Biomedical subjects
Publications and source records attributed to R S Koff.
Development of colon cancer is now believed to result from a series of inherited or acquired mutations in DNA. Convincing evidence that colonoscopic polypectomy prevents colorectal cancer is now available. A consensus panel recommended that all patients with duodenal and gastric ulcers who are infected with H pylori on first presentation be treated with antimicrobial agents.
OBJECTIVE: To estimate the cost-effectiveness of interferon-alpha 2B for the treatment of patients with chronic hepatitis B infection who are positive for hepatitis B e antigen (HBeAg). DESIGN: Meta-analysis of nine randomized controlled trials and cost-effectiveness analysis, projecting the clinical and economic outcomes expected from changes in serologic markers of hepatitis B viral replication. DATA SOURCES: MEDLINE search, expert panel opinion, hospital cost data, and adjusted physician charges. PATIENTS: 552 patients with confirmed chronic hepatitis B infection who were positive for HBeAg. INTERVENTION: Interferon-alpha 2b. MEASUREMENTS: Lifetime incidence of cirrhosis and hepatocellular carcinoma; life expectancy; quality-adjusted life expectancy; and costs and marginal cost-effectiveness ratios from a societal perspective. RESULTS: Interferon-alpha 2b increases the likelihood of becoming negative for HBeAg from 9.1% to 45.6% (difference, 36.5%; 95% CI, 23.7% to 49.2%) and of becoming negative for hepatitis B surface antigen from 1.7% to 7.7% (difference, 6.0%; CI, 2.8% to 9.3%) in the first year. For a 35-year-old person with chronic hepatitis B who is HBeAg positive, our analysis suggests that interferon-alpha 2b will increase life expectancy by 3.1 years or 3.4 quality-adjusted life-years and will decrease projected lifetime costs, even if future savings are discounted; thus, interferon-alpha 2b is the dominant strategy. Even with the model biased strongly in favor of standard care, the marginal cost-effectiveness ratio of interferon did not exceed $12,000 per life-year gained. CONCLUSIONS: Interferon-alpha 2b should prolong life and lower costs for patients with chronic hepatitis B who are HBeAg positive.
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OBJECTIVE: To examine the association between current alcohol consumption and major upper gastrointestinal bleeding. METHODS: In a case-control study in the United States, Sweden, and Hungary, 1004 incident cases with upper gastrointestinal bleeding without predisposing factors were compared with 2446 controls. Relative risks for categories of alcohol consumption (based on the number of drinks currently consumed/wk) were estimated using logistic regression; the potential confounding effects of cigarettes, nonsteroidal anti-inflammatory drugs, and other factors were controlled simultaneously. RESULTS: Compared with drinkers of < one drink/wk, the relative risks among other current drinkers ranged from 0.8 for 1-6 drinks/wk to 6.3 for > or = 35 drinks; the trend was statistically significant (p < 0.001). A significantly increased relative risk was seen for the heaviest consumption category within various subgroups: gastric and duodenal hemorrhage; males and females; age < 60 yr and > or = 60 yr; and those who consumed beer, wine, liquor, or a combination of beverages. CONCLUSIONS: These findings provide evidence that consumption of alcohol increases the risk of major gastric and duodenal bleeding in nonpredisposed individuals.
Lectin-affinity analyses with Lens culinaris agglutinin (LCA) and other lectins have demonstrated that the glycosylation of alpha-fetoprotein (AFP) secreted by hepatocellular carcinomas (HCC) is frequently altered when the serum AFP concentration is increased. To determine if AFP LCA-binding properties are altered in patients with HCC whose serum AFP concentration is normal, the percentage of LCA-binding AFP in serum from white newborns, white normal adults, white patients with chronic hepatitis and hereditary tyrosinemia and white and black patients with HCC were determined. The serum LCA-binding AFP fraction was low in newborns (1-4%) and normal adults (1-8%). There was a significant increase in LCA-binding AFP in patients with chronic hepatitis (10-24%) and hereditary tyrosinemia (5-35%). The AFP LCA-binding fraction was clearly abnormal (greater than 40%) in three of the white patients with an HCC and a normal serum AFP concentration, and the range of values (10-63%) in these HCC patients was similar to that seen in both white and black patients with HCC accompanied by increased AFP concentrations.
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Hepatitis A is an acute, necroinflammatory disease of the liver which results from infection by the hepatitis A virus (HAV). The mean incubation period is approximately 30 days. Although the disease is usually self-limited, the severity of illness is age-dependent. In children, hepatitis A is usually asymptomatic, while in adults, symptomatic infection is characteristic and jaundice is common. Fulminant hepatitis A is rare and is also age-dependent. The onset of hepatitis A is often abrupt and characteristic prodromal symptoms are followed, within a few days to a week, by dark urine and jaundice. Mild to moderate tenderness over an enlarged liver is usually detected. Serum alanine and aspartate aminotransferase levels usually both rise rapidly during the prodromal period, reach peak levels and then decrease by approximately 75% per week. Serum bilirubin concentrations reach peak levels later and decline less rapidly than serum aminotransferases. Nonetheless, the period of jaundice persists for < 2 weeks in approximately 85% of cases. Nearly all adult patients with clinically apparent disease experience complete clinical recovery with restoration of normal serum bilirubin and aminotransferase values by 6 months. Relapses and prolonged cholestasis are unusual manifestations of hepatitis A, and even in these circumstances, recovery is the rule and chronic hepatitis is not seen. The diagnosis of hepatitis A requires the detection of immunoglobulin M antibody to HAV in a patient who presents with, or has recently had, clinical features of hepatitis (icteric or anicteric disease) or in an individual with inapparent, asymptomatic infection in whom serum aminotransferase elevations may be detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Nitrofurantoin-induced hepatic injury has been established unequivocally as an entity by rechallenge experiences. We reviewed 12 previously reported cases in which rechallenge was described. The longest reported interval between initial injury and rechallenge-provoked injury was 4 yr. We report a 56-yr-old woman who experienced severe hepatocellular injury with brief low-dose administration of nitrofurantoin 17 yr after an initial hepatitis-like illness associated with ingestion of the drug. Despite a temporal relationship to nitrofurantoin administration and histologic features compatible with drug-induced hepatitis, the initial bout of hepatitis had been termed "infectious." Our case appears remarkable for the long interval between initial injury and rechallenge-induced injury. The severity of the hepatic injury seen on rechallenge underscores the concept that the inadvertent rechallenge can be dangerous. Failure to identify the first bout of hepatitis as nitrofurantoin-related, and failure to inform the patient about the possible relationship to nitrofurantoin, raises important risk-management concerns, because hepatic memory of nitrofurantoin hypersensitivity appears to be of long duration.
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