Studies concerning the genetic relatedness between chronic lymphocytic leukemia and the more aggressive B-cell cancers that develop in about 10% of affected persons were reviewed. These B-cell cancers include large B-cell lymphoma (the Richter syndrome), prolymphocytic transformation, acute lymphoblastic leukemia, and multiple myeloma. Two possible relations were evaluated: development from the chronic lymphocytic leukemia clone (clonal evolution) and development of a genetically unrelated, independent second cancer.

To update our knowledge about normal absolute values for CD4+ and CD8+ peripheral T-lymphocyte subsets and to show how these values are influenced by infectious disease. These data are discussed in the context of a newly identified syndrome, idiopathic CD4+ T lymphocytopenia and severe unexplained human immunodeficiency virus (HIV)-negative immune suppression (ICL/SUHIS).

Healers must try to understand what the illness means to the patient and create a therapeutic sense of connection in the patient-clinician relationship. A favorable climate for "connexional" experiences can be created through the use of various interviewing techniques. Attending to rapport, silencing internal talk, accessing unconscious processes, and communicating understanding can help clinicians enhance their sensitivity to the subtle clues on which issues of meaning and connection often depend. Several risks are associated with the establishment of closer patient-clinician relationships, including dependence and power issues, sexual attraction, and deeper exposure of the clinician to the patient's pain. Prepared with an awareness of these risks and techniques to address them, clinicians are encouraged to deepen their level of dialogue with patients, to compare their experiences with those of other clinicians, and to thereby develop a more systematic understanding of therapeutic relationships.

To assess by analysis of published controlled trials the efficacy of cognitive behavioral therapies (such as biofeedback, relaxation, meditation) for essential hypertension.

To evaluate the possibility that fibrinogen represents a cardiovascular risk factor.

To describe nodular lymphangitis by reviewing the clinical and epidemiologic features of this disease with an emphasis on distinguishing specific etiologic agents.

To review published evidence on the use of ambulatory and self-measurement devices in the diagnosis and management of hypertension.

To review the current state of knowledge regarding risk factors for prostate cancer.

To provide physicians with a review of diagnosis, screening, staging evaluation, treatment options, prognosis, psychosocial issues, economic considerations, and future research directions in the management of patients with all stages of prostate cancer.

Common variable immunodeficiency (CVI) is a heterogenous immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and various immunologic abnormalities. In addition to recurrent infections, patients with this syndrome also have an increased incidence of autoimmune disease and malignancy. Because the spectrum of associated diseases is broad, patients with CVI are seen by various medical specialists. This review discusses the pathogenesis, clinical manifestations, diagnosis, and treatment of CVI.

To evaluate information on the prevalence and rate of progression of atherosclerotic renovascular disease and the effect of angiotensin-converting enzyme inhibition on this process, with the goal of developing a rational approach to the diagnosis and management of this disorder.

The new knowledge of the regulation of cell growth and the genetic and biochemical changes that lead to malignancy have created many new opportunities for cancer drug discovery. These new targets include oncogenes, growth factors and their receptors, signal transduction pathways, and cell differentiation signals. Attempts to identify new therapies based on these targets can complement traditional drug discovery efforts that rely on high-volume screening of candidate natural products and synthetic chemicals against human tumor cell lines and against defined molecular reactions. Through modern computer-based data analysis, drug screening data can be used to establish mechanism of drug action of new agents; these analyses shed light on patterns of cross-resistance of new compounds and their interactions with defined molecular targets as well as allow selection of chemically and biologically unique agents as candidates for clinical development.

Immunocyte and germ cell neoplasms, often curable by chemotherapy, arise from normal tissues most vulnerable to the effects of cytotoxic drugs; generalizing from these results to treating other tumors with such agents may not be entirely valid. Our limited success in treating epithelial neoplasms may be due to insensitivity rather than to drug resistance. Well-designed attempts to overcome resistance have been unsuccessful. The acquired immunodeficiency syndrome has not confirmed the putative role of immune surveillance in the pathogenesis of most neoplasms. The limited success of the most elaborate immunotherapies suggests that they, too, are nonspecific cell-killing techniques. Immunologic and cytotoxic drug therapies deserve further investigation but on a smaller scale. Neoplastic cell molecular biology, unknown when these therapies were developed, is being rapidly elucidated and may make it possible to treat malignancies by modulating cell physiology. Success of therapies based on the advances, in molecular biology, is not more uncertain than that of traditional treatments. Differentiation-induction techniques have already induced remissions in patients with acute promyelocytic leukemia and squamous cell carcinomas.

Clinicians and policymakers are recognizing the importance of measuring health-related quality of life (HRQL) to inform patient management and policy decisions. Self- or interviewer-administered questionnaires can be used to measure cross-sectional differences in quality of life between patients at a point in time (discriminative instruments) or longitudinal changes in HRQL within patients during a period of time (evaluative instruments). Both discriminative and evaluative instruments must be valid (really measuring what they are supposed to measure) and have a high ratio of signal to noise (reliability and responsiveness, respectively). Reliable discriminative instruments are able to reproducibly differentiate between persons. Responsive evaluative measures are able to detect important changes in HRQL during a period of time, even if those changes are small. Health-related quality of life measures should also be interpretable--that is, clinicians and policymakers must be able to identify differences in scores that correspond to trivial, small, moderate, and large differences. Two basic approaches to quality-of-life measurement are available: generic instruments that provide a summary of HRQL; and specific instruments that focus on problems associated with single disease states, patient groups, or areas of function. Generic instruments include health profiles and instruments that generate health utilities. The approaches are not mutually exclusive. Each approach has its strengths and weaknesses and may be suitable for different circumstances. Investigations in HRQL have led to instruments suitable for detecting minimally important effects in clinical trials, for measuring the health of populations, and for providing information for policy decisions.

The introduction of penicillin 50 years ago was followed by an extraordinary period of discovery, exuberant use, and predictable obsolescence. Resistant bacterial strains have emerged and have spread throughout the world because of the remarkable genetic plasticity of the microorganisms, heavy selective pressures of use, and the mobility of the world population. New and more expensive drugs have appeared almost in the nick of time, but it is doubtful that they will keep pace. The problem of resistance to antimicrobial drugs is particularly troublesome in developing countries. The underlying problems are largely economic and societal, and no ready solutions are available. An urgent need exists for more appropriate selection and use of antimicrobial drugs in the developed as well as in developing countries. The focus in developing countries should be on the availability of safe and effective drugs and on the enforcement of more responsible national drug policies. These issues must be addressed by the collective action of governments, the pharmaceutical industry, health care providers, and consumers. The developed countries have an important stake in the ways in which antibiotics are used in developing countries because resistant microorganisms do not recognize national boundaries.

To review the medications that influence glucose metabolism and to examine the mechanisms of these medications on glucose metabolism.

To assess the effectiveness of the newer 5-aminosalicylic acid (5-ASA) delivery systems compared with placebo or sulfasalazine for the treatment of active ulcerative colitis and for the maintenance of remission.

Medical technology assessment seeks to improve the care of individual patients (the conventional unit of clinical practice) through evaluation studies conducted in groups of patients (the conventional unit of clinical investigation). This distinction between individuals and groups has practical relevance to the design, analysis, and clinical applicability of technology assessment studies. We define several biased perspectives about technology assessment that derive from the distinction between individuals and groups: a misguided emphasis on efficacy versus effectiveness, on statistical significance versus clinical importance, and on objective versus subjective outcomes. In each case, we contrast these alternative perspectives and speculate on their implications for health care policy.

To present an overview of the applicability of heart rate variability measurements in medicine.