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).

Diffuse pagetoid squamous cell carcinoma in situ of the esophagus: a case report.

BACKGROUND: In Western countries, esophageal squamous cell carcinoma is usually advanced at presentation and is rarely diagnosed in situ. The authors studied an in situ squamous cell carcinoma that occupied the entire mucosa of a 9 cm length of esophagus, causing dysphagia for solid food in a woman aged 68 years. METHODS: The esophagectomy specimen contained a circumferential region of depressed tan mucosa in the middle and lower thirds, bordered above and below by normal squamous mucosa, without ulcer, stricture, or mass. The entire lesion was submitted for histology and evaluated with immunostains for cytokeratins and markers of Paget's cells, p53 mutation, and proliferation. RESULTS: The lesion involved 45 cm2 of mucosa. Large, atypical cells with frequent mitoses occupied the basal layers of the squamous epithelium and were often separated from more superficial maturing cells by acantholysis. Pagetoid spread of tumor cells into nonneoplastic surface and gland duct epithelium was prominent. The tumor cells expressed cytokeratins of low molecular weight, p53 gene product, and proliferating cell nuclear antigen (PCNA), but lacked markers usually seen in Paget's cells in the breast or vulva. No invasion was evident. CONCLUSIONS: This extensive in situ squamous cell carcinoma of the esophagus resulted from pagetoid spread of tumor cells. These cells had a phenotype suggestive of origin from primitive epidermal stem cells and also had overexpressed p53 and PCNA, but they lacked the capacity to penetrate the basement membrane. Flat, erythematous areas of esophageal mucosa seen during endoscopy could represent early squamous cell carcinoma and should be biopsied.

Vascular compression of the esophagus: a manometric and radiologic study.

This study was undertaken to determine the prevalence of vascular compression in manometric tracings and to determine whether these findings had any clinical significance. Vascular compression, defined as a localized area of elevated intraesophageal resting pressure > 4 mm Hg with superimposed cyclic pressure spikes with a frequency of 60-100/min, was noted in 55 of 241 consecutive tracings. The groups with and without vascular compression were similar with regard to mean age, sex, and prevalence of dysphagia. Radiographs were available for 29 of the 55 and showed compression in 18, but there was no relationship with the manometric findings, except for a trend towards finding a positive esophagogram with amplitudes > 16 mm Hg. Eleven tracings showed absent "relaxation" of this elevation of pressure in response to swallows, and five of six available esophagograms showed a corresponding area of compression. We conclude that manometric evidence of vascular compression is common and generally has no clear relationship with esophagographic findings or dysphagia. However, the combined findings of marked increases in pressure and absence of relaxation in response to swallows may indicate evidence for a vascular cause of dysphagia.

Detection of complement activation in immune complex diseases: six methods compared.

We compared the performance of six complement tests: electrophoresis, immunofixation, immunoelectrophoresis, and nephelometric quantifications of C3, C4, and C3d. We used 123 blood samples from 60 control subjects and 63 patients with immune complex diseases: systemic lupus erythematosus, idiopathic thrombocytopenic purpura, rheumatoid arthritis, acquired immunodeficiency syndrome, renal diseases, vasculitis, cryoglobulinemia, Gram-negative bacteremia, Hashimoto's thyroiditis, rheumatic heart disease, malaria, and chronic active hepatitis. Immunofixation and quantification of C3d were better for detecting complement activation, their sensitivity rates (90.5% and 89.3%, respectively) being higher than those of the other tests studied. Immunofixation is a relatively simple and inexpensive test, provides good resolution of protein bands, and yields results that are easily quantified with a densitometer. Nephelometry of C3d provides more rapid and accurate quantitative results than immunofixation, but commercial reagents are not yet available. The causes of false-positive results in complement tests and the mechanisms of complement activation in AIDS are also discussed.