Case Report: A patient with severe peritonitis

No Abstrac

The Epidemiology, Management, Outcomes and Areas for Improvement of Burn Care in Central Malawi: An Observational Study

This report describes the epidemiology of burn injuries and quantifies the appropriateness of use of available interventions at Kamuzu Central Hospital, Malawi, between July 2008 and June 2009 (370 burn patients). Burns accounted for 4.4% of all injuries and 25.9% of all burns presenting to the hospital were admitted. Most patients (67.6%) were < 15 years old and 56.2% were male. The most frequent cause was scalding (51.4%). Burns occurred most frequently in the cool, dry season and in the evening. The mean burn surface area (second/third degree) was 14.1% and most burns (74%) presented within 8 h. The commonest procedure was debridement and/or amputation. The mean hospital stay was 21.1 days, in-hospital mortality was 27% and wound infection rate was 31%. Available interventions (intravenous fluids, nutrition therapy, physiotherapy) were misapplied in 59% of cases. It is concluded that primary prevention should address paediatric and scald burns, and secondary prevention should train providers to use available interventions appropriately

Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial.

BACKGROUND: Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ), given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age. METHODS AND FINDINGS: SMC was introduced into three districts over three years in central Senegal using a stepped-wedge cluster-randomised design. A census of the population was undertaken and a surveillance system was established to record all deaths and to record all cases of malaria seen at health facilities. A pharmacovigilance system was put in place to detect adverse drug reactions. Fifty-four health posts were randomised. Nine started implementation of SMC in 2008, 18 in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first year of implementation, SMC was delivered to children aged 3-59 months; the age range was then extended for the latter two years of the study to include children up to 10 years of age. Cluster sample surveys at the end of each transmission season were done to measure coverage of SMC and the prevalence of parasitaemia and anaemia, to monitor molecular markers of drug resistance, and to measure insecticide-treated net (ITN) use. Entomological monitoring and assessment of costs of delivery in each health post and of community attitudes to SMC were also undertaken. About 780,000 treatments were administered over three years. Coverage exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate ratio [SMC: no SMC] was 0.90, 95% CI 0.68-1.2, p = 0.496). A reduction of 60% (95% CI 54%-64%, p < 0.001) in the incidence of malaria cases confirmed by a rapid diagnostic test (RDT) and a reduction of 69% (95% CI 65%-72%, p < 0.001) in the number of treatments for malaria (confirmed and unconfirmed) was observed in children. In areas where SMC was implemented, incidence of confirmed malaria in adults and in children too old to receive SMC was reduced by 26% (95% CI 18%-33%, p < 0.001) and the total number of treatments for malaria (confirmed and unconfirmed) in these older age groups was reduced by 29% (95% CI 21%-35%, p < 0.001). One hundred and twenty-three children were admitted to hospital with a diagnosis of severe malaria, with 64 in control areas and 59 in SMC areas, showing a reduction in the incidence rate of severe disease of 45% (95% CI 5%-68%, p = 0.031). Estimates of the reduction in the prevalence of parasitaemia at the end of the transmission season in SMC areas were 68% (95% CI 35%-85%) p = 0.002 in 2008, 84% (95% CI 58%-94%, p < 0.001) in 2009, and 30% (95% CI -130%-79%, p = 0.56) in 2010. SMC was well tolerated with no serious adverse reactions attributable to SMC drugs. Vomiting was the most commonly reported mild adverse event but was reported in less than 1% of treatments. The average cost of delivery was US$0.50 per child per month, but varied widely depending on the size of the health post. Limitations included the low rate of mortality, which limited our ability to detect an effect on this endpoint. CONCLUSIONS: SMC substantially reduced the incidence of outpatient cases of malaria and of severe malaria in children, but no difference in all-cause mortality was observed. Introduction of SMC was associated with an overall reduction in malaria incidence in untreated age groups. In many areas of Africa with seasonal malaria, there is a substantial burden in older children that could be prevented by SMC. SMC in older children is well tolerated and effective and can contribute to reducing malaria transmission. TRIAL REGISTRATION: ClinicalTrials.gov NCT00712374

Biomarker-based prediction of inflammatory bowel disease-related colorectal cancer: a case–control study

