Cancer family syndrome: marker studies.

Individuals from kindreds with the cancer family syndrome (CFS) have an increased hereditary risk for the development of adenocarcinoma of the colon in childhood and early adulthood. Previous studies have suggested that this high occurrence of adenocarcinoma may be due to a genetic defect in the control of colonic epithelial proliferation. Others have suggested that these families may have an underlying abnormality in immunologic tumor surveillance. We have investigated these possibilities in 15 cancer-free, at-risk individuals (10 children, ages 3-15 yr, and 5 adults) from two unrelated CFS kindreds. Colonic mucosal proliferative activity was studied by in vitro autoradiography after tritiated thymidine labeling in 7 subjects. The mean labeling index (12.7 +/- 0.9%) was comparable to that in controls, as was the distribution of thymidine labeling. Immunologic evaluation revealed depressed lymphocyte culture responses to stimulation by microbial antigens, but not to that by mitogens. Mixed lymphocyte culture responses were depressed in 4 of 8 subjects, but became normal in 2 of these after filtration through a Sephadex G10 column. Natural killer cell cytotoxicity was significantly depressed in 5 of 13 subjects, and borderline normal in another 3 subjects. These data suggest that many cancer-free members of CFS kindreds have a spectrum of in vitro cell-mediated immunologic defects that might interfere in vivo with the recognition or killing of incipient tumor cells.

Peripheral neuropathy in Crohn's disease patients treated with metronidazole.

Thirteen pediatric patients with Crohn's disease, aged 12-22 yr, were studied to assess the prevalence of peripheral neuropathy due to oral metronidazole. After 4-11 mo of therapy, 11 of 13 patients (85%) had a sensory peripheral neuropathy, determined by abnormal neurologic examinations or reduced nerve conduction velocities, or both. Only 6 of the 11 patients were symptomatic. Nine of 11 patients with peripheral neuropathy had their metronidazole discontinued and 2 had the dose reduced to less than 10 mg/kg X day. Follow-up evaluations of the 9 patients whose metronidazole had been discontinued 5.5-13 mo earlier demonstrated complete resolution of the peripheral neuropathy in 5, improvement in 3, and no change in 1. In the 2 patients whose metronidazole dose was reduced, 1 showed worsening and 1 showed complete resolution of the neuropathy after 10-12 mo of continued therapy.

Progressive esophageal dysfunction in chronic granulomatous disease.

Chronic granulomatous disease of childhood (CGD), a hereditary disorder of neutrophil function, affects the gastrointestinal tract in a variety of ways. Esophageal involvement has only rarely been reported. An 11-year-old boy with CGD and progressive esophageal dysmotility is described. Repeated radiographic, endoscopic, and motility studies revealed a markedly atonic esophagus with varying function of the lower esophageal sphincter. Pharmacologic therapy and esophageal dilatations were unsuccessful in establishing adequate esophageal function. A feeding gastrostomy was required for nutritional support.