--To review current knowledge regarding human immunodeficiency virus (HIV) infection in women and to derive from that data standards of care.

--To assess the efficacy of intrathecal therapy with tetanus antibody (antitetanus equine serum or human tetanus immune globulin) in neonatal and adult tetanus using meta-analytical techniques.

Atrial fibrillation is the most common of all sustained cardiac arrhythmias, yet it has no effective medical or surgical therapy. During the past decade, multipoint computerized electrophysiological mapping systems were used to map both experimental and human atrial fibrillation. On the basis of these studies, a new surgical procedure was developed for atrial fibrillation. Between September 25, 1987, and July 1, 1991, this procedure was applied in 22 patients with paroxysmal atrial flutter (n = 2), paroxysmal atrial fibrillation (n = 11), or chronic atrial fibrillation (n = 9) of 2 to 21 years' duration. All patients were refractory to all antiarrhythmic medications, and each patient failed to receive the desired therapeutic benefits of an average of five drugs administered preoperatively. There were no operative deaths and all perioperative morbidity resolved. All 22 patients have been successfully treated for atrial fibrillation with surgery alone. Three patients developed one late isolated episode of atrial flutter at 5, 6, and 15 months postoperatively, and each of these patient's symptoms is now controlled by a single antiarrhythmic drug. Preservation of atrial transport function has been documented in all patients postoperatively, and all have experienced marked clinical improvement.

The recently initiated human genome project is a large international effort to elucidate the genetic architecture of the genomes of man and several model organisms. The initial phases of this endeavor involve the establishment of rough blueprints (maps) of the genetic landscape of these genomes, with the long-term goal of determining their precise nucleotide sequences and identifying the genes. The knowledge gained by these studies will provide a vital tool for the study of many biologic processes and will have a profound impact on clinical medicine.

OBJECTIVE - To evaluate new treatments directed against endotoxin, tumor necrosis factor alpha, and interleukin 1 for use in sepsis and related disorders (sepsis syndrome and septic shock). DATA SOURCES - Investigations of these treatments in animal models, healthy human volunteers, and patients with sepsis and related disorders. STUDY SELECTION - Particular attention was paid to studies of patients with sepsis and related disorders, especially randomized, double-blind, controlled trials. DATA EXTRACTION - Animal studies and investigations with human volunteers were judged by how closely the experimental model replicated the clinical disorder (sepsis). Patient trials were assessed by sample size and design. Results of all studies were used to evaluate the likelihood that a given treatment would reduce mortality. DATA SYNTHESIS - Direct comparison of E5 and HA-1A antibody studies is difficult because of differences in their design, definitions of shock, and methods of subgroup analysis. However, both antibodies improve outcome in some subgroups: E5 benefits patients with gram-negative infection (bacteremic or focal) who do not have refractory shock, and HA-1A benefits those with gram-negative bacteremia (regardless of whether shock is present) but not those with focal gram-negative infection. Two agents that may be beneficial in gram-positive and gram-negative infection are monoclonal antibodies to tumor necrosis factor alpha and receptor antagonists to interleukin 1. Preliminary results with both are reviewed. CONCLUSIONS - All three types of treatment may improve outcome in sepsis. The best results will probably be obtained with combination therapy that interrupts multiple points of the inflammatory cascade underlying sepsis.

The interferons (IFN) are one of the body's natural defensive responses to such foreign components as microbes, tumors, and antigens. The IFN response begins with the production of the IFN proteins (alpha, beta, and gamma), which then induce the antiviral, antimicrobial, antitumor, and immunomodulatory actions of IFN. Recent advances have led to Food and Drug Administration approval of five clinical indications for IFN. Interferon alfa is approved for hairy-cell leukemia, condyloma acuminatum, Kaposi's sarcoma in the acquired immunodeficiency syndrome, and non-A, non-B (type C) viral hepatitis. Interferon gamma has properties distinctive from those of IFNs alpha and beta and is approved as an immunomodulatory treatment for chronic granulomatous disease. Promising clinical results with IFNs have also been reported for basal cell carcinoma, chronic myelogenous leukemia, cutaneous squamous cell carcinoma, early human immunodeficiency virus infection, hepatitis B, and laryngeal papillomatosis. Future clinical uses of IFNs may emphasize combination therapy with other cytokines, chemotherapy, radiation, surgery, hyperthermia, or hormones.

The nation has experienced a marked increase in measles cases during 1989 and 1990. Almost one half of all cases have occurred in unvaccinated preschool children, mostly minorities. The principal cause for the epidemic is failure to provide vaccine to vulnerable children on schedule. Major reasons for the low vaccine coverage exist within the health care system itself, which creates barriers to obtaining immunization and fails to take advantage of many opportunities to provide vaccines to children. Ideally, immunizations should be given as part of a comprehensive child health care program. However, immunization cannot await the development of such an ideal system. Essential changes can and should be made now. Specific recommendations include improved availability of immunization; improved management of immunization services; improved capacity to measure childhood immunization status; implementation of the two-dose measles vaccine strategy; and laboratory, epidemiologic, and operational studies to further define the determinants of decreased vaccine coverage and to develop new combinations of vaccines that can be administered earlier in life. The measles epidemic may be a warning flag of problems with our system of primary health care.

