Development of the Motor Neuron Disease Carer Questionnaire.

Our objective was to develop a validated questionnaire that can measure the extent to which dimensions of caring affect the health of carers of patients with motor neuron disease. An initial 190-item questionnaire was developed from in-depth interviews, focus groups and two pilot studies with carers. Factor analysis was applied to the data obtained from a large survey in the UK that identified the underlying dimensions of caring.

Effect of short-term free Fatty acids elevation on mitochondrial function in skeletal muscle of healthy individuals.

Context: Mitochondrial dysfunction has been proposed as an underlying mechanism in the pathogenesis of insulin resistance and type 2 diabetes mellitus.

Objective: To determine whether mitochondrial dysfunction plays a role in the free fatty acid (FFA)-induced impairment in insulin action in skeletal muscle of healthy subjects.

Design: Eleven lean normal glucose tolerant individuals received 8 h lipid and saline infusion on separate days with a euglycemic insulin clamp during the last 2 h.

Intracellular accumulation of efavirenz and nevirapine is independent of P-glycoprotein activity in cultured CD4 T cells and primary human lymphocytes.

Background: Interaction of antiretrovirals with drug transporters such as P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), breast cancer resistance protein (BCRP) and solute carrier organic anion transporter (SLCO) may influence the emergence of viral mutants by altering intracellular drug concentrations. Here we characterize the effect of transporter expression in a variety of cell types such as control CEM, CEM(VBL) (P-gp-overexpressing), CEM(E1000) (MRP1-overexpressing), MT4, control MDCKII, MDCKII(MDR1) (P-gp-overexpressing) and peripheral blood mononuclear cells (PBMCs) on the uptake of [(14)C]efavirenz and [(3)H]nevirapine. We also investigated the lipophilicity of [(14)C]efavirenz and [(3)H]nevirapine.

Characterization of p-phenylenediamine-albumin binding sites and T-cell responses to hapten-modified protein.

Exposure to p-phenylenediamine (PPD) is associated with the development of T-cell-mediated allergic contact dermatitis. The purpose of this study was to define the nature of the interaction of PPD with the protein and the antigenic determinant that stimulates T cells. Mass spectrometry was employed to show that PPD oxidation products bind irreversibly to cysteine (Cys, position 34) in human serum albumin (HSA).

Effects of dietary intervention and quadriceps strengthening exercises on pain and function in overweight people with knee pain: randomised controlled trial.

Objective: To determine whether dietary intervention or knee strengthening exercise, or both, can reduce knee pain and improve knee function in overweight and obese adults in the community.

Design: Pragmatic factorial randomised controlled trial.

Setting: Five general practices in Nottingham.

Lifestyle interventions for knee pain in overweight and obese adults aged > or = 45: economic evaluation of randomised controlled trial.

Objective: To estimate the cost effectiveness of four different lifestyle interventions for knee pain.

Design: Cost utility analysis of randomised controlled trial.

Setting: Five general practices in the United Kingdom.

Effects of ewe size and nutrition on fetal mammary gland development and lactational performance of offspring at their first lactation.

Many environmental factors applied postnatally are known to affect milk production of the dam, but to date, the effects of different fetal environments on subsequent first lactational performance of the offspring have not been reported. Four hundred fifty heavy (H; 60.8 kg +/- 0.

Measurement of CD4+ and CD8+ T-lymphocyte cytokine secretion and gene expression changes in p-phenylenediamine allergic patients and tolerant individuals.

Factors predisposing to individual susceptibility to contact allergic dermatitis are ill defined. This study was designed to characterize the response of allergic and tolerant individuals' T-lymphocytes after exposure to p-phenylenediamine (PPD). Peripheral blood mononuclear cells (PBMCs) from allergic patients proliferated when treated with PPD and Bandrowski's base (BB) and secreted IL-1alpha, -1beta, -4, -5, -6, -8, -10, and -13; IFN-gamma; tumor necrosis factor-alpha; MIP-1alpha/beta; MCP-1 (monocyte chemotactic protein-1); and RANTES.

