Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials.

Background: A one-dose-fits-all approach to use of aspirin has yielded only modest benefits in long-term prevention of cardiovascular events, possibly due to underdosing in patients of large body size and excess dosing in patients of small body size, which might also affect other outcomes.

Methods: Using individual patient data, we analysed the modifying effects of bodyweight (10 kg bands) and height (10 cm bands) on the effects of low doses (≤100 mg) and higher doses (300-325 mg or ≥500 mg) of aspirin in randomised trials of aspirin in primary prevention of cardiovascular events. We stratified the findings by age, sex, and vascular risk factors, and validated them in trials of aspirin in secondary prevention of stroke.

Severe malarial thrombocytopenia: a risk factor for mortality in Papua, Indonesia.

Background: The significance of thrombocytopenia to the morbidity and mortality of malaria is poorly defined. We compared the platelet counts and clinical correlates of patients with and those without malaria in southern Papua, Indonesia.

Methods: Data were collated on patients presenting to a referral hospital between April 2004 and December 2012.

Decreased endothelial nitric oxide bioavailability, impaired microvascular function, and increased tissue oxygen consumption in children with falciparum malaria.

Endothelial nitric oxide (NO) bioavailability, microvascular function, and host oxygen consumption have not been assessed in pediatric malaria. We measured NO-dependent endothelial function by using peripheral artery tonometry to determine the reactive hyperemia index (RHI), and microvascular function and oxygen consumption (VO2) using near infrared resonance spectroscopy in 13 Indonesian children with severe falciparum malaria and 15 with moderately severe falciparum malaria. Compared with 19 controls, children with severe malaria and those with moderately severe malaria had lower RHIs (P = .

C-reactive protein: the underlying cause of microvascular dysfunction in rheumatoid arthritis.

Objective: RA is a chronic autoimmune inflammatory condition associated with increased cardiovascular morbidity and mortality. Endothelial dysfunction, a marker of early atherosclerotic disease, occurs in some inflammatory diseases but this relationship has not been previously explored within the microvasculature of patients with RA. We therefore assessed forearm microvascular endothelial function in patients with RA and determined its relationship to RA disease activity and inflammation.

Current concepts in assessment of microvascular endothelial function using laser Doppler imaging and iontophoresis.

Effective evaluation of endothelial function is a powerful tool for determining patients at risk of development and progression of cardiovascular disease. As an alternative to invasive tests of endothelial function, several noninvasive methods have been developed, including the use of laser Doppler flowmetry/imaging to measure cutaneous perfusion accompanied by iontophoresis of acetylcholine and sodium nitroprusside. It is clear from previous studies that this technique provides an easy, validated, and reproducible method for investigators to assess and monitor endothelial function in patients with a variety of pathologic conditions, but it may also be used to examine disease progression over time and responsiveness to treatment, thereby facilitating clinical trials.

Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis.

Objectives: Dose-dependant gastrointestinal and cardiovascular side-effects limit the use of NSAIDs in the management of RA. The n-3 essential fatty acids (EFAs) have previously demonstrated some anti-inflammatory and NSAID-sparing properties. The objective of this study was to determine whether cod liver oil supplementation helps reduce daily NSAID requirement of patients with RA.

Relationship between peripheral and coronary function using laser Doppler imaging and transthoracic echocardiography.

Vascular dysfunction in the coronary and peripheral circulations is an early prognostic marker of future cardiovascular events. Measurements of coronary and peripheral vascular function in resistance vessels can be made, but rely on invasive procedures, which make them unsuitable for routine application. An assessment of the direct correlation between vascular responses in skin and coronary vessels has not been made previously.

Dual-energy X-ray absorptiometry applied to the assessment of tibial subchondral bone mineral density in osteoarthritis of the knee.

Objective: Plain X-ray is an imprecise tool for monitoring the subchondral bony changes associated with the development of knee osteoarthritis (OA). Our objective was to develop and validate a technique for assessing tibial subchondral bone density (BMD) in knee OA using dual energy X-ray absorptiometry (DXA).

Design: Patients with OA of at least one knee underwent DXA scanning of both knees.

A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis.

Objectives: To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis.

Methods: A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo.

Dendritic cell-based assays, but not mannosylation of antigen, improves detection of T-cell responses to proinsulin in type 1 diabetes.

In vitro detection of T-cell responses to autoantigens in type 1 diabetes is recognized as being technically challenging. We aimed to accurately measure cellular responses to proinsulin in patients with diabetes, and speculated that presentation of antigen by dendritic cells (DCs) would enhance the sensitivity of the peripheral blood assay. Antigen was mannosylated to facilitate uptake through DC surface mannose receptors to further improve the assay.

Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial.

Background: Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis. The benefits of infliximab in Crohn's disease are established. We investigated its efficacy in ulcerative colitis.

