Showing papers by "Simon Murch published in 2012"

Enterotoxin-producing staphylococci cause intestinal inflammation by a combination of direct epithelial cytopathy and superantigen-mediated T-cell activation.

Abstract: Background: Enterotoxin-producing Staphylococcus aureus may cause severe inflammatory intestinal disease, particularly in infants or immunodeficient or elderly patients. They are also recognized to be associated with sudden infant death syndrome. Little is known, however, about mucosal responses to staphylococci. Methods: The mucosal lesion in three infants with staphylococcal enterocolitis was assessed by immunohistochemistry and electron microscopy. The organisms underwent extensive molecular analysis. Their toxins were assessed for capacity to induce T-cell activation and host mucosal responses examined by in vitro organ culture. Epithelial responses were studied by coculture with HEp-2 and Caco-2 cells. Results: Intestinal biopsies from the patients showed marked epithelial damage with mucosal inflammation. The three staphylococci, representing two distinct clones, were methicillin-sensitive, producing SEG/I enterotoxins and Rho-inactivating EDIN toxins. Their enterotoxins potently activated T cells, but only whole organisms could induce in vitro enteropathy, characterized by remarkable epithelial desquamation uninhibited by tacrolimus. EDIN-producing staphylococci, but not their supernatants, induced striking cytopathy in HEp-2 epithelial cells but not in Caco-2 cells. Although HEp-2 and Caco-2 cells produced similar IL-8, CCL20, and cathelicidin LL37 responses upon bacterial exposure, only Caco-2 cells expressed mRNA for the β-defensins HBD2 and HBD3, while HEp-2 cells were unable to do so. Conclusions: Staphylococci induce enterocolitis by a combination of direct enterocyte cytopathy mediated by EDIN toxins, disrupting the epithelial barrier, and enterotoxin superantigen-induced mucosal T-cell activation. Gut epithelial production of β-defensins may contribute to host defense against invasive staphylococcal disease. (Inflamm Bowel Dis 2011;)

Diagnosing coeliac disease

Abstract: Guidelines from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) for diagnosis and treatment of coeliac disease (CD) have not been revisited for 20 years. During this time, the perception of CD has changed from a rather uncommon enteropathy presenting in childhood, with obvious gastrointestinal symptoms, to a much more common multiorgan disease with a strong genetic predisposition (mainly associated with human leucocyte antigen (HLA)-DQ2 and HLA-DQ8). Previous ESPGHAN diagnostic criteria1 stated that histological confirmation of the typical changes of CD in the small intestine were mandatory for diagnosis and that a gluten challenge, and rebiopsy would need to be performed in those children under the age of 2 years diagnosed as having CD. Since that time, largely because of the increasing availability of specific serological testing, it has become clear that CD may present with a large variety of non-specific signs and symptoms, rather than a specific gastrointestinal presentation.