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Objective: To determine the prevalence of antibodies to hepatitis C virus (anti-HCV) among patients undergoing liver transplantation and the relation between anti-HCV and post-transplant hepatitis.Design: Retrospective cohort.Patients: Serum samples from 128 patients who underwent liver transplantation. Sixty-six patients who had 6 months of follow-up and for whom both pretransplant and post-transplant serum samples were available were included in a study to asses the relation between anti-HCV and post-transplant hepatitis.Measurements: Sera were tested for anti-HCV using an enzyme-linked immunosorbent assay (ELISA) and, if positive, two confirmatory tests were done. Patients had a biopsy every week until two specimens showed no abnormal findings.Main Results: Only patients with chronic non-A, non-B hepatitis (15 of 30; 50%), alcoholic cirrhosis (7 of 19; 37%), and chronic hepatitis B infection (3 of 11; 27%) were anti-HCV positive. No patient with another form of chronic liver disease or with acute liver failure due to non-A, non-B hepatitis was anti-HCV positive. After transplantation, loss of anti-HCV was frequent and acquisition rare. Hepatitis developed in the graft in 17% of patients, but the incidence was similar among anti-HCV negative and anti-HCV-positive patients.Conclusions: Hepatitis C virus is a common cause of chronic liver disease in patients requiring liver transplantation, but anti-HCV is rarely found in patients with acute liver failure. Previous HCV infection, based on detection of anti-HCV, is not an independent risk factor for post-transplant hepatitis. [ABSTRACT FROM AUTHOR]

Deals with a study which examined the prevalence of anti-hepatitis C virus (HCV) antibodies and the factors that predispose patients to have antibody to HCV. Methods; Results; Discussion.

We investigated the effect of thalidomide, a compound with immunomodulatory and antiangiogenic properties, on lipopolysaccharide (LPS)-mediated induction of cyclooxygenase-2 (Cox-2) and prostaglandin (PG) biosynthesis in murine macrophages. Thalidomide caused a dose-dependent inhibition of LPS-mediated induction of PGE(2) synthesis in RAW 264.7 cells. The induction of Cox-2 protein and mRNA by LPS was also suppressed by thalidomide. Based on the results of nuclear run-off assays and transient transfections, treatment with LPS stimulated Cox-2 transcription, an effect that was unaffected by thalidomide. Thalidomide decreased the stability of Cox-2 mRNA. A series of structural analogues of thalidomide also inhibited LPS-mediated induction of Cox-2 and PGE(2) synthesis. Taken together, these data provide new insights into the antineoplastic and anti-inflammatory properties of thalidomide.

Background & Aims: Thalidomide decreases production of tumor necrosis factor alpha, a proinflammatory cytokine associated with Crohn's disease (CD). In this study the safety, tolerance, and efficacy of low-dose thalidomide were evaluated for treatment of moderate-to-severe, steroid-dependent CD., Methods: Twelve adult male patients with Crohn's Disease Activity Index (CDAI) scores of > or = 250 and < or = 500 despite > or = 20 mg prednisone/day were enrolled. The first 6 patients received 50 mg thalidomide every night, the next 6 received 100 mg every night. Steroid doses were stable during the first 4 weeks of treatment, then tapered during weeks 5-12. CDAI was used to assess response., Results: (1) Disease activity improved consistently in all patients during weeks 1-4: 58% response, 17% remission. (2) Clinical improvement was generally maintained despite steroid taper during weeks 5-12. All patients were able to reduce steroids by >/=50%. Forty-four percent discontinued steroids entirely. In weeks 5-12, 70% of patients responded and 20% achieved remission. (3) Side effects were mild and mostly transient, with the most common being drowsiness, peripheral neuropathy, edema, and dermatitis., Conclusions: Low-dose thalidomide appears to be well tolerated and effective over a 12-week period. Results of this pilot study support the need for controlled multicenter trials of thalidomide for treatment of CD.

Hepatitis-associated aplastic anemia (HAAA) is an uncommon disorder that usually is not due to hepatitis A or B virus infection. Hepatitis C virus (HCV) seropositivity is infrequently observed in aplastic anemia (AA) patients who have not been extensively transfused. However, HCV seropositivity may not be detected until several weeks or months after viral infection and AA patients may exhibit defective humoral immunity. Therefore, we evaluated sera from AA patients for the presence of HCV viremia using a reverse transcriptase polymerase chain reaction (RT-PCR) based assay and several serologic assays for HCV antibodies. Serum samples from 90 AA patients who presented to the UCLA Medical Center between March 1984 and February 1990 were analyzed. Overall, 17 patients were found to have HCV viremia by RT-PCR assay, of whom 14 had a positive second-generation HCV enzyme immunoassay (EIA-2) and only 6 were EIA-1 reactive. The frequency of HCV viremia increased with the duration of time between diagnosis and sample procurement, and the number of blood products transfused prior to sampling (P = 0.026). No patient who received fewer than 20 U of blood products or who was sampled less than 20 days after diagnosis had a positive HCV RT-PCR result. Of four patients with hepatitis-associated AA (HAAA), one who was sampled 23 days after diagnosis had hepatitis C viremia and a reactive EIA-2 assay. Therefore, the high frequency of HCV viremia in this patient population is most likely due to transfusion with contaminated blood products prior to the introduction of routine blood donor screening for HCV.

