A randomized trial of prolonged high dose of interferon plus ribavirin for hepatitis C patients nonresponders to interferon alone.

Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN) alone with the standard dose of IFN [3 million units (MU) thrice weekly (TIW)] plus ribavirin for 24 weeks has yielded low sustained virological response (SVR), averaging 8%. The aim of the present, open-labelled, randomized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders. One hundred and fifty-one patients were randomized to receive 5 MU daily of IFN alfa-2b (group 1, n = 73) or 5 MU TIW of IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention-to-treat analysis, the sustained virological response (SVR) at 24-week follow-up was 33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and 18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4 patients the SVR was 29 and 11% for age younger or older than 40 years. Compared with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to retreatment was 3.0-fold (1.17-8.0) in younger genotype 1/4 patients and 8.4-fold (3.0-23.29) in older genotype 1/4 patients. In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to benefit. Induction therapy does not improve SVR.

Efficacy of prolonged 5 million units of interferon in combination with ribavirin for relapser patients with chronic hepatitis C.

summary. Retreatment of relapser patients with chronic hepatitis C with the standard dose of interferon (IFN) of 3 million units (MU) thrice weekly (tiw) plus ribavirin for 24 weeks achieves a sustained response in 30 and 73% of patients with genotype 1 and 2 or 3, respectively. The aim of this study was to evaluate the efficacy and safety of IFN alpha-2b induction therapy, followed by prolonged treatment with a high dose of IFN alpha-2b plus ribavirin in relapser patients. A total of 119 patients were randomized to receive IFN alpha-2b 5 MU daily (Group A: 59 patients) or IFN alpha-2b 5 MU tiw (Group B: 60 patients) for 4 weeks followed by IFN (5 MU tiw) and ribavirin (1000-1200 mg/day) for 48 weeks in both groups. The primary end point was hepatitis C virus (HCV)-RNA clearance at week 24 after the end of treatment. A sustained virological response (SVR) was achieved in 68 and 60% of Group A and B patients, respectively (P = 0.37). Logistic regression analysis identified genotype 2 or 3 as the only independent factor associated with response, whereas induction regimen and baseline viraemia levels did not affect the response. The overall SVR was 53 and 72% in patients with genotype 1 or 4 and 2 or 3, respectively. In conclusion, induction IFN therapy does not enhance the SVR to a 48-week combination therapy. Our study suggests that relapsed patients with genotype 1 or 4 may achieve significant response rates of approximately 50%, if retreated with 5 MU tiw IFN plus ribavirin for 48 weeks.

Liquid stool incontinence with severe urgency: anorectal function and effective biofeedback treatment.

The motor and sensory function of the anorectum is well characterised in patients with solid stool incontinence. Fewer data are available in the case of liquid stool incontinence. Anorectal sensorimotor function was studied in 16 patients with liquid stool incontinence and severe urgency (10 with diarrhoea) unresponsive to conventional medical treatment, and in 16 healthy volunteers. The only significant difference found between incontinent patients and controls was a reduction in squeeze duration (p < 0.0001). Fourteen patients were selected to receive biofeedback treatment. Treatment was associated with a substantial improvement in continence in 12 patients and with a significant decrease in urgency (p < 0.05). Bowel frequency was not significantly influenced. Most patients showed a persistent improvement in anal motor function. Functional parameters were not predictive of outcome of treatment; the poor responders showed major psychological problems. In conclusion, an anal motor deficit is often present in disabling liquid stool incontinence. Biofeedback may improve anal continence in 75% of patients.

Effect of nifedipine on mouth-to-cecum transit of liquid meal in normal subjects.

Nifedipine has been shown to inhibit small bowel motility and to increase ileal water and electrolyte absorption in animals, but few reports are available in human subjects. The drug has been reported to influence esophageal and colon motility in man, without affecting gastric emptying. We performed a double-blind, controlled, crossover, randomized study to investigate the effect of oral nifedipine 30 mg vs placebo on the orocecal transit time of a lactulose-labeled, liquid caloric meal in nine healthy volunteers, and its correlation with plasma nifedipine concentration. The transit time was measured using the breath hydrogen test. The drug study was preceded by a reproducibility study, which showed a mean variation in transit time of 8.3% (+/- 1%, SE). Nifedipine significantly increased orocecal transit time compared to placebo (nifedipine 131 +/- 16; placebo 104 +/- 14.5 min; P < 0.05). This effect correlated well with plasma nifedipine concentration expressed as area under the curve (r = 0.92, P < 0.004). Nifedipine 30 mg significantly delays orocecal transit of a liquid caloric meal. The small bowel is likely to be the site of action. These findings may afford a rational basis for investigating a possible antidiarrheal role of nifedipine.

Does the combination of a human fibrin sealant with ranitidine accelerate the healing of duodenal ulcer?

Human fibrin sealant (Tissucol) has been used in surgery for its haemostatic and sealing actions and stimulating effect on tissue regeneration. Recently it has been used in endoscopy, but controlled trials are not yet available. The aim of this study was to evaluate the efficacy of Tissucol on the healing rate of duodenal ulcers (DU). Thirty nine previously untreated DU patients received ranitidine 150 bid plus endoscopically applied either placebo (19 patients) or Tissucol (20 patients). Sixty-five percent of the patients in the Tissucol group and 21% in the control group healed after two weeks (p less than 0.02), 75 and 52.6% respectively after 4 weeks (NS). The endoscopic application of Tissucol seems to influence the healing of duodenal ulcer and its use could be suggested in selected patients with DU.

Isoamylase determination by isoelectric focusing in pancreatic disorders. A potential clinical aid.

Isoamylase analysis by isoelectric focusing was performed in the serum of 30 healthy volunteers, 65 patients with acute or chronic pancreatic diseases, nine with acute abdomen, four with macroamylasemia, and four with duodenal duplication. In controls, up to four fractions (2 salivary, 2 pancreatic) were found; the pancreatic fractions were as a mean 44.7% (SD 8.6) of total. In chronic pancreatitis, only patients with steatorrhea showed a significant reduction of pancreatic isoamylase (p less than 0.001). In all patients with acute pancreatitis or pseudocysts, an additional fraction (similar to the so-called P3 fraction) was resolved. Moreover, additional isoenzymes were found in all patients with severe acute pancreatitis or pseudocysts, and not in controls or patients with mild forms, acute abdomen or duodenal duplication. A similar pattern was shown in a stored control serum after 10 mo at -20 degrees C. These fractions disappeared after successful surgical drainage. No specific alteration was found in pancreatic cancer. Amylase fractionation by isoelectric focusing can be used to confirm an acute pancreatitis, and to monitor patients with pancreatic pseudocysts and collections after surgical drainage.