To discuss the diagnosis and treatment of malignant pericardial effusion and focus on quantitating the success and complication rates of the many treatment modalities and updating recent advances in the field.

To estimate the overall efficacy and optimal use of the nicotine patch for treating tobacco dependence.

While several methods of prophylaxis have been shown to reduce the risk of venous thromboembolism following total hip replacement, the safest and most effective agent is unclear. To clarify this issue, we performed a meta-analysis of the randomized trials of methods used to prevent venous thromboembolism following total hip replacement.

To estimate the importance and implications of placebo effects in pain treatment and research from the existing literature, with emphasis on their magnitude and duration, the conditions influencing them, and proposed explanations.

To compare the health care utilization, expenditure, quality of care, and satisfaction since 1980 of enrollees in managed care and indemnity plans.

To provide estimates of patient outcomes following tricompartmental knee replacement and to examine variation in outcomes due to patient and prosthesis characteristics.

Data from large and small clinical trials reflect major differences in the pathophysiology, treatment, and prognosis of left ventricular (LV) systolic and diastolic dysfunction. These studies also indicate that medical therapy can benefit patients with LV dysfunction regardless of whether or not they are symptomatic. Because the descriptive term congestive heart failure does not provide for these important distinctions, a new classification of LV dysfunction has been developed in which patients with LV dysfunction are categorized on the basis of normal or abnormal systolic function. This classification is based on a simple assessment of LV function, it is applicable to patients without symptoms, and it reflects differences in treatment and prognosis. Those with clinically significant LV systolic dysfunction (ie, an LV ejection fraction < 40%) benefit from therapy whether or not they have symptoms of heart failure. Those with LV dysfunction and a normal LV ejection fraction (ie, diastolic dysfunction) also benefit from medical therapy. Annual mortality is higher in those with systolic dysfunction than in those with diastolic dysfunction, but within each of these categories mortality is higher in those with symptoms than in those without. This classification can be useful in the diagnosis and treatment of individual patients as well as in epidemiologic surveys designed to assess medical practice patterns.

The demand for medical services such as critical care is likely to often exceed supply. In the setting of these constraining conditions, institutions and individual providers of critical care must use some moral framework for distributing the available resources efficiently and equitably. Guidelines are therefore provided for triage of critically ill patients. There are several general principles that should guide decision making: providers should advocate for patients; members of the provider team should collaborate; care must be restricted in an equitable system; decisions to give care should be based on expected benefit; mechanisms for alternative care should be planned; explicit policies should be written; prior public notification is necessary. Patients who are not expected to benefit from intensive care, such as those with imminently fatal illnesses or permanent unconsciousness, should not be placed in the intensive care unit. Hospitals should assign individuals the responsibility of intensive care triage, and a committee should oversee the performance of this responsibility to facilitate the most efficient and equitable use of intensive care.

To quantify the efficacy of BCG vaccine against tuberculosis (TB).

Fragile X syndrome is a common cause of mental retardation that is inherited as an X-linked dominant disorder with reduced penetrance. Fragile X syndrome has been shown to be caused by an unstable CGG repeat within the fragile X mental retardation-1 (FMR1) gene. The repeat is normally polymorphic with six to 52 repeats, while affected males and females exhibit a massive expansion resulting in 230 to more than 1000 repeats. Such expansions, called "full mutations," are associated with abnormal methylation of the FMR1 gene leading to transcriptional suppression. The resulting absence of the encoded protein, FMRP, a cytosolic RNA-binding protein, is believed to result in the phenotype. Nonpenetrant male carriers and many female carriers exhibit premutation alleles of intermediate length (50 to 230 repeats), which are normally expressed. Male carriers transmit only unstable premutations while female premutation carriers can have carrier offspring with premutations or affected children with full mutations. The risk of having an affected child is directly related to the number of maternal repeats, with sequentially increasing probabilities of these alleles converting to full mutations as they are transmitted to subsequent generations. Advances have led to highly accurate laboratory diagnoses of both carrier and affected individuals as well as markedly improved prenatal diagnosis. In addition, a previously unrecognized class of mutation, later found responsible for several other important genetic diseases, has emerged.

OBJECTIVE--This review of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) provides an overview of a common but complex problem found in critically ill patients. It emphasizes definitions, common clinical patterns, metabolic responses, and pathophysiological changes. A brief discussion of treatment concepts is also included. DATA SOURCES--Data for this review were gathered from peer-reviewed journals, review articles by experts in SIRS/MODS, and selections from reference volumes written on SIRS/MODS. STUDY SELECTION--Reference selections were chosen on the basis of quality of research. Peer-reviewed journals were given primary consideration. Those review articles cited were felt to be essential to any discussion of SIRS/MODS. DATA EXTRACTION--Where possible, randomized, controlled, prospective studies were reviewed and conclusions used in this overview of SIRS/MODS. CONCLUSION--Our ability to care for critically ill patients has led to a new problem, SIRS and eventually MODS, which may become progressive organ failure and death. Unfortunately, these conditions are extremely frequent and carry high mortality rates. Increased oxygen consumption demands highlight the physiological response. The typical metabolic responses are characterized by hyperglycemia and accelerated protein catabolism. Unrecognized perfusion deficits, an uncontrolled septic focus, a persistent source of inflammation, or injured tissue is commonly present with SIRS/MODS and should be corrected. Restoration of oxygen transport and metabolic support are also important components of treatment. The cause of SIRS/MODS is complex and not fully understood, but multiple mediators and stimulated macrophages likely are important components and areas where treatment may well be focused.

To reevaluate the risk associated with in utero exposure to lithium.

Gene therapy for hemophilia A and B, now in the developmental stage, holds promise of a therapeutic revolution, resulting in amelioration or cure of the hemorrhagic diatheses. The genes for factor VIII and IX have been cloned, and vectors for the transfer of their cDNA into cells have been developed. Although viral and nonviral constructs containing the hemophilia gene have been used, most often modified retroviruses or adenoviruses have been employed. Cells that have been targeted for genetic modification to produce the antihemophilic proteins include hepatocytes, muscle cells, endothelial cells, keratinocytes, and fibroblasts. The delivery system may be (1) ex vivo, with implantation of modified cultured hemophilic cells in the donor, either in tissues or in semipermeable capsules, or (2) in vivo, the vector being delivered directly to target cells, genetically modifying them in situ. Successful in vivo therapy has been demonstrated in a hemophilic animal model, with conversion to a less severe hemophilic state.