risperidone and olanzapine were least likely to be hospitalized. CONCLUSION: There were some regional differences noted in both utilization of types of antipsychotic medications and hospitalization rates. In this sample of stable out-patients over 70% who started on monotherapy with clozapine, risperidone, olanzapine and quetiapine remained on the same medication over the 2-year study period.

Academic Medical Centers↗

Outcome on quality of life in a Canadian national sample of patients with schizophrenia and related psychotic disorders.

OBJECTIVE: To examine changes in subjective and objective dimensions of quality of life (QoL) in a large Canadian sample of patients with diagnosis of schizophrenia or schizoaffective disorder treated in academic and non-academic settings over a 2-year period. METHOD: Patients recruited in the study across the country were assessed for QoL and functioning using the Client and Provider versions of the Wisconsin Quality of Life Questionnaire (WQoL) and the Short Form-36 (SF-36) at baseline (n = 448), 1 year (n = 308-353) and 2 years (188-297). Data were analyzed to examine change across time using multivariate analyses controlling for potential influence of variables such as age, regional variation, gender, duration of illness, type of treatment taken and baseline measures of symptoms and QoL. RESULTS: The weighted quality of life index (W-QoL-I) showed a significant change on both the client and the provider versions of the WQoL while the physical and mental composites of the SF-36 showed change only at 2 years. These changes were influenced significantly by baseline scores on W-QoL-I and in the case of provider version of the WQoL by baseline Brief Psychiatric Rating Scale (BPRS) scores. Regional variation or type of medication had no impact on improvement in QoL. CONCLUSION: Within a naturalistic sample of schizophrenia patients treated and followed in routine care the overall QoL showed an improvement over time but this improvement was not influenced by the type of medication prescribed.

Academic Medical Centers↗

Resource utilization in a Canadian national study of people with schizophrenia and related psychotic disorders.

OBJECTIVE: To determine how the use of the newer, so called atypical antipsychotic medications, effects the pharmacoeconomic treatment burden of schizophrenia and related conditions and to provide a clear comparison of the costs and risks associated with these atypical drugs. METHOD: In this 2-year, open-label, prospective study, resource utilization (RU) data were collected on 160 patients with these conditions. A comparison between risks and costs was performed by combining the generalized CNOMSS data on both economic factors and risk assessments. RESULTS: The main findings of the study were that the total adjusted 1- and 2-year costs were lowest for quetiapine. Drug acquisition costs were lowest for risperidone for both the 1- and 2-year cohorts. Clozapine use was predictably associated with the highest overall and medication costs at both 1 and 2 years. CONCLUSION: Treatment with risperidone or quetiapine was associated with the lowest overall costs when compared with olanzapine or clozapine.

Adult↗