Regular colonoscopic surveillance for detection of dysplasia is recommended in longstanding inflammatory bowel disease (IBD), however, its sensitivity is disputed. Screening accuracy may increase by using a biomarker-based surveillance strategy.A case-control study was performed to determine the prognostic value of DNA ploidy and p53 in IBD-related neoplasia. Cases with IBD-related colorectal cancer (CRC), detected in our surveillance program between 1985-2008, were selected and matched with two controls, for age, gender, disease characteristics, interval of follow-up, PSC, and previous surgery. Biopsies were assessed for DNA ploidy, p53, grade of inflammation and neoplasia. Progression to neoplasia was analyzed with Cox regression analysis, adjusting for potentially confounding variables.Adjusting for age, we found statistically significant Hazard ratios (HR) between development of CRC, and low grade dysplasia (HR5.5; 95%CI 2.6-11.5), abnormal DNA ploidy (DNA index (DI) 1.06-1.34, HR4.7; 95%CI 2.9-7.8 and DI>1.34, HR6.6; 95%CI 3.7-11.7) and p53 immunopositivity (HR3.0; 95%CI 1.9-4.7) over time. When adjusting for all confounders, abnormal DNA ploidy (DI 1.06-1.34, HR4.7; 95%CI 2.7-7.9 and DI>1.34, HR5.0; 95%CI 2.5-10.0) and p53 immunopositivity (HR1.7; 95%CI 1.0-3.1) remained statistically significant predictive of neoplasia. In longstanding IBD, abnormal DNA ploidy and p53 immunopositivity are important risk factors of developing CRC. The yield of surveillance may potentially increase by adding these biomarkers to the routine assessment of biopsies

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Oxygen saturation and outcomes in preterm infants

BACKGROUN

Population-based estimates of the prevalence of FMR1 expansion mutations in women with early menopause and primary ovarian insufficiency

PURPOSE: Primary ovarian insufficiency before the age of 40 years affects 1% of the female population and is characterized by permanent cessation of menstruation. Genetic causes include FMR1 expansion mutations. Previous studies have estimated mutation prevalence in clinical referrals for primary ovarian insufficiency, but these are likely to be biased as compared with cases in the general population. The prevalence of FMR1 expansion mutations in early menopause (between the ages of 40 and 45 years) has not been published. METHODS: We studied FMR1 CGG repeat number in more than 2,000 women from the Breakthrough Generations Study who underwent menopause before the age of 46 years. We determined the prevalence of premutation (55–200 CGG repeats) and intermediate (45–54 CGG repeats) alleles in women with primary ovarian insufficiency (n = 254) and early menopause (n = 1,881). RESULTS: The prevalence of the premutation was 2.0% in primary ovarian insufficiency, 0.7% in early menopause, and 0.4% in controls, corresponding to odds ratios of 5.4 (95% confidence interval = 1.7–17.4; P = 0.004) for primary ovarian insufficiency and 2.0 (95% confidence interval = 0.8–5.1; P = 0.12) for early menopause. Combining primary ovarian insufficiency and early menopause gave an odds ratio of 2.4 (95% confidence interval = 1.02–5.8; P = 0.04). Intermediate alleles were not significant risk factors for either early menopause or primary ovarian insufficiency. CONCLUSION: FMR1 premutations are not as prevalent in women with ovarian insufficiency as previous estimates have suggested, but they still represent a substantial cause of primary ovarian insufficiency and early menopause

Mast cell tryptase stimulates myoblast proliferation; a mechanism relying on protease-activated receptor-2 and cyclooxygenase-2

<p>Abstract</p> <p>Background</p> <p>Mast cells contribute to tissue repair in fibrous tissues by stimulating proliferation of fibroblasts through the release of tryptase which activates protease-activated receptor-2 (PAR-2). The possibility that a tryptase/PAR-2 signaling pathway exists in skeletal muscle cell has never been investigated. The aim of this study was to evaluate whether tryptase can stimulate myoblast proliferation and determine the downstream cascade.</p> <p>Methods</p> <p>Proliferation of L6 rat skeletal myoblasts stimulated with PAR-2 agonists (tryptase, trypsin and SLIGKV) was assessed. The specificity of the tryptase effect was evaluated with a specific inhibitor, APC-366. Western blot analyses were used to evaluate the expression and functionality of PAR-2 receptor and to assess the expression of COX-2. COX-2 activity was evaluated with a commercial activity assay kit and by measurement of PGF₂α production. Proliferation assays were also performed in presence of different prostaglandins (PGs).</p> <p>Results</p> <p>Tryptase increased L6 myoblast proliferation by 35% above control group and this effect was completely inhibited by APC-366. We confirmed the expression of PAR-2 receptor <it>in vivo </it>in skeletal muscle cells and in satellite cells and <it>in vitro </it>in L6 cells, where PAR-2 was found to be functional. Trypsin and SLIGKV increased L6 cells proliferation by 76% and 26% above control, respectively. COX-2 activity was increased following stimulation with PAR-2 agonist but its expression remained unchanged. Inhibition of COX-2 activity by NS-398 abolished the stimulation of cell proliferation induced by tryptase and trypsin. Finally, 15-deoxy-Δ-^12,14-prostaglandin J₂(15Δ-PGJ₂), a product of COX-2-derived prostaglandin D₂, stimulated myoblast proliferation, but not PGE₂and PGF₂α.</p> <p>Conclusions</p> <p>Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2.</p