Tests for resistance to HIV drugs are available for clinical use; however, their predictive value has not been fully assessed.

Although guidelines recommend angiotensin-converting enzyme inhibitors for diabetic patients with microalbuminuria, this strategy requires that providers adhere to screening recommendations. In addition, the benefit of angiotensin-converting enzyme inhibitors in normoalbuminuric patients was recently demonstrated.

The stiff-person syndrome, a rare and disabling disorder, is characterized by muscle rigidity and episodic spasms that involve axial and limb musculature. Continuous contraction of agonist and antagonist muscles caused by involuntary motor-unit firing at rest are the hallmark clinical and electrophysiologic signs of the disease. Except for global muscle stiffness, results of neurologic examination are usually normal. Results of conventional computed tomography and magnetic resonance imaging of the brain are also normal. The cause of the stiff-person syndrome is unknown; however, an autoimmune pathogenesis is suspected because of 1) the presence of antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA); 2) the association of the disease with other autoimmune conditions; 3) the presence of various autoantibodies; and 4) a strong immunogenetic association. Anti-GAD antibodies, which are found in high titers in most patients, seem to be directed against conformational forms of GAD. New evidence suggests that these antibodies may be pathogenic because they interfere with the synthesis of GABA. In addition, a reduction in brain levels of GABA, which is prominent in the motor cortex, has been demonstrated with magnetic resonance spectroscopy in patients with the stiff-person syndrome. The stiff-person syndrome is clinically elusive but potentially treatable and should be considered in patients with unexplained stiffness and spasms. Drugs that enhance GABA neurotransmission, such as diazepam, vigabatrin, and baclofen, provide mild to modest relief of clinical symptoms. Immunomodulatory agents, such as steroids, plasmapheresis, and intravenous immunoglobulin, seem to offer substantial improvement. Results of an ongoing controlled trial will elucidate the role of these agents in the treatment of the disease.

Regular testing of military personnel identifies early HIV infection; this identification provides a sentinel cohort in which to describe the evolving molecular epidemiology of HIV-1 transmission.

Although influenza vaccination is recommended in persons infected with HIV-1, its efficacy is unknown.

Intravenous therapy in the outpatient and home settings is commonplace for many diseases and nutritional disorders. Few data are available on the rate of and risk factors for bloodstream infection among patients receiving such therapy.

The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. Elevated homocysteine concentrations are associated with an increased risk for vascular disease.

For patients infected with HIV, plasma HIV viral load in early disease predicts long-term prognosis. However, the implications of viral load measurements late in HIV disease are uncertain.

Little is known about patients' preferences for site of terminal care.

Despite the mortality benefits of breast cancer screening, not all women receive regular mammography. Such factors as age, socioeconomic status, and physician recommendation have been associated with greater use of screening. However, we do not know whether having an abnormal mammogram affects future screening.

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.

Adrenocortical masses are among the most common tumors in humans. However, only a small proportion of these tumors cause endocrine diseases (such as primary hyperaldosteronism, hypercortisolism, hyperandrogenism, or hyperestrogenism), and less than 1% are malignant. In recent years, several of the molecular and cellular mechanisms involved in adrenal tumorigenesis have been unraveled. As a result, alterations in intercellular communication, local production of growth factors and cytokines, and aberrant expression of ectopic receptors on adrenal tumor cells have been implicated in adrenal cell growth, hyperplasia, tumor formation, and autonomous hormone production. Genetic and chromosomal abnormalities, including several chromosomal loci and the genes coding for p53, p57, and insulin-like growth factor II, have been reported in adrenal tumors. In addition, chromosomal markers have been identified in several familial syndromes associated with adrenal tumors; these include menin, which is responsible for multiple endocrine neoplasia type I, and the hybrid gene that causes glucocorticoid-remediable hyperaldosteronism. Algorithms for endocrine testing and imaging procedures are now available to codify screening for, confirmation of, and differentiation of causes of primary hyperaldosteronism and the Cushing syndrome. Improved radiologic, computerized radiologic, and magnetic resonance imaging techniques, as well as selective catheterization studies, are useful in localizing adrenal tumors and in distinguishing between benign and malignant lesions and between functional and nonfunctional nodules. Finally, recent refinements in the field of minimally invasive general surgery have made laparoscopic adrenalectomy the method of choice for removing adrenal tumors; this type of surgery allows shorter hospital stays, lower morbidity rates, and faster recovery.

The autoimmune lymphoproliferative syndrome (ALPS) affords novel insights into the mechanisms that regulate lymphocyte homeostasis and underlie the development of autoimmunity. This syndrome arises early in childhood in persons who inherit mutations in genes that mediate apoptosis, or programmed cell death. The timely deletion of lymphocytes is a way to prevent their accumulation and the persistence of cells that can react against the body's own antigens. In ALPS, defective lymphocyte apoptosis permits chronic, nonmalignant adenopathy and splenomegaly; the survival of normally uncommon "double-negative" CD3+ CD4- CD8- T cells; and the development of autoimmune disease. Most cases of ALPS involve heterozygous mutations in the lymphocyte surface protein Fas that impair a major apoptotic pathway. Detailed immunologic investigations of the cellular and cytokine profiles in ALPS show a prominent skewing toward a T-helper 2 phenotype; this provides a rational explanation for the humoral autoimmunity typical of patients with ALPS. Prospective evaluations of 26 patients and their families show an ever-expanding spectrum of ALPS and its major complications: hypersplenism, autoimmune hemolytic anemia, thrombocytopenia, and neutropenia. Defective apoptosis may also contribute to a heightened risk for lymphoma.

To review clinical data on raloxifene hydrochloride, a selective estrogen receptor modulator that was recently approved for the prevention of osteoporosis in postmenopausal women.

Influenza vaccine is underused in groups targeted for vaccination.