Comparative effects of different doses of ribavirin plus interferon-alpha2b for therapy of chronic hepatitis C: results of a controlled, randomized trial.

Compared to either drug alone, therapy with the combination of ribavirin and interferon-alpha leads to improved rates of response in patients with chronic hepatitis C. Side effects often mandate downward dose adjustment or cessation of therapy, and the optimal dose of ribavirin has not been established. The aim of this study was to learn whether 600 mg ribavirin per day would prove as efficacious as 1,000-1,200 mg/day when combined with interferon (3 million units thrice weekly) for therapy of patients previously treated with standard interferon who had failed to respond or who had relapsed. We enrolled 69 patients with chronic hepatitis C and compensated liver disease: 45 were men, 65 were Caucasian, 48 were infected with genotype 1 hepatitis C virus. By random assignment, 35 received 600 mg ribavirin/day (group A), whereas the other 34 received 1,000 mg (< or = 75 kg body wt) or 1,200 mg/day (>75 kg body wt) (group B). At baseline, the two groups were well matched for demographic and laboratory features. In both groups, mean serum levels of alanine aminotransferase (ALT) and hepatitis C viral (HCV) RNA levels fell promptly and remained significantly lower than baseline throughout 24 weeks of therapy. There was no significant difference in mean levels of ALT or HCV RNA during therapy or at the end of follow-up (24 weeks after cessation of therapy). At the end of 24 weeks of posttherapy follow-up, 12 patients in each group had undetectable HCV RNA in serum, whereas 11 (31%) in group A and 9 (26.5%) in group B had normal serum ALT levels. The lower doses of ribavirin (group A) were tolerated better. In conclusion, in previous nonresponders or relapsers to interferon done, combination therapy with interferon-alpha2b (3 MU thrice weekly) + 600 mg ribavirin/day is tolerated better and is as effective as interferon plus higher (standard) doses of ribavirin (1,000-1,200 mg/day).

Intrapancreatic ciliated enteric duplication cyst presenting with biliary obstruction.

A 46-yr-old man presenting with biliary obstruction from an intrapancreatic tumor underwent pancreaticoduodenectomy. The pathology report showed the tumor to be an enteric duplication cyst. Diagnostic imaging features and operative management are discussed.

Cytomegalovirus gastritis associated with pseudolymphoma.

A man who previously had several episodes of upper gastrointestinal hemorrhage from erosive gastritis developed recurrent hemorrhage. Endoscopy showed punctate hemorrhages in the fundus and body of the stomach, plus a discrete area of thickened folds in the anterior wall. Biopsies revealed a dense mucosal infiltrate that included cytomegaloviral inclusions. Bleeding continued despite treatment with blood transfusions and ranitidine. Because of continued hemorrhage, and to distinguish the cause of the thickened folds, surgical biopsy was performed that showed lymphoid germinal formations, characteristic of pseudolymphoma. He responded to i.v. ganciclovir and has had no further bleeding during 2 years of follow-up.

Effects of phototherapy on the activity of microsomal mixed-function monooxygenases and the pharmacokinetics of [14C] hexobarbital in jaundiced and heterozygous Gunn rats.

We assessed the effects of in vivo phototherapy of Gunn rats on the activity of hepatic microsomal mixed-function monoxygenases and on the in vivo pharmacokinetics of [14C]HB. In experiment 1 no serial changes were seen in activities of hexobarbital hydroxylase or benzo(a)pyrene hydroxylase in hepatic microsomes isolated after 2, 4 or 7 days from homozygous jaundiced female Gunn rats exposed to continuous phototherapy or in matched Gunn rats maintained under dim light. In experiment 2 homozygous jaundiced (jj) and heterozygous nonjaundiced (Jj) Gunn rats of both sexes each received i.v. [14C]HB on 2 successive days. In random order, each was exposed on the first or second day to phototherapy for 5.5 hr, beginning 0.5 hr before the administration of HB; otherwise, each was kept under dim light. Plasma [14C]HB in arterial blood samples was separated chromatographically from its labeled metabolites, and biexponential plasma disappearance curves for [14C]HB were analyzed by a SAAM-23 computer program. Clearances in female rats were much slower. In both sexes, the total body clearance and volume of distribution of HB were decreased by 20% during phototherapy of the jj but not the Jj rats; terminal plasma half-life was unchanged. In experiment 3 direct in vitro illumination of [14C]HB did not cause photodegradation of this compound, despite the presence of albumin with or without bilirubin.

The advantages of the 30-cm flexible sigmoidoscope over the 60-cm flexible sigmoidoscope.

To determine the optimal length of the flexible fiberoptic sigmoidoscope we performed a randomized, blinded comparison study of the standard 60-cm instrument with a prototype 30-cm instrument with identical design features. Ninety-six male patients referred for symptom evaluation underwent examination with both instruments in random order by different examiners; positive examinations were followed by colonoscopy or surgery. Performance of the 30-cm sigmoidoscope compared with the 60-cm instrument revealed that the former was significantly more likely to yield a complete examination (74 vs. 32 examinations, p less than 0.002), took less time to perform (6.4 vs. 9.8 min, p less than 0.0001), and was more acceptable to patients and physicians. The 30-cm instrument was not significantly less effective than the 60-cm instrument in detecting polyps (21 vs. 25), adenocarcinoma (six for each), and inflammatory lesions. For these reasons, we conclude that the 30-cm flexible sigmoidoscope has a role in the evaluation of colorectal complaints.

Purification and characterization of human liver-specific membrane lipoprotein (LSP).

A liver-specific lipoprotein (LSP) which is present in 105,000 g supernatants of human liver has previously been shown to produce a lesion resembling chronic active hepatitis in rabbits immunized with human liver fractions containing this lipoprotein. In addition, it has been implicated as the principal target antigen involved in the liver cell cytotoxicity exhibited in vitro by lymphocytes from patients with chronic active hepatitis. The organ-specificity and species cross-reactivity of LSP is confirmed. Although very labile, is has been prepared in a stable form by gel filtration of Sepharose 6B in a Tris buffer containing 1 mm disodium EDTA. LSP is also stable in a borate buffer containing EDTA but is unstable in a number of other buffer systems tested. When prepared by this method it contains approximately 2% albumin as the only detectable contaminant. Gel filtration studies on the apoprotein of LSP revealed that it has an apparent mol. wt of between 4 X 10(6) and 20 X 10(6). SDA-polyacrylamide gel electrophoresis indicated that the lipoprotein may be composed of up to thirteen sub-units of different molecular sizes.