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Objective. To assess the risk of serious liver disease in patients with rheumatoid arthritis (RA) taking methotrexate (MTX).Methods. We surveyed members of the American College of Rheumatology to determine previous use of MTX in the treatment of rheumatoid arthritis and to identify cases of cirrhosis and liver failure. Cases were confirmed by review of pathology specimens, findings from diagnostic testing, and clinical presentations. A caswontrol study was then conducted to ascertain prognostic factors. Case and control medical records

Acetaminophen has been used safely and effectively for many years to manage pain and/or fever in patients of all ages. It is commonly recommended as first-line therapy for a variety of patients and conditions, including the elderly, children with viral illnesses, and patients with osteoarthritis, gastrointestinal conditions, bleeding disorders, cardiovascular disease, or renal disease. However, its use is often avoided in patients with chronic liver disease. The perception that acetaminophen should be avoided in such patients arose from awareness of the association between massive acetaminophen overdose and hepatotoxicity, combined with a lack of understanding of the metabolism of acetaminophen in patients with liver disease. There are various theoretical mechanisms of acetaminophen hepatotoxicity in chronic liver disease including: altered metabolism and depleted glutathione stores that would be expected to increase accumulation of the hepatotoxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI). Available studies in patients with chronic liver disease, however, have shown that although the half-life of acetaminophen may be prolonged, cytochrome P-450 activity is not increased and glutathione stores are not depleted to critical levels in those taking recommended doses. Furthermore, acetaminophen has been studied in a variety of liver diseases without evidence of increased risk of hepatotoxicity at currently recommended doses. Therefore, acetaminophen can be used safely in patients with liver disease and is a preferred analgesic/antipyretic because of the absence of the platelet impairment, gastrointestinal toxicity, and nephrotoxicity associated with nonsteroidal antiinflammatory drugs.

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We compared gastric pH values after therapeutic doses of lansoprazole and omeprazole in 17 healthy adult men. The pharmacokinetics of the two drugs were studied. A three-way crossover design compared the effects on gastric pH of 15 and 30 mg lansoprazole and 20 mg omeprazole--each given once daily for 5 days. Ambulatory 24-h intragastric pH levels were measured before dosing, after the first and fifth doses in each period, and 15 days after each dosing period. A positive relationship between the lansoprazole or omeprazole area under the curve (AUCs) and the 24-h mean pH values was found for each regimen. No differences in maximum concentration (Cmax) and AUC were noted from day 1 to day 5 for the two lansoprazole doses. With omeprazole, both Cmax and AUC levels were greater on day 5 than on day 1. All three regimens increased 24-h mean gastric pH, although 30 mg lansoprazole had the most significant effect. The percentage of time that gastric pH was >3, >4, and >5 was also significantly higher with 30 mg lansoprazole. All three regimens were associated with reversible elevations of serum gastrin, which more than doubled at some points. No clinically significant adverse events were documented.

Diabetes mellitus is the fifth leading cause of death in the United States; 17 million people are affected. Liver disease is one of the leading causes of death in persons with type 2 diabetes. The standardized mortality rate for death from liver disease is greater than that for cardiovascular disease. The spectrum of liver disease in type 2 diabetes ranges from nonalcoholic fatty liver disease to cirrhosis and hepatocellular carcinoma. The incidence of hepatitis C and acute liver failure is also increased. Nonalcoholic fatty liver disease is now considered part of the metabolic syndrome, and, with alcohol and hepatitis C, is the most common cause of chronic liver disease in the United States. Weight reduction and exercise are the mainstays of treatment for nonalcoholic fatty liver disease, but there are promising results with the new thiazolidinediones (pioglitazone and rosiglitazone) as well as metformin and 3-hydroxy-3-methylglutaryl coenzyme A inhibitors.

Bloating is a common symptom in otherwise healthy adults, and is often associated with but not predictive of functional bowel disorders. Smoking and high-dose aspirin are associated with bloating while physical activity is not.