Ileitis associated with Meckel's diverticulum.

AIMS: Histological features of chronic active ileitis in the small intestine neighbouring a Meckel's diverticulum raise the possibility of concurrent Crohn's disease. Several studies have reported a significant association between Meckel's diverticulum and Crohn's disease, whereas some case reports have proposed that the ileitis is attributable to acid-secreting gastric heterotopia. The aim of this study was to evaluate the incidence, histomorphology and clinical follow-up of Meckel's diverticulum-associated ileitis. METHODS AND RESULTS: Medical records and slides from 48 consecutive surgical resections performed for Meckel's diverticulum were reviewed. Nine of 48 adults had significant inflammatory changes in the small intestine neighbouring the diverticulum. Two were transmural ulcers attributable to ingestion of a sharp object. Two patients had established Crohn's disease, both with long segments (>95 mm) of transmural inflammation located >100 mm from the diverticulum. The remaining five patients had inflammatory changes (ulceration, pseudopyloric metaplasia, submucosal fibrosis, and muscularis mucosa hyperplasia) confined to a short segment (<20 mm) of mucosa/submucosa within 50-60 mm of the diverticulum. Two had gastric heterotopia in the diverticulum. None of these five patients used non-steroidal anti-inflammatory drugs (NSAIDs). On follow-up, none had symptoms, imaging or pathology suggestive of Crohn's disease. CONCLUSIONS: Ileitis affecting a short segment of mucosa and submucosa in the small intestine near a Meckel's diverticulum is relatively common, and is not necessarily related to Crohn's disease.

Glutamatergic calcium dynamics and deregulation of rat retinal ganglion cells.

A rise in intracellular calcium levels ([Ca(2+)](i)) is a key trigger for the lethal effects of the excitatory neurotransmitter glutamate in various central neurons, but a consensus has not been reached on the pathways that mediate glutamate-dependent increases of [Ca(2+)](i) in retinal ganglion cells (RGCs). Using Ca(2+) imaging techniques we demonstrated that, in the absence of external Mg(2+), the Ca(2+) signal evoked by glutamate was predominantly mediated by NMDA-type glutamate receptors (NMDA-Rs) in immunopanned RGCs isolated from neonatal or adult rats. Voltage-gated Ca(2+) channels and AMPA/kainate-Rs contributed a smaller portion of the Ca(2+) response at saturating concentrations of glutamate. Consistent with NMDA-R involvement, extracellular Mg(2+) inhibited RGC glutamate responses, while glycine had a potentiating effect. With Mg(2+) present externally, the effect of AMPA/kainate-R antagonists was enhanced and both NMDA- and AMPA/kainate-R antagonists greatly reduced the glutamate-induced increases of RGC [Ca(2+)](i). This finding indicates that the primary contribution of AMPA/kainate-Rs to RGC glutamatergic Ca(2+) dynamics is through the depolarization-dependent relief of the Mg(2+) block of NMDA-R channels. The effect of glutamate receptor antagonists on glutamatergic Ca(2+) signals from RGCs in adult rat retinal wholemounts yielded results similar to those obtained using immunopanned RGCs. Additional experiments on isolated RGCs revealed that during a 1 h glutamate (10-1000 microm) exposure, 18-28% of RGCs exhibited delayed Ca(2+) deregulation (DCD) and the RGCs that underwent DCD were positive for the death marker annexin V. RGCs with larger glutamate-evoked Ca(2+) signals were more likely to undergo DCD, and NMDA-R blockade significantly reduced the occurrence of DCD. Identifying the mechanisms underlying RGC excitotoxicity aids in our understanding of the pathophysiology of retinal ischaemia, and this work establishes a major role for NMDA-R-mediated increases in [Ca(2+)](i) in glutamate-related RGC death.