Impaired regulation of the TNF-alpha converting enzyme/tissue inhibitor of metalloproteinase 3 proteolytic system in skeletal muscle of obese type 2 diabetic patients: a new mechanism of insulin resistance in humans.

Aims/hypothesis: TNF-alpha levels are increased in obesity and type 2 diabetes. The regulation of TNF-alpha converting enzyme (TACE) and its inhibitor, tissue inhibitor of metalloproteinase 3 (TIMP3), in human type 2 diabetes is unknown.

Methods: We examined TACE/TIMP3 regulation: (1) in lean and obese normal glucose tolerant (NGT) individuals and in type 2 diabetes patients; (2) following 6 h of lipid/saline infusion in NGT individuals; and (3) in cultured human myotubes from lean NGT individuals incubated with palmitate.

Comparing the performance of the EQ-5D and SF-6D when measuring the benefits of alleviating knee pain.

Objective: To assess the practicality, validity and responsiveness of using each of two utility measures (the EQ-5D and SF-6D) to measure the benefits of alleviating knee pain.

Methods: Participants in a randomised controlled trial, which was designed to compare four different interventions for people with self-reported knee pain, were asked to complete the EQ-5D, SF-6D, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at both pre- and post-intervention. For both utility measures, we assessed their practicality (completion rate), construct validity (ability to discriminate between baseline WOMAC severity levels), and responsiveness (ability to discriminate between three groups: those whose total WOMAC score, i) did not improve, ii) improved by <20%, and iii) improved by > or = 20%).

Comparing cost-utility estimates: does the choice of EQ-5D or SF-6D matter?

Background: A number of different measures can be used within cost-utility analyses, we compared results according to both the EQ-5D and SF-6D.

Methods: A randomized trial was conducted to compare 4 options for people with knee pain. Over the 2 year trial period, the change in cost to health-service was estimated, and both the EQ-5D and SF-6D were used to estimate the change in quality-adjusted life years (QALYs).

A mechanistic investigation into the irreversible protein binding and antigenicity of p-phenylenediamine.

Exposure to the skin sensitizer p-phenylenediamine (PPD) is associated with allergic contact dermatitis; however, the ability of PPD to modify protein has not been fully investigated. The aims of this study were to characterize the reactions of PPD and the structurally related chemical 2,5-dimethyl-1,4-benzoquinonediamine with model nucleophiles, a synthetic peptide (DS3) containing each of the naturally occurring amino acids and His-tagged glutathione-S-transferase pi (GSTP), and to explore the effect of dimethyl substitution on PPD-specific T-cell responses using lymphocytes from allergic patients. The reductive soft nucleophiles N-acetyl cysteine and glutathione prevented PPD self-conjugation reactions and Bandrowski's base formation, but no adducts were detected.

Outcome measures used in forensic mental health research: a structured review.

Background: The evidence base for forensic mental health (FMH) services has been developing since the late 1990s. Are outcome measures sound enough for the evaluation tasks?

Aims: To identify, from published literature, outcome measures used in FMH research and, where feasible, assess their quality.

Method: A structured review was undertaken of trials and intervention studies published between 1990 and 2006.

Pioglitazone stimulates AMP-activated protein kinase signalling and increases the expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation in human skeletal muscle in vivo: a randomised trial.

Aims/hypothesis: The molecular mechanisms by which thiazolidinediones improve insulin sensitivity in type 2 diabetes are not fully understood. We hypothesised that pioglitazone would activate the adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway and increase the expression of genes involved in adiponectin signalling, NEFA oxidation and mitochondrial function in human skeletal muscle.

Methods: A randomised, double-blind, parallel study was performed in 26 drug-naive type 2 diabetes patients treated with: (1) pioglitazone (n = 14) or (2) aggressive nutritional therapy (n = 12) to reduce HbA(1c) to levels observed in the pioglitazone-treated group.

Investigation of the immunogenicity of p-phenylenediamine and Bandrowski's base in the mouse.

p-Phenylenediamine (PPD) exposure is associated with T-cell mediated contact dermatitis. T-cells from allergic patients proliferate following exposure to PPD and the oxido-conjugation product Bandrowski's base (BB). Both compounds are classified as sensitizers in the local lymph node assay; however, because of their instability the nature of the antigenic determinant remains ill-defined.

