Discovery that the hormone erythropoietin (EPO) and its receptor play a significant biological role in tissues outside of the hematopoietic system has fueled significant interest in EPO as a novel cytoprotective agent in both neuronal and vascular systems. Erythropoietin is now considered to have applicability in a variety of disorders that include cerebral ischemia, myocardial infarction, and chronic congestive heart failure. Erythropoietin modulates a broad array of cellular processes that include progenitor stem cell development, cellular integrity, and angiogenesis. As a result, cellular protection by EPO is robust and EPO inhibits the apoptotic mechanisms of injury, including the preservation of cellular membrane asymmetry to prevent inflammation. As the investigation into clinical applications for EPO that maximize efficacy and minimize toxicity progresses, a deeper appreciation for the novel roles that EPO plays in the brain and heart and throughout the entire body should be acquired.

Although acetylsalicylic acid (aspirin) is commonly used for patients with chronic cardiovascular disease, a minority of patients have a sensitivity to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

The prevalence of mixed dementia, defined as the coexistence of Alzheimer disease (AD) and vascular dementia (VaD), is likely to increase as the population ages.

Although recent US Preventive Services Task Force guidelines recommend bone densitometry for all women older than 65 years, identifying younger women at increased risk for osteoporosis and women with occult vertebral fractures remains a clinical challenge. We investigated whether physical signs are useful as a screening tool either for early referral to bone densitometry or for occult spinal fractures.

Intense work demands, limited control, and a high degree of work-home interference abound in residency training programs and should strongly predispose resident physicians to burnout as they do other health care professionals. This article reviews studies in the medical literature that address the level of burnout and associated personal and work factors, health and performance issues, and resources and interventions in residents. MEDLINE and PubMed databases were searched for peer-reviewed, English-language studies reporting primary data on burnout or dimensions of burnout among residents, published between 1983 and 2004, using combinations of the Medical Subject Heading terms burnout, professional, emotional exhaustion, cynicism, depersonalization and internship and residency, housestaff, intern, resident, or physicians in training and by examining reference lists of retrieved articles for relevant studies. A total of 15 heterogeneous articles on resident burnout were thus identified. The studies suggest that burnout levels are high among residents and may be associated with depression and problematic patient care. However, currently available data are insufficient to identify causal relationships and do not support using demographic or personality characteristics to identify at-risk residents. Moreover, given the heterogeneous nature and limitations of the available studies, as well as the importance of having rigorous data to understand and prevent resident burnout, large, prospective studies are needed.

Implantable cardioverter defibrillator (ICD) therapy is effective in primary and secondary prevention of sudden cardiac death among patients with prior myocardial infarction and depressed ejection fraction. However, conclusive evidence of survival benefit in patients with nonischemic cardiomyopathy (NICM) is still lacking.

The incidence of cutaneous melanoma has increased over the past several decades, making its early diagnosis a continuing public health priority. The ABCD (Asymmetry, Border irregularity, Color variegation, Diameter >6 mm) acronym for the appraisal of cutaneous pigmented lesions was devised in 1985 and has been widely adopted but requires reexamination in light of recent data regarding the existence of small-diameter (< or =6 mm) melanomas.

Inverse associations between birth weight and subsequent blood cholesterol levels have been used to support the "fetal origins" hypothesis of the relevance of fetal nutrition to adult disease.

In recent years, US patients have increasingly been the first to receive new medications, some of which are subsequently discovered to have suspected adverse drug reactions (SADRs). As a result, the challenge of early detection has largely shifted to the US postmarketing systems.

The optimal management of fibromyalgia syndrome (FMS) is unclear and comprehensive evidence-based guidelines have not been reported.

In the past, cancer patients entering phase 1 studies confronted the prospects of high risk and unlikely benefit. Over the last decade, cancer drugs under development have become more targeted, and the clinical research environment has become more scrutinized. The impact of these changes on the risks and benefits to patients who participate in phase 1 cancer trials is unknown.

History taking and clinical tests are commonly used to diagnose shoulder pain. Unclear is whether tests and history accurately diagnose instability or intra-articular pathology (IAP).

Atherothrombosis is a pathophysiologic process that results in clinical ischemic events affecting the cerebral, coronary, and peripheral arterial circulation. Antiplatelet agents, used alone or in combination, are effective in preventing recurrent vascular events among individuals with established vascular disease.

About 5% of the US population is morbidly obese. This disease remains largely refractory to diet and drug therapy, but generally responds well to bariatric surgery.

Although it is common practice to read tests with clinical information, whether this improves or decreases the accuracy of test reading is uncertain.

Available data suggest that prospective research participants may frequently not understand information disclosed to them in the informed consent process. Little is known about how understanding can be improved.

A family history of certain cancers is associated with an increased risk of developing cancer. Both cancer screening and genetic services referral decisions are often based on self-reported pedigree information.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure emphasizes the importance of systolic hypertension (SH), defined as systolic blood pressure (SBP) of at least 140 mm Hg and diastolic blood pressure of less than 90 mm Hg, in older persons (> or =60 years).

The concept of manipulation of the vascular bed to either increase or decrease the number of blood vessels has attracted considerable interest. This review focuses on angiogenesis as a therapeutic target, particularly in the context of cancer and arthritis, as well as on promoting angiogenesis in cardiovascular disease and the healing of bone fractures. Although once touted almost as a panacea for treatment of tumors, as well as other diseases associated with angiogenesis, such as diabetic retinopathy or rheumatoid arthritis, it is now clear that such enthusiasm was somewhat premature. Similarly, some clinical trials of therapeutic angiogenesis for the management of cardiovascular disease have been disappointing. Nevertheless, this exciting field of research holds promise for more targeted therapies.

Irritable bowel syndrome (IBS), which affects 11% to 14% of the population, is a puzzling condition with multiple models of pathophysiology including altered motility, visceral hypersensitivity, abnormal brain-gut interaction, autonomic dysfunction, and immune activation. Although no conceptual framework accounts for all the symptoms and observations in IBS, a unifying explanation may exist since 92% of these patients share the symptom of bloating regardless of their predominant complaint.