While the upper airway normally remains patent during quiet breathing in wakefulness and sleep, patients with obstructive sleep apnea have repetitive periods of upper airway closure during sleep. The upper airway closures usually occur at various sites in the pharynx. The patency of the potentially collapsible pharynx during inspiration depends on the balance between subatmospheric pressure in the pharyngeal airway and airway dilating forces generated by pharyngeal muscles. The pressure required to collapse the upper airway in the absence of upper airway muscle activity, ie, closing pressure, is normally subatmospheric. In obstructive sleep apnea, positive pressures are required to maintain patency of the passive upper airway. The pathophysiologic mechanisms underlying upper airway closures during sleep form the basis for the treatment of obstructive sleep apnea. In general, these treatment modalities attempt to (1) raise the pharyngeal pressure above the closing pressure, (2) decrease the closing pressure, or (3) increase upper airway muscle activity.

The availability of potent antihypertensive drugs that will decrease markedly elevated blood pressure within minutes to hours has changed the concepts of definition and therapy of hypertensive emergencies and urgencies. Intravenous infusion of sodium nitroprusside can be used in the truly emergent situation and is effective, reliable, and safe. While oral therapy is more convenient, it is not as consistently effective as parenteral administration and can lead to excessive reductions in blood pressure that are more difficult to manage than when short-acting agents are given intravenously.

Environmental, occupational, and recreational exposures to carcinogens contribute to cancer risk in humans. Cancer formation is a multistage process involving tumor initiation, promotion, conversion, and progression. Carcinogens can affect any of these stages through genetic and epigenetic mechanisms. The association of a suspected carcinogenic exposure and cancer risk can be studied in populations with classic epidemiologic techniques. However, these techniques are not applicable to the assessment of risk in individuals. Molecular epidemiology, in contrast, is a field that integrates molecular biology, in vitro and in vivo laboratory models, biochemistry, and epidemiology to infer individual cancer risk. Carcinogen-macromolecular adduct levels, and somatic cell mutations can be measured to determine the biologically effective dose of a carcinogen. Molecular epidemiology also explores host cancer susceptibilities, such as carcinogen metabolic activation, DNA repair, endogenous mutation rates, and inheritance of mutated tumor suppressor genes. Substantial interindividual variation for each of these biologic end points has been shown and, therefore, highlights the need for assessing cancer risk on an individual basis. Given the pace of the last decade, it is feasible that the next 10 years will allow molecular epidemiologists to develop a cancer-risk profile for an individual that includes assessment of a number of factors. This will help focus preventive strategies and strengthen quantitative risk assessments.

Occupational diseases account each year in the United States for an estimated 50,000 to 70,000 deaths and 350,000 new cases of illness. Often, however, occupational diseases are not correctly diagnosed, because they mimic diseases due to other causes and because most physicians are not well trained in their recognition. Opportunities for prevention and treatment are therefore lost. The occupational history is the most effective means for proper diagnosis of occupational illness. It should routinely be obtained for every patient. A brief but systematic guide for obtaining an occupational history is presented in this report. Also, approaches are summarized for the recognition and diagnosis of such important occupational diseases as occupational cancer, asbestosis and other respiratory disorders, and occupational neuropsychologic disorders. The management and prevention of occupational diseases depend on reduction of hazardous exposures in the workplace and better education of workers, industrial managers, and physicians. This report outlines a program for the control of occupational disease based on (1) preventing exposures in the workplace, (2) premarket toxicity testing of new chemicals and technologies, and (3) astute clinical diagnosis.

The focus of public health concern and research in regard to environmental lung diseases has changed across the century. Illustrative agents include radon, indoor asbestos, environmental tobacco smoke, acidic aerosols, and oxidant gases. Tremendous progress has been made in understanding and preventing environmental lung diseases. However, we remain concerned about adverse consequences of breathing polluted outdoor and indoor air. In the persistent concerns about adverse effects of polluted air on the lung, a new emphasis is pervasive; the focus has shifted from avoiding clinical disease among highly exposed individuals to protecting the population from an unacceptable burden of risk. The technique of quantitative risk assessment has become increasingly important for characterizing the safety of environmental agents. The resulting emphasis on the final risk projection and attendant uncertainties may overly emphasize gaps in our knowledge.

The mortality from septic shock continues to range between 40% to 60% despite advances in cardiovascular support and antibiotic therapy. Impairment of host defenses predisposes to the development of both severe infection and septic shock. The activation of a myriad of cellular and plasma mediators by microbial toxins produces the systemic and metabolic manifestations of sepsis. The clinical presentation includes characteristic clinical, hemodynamic, and laboratory abnormalities. Multiple organ systems are involved during septic shock, with outcome dependent on the circulatory response and the development of sequential organ failures. Initial resuscitation is directed at restoring tissue perfusion with fluids and vasoactive drugs, guided by assessment of the patient's hemodynamic status. Identification of the site of infection and choice of appropriate antibiotics are critical to the success of therapy. Newer therapeutic modalities include immunologic interventions that attenuate mediator activity and modulate the immune response. Pharmacologic therapies are also being developed that are aimed at blocking the actions of specific mediators.

Future advances in ultrasonography will undoubtedly occur in three major areas: diagnostic capability, instrumentation, and clinical applications. In the area of diagnostic capability, spatial and contrast resolution offer excellent opportunities for improvement. Continued research into tissue characterization is worthwhile, even though efforts to date have been more frustrating than fulfilling. Blood flow studies and new contrast agents are among the more promising areas for future development. New techniques of signal detection, analysis, and display in Doppler imaging may overcome some present limitations, including those in color flow imaging.