Efficacy of high-dose interferon in combination with ribavirin in patients with chronic hepatitis C resistant to interferon alone.

OBJECTIVE: Interferon combined with ribavirin has efficacy in the treatment of patients with chronic hepatitis C virus (HCV) infection. However, its utility in patients who have not responded to prior interferon therapy is not clear. Furthermore, the effect of using an increased dose of interferon in combination with ribavirin in patients with chronic hepatitis C resistant to conventional doses of interferon is not known. The aim of our study was to evaluate the effect of high-dose interferon in combination with ribavirin on the efficacy of treating patients with chronic hepatitis C resistant to interferon monotherapy in a large multicenter trial. METHODS: We randomized 154 patients with chronic hepatitis C who failed to achieve a sustained response with prior interferon therapy to receive either 3 or 5 MU of interferon alpha-2b and ribavirin (1000-1200 mg/day) for 12 months. There were 119 patients who had not responded and 35 who initially responded but relapsed after prior interferon monotherapy. Serum HCV RNA levels were measured at entry, 6, and 12 months of treatment and at the end of a 6-month follow-up period. RESULTS: The mean age of the subjects was 47 yr (range 28-68 yr), and 110 (71.4%) were men. One hundred thirty-two patients (86%) had HCV genotype 1, whereas 21 (14%) had cirrhosis. Eighty-one subjects (53%) were randomized to receive 3 MU of interferon alpha-2b. Fifteen of 35 relapse subjects (43%) and 12 of 119 prior nonresponder entrants (10%) achieved a sustained virological response to the 12-month course of treatment. Overall, 11 of 81 patients (14%) receiving 3 MU, and 16 of 73 patients (22%) receiving 5 MU of interferon maintained an undetectable HCV RNA level after cessation of therapy. The difference in sustained response rates between the two interferon dosage groups did not reach statistical significance (p = 0.09). However, among the nonresponder patients alone, there was an increased sustained response in the high-dose interferon group compared with the standard interferon dose group (15.5% vs 4.9%, p = 0.055). Twenty-six patients discontinued therapy before 6 months, including 10 patients (12.3%) in the 3-MU and 16 patients (21.9%) in the 5-MU groups (p = 0.17). CONCLUSIONS: Sustained virological response to combined interferon alpha-2b and ribavirin was significantly higher in relapse patients than those who did not respond to prior interferon monotherapy. Although, when all treated patients were analyzed, there was no significant difference in sustained response between subjects receiving 3 and 5 MU of interferon, among the prior nonresponder patients, treatment with 5 MU of interferon with ribavirin resulted in a slightly increased response compared with treatment with the standard interferon dosage. The tolerability of the treatment regimens was comparable.

The effect of cisapride on segmental colonic transit time in patients with spinal cord injury.

OBJECTIVES: The pathophysiological consequences of spinal cord injury (SCI) on function of the colon are complex and poorly understood. Regardless of the mechanism, many patients with SCI have deficient bowel control, which is frustrating and difficult to treat. We designed a study to assess whether a new prokinetic medication, cisapride, might be useful in this setting. METHODS: Total and segmental colonic transit time were measured using the radiopaque marker technique in nine subjects with spinal cord injury and seven control subjects after the double-blind administration of cisapride (10 mg q.i.d.) or placebo. RESULTS: In five quadriplegic subjects with prolonged colonic transit time, administration of cisapride was found to reduce left-sided colonic transit time from 24.2 to 13.8 h. In three of these five subjects, cisapride administration resulted in subjective improvement. No effect of cisapride on right-sided, rectosigmoid, or total colonic transit time was observed. CONCLUSION: The data suggest that cisapride might be a useful adjunctive measure in treating a subset of SCI patients with colonic inertia, but a larger study is needed before this can be routinely recommended.

Endoscopic management of primary sclerosing cholangitis: review, and report of an open series.

Of the multiple treatment options available to physicians managing patients with primary sclerosing cholangitis (PSC), no single form of therapy has proven to be efficacious or to improve the clinical outcome of affected patients. Surgical and radiological methods require multiple procedures which are associated with increased morbidity, the most serious being sepsis. Endoscopic therapy is safer and easier to perform, and has been shown to provide symptomatic as well as objective improvement in affected patients. It, too, is associated with some complications, although less serious than other alternative treatments, but it is not effective in protracted disease. The potential of overlooking or missing cholangiocarcinoma is more apparent when nonsurgical techniques are employed. In this review we will discuss the various endoscopic treatment modalities utilized in PSC disease, and include the results that have been obtained with these techniques since they were incorporated into our armamentarium in 1983.

Vitamin B6 status of young men, women, and women using oral contraceptives.

Vitamin B6 intakes of 33 males, 73 females, and 46 females using oral contraceptives, all 18- to 25-year-old students, were compared to coenzyme stimulation of erythrocyte alanine aminotransferase activities of blood samples obtained from these subjects in order to ascertain the vitamin B6 status and perhaps the requirements of this population group. Trained interviewers obtained 24-hour recalls; subjects supplied 2-day food records. Dietary record analyses revealed that students reported consuming slightly less kilocalories, more protein, and considerably less vitamin B6 than the 1974 recommended dietary allowances. Erthrocyte alanine aminotransferase activities, with and without additional coenzyme, of blood samples from the 3 groups were significantly different from each other; per cent coenzyme stimulation of enzymatic activity of females and females on oral contraceptives were significantly different from each other. Enzyme data were not significantly affected by race, age, income, food budget, preparation of own food, frequency of eating out, or vitamin supplementation. Several subjects in all 3 groups had high per cent stimulation values which is considered to be indicative of subclinical vitamin B6 deficiency. Subjects with values near 0 per cent stimulation had varying vitamin B6 intakes thus perhaps indicating large individual variations in vitamin B6 requirements.

PIP: The Vitamin-B6 with content of diets of 33 young adult male students, 73 female students, and 46 female students taking oral contraceptives (OCs) were compared the percent coenzyme stimulation of erythrocyte alanine aminotransferase activity (EAA) in blood samples. 24-hour recall data were significantly higher than that obtained from 2-day consumption records (p less than .05). Males consumed significantly greater quantities of kilocalories, protein, and Vitamin-B6 than either of the female groups ( less than .01). Intakes for both groups of females were similar. Only proteins were consumed in amounts above the 1974 recommended daily allowances. EAA activities, with and without coenzyme stimulation, were significantly different among the 3 groups (p less than .01). The percent coenzyme stimulation of enzyme activity was significantly different between the female groups (p less than .01). Race, age, income, food budget, preparation of food, and vitamin supplements did not markedly affect enzyme data. High percent stimulation values in several subjects in each group indicated subclinical Vitamin-B6 deficiency. The results indicate that the Vitamin-B6 requirements of individuals in each group varied considerably.