Treatment of Wilson's disease with zinc: III. Prevention of reaccumulation of hepatic copper.

Twelve patients with Wilson's disease, most of whom had received intensive treatment with penicillamine, were given zinc therapy as their sole medication for copper control. Serial liver biopsies were performed during a 12- to 20-month follow-up period to determine whether hepatic copper reaccumulates during zinc therapy. Mean baseline liver copper concentration was 255 micrograms/gm dry weight, whereas the mean value after therapy was 239 micrograms. No patient demonstrated hepatic reaccumulation of copper during zinc therapy. Copper balance, 24-hour urinary copper excretion, and nonceruloplasmin plasma copper concentration all indicated good copper control during zinc therapy. Hepatic zinc concentration increased twofold to threefold over baseline values but no toxicity was seen. Hepatic zinc concentrations appeared to reach a plateau after 12 to 18 months of zinc therapy. We conclude that oral zinc as the sole maintenance therapy in patients with Wilson's disease prevents hepatic reaccumulation of copper.

Gastroduodenal ulcerations in patients receiving selective hepatic artery infusion chemotherapy.

Ninety-three patients with liver metastases underwent selective hepatic arterial infusion of chemotherapeutic agents through a surgically implanted hepatic artery catheter and pump. Fourteen patients who developed upper gastrointestinal symptoms at some time during the course of treatment were found to have gastroduodenal disease endoscopically. The severity of symptoms did not necessarily correlate with severity of endoscopic findings. There was no temporal relation between 5-fluoro-2'-deoxuridine infusion and symptoms; however, with mitomycin C, symptoms worsened in five of eight patients within 2 wk of the initial injection. Patients who received mitomycin C had more severe endoscopic findings and two of the 14 patients required partial or total gastrectomy. When biodegradable starch microspheres were coadministered with mitomycin C this was not associated with a higher incidence of gastroduodenal disease. The early experience with therapy using this system has been associated with a significant incidence of upper gastrointestinal symptoms. The presence of gastrointestinal symptoms in such patients should alert one to potentially serious disease.

Correlation of histopathologic evidence of disease activity with the presence of immunoglobulin-containing cells in the colons of patients with inflammatory bowel disease.

Immunofluorescence of formalin-fixed, paraffin-embedded tissues was performed to study the plasma cell population in 114 colonic specimens from 58 patients. Correlation of the histopathologic stage of disease activity with the isotypes and numbers of immunoglobulin-containing cells in the lamina propria demonstrated highly significant (P less than 0.001) increases in the mean numbers of IgG- (18-fold), IgA- (twofold) and IgM- (sixfold) containing cells in specimens from patients with active inflammatory bowel disease as compared with control specimens. Increased numbers of immunoglobulin-containing cells were uncommon in inactive inflammatory bowel disease and in reactive mucosa. No deposition of immunoglobulin-containing immune complexes was found at any stage of disease activity. These findings suggest that immune complex-mediated damage does not play a major role in the epithelial damage in inflammatory bowel disease. In future studies, it will be of importance to determine whether the antibody from immunoglobulin-containing cells seen in patients with inflammatory bowel disease can effect damage via an antibody-dependent cell-mediated cytotoxicity mechanism.

Comparative bioavailability study of two tablet formulations of cimetidine.

A two-way crossover bioavailability study of two commercial cimetidine formulations was performed on 24 healthy male volunteers. Drug was administered after an overnight fast and plasma samples were withdrawn periodically for 12 h. Urine was collected throughout the study period. Results indicated that the two formulations were bioequivalent since no statistically significant difference in means was detected for any of the parameters studied. Extensive interpatient variation in cimetidine blood concentration was observed during both treatments.