The development of new medicines suffers from attrition, especially in the pipeline. Eight out nine drug candidates entering clinical testing phase fail, mostly due to poor safety and efficacy. low predictive value animal models, used earlier phases development, for effects humans poses a major problem. In particular, disposition can markedly differentiate experimental animals versus humans. Me...

Mutation of the Foxp3 transcription factor in Scurfy (Sf) mice results in complete absence of the CD4+Foxp3+ regulatory T cells (Tregs), severe multiorgan autoimmune syndrome, and early death at 4 wk of age. However, Sf mice simultaneously bearing the Il2-/- (Sf.Il2-/-) or Faslpr/lpr gene (Sf.Faslpr/lpr) have extended lifespan despite totally lacking Tregs, indicating a role of IL-2 and CD95 (F...

A case of adult onset Still's disease in an elderly woman, that was associated with severe respiratory failure and multiorgan dysfunction, is reported. Histopathology was confirmed on open lung biopsy.

Congenital disorders of glycosylation are a rare group of metabolic disorders that can result in multiorgan disease. This article describes a novel finding of macular hypoplasia in congenital disorders of glycosylation type Ia.

Chronic graft-versus-host disease (cGVHD) is a significant roadblock to long-term hematopoietic stem cell (HSC) transplantation success. Effective treatments for cGVHD have been difficult to develop, in part because of a paucity of animal models that recapitulate the multiorgan pathologies observed in clinical cGVHD. Here we present an analysis of the pathology that occurs in immunodeficient mi...

OBJECTIVE To determine the factors leading to in-hospital mortality within 28 days in hospitalized patients with ARDS. It was a prospective observational cohort study conducted in Intensive Care Unit of Aga Khan University Hospital Karachi from March to August 2011. METHODOLOGY Data was collected from patients admitted in the intensive care unit on the basis of inclusion and exclusion criteri...

BACKGROUND : We attempted to ascertain whether pre-existing inflammatory state [caused by exogenous administration of lipopolysaccharide (LPS)] exacerbated multiorgan dysfunction in experimental heatstroke. DESIGN : Immediately after the start of heat stress (42 degrees C), anesthetized rats were divided into 2 major groups and given 0.9% NaCl solution (10 mL/kg of body weight, intravenously)...

INTRODUCTION Leptospirosis has recently come to international attention as a globally important re-emerging infectious disease. Our case is unusual given the season, location and setting in which leptospirosis occurred. According to the New York City Board of Health, there were only two other cases of leptospirosis in New York City in the year that our patient was diagnosed. CASE PRESENTATION...