MULTI-CENTRE STUDIES OF THE GLOBAL IMPACT OF ENDOMETRIOSIS AND THE PREDICTIVE VALUE OF ASSOCIATED SYMPTOMS.

Introduction: Endometriosis can be difficult to diagnose clinically and models that use symptoms to predict whether the disease is present or not are based on limited patient populations. Endometriosis also influences health-related quality of life, but little is known about its impact across the world. We therefore initiated two integrated multicentre studies to collect prospective, standardised, epidemiological data, to 1) examine the global impact of endometriosis and relative effect of risk-factors, and 2) develop a symptom-based diagnostic tool.

Genome-wide linkage scan for genes influencing plasma triglyceride levels in the Veterans Administration Genetic Epidemiology Study.

Objective: Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes.

Research Design And Methods: We used phenotypic and genotypic data from 1,026 individuals distributed across 294 Mexican-American families, who were ascertained for type 2 diabetes, from the Veterans Administration Genetic Epidemiology Study (VAGES).

Evaluation of the American version of the 30-item Endometriosis Health Profile (EHP-30).

Objectives: Health status instruments, which measure the subjective functioning and well-being of respondents, are increasingly being used in international, multi-centre trials of new treatments. If the results of such trials in different countries are to be pooled, it is vitally important for researchers to know how comparable the instruments are across cultures. In this study, we evaluated the response rate, data quality, score reliability and scaling assumptions of the 30-item Endometriosis Health Profile (EHP-30) in the USA.

Quality of life in amyotrophic lateral sclerosis/motor neuron disease: a structured review.

Amyotrophic lateral sclerosis/motor neuron disease and other related disorders are fatal progressive neurodegenerative conditions that have a substantial impact on quality of life (QoL). This systematic review examines the different methods and instruments used to assess QoL in this condition from which recommendations are made of those that evidence suggests are the most appropriate. Databases were used to survey the available literature to cover as many different approaches and papers as possible.

Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects.

OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle.

Do estimates of cost-utility based on the EQ-5D differ from those based on the mapping of utility scores?

Background: Mapping has been used to convert scores from condition-specific measures into utility scores, and to produce estimates of cost-effectiveness. We sought to compare the QALY gains, and incremental cost per QALY estimates, predicted on the basis of mapping to those based on actual EQ-5D scores.

Methods: In order to compare 4 different interventions 389 individuals were asked to complete both the EQ-5D and the Western Ontartio and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, 6, 12, and 24 months post-intervention.

Global relationship between the proteome and transcriptome of human skeletal muscle.

Skeletal muscle is one of the largest tissues in the human body. Changes in mRNA and protein abundance in this tissue are central to a large number of metabolic and other disorders, including, commonly, insulin resistance. Proteomic and microarray analyses are important approaches for gaining insight into the molecular and biochemical basis for normal and pathophysiological conditions.

Autosomal genome-wide linkage analysis to identify loci for gallbladder wall thickness in Mexican Americans.

The significance of gallbladder wall thickness (GBWT) in regard to gallbladder disease (GBD) is not completely understood. Thickening of the gallbladder wall has been observed in patients with acute calculous and acalculous cholecystitis and chronic cholecystitis. However, various pathologic processes, such as gallbladder cancer and nonbiliary disorders such as liver cirrhosis and viral hepatitis, could also cause thickening of the gallbladder wall.

The relationship between fasting hyperglycemia and insulin secretion in subjects with normal or impaired glucose tolerance.

To assess the relationship between the fasting plasma glucose (FPG) concentration and insulin secretion in normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subjects, 531 nondiabetic subjects with NGT (n = 293) and IGT (n = 238; 310 Japanese and 232 Mexican Americans) received an oral glucose tolerance test (OGTT) with measurement of plasma glucose, insulin, and C-peptide every 30 min. The insulin secretion rate was determined by plasma C-peptide deconvolution. Insulin sensitivity (Matsuda index) was measured from plasma insulin and glucose concentrations.