Imported fire ants now infest more than 310 million acres in the United States and Puerto Rico. Colonies have been found in Arizona, California, New Mexico, and Virginia. Available reports suggest that each year, fire ants sting more than 50% of persons in endemic areas, resulting in a variety of medical consequences.

The 1996 Bethesda Conference acknowledged left ventricular hypertrophy, hyperhomocysteinemia, lipoprotein(a) excess, hypertriglyceridemia, oxidative stress, and hyperfibrinogenemia as possible new cardiac risk factors. This review summarizes the current literature that supports these conditions as cardiac risk factors. Left ventricular hypertrophy is an independent risk factor for vascular disease. Improvement or progression of left ventricular hypertrophy influences subsequent cardiovascular complications. Clinical trials are under way to assess the potential benefit of decreasing homocysteine levels. The role of lipoprotein(a) excess in vascular disease is controversial. The atherogenic potential of lipoprotein(a) seems to be neutralized by effective reduction of low-density lipoprotein cholesterol levels. Increasing evidence supports an independent role of hypertriglyceridemia in cardiovascular disease and a possible clinical benefit from decreasing triglyceride levels. Among antioxidant micronutrients, supplementation with vitamin E has been shown to be beneficial in primary and secondary prevention studies. Data supporting the use of other antioxidants are much weaker. Preliminary evidence suggests that reducing fibrinogen levels in patients with high baseline levels and coronary disease may be beneficial. Despite the potential relation between new risk factors and cardiovascular disease, routine clinical application of these conditions as cardiovascular risk factors would be premature. Evidence is needed that these conditions extend prognostic ability beyond conventional risk factors and that modification of these conditions can reduce the risk for cardiovascular events.

To review epidemiologic studies on the association between homocyst(e)ine level and risk for cardiovascular disease and the potential benefits of homocysteine-decreasing therapies.

Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. An elevated rate of basal hepatic glucose production in the presence of hyperinsulinemia is the primary cause of fasting hyperglycemia; after a meal, impaired suppression of hepatic glucose production by insulin and decreased insulin-mediated glucose uptake by muscle contribute almost equally to postprandial hyperglycemia. In the United States, five classes of oral agents, each of which works through a different mechanism of action, are currently available to improve glycemic control in patients with type 2 diabetes. The recently completed United Kingdom Prospective Diabetes Study (UKPDS) has shown that type 2 diabetes mellitus is a progressive disorder that can be treated initially with oral agent monotherapy but will eventually require the addition of other oral agents, and that in many patients, insulin therapy will be needed to achieve targeted glycemic levels. In the UKPDS, improved glycemic control, irrespective of the agent used (sulfonylureas, metformin, or insulin), decreased the incidence of microvascular complications (retinopathy, neuropathy, and nephropathy). This review examines the goals of antihyperglycemic therapy and reviews the mechanism of action, efficacy, nonglycemic benefits, cost, and safety profile of each of the five approved classes of oral agents. A rationale for the use of these oral agents as monotherapy, in combination with each other, and in combination with insulin is provided.

Chronic myelogenous leukemia is a myeloproliferative disorder. It is characterized by a biphasic or triphasic clinical course in which a benign chronic phase is followed by transformation into an accelerated and blastic phase. On a cytogenetic and molecular level, most patients with chronic myelogenous leukemia demonstrate BCR-ABL fusion genes in hematopoietic progenitor cells, which result from a reciprocal translocation between chromosomes 9 and 22; this translocation leads to a shortened chromosome 22, called the Philadelphia chromosome. Translation of the fusion products yields chimeric proteins of variable size that have increased tyrosine kinase activity. Conventional chemotherapy with hydroxyurea or busulfan can achieve hematologic control but cannot modify the natural disease course, which inevitably terminates in a rapidly fatal blastic phase. Since its introduction in the 1980s, allogeneic stem-cell transplantation has provided the groundwork for a cure of chronic myelogenous leukemia. However, few patients are eligible for this treatment because of donor availability and age restrictions. Therapy with interferon-alpha alone or in combination with cytarabine suppresses the leukemic clone, produces cytogenetic remissions, and prolongs survival. It is an effective alternative first-line treatment for patients ineligible for transplantation. New drugs active against chronic myelogenous leukemia may show increased activity in the transformed phases of the disease. Novel therapies and concepts are developing rapidly; targeted molecules are tyrosine kinases, ras, and messenger RNA through antisense oligonucleotides. Alternative transplantation options, such as stem cells from autologous sources and matched unrelated donors, are expanding. Immunomodulation by adoptive immunotherapy and vaccine strategies hold significant promise for the cure of chronic myelogenous leukemia.

