Human immunodeficiency virus (HIV) tests are essential for detecting asymptomatic infection and are helpful in confirming the diagnoses of acquired immunodeficiency syndrome-related complex and acquired immunodeficiency syndrome. Nonetheless, many aspects of their use remain controversial, partly because of concerns about test accuracy. This article reviews the scientific basis for the evaluation, performance, and use of the most commonly employed HIV assays. Current test performance could be improved by better standardization of test procedures and institution of mandatory proficiency testing and licensure of clinical laboratories that perform HIV testing. Test utility could be enhanced by sequencing tests more appropriately and by interpreting test results in conjunction with the clinical purpose for which the test is being used and the characteristics of the population under study. Finally, HIV tests should be evaluated in a manner that minimizes spectrum and referral bias and inadequate reference standard confirmation, problems that have affected the evaluation of current tests.

This report discusses experimental and clinical applications of positron emission tomography to the heart, including measurements of blood flow to the myocardium and studies of metabolism and experimental injury. Most initial clinical studies have concentrated on ischemic heart disease, but the technique also has potential for investigation of cardiomyopathies, studying the neural control of the heart, and evaluating the effects of drugs on cardiac tissues.

We describe a patient who presented with renal failure after a one-year period of unprotected heavy occupational exposure to organic solvents. Renal biopsy results and serological findings were diagnostic of anti-glomerular basement membrane antibody-mediated glomerulonephritis. An analytic review of the literature revealed substantial evidence linking solvent exposure to the development of glomerulonephritis (GN), with seven of nine case-control studies demonstrating a statistically significant association. Odds ratios were reported by or could be calculated for six of these studies, and the five positive studies detected a 2.8- to 8.9-fold increased risk for GN among solvent-exposed individuals. The findings in several of these studies of dose-response relationships, the reports of variations in disease severity in relation to exposure intensity, and the absence of alternative explanations for the association provide additional supportive evidence for a solvent effect. In the majority of cases of anti-glomerular basement membrane antibody-mediated GN and other types of GN, there is no remarkable preceding exposure to organic solvents. However, we conclude that in the case presented herein and in cases of GN with similar exposure histories, solvent exposure may play a significant contributing role in the development of GN.

This report describes the current and potential uses of positron emission tomography in clinical medicine and research related to oncology. Assessment will be possible of metabolism and physiology of tumors and their effects on adjacent tissues. Specific probes are likely to be developed for target sites on tumors, including monoclonal antibodies and specific growth factors that recognize tumors. To date, most oncological applications of positron emission tomography tracers have been qualitative; in the future, quantitative metabolic measurements should aid in the evaluation of tumor biology and response to treatment.

Positron emission tomography (PET) can probe biochemical pathways in vivo and can provide quantitative data; for that purpose, tracers labeled with positron-emitting radioisotopes are essential. This report describes the tracers that are being used or that may have future use, their production by cyclotrons, and other needed resources for PET imaging. Current routine and automated methods for convenient production of labeled compounds, coupled with simple computer-controlled accelerators, can support the creation of clinical PET centers in any large medical institution, obviating the need for in-depth research teams. An alternate approach involves the development of regional centers that provide in-house service and that supply fluorine 18- and carbon 11-labeled compounds to nearby hospitals with PET machines.

The practice of biology and medicine has been revolutionized during the past ten years by the advent of three biotechnologies--recombinant DNA techniques, the monoclonal antibody technology, and the development of microchemical instrumentation, machines that permit the rapid and effective synthesis and sequence analysis of proteins and genes. In this article, these powerful biotechnologies will be discussed, with particular emphasis on microchemical instrumentation, a major focus of my efforts for the past 15 years. I will also discuss two fundamental problems in modern medicine that are being explored in my laboratory using these techniques--genetic engineering of the nervous system and the mapping and sequencing of the human genome.

This report, the first in a three-part series on drug abuse by athletes, responds to adopted Resolution 4 (1984 Annual Meeting) and to Resolution 57 (1986 Annual Meeting), "Human Growth Hormone," which was referred to the Board of Trustees for action. Subsequent reports will cover other classes of abused drugs.

To understand why the dexamethasone suppression test (DST) for the diagnosis of depression became widely accepted and later rejected, we reviewed the sequence of publications in the DST literature. To evaluate the events, we developed and applied concepts of a five-phase process that can be used to assess the clinical utility of diagnostic marker tests. The review showed that when the DST was introduced into the clinical arena, the initial and final two phases of testing (I, IV, and V) had not been adequately conducted. When these phases of testing were suitably checked many years later, the Phase I studies (exploring basic mechanics of test procedures) showed that dexamethasone had variable bioavailability and that the cortisol assay procedure was unreliable. The Phase IV and V studies (examining test results in groups with suitably broad spectrums of cases and controls) showed that the test did not differentiate depression from most pertinent comorbid conditions. Beyond application to the specific problems of the DST, the proposed five phases of development and evaluation for diagnostic marker tests can be used to plan suitable research and avoid similar problems in the future.

This article reviews progress in cancer control and objectives for achieving further control. In particular, rather than relying on a single composite statistic such as the age-adjusted mortality rate, this review stresses trends in cancer mortality in the United States using a cohort analysis. That method reveals a decline in cancer mortality beginning with young children in the 1950s and proceeding up the age scale in subsequent decades to those persons who were approximately 50 years of age in the mid-1980s. From age 55 years upward, the continuing increase in cancer mortality is due to epidemic lung cancer. The principal cause of that disease and what must be done to control it are well understood. The objectives for cancer control by the year 2000 set by the National Cancer Institute and the feasibility of reducing cancer mortality by as much as 25% to 50% are also considered. Increased cancer prevention research is needed.

Meta-analysis is being used with increasing frequency in clinical medicine as an attempt to improve on traditional methods of narrative review by systematically aggregating information and quantifying its impact. Combining data from several studies using meta-analysis can increase statistical power, provide insight into the nature of relationships among variables, and increase generalizability of results more rigorously than less quantitative review methods. Like all review methods, meta-analysis can be limited by sampling bias, inadequate data, and biased outcome interpretation. Still, the advantages noted above make meta-analysis a methodology that warrants testing and empirical evaluation.

Aminophylline is routinely recommended as a basic part of the emergency treatment of asthma. A comprehensive search found 13 reports of controlled trials of intravenous aminophylline therapy in severe, acute asthma. These studies compared aminophylline therapy with treatment with either albuterol (salbutamol), epinephrine, or other bronchodilators. The 13 reports did not agree. Seven reported no difference in spirometric values between aminophylline treatment and the control regimens. Three found aminophylline treatment superior. Three favored the control regimen. The results of the 13 trials were reanalyzed and pooled. Overall, there was no difference between the aminophylline-treated groups and the control groups. Sensitivity analysis suggests that aminophylline therapy is ineffective alone but may be more effective than single-drug therapy when combined with an injected beta-agonist. Despite widespread practice, available trials do not provide adequate evidence to support or reject the use of aminophylline in the treatment of severe, acute asthma.