A general autoimmunity gene (PTPN22) is not associated with inflammatory bowel disease in a British population.

A single-nucleotide polymorphism (C1858T) causing an amino acid substitution (R620W) in the lymphoid protein tyrosine phosphatase gene PTPN22 has been implicated in type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, juvenile idiopathic arthritis and Hashimoto's thyroiditis, thus revealing a general role for this gene in autoimmune disease. We investigated the association of the C1858T variant in an additional autoimmune disease population by performing a case-control study of 514 British individuals with inflammatory bowel disease (IBD) [294 with Crohn's disease (CD) and 220 with ulcerative colitis (UC)] and 374 normal controls. No significant differences in genotype or allele frequencies were observed between IBD, CD or UC and controls, indicating that PTPN22 does not influence risk of IBD.

Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease.

In postmortem Huntington's disease brains, mutant htt is present in both nuclear and cytoplasmic compartments. To dissect the impact of nuclear and extranuclear mutant htt on the initiation and progression of disease, we generated a series of transgenic mouse lines in which nuclear localization or nuclear export signal sequences have been placed N-terminal to the htt exon 1 protein carrying 144 glutamines. Our data indicate that the exon 1 mutant protein is present in the nucleus as part of an oligomeric or aggregation complex.

Low density lipoprotein apolipoprotein B metabolism in treatment-naive HIV patients and patients on antiretroviral therapy.

Background: Dyslipidaemia and lipodystrophy have been described in treated HIV patients and in a small percentage of untreated HIV patients. Lipodystrophy in these patients has been shown to be associated with a lower expression of low density lipoprotein (LDL) receptors.

Methods: We have investigated the effect of antiretroviral treatment with either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) on body fat distribution and LDL apolipoprotein B (apoB) kinetics in 12 HIV-negative controls and 52 HIV-infected patients, including antiretroviral treatment-naive (TN) patients (n=13) and patients taking two nucleoside analogues plus either a PI (n=15) or an NNRTI (n=24).

History of genetic disease: the molecular genetics of Huntington disease - a history.

The Huntington disease gene was mapped to human chromosome 4p in 1983 and 10 years later the pathogenic mutation was identified as a CAG-repeat expansion. Our current understanding of the molecular pathogenesis of Huntington disease could never have been achieved without the recent progress in the field of molecular genetics. We are now equipped with powerful genetic models that continue to uncover new aspects of the pathogenesis of Huntington disease and will be instrumental for the development of therapeutic approaches for this disease.

Broad Outcome Measures May Underestimate Effectiveness: An Instrument Comparison Study.

Background:   Outcome measures are routinely used in child and adolescent mental health services to demonstrate the effectiveness or otherwise of interventions.

Methods:   We followed up a consecutive sample from a large teaching hospital's Obsessive Compulsive Disorder (OCD) service for young people, comparing improvements using instruments of differing broadness.

Results:   The effect size of improvement decreased as the breadth of the questionnaire increased.

Evaluation of the benzothiazole aggregation inhibitors riluzole and PGL-135 as therapeutics for Huntington's disease.

Huntington's disease (HD) is an inherited progressive neurological disorder for which there is no effective therapy. It is caused by a CAG/polyglutamine repeat expansion that leads to abnormal protein aggregation and deposition in the brain. Several compounds have been shown to disrupt the aggregation process in vitro, including a number of benzothiazoles.

Endothelial function and weight loss in obese humans.

Background: Obesity is a major risk factor for the development of endothelial dysfunction. We explored the effect of different degrees of body mass on endothelial function, lipids, systemic inflammation and glucose homeostasis and the effect of surgically-induced weight loss on endothelial function in severely obese humans.

Methods: A cross-sectional study of healthy subjects across a wide range of body fatness was performed to characterize the effect of obesity on flow-mediated dilatation (FMD), systemic inflammation, blood pressure and insulin sensitivity.

Interventions for foot disease in rheumatoid arthritis: a systematic review.

Objective: To systematically review medical and surgical foot intervention studies in rheumatoid arthritis (RA), focusing on clinical efficacy, study quality, and risk of harm.

Methods: We searched appropriate databases using a combination of the terms "rheumatoid arthritis" and "foot" against terms indicating treatment; we also hand-searched references. We selected articles in English (1968-2003) comprising randomized controlled trials (RCTs), controlled clinical trials (CCTs), prospective observational studies, and large retrospective observational surgical studies (> 50 cases).

Muscle metabolites, detected in urine by proton spectroscopy, correlate with disease damage in juvenile idiopathic inflammatory myopathies.

Objective: To assess for novel markers of muscle damage using urinary muscle metabolites by 1H magnetic resonance spectroscopy in patients with juvenile idiopathic inflammatory myopathy (IIM).

Methods: Creatine (Cr), choline (Cho), betaine (Bet), glycine (Gly), trimethylamine oxide (TMAO), and several other metabolites were measured in first morning void urine samples from 45 patients with juvenile IIM and from 35 healthy age-matched controls, and correlated with measures of myositis disease activity and damage. Urinary metabolite to age-adjusted creatinine (Cn) ratios were examined.

Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis.

Background: Idiopathic inflammatory myopathies are chronic skeletal diseases with significant mortality and morbidity despite treatment by corticosteroids. Immunosuppressive agents and immunomodulatory therapy are used to improve disease control and reduce the long-term side effects of corticosteroids. While these treatments are used commonly in routine clinical practice, the optimal therapeutic regimen remains unclear.

