The rapid growth of the Internet has triggered an information revolution of unprecedented magnitude. Despite its obvious benefits, the increase in the availability of information could also result in many potentially harmful effects on both consumers and health professionals who do not use it appropriately.

The most serious complication of deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE) is fatal PE. However, reliable estimates as to the risk of fatal PE in patients with treated DVT or PE are lacking.

Published reports indicate that 2.5% of deaths in the Netherlands are the result of euthanasia or physician-assisted suicide. It is not known how many patients make these requests in the United States, but the issue has gained considerable attention, including that of the Supreme Court. The focus of the writing and discussion regarding the request to die has been on a patient's capacity. There has not been an adequate focus on the possible meanings contained within the request to die. A patient's request to die is a situation that requires the physician to engage in a dialogue to understand what the request means, including whether the request arises from a clinically significant depression or inadequately treated pain. This article outlines some of the thoughts and emotions that could underlie the patient's request to die. Recommendations are made regarding the role of the primary care physician and the role of the psychiatric consultant in the exploration of the meaning of the request.

Acute lower respiratory tract illness is common among children seen in primary care. We reviewed the accuracy and precision of the clinical examination in detecting pneumonia in children. Although most cases are viral, it is important to identify bacterial pneumonia to provide appropriate therapy. Studies were identified by searching MEDLINE from 1982 to 1995, reviewing reference lists, reviewing a published compendium of studies of the clinical examination, and consulting experts. Observer agreement is good for most signs on the clinical examination. Each study was reviewed by 2 observers and graded for methodologic quality. There is better agreement about signs that can be observed (eg, use of accessory muscles, color, attentiveness; kappa, 0.48-0.66) than signs that require auscultation of the chest (eg, adventitious sounds; kappa, 0.3). Measurements of the respiratory rate are enhanced by counting for 60 seconds. The best individual finding for ruling out pneumonia is the absence of tachypnea. Chest indrawing, and other signs of increased work of breathing, increases the likelihood of pneumonia. If all clinical signs (respiratory rate, auscultation, and work of breathing) are negative, the chest x-ray findings are unlikely to be positive. Studies are needed to assess the value of clinical findings when they are used together.

The death of cells in tissues of humans and other multicellular organisms is neither always abnormal nor always detrimental. Although necrosis ensues at the sites of massive cellular injury, most cells in the body die through a more subtle, noninflammatory, energy-dependent form of cell death called apoptosis. The number of cells in tissues is determined by the homeostatic balance between proliferation of new cells and death of senescent cells; the rates of proliferation and apoptosis vary widely from tissue to tissue. Recent research into the molecular mechanisms of apoptosis has revealed that apoptosis is a genetically programmed process that can become deranged when the components of the cellular apoptotic machinery are mutated or present in inappropriate quantities. Dysregulation of apoptosis is associated with the pathogenesis of a wide array of diseases: cancer, neurodegeneration, autoimmunity, heart disease, and other disorders. Products of genes involved in the regulation and execution of apoptosis are potentially excellent targets for diagnosis and therapeutic intervention in disease processes, and they offer renewed hope for cures and treatments for a wide array of maladies.

To review the scientific literature on the effectiveness of rapid opioid detoxification (RD) (opioid withdrawal precipitated by naloxone hydrochloride or naltrexone) and ultrarapid opioid detoxification (URD) (opioid withdrawal precipitated by naloxone or naltrexone under anesthesia or heavy sedation) techniques.

In the present era of cost containment, physicians need reliable data about specific interventions. The objectives of this study were to assist practitioners in interpretation of economic analyses and estimation of their own costs of implementing recommended interventions.

To evaluate the efficacy of benzodiazepines and zolpidem tartrate in chronic insomnia based on a quantitative review of literature.

To provide a quantitative review of the treatment effects of primary coronary angioplasty vs intravenous thrombolysis for acute myocardial infarction.

A number of novel biologic agents are being introduced to replace, enhance, or modulate immune responses in medical illnesses. The use of these therapies has become crucial in treating some of these diseases, yet there is relatively little available information about their cost-effectiveness. Two examples are presented. Interferon gamma, used in chronic granulomatous disease, costs about $140 for a 100-microg vial; yearly costs average $21840 per patient. Study data estimated a 69% to 76% reduction in serious illness with interferon gamma treatment; a reduced incidence of infections could cover drug costs. Intravenous immunoglobulin is used lifelong in antibody deficiency and clearly reduces the number of serious illnesses. Projected savings derive from fewer hospital admissions and reduced organ damage, but infusion costs vary widely because of the prices charged for the drug and infusion services.

Immunopharmacology has changed dramatically over the past 25 years. Although a variety of traditional nonspecific immunosuppressive drug therapies are available for the treatment of autoimmune disease and organ transplantation rejection, with advances in cell biology and monoclonal antibody technology, a highly specific antibody can be engineered to cell surface determinants on immune cells or tumors or to neutralize inflammatory and immune mediators from an immune response. Many of these modalities are still in early phases of study for the treatment of autoimmune disease. In addition to therapies that suppress immune responses, advances in molecular biology have led to new agents and methods to enhance immune responses and correct immune deficits, such as growth factor replacement and cytokine therapies. Finally, gene therapy is a method for the long-term treatment of disorders in which a defective gene leads to disease.

