Faculty Bibliography

BACKGROUND & AIMS/OBJECTIVE:Antibiotic-associated pseudomembranous colitis in humans is caused by proliferation of Clostridium difficile, which elaborates an enterotoxin toxin A that causes epithelial damage and altered motility in rabbit small intestine. The aim of this study was to assess the effects of toxin A on rabbit distal colonic motility and to relate this to histological damage and inflammatory mediator production. METHODS:Two hundred micrograms per milliliter of toxin A was placed in a distal colonic loop in anesthetized rabbits, and myoelectric activity was recorded for the following 7 hours. The colon was histologically evaluated and assayed for eicosanoid production. The effects of toxin A on longitudinal and circular muscle were also assessed in vitro. RESULTS:Beginning 1 hour after instillation, toxin A caused a significant increase in the number of spike bursts without altering slow wave frequency; this was associated with an increase in mucosal neutrophils and increased production of prostaglandin E2 and leukotrienes B4 and C4/D4/E4. Seven hours after administration of toxin A, mediator levels and myoelectric activity remained increased but significant mucosal damage was now also present. Toxin A did not affect longitudinal or circular muscle in vitro. CONCLUSIONS:C. difficile toxin A caused a significant neutrophil infiltration and an increased myoelectric activity before producing mucosal damage. The myoelectric effect may be indirect, resulting from the production of motility-altering arachidonic acid metabolites.

Dysphagia can be caused by a host of factors, most of which are structural or functional. However, despite extensive evaluations, a certain number of patients have unexplained dysphagia. We present an extremely unusual case whereby a patient with an acute left hemispheric cerebral vascular accident presents with dysphagia as his sole complaint and after extensive neurological, gastroenterological, and radiographic examinations is found to have cricopharyngeal dysfunction. The etiology of this defect was not at all clinically apparent and, ultimately, magnetic resonance imaging (MRI) was performed which revealed a chronic infarction of the right frontal lobe and a smaller acute infarction in the same location of the left. This case demonstrates that swallowing disorders may be the sole presentation of stroke and that, if extensive evaluations of such patients fail to yield an etiology, one must strongly consider MRI as a tool for diagnosis, even if a CT scan is negative.

We present a case of a 22-yr-old female who developed acute pancreatitis coincident with metronidazole therapy, with documented recurrence when inadvertently rechallenged on two separate occasions. These episodes were unrelated to alcohol ingestion, gallbladder disease, or other known causes of pancreatitis. Only one other case of metronidazole-induced pancreatitis was found in the English literature. Known toxicities of metronidazole are discussed, as well as potential mechanisms by which metronidazole may have induced pancreatitis in our patient. Since metronidazole is used to treat a host of infectious and inflammatory conditions, its causal relationship with pancreatitis must be carefully considered. We suggest that metronidazole be discontinued when clinical or biochemical features of acute pancreatitis occur, once other known causes of pancreatitis have been excluded.