36 research outputs found

    Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies.

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    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies (including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our  understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA

    A second generation human haplotype map of over 3.1 million SNPs

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    We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r(2) of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r(2) of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62863/1/nature06258.pd

    Infective endocarditis in the adult patient

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    Infective endocarditis (IE) is an uncommon disease with a high morbidity and mortality. The basic pathology involves adherence of microorganisms to areas of endothelial damage or associated implanted medical devices, such as prosthetic valves or pacemakers, resulting in localized infection and formation of vegetations. Complications include sepsis, valvular failure and embolization. Staphylococci and streptococci are the predominant causes of IE. Blood cultures and echocardiography are key diagnostic tests, but a diagnosis of IE can still be difficult to establish. Serological tests, particularly for fastidious microorganisms, can assist when blood cultures are negative. The Duke criteria can aid diagnosis but lack sensitivity, particularly when blood cultures are negative or transthoracic echocardiography images are non-diagnostic. Antibiotics are the mainstay of treatment, but surgical debridement and valvular surgery are frequently required. Recent changes in antibiotic prophylaxis for those considered to be at risk of IE have reduced the number of patients given antimicrobials by dental practitioners. This article summarizes how to diagnose IE and outlines current antibiotic treatment regimens

    Laparoscopic ventral hernia repair: a systematic review

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    BackgroundLaparoscopic ventral hernia repair may be an alternative to open mesh repair as it avoids a large abdominal incision, and thus potentially reduces pain and hospital stay. This review aimed to assess the safety and efficacy of laparoscopic ventral hernia repair in comparison with open ventral hernia repair.MethodA systematic review was conducted, with comprehensive searches identifying six randomised controlled trials (RCTs) and eight nonrandomised comparative studies.ResultsThe laparoscopic approach may have a lower recurrence rate than the open approach and required a shorter hospital stay. Five RCTs (Barbaros et al., Hernia 11:51-56, 2007; Misra et al., Surg Endosc 20:1839-1845, 2006; Navarra et al., Surg Laparosc Endosc Percutan Tech 17:86-90, 2007; Moreno-Egea et al., Arch Surg 137:266-1268, 2002; Carbajo et al., Surg Endosc 13:250-252, 1999) reported no conversion (0%) to open surgery, and four nonrandomised studies reported conversions to open surgery ranging from 0% to 14%. Open approach complications generally were wound related, whereas the laparoscopic approach reported both wound- and procedure-related complications and these appeared to be less frequently reported.ConclusionBased on current evidence, the relative safety and efficacy of the laparoscopic approach in comparison with the open approach remains uncertain. The laparoscopic approach may be more suitable for straightforward hernias, with open repair reserved for the more complex hernias. Laparoscopic ventral hernia repair appears to be an acceptable alternative that can be offered by surgeons proficient in advanced laparoscopic techniques.Clarabelle T. Pham, Caryn L. Perera, D. Scott Watkin, Guy J. Madder
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