Depot perphenazine decanoate and enanthate for schizophrenia.

Background: Antipsychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain.

A meta-analysis of the efficacy and toxicity of combining disease-modifying anti-rheumatic drugs in rheumatoid arthritis based on patient withdrawal.

Introduction: Combinations of disease-modifying anti-rheumatic drugs (DMARDs) are increasingly used to treat rheumatoid arthritis (RA). Early trials showed their toxicity while recent trials suggest superior efficacy. Trials of DMARD combinations have enrolled different types of patient (early or established RA), used different designs (step-up, parallel or step-down) and utilized a range of outcome measures.

Some structural determinants of the antiproliferative effect of heparin-like molecules on human airway smooth muscle.

Accumulation of airway smooth muscle (ASM) and its infiltration by mast cells are key pathological features of airway remodelling in asthma. Heparin, a major component of mast cell granules, inhibits ASM proliferation by an unknown mechanism. Here, unfractionated heparins and related glycosaminoglycans having structurally heterogeneous polysaccharide side chains that varied in molecular weight, sulphation and anionic charge were used to identify features of the heparin molecule that were required for its antiproliferative activity in cultured human ASM cells.

The inhibition of human mesangial cell proliferation by S-trans, trans-farnesylthiosalicylic acid.

Background: Many of the proliferative cytokines implicated in human mesangial cell (HMC) proliferation signal through the superfamily of Ras GTPases. The Ras antagonist, S-trans, trans- farnesylthiosalicylic acid (FTS), was used to investigate the effects of the inhibition of Ras signaling on HMC proliferation.

Methods: Ras expression and membrane localization, MAPK, and Akt activation were analyzed by Western blotting.

Laparoscopic management of cryptorchidism in adults.

Objectives: Little is reported on the management of impalpable testis in adults. We present the impact of laparoscopy in this patient group.

Patients And Methods: Twelve adult patients have been referred to our centre over the last year, with impalpable testis.

Volvulus--a rare complication of ileal conduit.

Conduit volvulus is a very rare complication of ileal conduit. To date, only seven surgically confirmed cases have been reported. Conduit volvulus is a potentially reversible cause of renal impairment in patients with urinary diversion.

Sphingosylphosphorylcholine-induced vasoconstriction of pulmonary artery: activation of non-store-operated Ca2+ entry.

Objective: Sphingosylphosphorylcholine (SPC) is an important lipid mediator that has been implicated in vascular disease. As it has not been studied in the pulmonary circulation, we examined its mechanisms of action in rat small intrapulmonary arteries (IPA).

Methods: IPA were mounted on a myograph for recording tension and intracellular Ca2+ concentration ([Ca2+]i).

Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity.

Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines. We used in situ hybridization and immunohistochemistry to examine the expression and cellular provenance of TSLP, Th2-attracting (thymus and activation-regulated chemokine (TARC)/CCL17, macrophage-derived chemokine (MDC)/CCL22, I-309/CCL1) and Th1-attracting (IFN-gamma-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T cell alpha-chemoattractant (I-TAC)/CXCL11) chemokines and expression of their receptors CCR4, CCR8, and CXCR3 in bronchial biopsies from 20 asthmatics and 15 normal controls.

Association of pulse waveform characteristics with birth weight in young adults.

Objective: An association between birth weight and blood pressure has been reported in many studies, but the strength of this association has been disputed. Birth weight could, however, be associated with alterations in the proximal arterial tree that have little effect on blood pressure. The objective of this study was to examine the relationship between birth weight and characteristics of the proximal arterial tree determined by pulse wave analysis.

Targeting albumin excretion rate in the treatment of the hypertensive diabetic patient with renal disease.

Combination of an angiotensin-converting enzyme inhibitor (ACEI) with an angiotensin II receptor blocker is advocated as a treatment option in diabetic patients with nephropathy and residual albuminuria while on antihypertensive therapy. Abrogation of albuminuria is a key treatment goal to prevent disease progression. The assumption is that albuminuria reduction is the result of more complete blockade of the renin angiotensin system; thus, the ACEI-angiotensin II receptor blocker combination would have a greater albuminuria-lowering effect than the combination of an ACEI with a calcium channel blocker such as amlodipine, which causes similar reductions in BP but does not affect the renin angiotensin system.

Factors influencing young women's decision making regarding hormonal contraceptives: a qualitative study.

Introduction: Discontinuation of hormonal contraceptives is correlated with the experience of unwanted effects and is an important cause of unwanted pregnancy. Previous studies have not identified the factors that influence whether a woman will switch to another hormonal contraceptive, switch back to condom use or stop contraception altogether when side effects are experienced.

Methods: This qualitative study used in-depth interviews to explore factors influencing young women's decision making regarding highly effective hormonal contraceptives in 51 women aged 16-25 years living in or just outside London, UK.

Laparoscopic ureteroneocystostomy for benign lower ureteric stricture: case study and literature review.

The surgical treatment of distal ureteric strictures depends on their length and aetiology. Laparoscopic procedures in this setting are uncommon. We describe a laparoscopic non-refluxing ureteroneocystostomy for a symptomatic distal ureteric stricture performed on a 26-year-old man.