J Markowitz

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

Thirteen pediatric patients with Crohns 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.

Home nocturnal supplemental nasogastric feedings in growth-retarded adolescents with Crohn's disease

We hypothesized that supplemental nutritional support delivered at home by nocturnal nasogastric feedings would result in accelerated growth in growth-retarded adolescents with Crohns disease. Eight Tanner stage I adolescents with Crohns disease, mean age 14 yr 5 mo, had a mean weight gain of 0.38 kg and height gain of 1.4 cm for the year before initiation of nasogastric feedings. All had been either asymptomatic or had only minimal symptoms in the year before the study, but were ingesting only 55%-80% of their daily required caloric intake. The subjects were taught to pass by themselves a nasogastric feeding tube, through which 1000-1500 ml of commercial, nonelemental isocaloric formula was infused during sleep to supplement their usual dietary intake. After 12 mo of nocturnal feedings, the subjects had a mean weight gain of 11.75 kg and a mean height gain of 6.98 cm. Six control subjects, matched for age and degree of growth and sexual retardation at the beginning of the study period, but who had refused the nasogastric feedings, had no change in weight and height during the same period of observation. We conclude that home nocturnal nasogastric feedings can achieve dramatic improvement in weight gain and linear growth in motivated adolescents with Crohns disease and growth retardation.

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.

Amyloidosis in children with inflammatory bowel disease

Reactive systemic or secondary amyloidosis occurs in 1-29% of adults with Crohns disease, but only sporadic cases of amyloidosis have been recognized in children with inflammatory bowel disease. We therefore have studied operative specimens (ileal, ileocolonic, and colonic) from 46 children (30 with Crohns disease and 16 with ulcerative colitis) to determine the frequency of amyloid deposits. Sections of bowel, skin, and lymph nodes (n = 940) were stained by Congo red and examined by light microscopy and by polarized light. Amyloid deposits were found in only one of 46 subjects, an 18-year-old girl who had had Crohns disease for 6 years. Intestinal amyloid deposits, present 16 months before the clinical diagnosis of amyloidosis, were patchy and seen predominantly in the intestinal mucosa. We conclude that amyloidosis is rare in children requiring surgery for Crohns disease and ulcerative colitis. Examination of Congo red-stained sections can detect even subclinical amyloidosis. The amyloid deposits in our patient, which were both patchy and consistently mucosal, suggest that multiple endoscopic biopsy samples, not necessarily containing submucosa, are sufficient for diagnosis.