Serial changes in static and dynamic cerebral autoregulation after acute ischaemic stroke.

Background: The longitudinal changes in static and dynamic cerebral autoregulation (CA) following acute ischaemic stroke are unknown and were assessed in this study.

Methods: Fifty-four ischaemic stroke patients were studied within 96 h of ischaemic stroke and again 7-14 days later, using transcranial Doppler techniques to measure CA. Results were compared to an age-, sex- and blood pressure (BP)-matched control group.

Humoral and cellular immune responses to proinsulin in adults with newly diagnosed type 1 diabetes.

Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by immunity against pancreatic islet-derived proteins. The object of this study was to measure antibody and T-cell responses against proinsulin (PI), an islet-derived protein, and to map its dominant T-cell epitopes.

Methods: Antibody responses to proinsulin, insulin, glutamic acid decarboxylase (GAD), protein tyrosine phosphatase IA-2 and islet-cell antigen were measured in 116 newly diagnosed diabetic subjects aged 16 to 40 years.

Application of a novel human cervical mucin-based assay demonstrates the absence of increased mucinase activity in bacterial vaginosis.

Enzymes produced in bacterial vaginosis (BV) have been proposed as possible mediators of pre-term birth. Most studies have concentrated on mid-trimester measurements of enzyme activity, and utilize synthetic substrates to measure enzyme activity, which may not accurately represent mucinase activity in vivo. We have developed a novel ELISA mucinase assay using biotinylated human cervical mucin as a substrate.

Continuous cardiac baroreceptor measurement during tilt in healthy elderly subjects.

Introduction: Abnormalities of cardiac baroreceptor sensitivity (BRS) may contribute towards the high prevalence of orthostatic hypotension and falls in the elderly. Most mathematical analyses used to determine BRS in the time or frequency domains assume a stationary physiological state and cannot be performed under dynamic change and therefore are not valid during tilt. We describe a new method of estimating BRS during tilt.

Mucinases and sialidases: their role in the pathogenesis of sexually transmitted infections in the female genital tract.

Background: Mucinases and sialidases contribute to the process of invasion and colonisation in many conditions and infections of the female reproductive tract by degrading the protective cervical mucus. The role of hydrolytic enzymes in the pathogenesis of sexually transmitted diseases and their effect on cervical mucus are discussed in this review.

Methods: Articles were searched for using the keywords "sialidase," "mucinase," "protease," and "sexually transmitted infections.

Systemic low-dose glucocorticoid treatment in rheumatoid arthritis.

Glucocorticoids provide a large, immediate improvement in the symptoms of rheumatoid arthritis. At doses acceptable for long-term treatment, however, symptoms gradually re-emerge. Relatively low doses of glucocorticoids can, for several years, substantially retard the rate of joint destruction shown on radiographs.

Endothelial dysfunction in chronic renal failure: roles of lipoprotein oxidation and pro-inflammatory cytokines.

Background: Chronic renal failure (CRF) is associated with an increased risk of ischaemic heart disease (IHD), but the mechanisms responsible are controversial. We investigated the relationship of two sets of candidate mechanisms-indices of LDL oxidation and markers of inflammatory activity-with vascular endothelial dysfunction (VED).

Methods: We carried out cross-sectional analysis of 23 dialysed and 16 non-dialysed CRF patients, 28 healthy controls, and 20 patients with stable angina and normal renal function.

Is there a place for intra-articular hyaluronate in osteoarthritis of the knee?

Viscosupplementation refers to the intra-articular injection of hyaluronic acid (HA) as a hyaluronate to relieve pain and improve function, usually in patients with knee OA. HA is the major constituent of a 1-2-micron layer on the surface of articular cartilage as well as a major constituent of synovial fluid (SF). Solutions of HA can act as lubricants when movements are slow and as shock absorbers when movements are fast.

Effect of vitamin C on ambulatory blood pressure and plasma lipids in older persons.

Objectives: To determine the effect of oral vitamin C supplements on ambulatory blood pressure and plasma lipids.

Design: A 6-month double-blind randomized placebo-controlled cross-over study with a 1 -week washout between cross-over periods.

Methods: Vitamin C 500 mg daily or matching placebo was given to 40 men and women aged between 60 and 80 years for 3 months each in a cross-over fashion.

Increased serum C reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee.

Objective: Raised serum C reactive protein (CRP) and hyaluronate (HA) concentrations predict the progression of knee osteoarthritis (OA) in the long term but the consistency of these relations with time is unknown. The purpose of this work was therefore to determine if raised CRP and HA at entry and three years before entry (-3 years) predict radiological progression of knee OA in a group of patients between entry and five years.

Methods: Knee radiographs from 90 patients with knee OA at entry and five years follow up were assessed for progression of disease over five years.