Treatment advances and outcomes data have raised new concerns about how to optimize care for patients with HIV infection. This paper reviews evidence on 1) the relation between experience and type of training and patient outcomes, 2) the relation between the components of primary care and patient outcomes, and 3) primary care physicians' basic HIV knowledge and skills in screening and prevention. Several studies indicate that greater experience in HIV care leads to improved patient outcomes. The relation between outcomes and type of training (subspecialist or generalist) is less clear, and studies have not distinguished between type of training and experience. Less experienced physicians may be able to provide high-quality care if appropriate consultation from expert physicians is available. Components of primary care, including accessibility, continuity, coordination, and comprehensiveness, are associated with better patient outcomes. Optimal care of HIV infection requires a combination of disease-specific expertise and primary care skills and organization. Criteria for expertise in HIV management should focus on actual patient care experience and HIV expertise rather than on subspecialty training per se. The management of HIV has become sufficiently complex that primary care physicians cannot be routinely expected to have extensive specialized knowledge in this area. However, many primary care physicians have weaknesses in the basic HIV-related skills that are needed in most settings, such as HIV test counseling and recognition of important HIV-related symptom complexes. Primary care physicians need to strengthen these basic HIV-related medical skills.

Recent studies showing a protective effect of tamoxifen in women at high risk for breast cancer have expanded the indications of the drug. While acting as an estrogen antagonist in the breast, tamoxifen can have estrogenic effects on the endometrium; consensus opinion is that tamoxifen increases the risk for endometrial cancer. Because an increasing number of women are taking tamoxifen, a strategy for gynecologic surveillance is needed. Studies examining the relation between risk for endometrial cancer and tamoxifen use have conflicting results. However, because of an overall interpretation that tamoxifen use slightly increases risk for endometrial cancer, some researchers advocate routine ultrasonography and endometrial biopsy for screening asymptomatic women receiving tamoxifen. This paper reviews the literature on endometrial cancer in women taking tamoxifen and the usefulness of various screening methods in this setting. Risk factors and screening criteria for endometrial cancer in the general population are discussed, and a strategy for surveillance of women taking tamoxifen is proposed. Patients should be screened for signs or symptoms of endometrial abnormality before taking tamoxifen. This evaluation, which should include a careful history, pelvic examination, and Papanicolaou smear, should be repeated annually while the patient is receiving tamoxifen. Although transvaginal ultrasonography is not recommended for routine screening, it is indicated if an adequate pelvic examination cannot be performed or if additional risk factors are present. The likelihood of abnormality is greater for patients who have abnormal bleeding, discharge, abnormal glandular cells on Papanicolaou smear, or an endometrial measurement on ultrasonography of more than 8 mm; these findings should prompt an aggressive evaluation of the endometrium.

To review the cause, epidemiology, pathophysiology, and treatment of cardiogenic shock.

General internists often care for patients with advanced cancer. These patients have substantial morbidity caused by moderate to severe pain and by spinal cord compression. With appropriate multidisciplinary care, pain can be controlled in 90% of patients who have advanced malignant conditions, and 90% of ambulatory patients with spinal cord compression can remain ambulatory. Guidelines have been developed for assessing and managing patients with these problems, but implementing the guidelines can be problematic for physicians who infrequently need to use them. This paper traces the last year of life of Mr. Simmons, a hypothetical patient who is dying of refractory prostate cancer. Mr. Simmons and his family interact with professionals from various disciplines during this year. Advance care planning is completed and activated. Practical suggestions are offered for assessment and treatment of all aspects of his pain, including its physical, psychological, social, and spiritual dimensions. The methods of pain relief used or discussed include nonpharmacologic techniques, nonopioid analgesics, opioids, adjuvant medications, radiation therapy, and radiopharmaceutical agents. Overcoming resistance to taking opioids; initiating, titrating, and changing opioid routes and agents; and preventing or relieving the side effects they induce are also covered. Data on assessment and treatment of spinal cord compression are reviewed. Physicians can use the techniques described to more readily implement existing guidelines and provide comfort and optimize quality of life for patients with advanced cancer.

