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Stepensky P.,Hadassah University Hospital | Bartram J.,Bone Marrow Transplant Unit | Barth T.F.,University of Ulm | Lehmberg K.,University of Hamburg | And 11 more authors.
Pediatric Blood and Cancer | Year: 2013

Background: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare primary immune disorder defined by mutations in the syntaxin binding protein 2 (STXBP2) alias MUNC18-2. Despite defective immunity and a hyper-inflammatory state, clinical findings such as neurological, gastrointestinal, and bleeding disorders are present in a significant number of patients and suggest an impaired expression and function of STXBP2 in cells other than cytotoxic lymphocytes. Procedure: We investigated four patients with FHL5 suffering from severe enteropathy and one of whom also had renal tubular dysfunction despite successful hematopoietic stem cell transplantation (HSCT). Gastrointestinal and renal biopsy specimens were analyzed by immunohistochemistry and electron microscopy. Results: Histopathology revealed an intracytoplasmatic accumulation of PAS-positive granules and an enlarged intracytoplasmatic CD10-positive band along the apical pole of enterocytes. Electron microscopy revealed short microvilli and granules filled with electro lucent material. In addition, we described mildly dilated renal tubules and electron micrographs displayed a higher number of cytoplasmic inclusions, electrodense lysosomal and electrolucent endosomal vesicles. Conclusion: Mutations in STXBP2 do not only affect cytotoxic T lymphocytes but also cause changes in the intestinal and renal epithelium resulting in severe, osmotic diarrhea and renal proximal tubular dysfunction. These defects persist after successful treatment of hemophagocytic lymphohistocytosis by HSCT. Clinical manifestations in FHL5 patients despite successful HSCT may therefore be related to defective membrane trafficking in the gut and kidney. © 2013 Wiley Periodicals, Inc. Source


Venkatesh K.,Center for Pediatric Gastroenterology | Cohen M.,Sheffield Childrens NHS Foundation Trust | Abou-Taleb A.,Center for Pediatric Gastroenterology | Thomas S.,Optiscan | And 2 more authors.
Gastrointestinal Endoscopy | Year: 2012

Background: The diagnosis of GERD is made by using a combination of clinical symptoms, pH study, endoscopy, and histology. Histologic changes include basal cell hyperplasia and papillary elongation. Confocal laser endomicroscopy (CLE) enables surface and subsurface imaging of living cells in vivo at ×1000 magnification and up to 250 μm below the tissue surface. In the esophagus, the distance between the surface to papillary (S-P) tip can be measured by using CLE. Objective: To measure the S-P distance in the esophagus in patients with reflux esophagitis and controls by using CLE and comparing with histologic measurements. Design: Retrospective analysis of a prospective database. Setting: Endoscopy unit of a tertiary-care children's hospital. Patients: This study involved 7 patients (5 female) with a median age of 7.6 years (range 1.8-15.5 years) and median weight of 23 kg (range 13.2-71 kg) and 16 controls with a median age of 12.0 years (range 2.2-15.3 years) and median weight of 38.2 kg (range 10.7-83 kg). Intervention: S-P distance was measured both by CLE and histology and was corrected for height for both patients and controls and the results compared. Main Outcome Measurements: To determine if there were significant differences in the S-P distance in patients with esophagitis and controls. Results: The median confocal and histologic measurements for S-P distance, corrected for patient height, were 0.19 μm/cm (range 0.10-0.49 μm/cm) and 0.58 μm/cm (range 0.29-0.76 μm/cm) and for controls were 0.44 μm/cm (range 0.20-0.93 μm/cm) and 1.07 μm/cm (range 0.76-0.1.57 μm/cm), respectively. Limitations: Small numbers involved in the study, reliance on only papillary elongation in arriving at a diagnosis. Conclusion: Measurement of the S-P distance by CLE will enable real-time diagnosis of GERD-related esophagitis during ongoing endoscopy. © 2012 American Society for Gastrointestinal Endoscopy. Source

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