Pentoxifylline for sickle-cell disease.

OBJECTIVE: To review the use of pentoxifylline for the prevention and treatment of acute vasoocclusive episodes (VOEs) in sickle-cell disease (SCD). DATA SOURCES: Searches of MEDLINE (1965-April 2000), International Pharmaceutical Abstracts (1970-April 2000), and Science Citation Index Expanded (1989-April 2000) were performed using the key search terms sickle-cell disease, pentoxifylline, oxypentifylline, and Trental. DATA SYNTHESIS: Patients with SCD commonly suffer from painful VOEs. Pentoxifylline may be useful in this condition due to its ability to increase red blood cell deformability and inhibit platelet aggregation. Laboratory evidence, an animal model, and case reports suggest a benefit, but available clinical studies are methodologically poor, and data analysis is often inappropriate or absent. Limited data suggest that pentoxifylline is beneficial for treatment of a VOE in progress, but no data exist demonstrating a reduction in the number of VOEs with chronic pentoxifylline therapy. CONCLUSIONS: Documentation of the efficacy of pentoxifylline for VOE prevention and treatment of SCD is poor, further studies are needed before its routine use is recommended.

Insulin and coronary artery disease: is syndrome X the unifying hypothesis?

OBJECTIVE: To review data supporting the hypothesis that syndrome X plays a major role in the pathogenesis of coronary artery disease (CAD), and the effects of lifestyle factors and pharmacologic interventions on insulin, other metabolic parameters, and outcomes. DATA SOURCES: MEDLINE (January 1966-August 1997) and Current Contents database searches identified applicable English-language experimental trials, epidemiologic studies, reviews, and editorials. STUDY SELECTION AND DATA EXTRACTION: Studies that were included addressed the role of insulin resistance and hyperinsulinemia in the pathogenesis of CAD or the effects of lifestyle factors and pharmacologic interventions on metabolic parameters and outcomes. DATA SYNTHESIS: The main characteristics of syndrome X are hyperinsulinemia and insulin resistance. These result in secondary syndrome X features, including hyperglycemia, increased very-low-density lipoprotein concentrations, decreased high-density lipoprotein cholesterol, and hypertension. Insulin resistance is worsened by obesity, and insulin has been shown to contribute to the development of hypertension. Other studies demonstrate that smoking adversely affects glucose and insulin concentrations. Animal studies have linked hyperinsulinemia and atherogenesis. These animal data have been confirmed by several large prospective and population studies that have identified associations between hyperinsulinemia and CAD. CONCLUSIONS: Strong evidence links insulin resistance and hyperinsulinemia to CAD. Lifestyle modifications play an important role in decreasing cardiovascular risk, and clinicians should strongly encourage such changes. Clinicians must also carefully consider the effects of antihypertensive, antihyperglycemic, and antidyslipidemic agents on patients' metabolic profiles when choosing appropriate therapeutic regimens. However, outcome data on many potentially beneficial agents, including calcium antagonists, alpha 1-adrenergic antagonists, angiotensin-converting enzyme inhibitors, metformin, acarbose, and troglitazone, are not yet available.

Management of obesity: medical treatment options.

Obesity is a common and serious health problem in the United States. Excess weight is associated with an increased mortality rate, as well as such risk factors as hypertension, hyperlipidemia and diabetes mellitus. Numerous treatments are available for obesity. Behavioral therapy, surgery and pharmacologic treatment have been used with varying degrees of success. Pharmacologic therapy includes primarily noradrenergic agents and/or serotonergic agents. Newer preparations are currently under development. Behavior modification, including regular exercise and the development of healthy eating habits remains the best hope for long-term weight loss. However, surgery or medication can be useful in specific circumstances.