Myocardial infarction often occurs among persons without traditional risk factors, and it has been hypothesized that assessment of "novel" markers may help identify persons who are prone to premature atherothrombosis. However, when considering the clinical utility of screening for any new marker for cardiovascular disease, physicians should consider whether there is a standardized and reproducible assay for the marker of interest; whether there is a consistent series of prospective epidemiologic studies indicating that baseline elevations of the novel marker predict future risk; and whether assessment of the novel marker adds to the predictive value of other plasma-based risk factors, specifically, the ratio of total cholesterol to high-density lipoprotein cholesterol. In this article, these criteria are used to evaluate five promising markers of cardiovascular risk: lipoprotein(a), total plasma homocysteine, fibrinolytic capacity, fibrinogen, and high-sensitivity C-reactive protein. Background is also provided to assist physicians in deciding whether one or more of these novel markers deserve clinical consideration in general outpatient settings.

Varicella-zoster virus has developed a complex strategy that allows it to remain latent in the body and avoid destruction by the immune system. Although varicella and zoster have been recognized since antiquity, several new clinical syndromes--including chronic chickenpox with persistent verrucous lesions and disseminated varicella without skin lesions--have been noted in patients with AIDS. Acyclovir has been the mainstay for treating severe varicella-zoster virus infections; however, newer antiviral agents, including valacyclovir and famciclovir, have expanded therapeutic options for treating adults with herpes zoster. The recently licensed live attenuated vaccine for varicella-zoster virus is effective in preventing chickenpox, and the vaccine's ability to stimulate immunity in seropositive adults suggests a promising strategy with which to modify the course of herpes zoster.

The term functional somatic syndrome has been applied to several related syndromes characterized more by symptoms, suffering, and disability than by consistently demonstrable tissue abnormality. These syndromes include multiple chemical sensitivity, the sick building syndrome, repetition stress injury, the side effects of silicone breast implants, the Gulf War syndrome, chronic whiplash, the chronic fatigue syndrome, the irritable bowel syndrome, and fibromyalgia. Patients with functional somatic syndromes have explicit and highly elaborated self-diagnoses, and their symptoms are often refractory to reassurance, explanation, and standard treatment of symptoms. They share similar phenomenologies, high rates of co-occurrence, similar epidemiologic characteristics, and higher-than-expected prevalences of psychiatric comorbidity. Although discrete pathophysiologic causes may ultimately be found in some patients with functional somatic syndromes, the suffering of these patients is exacerbated by a self-perpetuating, self-validating cycle in which common, endemic, somatic symptoms are incorrectly attributed to serious abnormality, reinforcing the patient's belief that he or she has a serious disease. Four psychosocial factors propel this cycle of symptom amplification: the belief that one has a serious disease; the expectation that one's condition is likely to worsen; the "sick role," including the effects of litigation and compensation; and the alarming portrayal of the condition as catastrophic and disabling. The climate surrounding functional somatic syndromes includes sensationalized media coverage, profound suspicion of medical expertise and physicians, the mobilization of parties with a vested self-interest in the status of functional somatic syndromes, litigation, and a clinical approach that overemphasizes the biomedical and ignores psychosocial factors. All of these influences exacerbate and perpetuate the somatic distress of patients with functional somatic syndromes, heighten their fears and pessimistic expectations, prolong their disability, and reinforce their sick role. A six-step strategy for helping patients with functional somatic syndromes is presented here.

To evaluate the efficacy of various ambulatory electrocardiographic monitors for the diagnosis of arrhythmia-related disorders and to provide recommendations for their use in clinical practice.

The past decade has witnessed a dramatic expansion in the scope of both mechanical and pharmacologic methods for opening occluded arteries in patients with acute myocardial infarction. Although the relative merits of conventional balloon angioplasty and thrombolysis have been evaluated, this old debate is being eclipsed by new comparisons. New device technologies, such as intracoronary stenting; more potent and more fibrin-specific thrombolytic agents; and new antithrombotic and antiplatelet agents all offer the potential for improved outcomes. But despite these recent developments, the time-dependent open artery hypothesis--which states that the achievement of early, full, and sustained reperfusion is associated with better outcomes--remains essentially unchanged. This article reviews data on the ability of six revascularization strategies--stand-alone thrombolysis, conventional percutaneous transluminal coronary angioplasty, stenting, glycoprotein IIb/IIIa inhibitors plus thrombolytic agents, glycoprotein IIb/IIIa inhibitors plus interventions, and the combination of pharmacologic and mechanical interventions--to produce early, full, and sustained reperfusion.

Low-molecular-weight heparins may simplify the management of deep venous thrombosis. A critical clinical issue is whether this more convenient therapy is as safe and effective as treatment with unfractionated heparin.

Low-molecular-weight heparins are effective for treating venous thrombosis, but their cost-effectiveness has not been rigorously assessed.