To review significant advances in the early diagnosis and treatment of medullary thyroid carcinoma in patients with the multiple endocrine neoplasia II (MEN II) syndromes, advances made possible by the application of recently discovered genetic information.

Fibrosis is the pathologic hallmark of many common diseases. Much information has recently emerged about the cellular and biochemical events that result in its development and progression. It is now known that in affected tissues, chronic inflammation generally precedes fibrosis and that inflammatory cell-derived cytokines are crucial mediators of fibrogenesis. Several cytokines have been identified that influence wound healing and tissue repair processes in vivo and that modulate the production of collagen in vitro. Of these, transforming growth factor-beta is of the most interest because this pleiotropic cytokine is expressed at high levels during tissue remodeling and greatly affects the formation of connective tissue. Furthermore, it has been recently shown that transforming growth factor-beta can stimulate the transcription of collagen genes through the production or activation of specific DNA-binding trans-acting factors. A precise understanding of the molecular mechanisms responsible for the effects of this cytokine on collagen gene expression may allow the design of selective therapeutic interventions aimed at retarding or preventing the development of fibrosis.

To evaluate, by meta-analysis, the accuracy of ultrasound screening for deep venous thrombosis in patients after orthopedic surgery.

To summarize the clinical symptoms of latex rubber allergy and provide guidelines for the management of this allergy.

The insulin-like growth factor (IGF) family of peptides, binding proteins, and receptors are important for normal human growth and development and are involved in the specialized functions of most physiologic systems. Most members of the IGF system are expressed by different cancer cells and may play an important role in the propagation of these malignancies. New therapies aimed at modulating various components of the IGF system could affect the progression and metastasis of cancer.

To review the status of artificial sensors in cardiac pacemakers and the rationale for developing pacing systems that use multiple sensors.

The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.

Right-sided endocarditis caused by Staphylococcus aureus is a frequent complication of injection drug use. Fortunately, the prognosis for this infection when treated with the standard regimen of 4 to 6 weeks of parenteral antistaphylococcal antibiotics is favorable. Nevertheless, in many cases, once drug users feel better, they leave the hospital against medical advice before completing the full course of antibiotic therapy. This problem has stimulated interest in shortening the duration of antibiotic to a penicillinase-resistant penicillin. Data from in vitro synergy studies and animal models of endocarditis suggest that S. aureus can be eradicated more quickly by combination therapy than by monotherapy. Reports of three prospective, nonrandomized clinical trials have been published that support the use of a 2-week course of a penicillinase-resistant penicillin and an aminoglycoside antibiotic to treat uncomplicated, exclusively right-sided endocarditis caused by methicillin-susceptible S. aureus in injection drug users.

To review the clinical features, pathogenetic mechanisms, and management of neurologic manifestations of human immunodeficiency virus (HIV) infection.

Asthma is characterized by inflammation, reversible airway obstruction, and increased airway responsiveness to various stimuli. It has received wide public attention in recent years because of increasing morbidity and deaths, particularly among black persons. The important role of inflammation in the immunopathogenesis of asthma has led to a newer therapeutic approach directed at interrupting this inflammatory process. Among immune regulatory pathways involved in asthma pathogenesis, two lymphokines appear to be particularly important in controlling IgE production. Interleukin-4 is required for IgE production; without it, IgE production is inhibited. Interferon-gamma can diminish cell priming for interleukin-4 production. Thus, the interplay of these two cytokines will determine whether cells that can make interleukin-4 will be produced and, therefore, whether IgE will be produced in response to allergic stimuli. Further, in response to appropriate stimuli, mast cells and eosinophils are attracted to airways and release cytokines, lipid mediators, and preformed substances that cause inflammation. Modern asthma treatment is directed at interrupting this inflammatory process and places a much greater emphasis on use of anti-inflammatory agents, such as aerosolized or parenteral corticosteroids, and on non-steroidal anti-inflammatory agents, such as cromolyn sodium and nedocromil sodium. Research advances without therapeutic application, however, limit success. Projects such as the National Institute of Allergy and Infectious Diseases' National Cooperative Inner-City Asthma Study, which is directed toward underserved populations, are intended to identify more clearly the factors responsible for increasing morbidity and to develop appropriate therapeutic interventions.

To review the biochemistry and biological activities of leukotrienes, focusing on their role in the mediation of inflammatory diseases.

To evaluate the quality of studies about drugs and food interactions with warfarin and their clinical relevance.

The development of a safe, effective preventive vaccine for human immunodeficiency virus (HIV) infection remains an area of vigorous research. Several highly innovative vaccine candidates are being developed, and more than 13 vaccine candidates have been tested in human phase I or II trials. All have produced antibody and several have produced modest neutralizing titers, but to date no reproducible evidence has suggested prolonged, high-titer neutralization across a diversity of HIV strains. Furthermore, only the live recombinant vector approaches have produced some evidence of cytotoxic T-cell responses. The principal obstacle to progress is the lack of definitive information on what constitutes a protective immune response. There is no animal model for HIV-induced disease. Hence, the identification of the correlates of immunity and more useful animal models is among the highest priorities for HIV vaccine research. Large-scale efficacy trials raise daunting scientific, ethical, and resource issues. Nonetheless, preparation in such trials is underway in order to be in a position to evaluate the most promising vaccine candidate.

To review recent studies of systemic therapy for mycosis fungoides and the Sézary syndrome (cutaneous T-cell lymphomas).

To assess the incidence of amiodarone-mediated aggravation of ventricular tachyarrhythmias or the development of new arrhythmias, such as torsade de pointes, in patients with cardiac disease.

To review current management of intractable constipation.

To review the radiofrequency ablation method, describe the technique, and discuss the indications, results, and limitations of its use in patients with cardiac tachyarrhythmias.

To review the epidemiology and causes of falls and fall-related injuries in nursing homes and to provide clinicians with a structured framework to evaluate and treat nursing home residents at risk for falls.

Heart failure is a progressive condition with a 5-year survival of less than 50%. This poor prognosis, which can be reproduced by overloading the hearts of experimental animals, may reflect molecular abnormalities caused when overload stimulates adult cardiac myocytes to undergo hypertrophy. Because these terminally differentiated cells have little or no capacity to divide, hypertrophy represents an unnatural growth response; however, the mechanism by which overload shortens survival remains speculative. Modification of this unnatural growth response by converting enzyme inhibitors and nitrates, which have growth inhibitory as well as vasodilator effects, may contribute to the ability of these drugs to improve prognosis in patients with heart failure.