Objective: We evaluated the efficacy and safety of a twice-daily dosage regimen of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal reflux disease (GERD) in patients with moderate intensity heartburn and no history of erosive esophagitis., Methods: After a 2-wk, single-blind, placebo run-in period, 398 patients who continued to experience moderate intensity heartburn were randomized to either placebo (n = 196) or cisapride 20 mg (n = 202) twice daily for 4 wk., Results: Compared with placebo, cisapride significantly reduced scores for daytime and nighttime heartburn (p < 0.001), total regurgitation (p < 0.001), eructation (p = 0.04), and early satiety (p = 0.04). Cisapride 20 mg b.i.d. was also superior to placebo in reducing total use of rescue antacid medication (p < 0.001); reducing, in concordance analyses, daytime and nighttime heartburn with antacid usage (p < 0.001); increasing the percentage of heartburn-free days and antacid-free nights (p < 0.5); and increasing the percentage of patients self-rated as having minimal or better symptomatic improvement (p = 0.01). Cisapride 20 mg b.i.d. was well tolerated. The most common adverse event in the cisapride group was diarrhea, reported by 10% of patients, compared with an incidence of 4% in the placebo group., Conclusion: Cisapride 20 mg b.i.d. was shown to be effective and safe for the short-term treatment of daytime and nighttime heartburn and for other symptoms associated with mild-moderate GERD.

Identification of inefficiencies is a first step to improving the quality of gastrointestinal (GI) care at the most reasonable cost. This analysis used administrative data to examine the healthcare utilization and associated costs of the management of GI illnesses in a 2.5 million-member private managed care plan containing many benefit designs. An overall incidence of 10% was found for GI conditions, with a preponderance in adults (patients older than 40 years) and women. The most frequently occurring conditions were abdominal pain, nonulcer peptic diseases, lower GI tract diseases, and other GI tract problems. These conditions, along with gallbladder/biliary tract disease, were also the most costly. Claims submitted for care during GI episodes averaged $17 per member per month. Increasing severity of condition was associated with substantial increases in utilization and costs (except for medication use). For most GI conditions, approximately 40% of charges were for professional services (procedures, tests, and visits) and 40% of charges were for facility admissions. The prescription utilization analysis indicated areas where utilization patterns may not match accepted guidelines, such as the low use of anti-Helicobacter pylori therapy, the possible concomitant use of nonsteroidal anti-inflammatory drugs in patients with upper GI diseases, and the use of narcotics in treating patients with lower GI disease and abdominal pain. Also, there was no clear relationship between medication utilization and disease severity. Thus, this analysis indicated that GI disease is a significant economic burden to managed care, and identified usage patterns that potentially could be modified to improve quality of care.

Hepatitis C virus (HCV) has been detected in peripheral blood mononuclear cells (PBMC) from persons chronically infected with HCV. Reports describe altered monocytic function during HCV infection; however, the immunologic consequences of HCV tropism for human macrophages are not well defined. Thus, the possibility that HCV infection of monocytes may alter patterns of cytokine release was investigated. The in vitro secretion of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta in response to phorbol myristate acetate-stimulated monocytes and PBMC of subjects chronically infected or not infected with HCV was compared. TNF-alpha and IL-1 beta release were suppressed in cells from infected subjects. Although virus-induced immunosuppression is not a major clinical syndrome of HCV infection, the findings support a hypothesis that HCV can induce selective defects in antigen-presenting cells that may enhance the ability of HCV to persist despite the presence of cytotoxic killer cells and antibody directed against HCV.

Plasmid DNA condensed by polylysine enhanced cationic-liposome-mediated transfection of Hep G2 cells. The luciferase expression plasmid pCMVL was complexed with the polycation poly-L-lysine and mixed with liposomes that contained a 1:1 molar ratio of the cationic lipid 1,2-dioleoyloxy-3-trimethyl-ammoniumpropane, with the neutral phospholipid 1,2-di-(cis-9-octadecenoyl)-sn-glycero-3-phosphoethanolamine. Polylysine enhanced cationic-liposome-mediated transfection of the hepatoblastoma cell line Hep G2 9-fold compared with pCMVL complexed alone with liposomes. The ratio of cationic to anionic charge of the polylysine-pCMVL complexes, and the quantity of cationic liposomes, are important determinants for optimal transfection of Hep G2 cells.