Cachexia represents the clinical consequence of a chronic, systemic inflammatory response, and its manifestations differ considerably from those of starvation. Although cachexia is classically associated with chronic infections and malignant conditions, some of its elements have been identified in a wide variety of chronic diseases and in aging persons. Cachexia has repeatedly been associated with adverse clinical outcomes. The changes seen in cachexia are multidimensional and highly coordinated. Most obvious is a redistribution of the body's protein content, with preferential depletion of skeletal muscle and an increase in the synthesis of proteins involved in the response to tissue injury-the so-called acute-phase response. The physiologic, metabolic, and behavioral changes of cachexia are tightly regulated by cytokines, which signal the synthesis of acute-phase proteins as well as changes in intermediary metabolism that provide substrate and energy. The metabolic adaptations, notably the increase in the rate of protein degradation, limit the ability of hypercaloric feeding to reverse the depletion of lean mass. Recent studies have demonstrated the ability of anabolic and anticatabolic agents to mitigate the loss of skeletal muscle and to improve clinical outcomes in selected circumstances. Preclinical initiatives target the cytokine regulation of protein metabolism. It should be stressed that metabolic manipulation in cachexia could have positive or negative clinical effects, which must be distinguished through appropriate clinical trials.

Since the publication of the second set of guidelines by the National Cholesterol Education Program, a solid body of data from landmark clinical studies has demonstrated that reduction in low-density lipoprotein (LDL) cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ("statin") therapy sharply diminishes the risk for coronary artery disease. These trials include the Scandinavian Simvastatin Survival Study, the West of Scotland Coronary Prevention Study, the Air Force/Texas Coronary Atherosclerosis Prevention Study, the Cholesterol and Recurrent Events investigation, and the Long-Term Intervention with Pravastatin in Ischaemic Disease trial. Coronary event rates and, in some cases, all-cause mortality decreased significantly after about 5 years of statin therapy in patients at risk for and those who had coronary artery disease at baseline. In contrast, recent subgroup analyses of these pivotal studies have in the aggregate challenged the premise that lower LDL cholesterol levels necessarily lead to further declines in risk for coronary artery disease, particularly among the patients most likely to be seen by the clinician: those with moderately elevated or normal cholesterol profiles. Indeed, when LDL cholesterol levels are in this range, further lowering with statin therapy elicits diminishing returns in terms of coronary event rates. These findings are readily accommodated by the curvilinear, or log-linear, model between serum cholesterol level and risk for coronary artery disease, which is predicated on data from large epidemiologic studies. In light of the current climate involving competing health care costs, the pursuit of progressively diminishing returns in terms of reductions in coronary artery disease risk through more aggressive lowering of LDL cholesterol levels appears to be unwarranted. Until data are published from ongoing randomized, clinical trials that can more effectively resolve the clinical utility of aggressive lipid-lowering strategies to improve coronary event rates, a prudent, evidence-based strategy seems warranted.

To review reported inflammatory reactions occurring after initiation of highly active antiretroviral therapy (HAART) in persons infected with HIV-1 and to explore the mechanisms leading to these reactions.

Clinical and virologic consequences of temporary interruption of HIV therapy are incompletely understood.

To investigate the effect of garlic on total cholesterol level in persons with elevated levels by conducting a meta-analysis of randomized, double-blind, placebo-controlled trials.

The optimal management of chronic abacterial prostatitis is not known. A systematic review of the literature was done to answer the following questions: Are there accurate, reliable tests to diagnose chronic abacterial prostatitis? Are there effective therapies for it?

To evaluate the efficacy of pharmacologic agents for the irritable bowel syndrome.

Patients, families, and health care providers have a right to expect that ethics consultants can deal competently with the complex issues that they are asked to address. The Society for Health and Human Values-Society for Bioethics Consultation Task Force on Standards for Bioethics Consultation explored core competencies and related issues in ethics consultation. This position paper summarizes the content of the resulting Task Force Report, which included nine general conclusions: 1) U.S. societal context makes "ethics facilitation" an appropriate approach to ethics consultation; 2) ethics facilitation requires certain core competencies; 3) core competencies can be acquired in various ways; 4) individual consultants, teams, or committees should have the core competencies for ethics consultation; 5) consult services should have policies that address access, patient notification, documentation, and case review; 6) abuse of power and conflicts of interest must be avoided; 7) ethics consultation must have institutional support; 8) evaluation of process, outcomes, and competencies is needed; and 9) certification of individuals and accreditation of programs are rejected.

Patients with heroin dependence frequently present to internists and other physicians for heroin-related medical, psychiatric, and behavioral health problems and often seek help with reducing their heroin use. Thus, physicians should be familiar with the identification and diagnosis of heroin dependence in their patients and be able to initiate treatment of heroin dependence both directly and by referral. Recent research has provided much information concerning effective pharmacologically based treatment approaches for managing opioid withdrawal and helping patients to remain abstinent Methadone maintenance and newer approaches using L-alpha acetylmethadol and buprenorphine seem to be particularly effective in promoting relapse prevention. Although these treatments are currently provided in special drug treatment settings, recent and ongoing research indicates that the physician's office may be an effective alternative site for these treatments.

The polycystic ovary syndrome (PCOS) is an extremely common disorder that occurs in 4% to 7% of women of reproductive age. Although PCOS is known to be associated with reproductive morbidity and increased risk for endometrial cancer, diagnosis is especially important because PCOS is now thought to increase metabolic and cardiovascular risks. These risks are strongly linked to insulin resistance and are compounded by the common occurrence of obesity, although insulin resistance and its associated risks are also present in nonobese women with PCOS. Women with PCOS are at increased risk for impaired glucose tolerance, type 2 diabetes mellitus, and hypertension. Cardiovascular disease is believed to be more prevalent in women with PCOS, and it has been estimated that such women also have a significantly increased risk for myocardial infarction. Many lipid abnormalities (most notably low high-density lipoprotein cholesterol levels and elevated triglyceride levels) and impaired fibrinolysis are seen in women with PCOS. Early diagnosis of the syndrome and close long-term follow-up and screening for diabetes and cardiovascular disease are warranted. An opportunity exists for preventive therapy, which should improve the reproductive, metabolic, and cardiovascular risks.

Interventions for infertility have greatly increased in number and sophistication. Women with multiple medical problems and women near or beyond menopause are now able to conceive. The internist will be called on to assess the risk that infertility interventions pose and to counsel patients accordingly. Knowledge of the medical illnesses associated with infertility, the types of infertility treatments available, and the medical complications of these interventions are required to properly assess this risk. Medical complications of infertility interventions can be direct effects of related drugs and technologies and indirect consequences of the induced pregnancy, multiple gestation, or associated medical conditions. This article reviews the definitions and scope of infertility, the interventions used for treatment of infertility, the medical complications of these interventions, the potential risks of fertility treatment in women unable to conceive spontaneously, and important issues for preconception counseling.

To conduct a systematic review of the available data on the efficacy of any form of "distant healing" (prayer, mental healing, Therapeutic Touch, or spiritual healing) as treatment for any medical condition.

To review the cause, pathophysiologic characteristics, cost, and treatment of alcohol-induced hangover.