Immunization is undergoing important changes, with improved vaccines replacing less immunogenic or less safe vaccines, new vaccines for common diseases such as chickenpox and hepatitis A infection, and improved immunization schedules. Immunization is also being transformed by basic work in molecular medicine. Vaccines made of DNA are being developed as a form of gene therapy that use the patient's own cellular machinery to make foreign proteins that stimulate an immune response. Currently immunization is used to protect patients prior to exposure to an infectious agent or during the incubation phase after exposure, but before disease has occurred. New technologies are being investigated to induce the immune system to fight infections that have already produced chronic disease such as acquired immunodeficiency syndrome and chronic hepatitis B virus infection.

The practice of clinical and experimental transplantation continues to evolve at a rapid pace. To appreciate the current transplant practices, it is first necessary to review transplant immunology in its proper context, ie, as a component of the complex series of events that promote the repair of damaged tissues. These processes are generally categorized as inflammation, immunity, and tissue repair/reinforcement. In general, there are 3 forms of graft rejection: hyperacute, acute, and chronic rejection. All 3 forms of graft rejection represent pathologic consequences of one or more of these repair-related processes. The various graft rejection responses also illustrate several complex immunologic principles that need to be considered. These include the definition of an alloantigen, the structure and function of major histocompatibility complex molecules, and the behavior of antigen-presenting cells and alloreactive T cells. This review combines these concepts and principles into a discussion of the 3 forms of graft rejection, each of which is addressed at the level of histopathology, pathobiology, incidence, and clinical strategies.

Immunohematology encompasses a broad array of clinical disorders in which immune reactions are involved in the pathogenesis of hematologic diseases. Immune reactions can involve the formed elements of the blood, producing hemolytic anemia, thrombocytopenia, or neutropenia. Autoimmune phenomena and drug-induced reactions are the most common mechanisms. In newborns, maternal antibodies can cross the placenta and destroy red blood cells, platelets, or neutrophils. Immune reactions can also occur during transfusion of blood products, leading to hemolysis, febrile reactions, allergic reactions, and lung injury. The role of leukocytes and cytokines released during blood component storage in mediating febrile transfusion reactions has prompted the increased use of leukocyte-reduced components. Immune reactions can occur to soluble clotting factors and can produce bleeding or thrombosis. Finally, immunohematologic features of B-cell disorders are considered.

Malignant tumors express antigens that may stimulate and serve as targets for antitumor immunity. Virally induced tumors usually contain integrated proviral genomes in theircellulargenomes and often express viral genome-encoded proteins that may stimulate specific host immune responses. Antigens unique to individual tumors that stimulate specific rejection of transplanted tumors have been demonstrated only in experimental animals. Other tumor antigens that potentially can stimulate immune responses are shared by different tumors. These include products of mutated or rearranged oncogenes or tumor-suppressor genes. Tumors may also overexpress tissue differentiation antigens or embryonic antigens, which also have the potential to be recognized by the immune system. The recent identification of tumor antigens recognized by cytotoxic T cells opens up new possibilities for constructing chemically defined antigens for specific immunotherapy. Treatment of malignant tumors in humans by immunologic approaches, although theoretically attractive, has not yet succeeded on a large scale. Important progress in immunotherapy of cancer is emerging with several different treatment modalities.

The immunologic cardiovascular diseases are a heterogeneous group of conditions. Many of these entities are associated with serious morbidity and mortality resulting from cardiac impairment, ischemic complications, or organ dysfunction, particularly of the kidneys, lung, and nervous system. The systemic nature of these conditions, coupled with vague symptoms and nonspecific initial physical findings, makes the differential diagnosis complicated. Research has identified specific mediators and primary origins in some conditions, with infections often being responsible. Immunosuppressive therapy, despite the potential complications, has improved the prognosis of some of the more serious immunologic cardiovascular diseases. Improvement in the treatment of immunologic cardiovascular diseases awaits identification of additional causes, improved definition of host factors that predispose an individual to develop these conditions, and better understanding of the immune dysregulation responsible for the progression of disease. The potential pathophysiologic role of immunologic mechanisms in common disorders such as congestive heart failure and atherosclerosis is intriguing and offers the possibility of novel therapies in these prevalent conditions.

Inflammatory disorders of the nervous and neuromuscular system are not uncommon despite the fact that immune privilege exists in much of the nervous system. Common immune-mediated neurologic diseases include multiple sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and idiopathic polymyositis. Environmental, genetic, and immunologic factors have been postulated to be involved in the pathogenesis of these diseases, but much remains to be elucidated about the specific identity and relative contributions of these factors. Several new therapies have become available for these diseases in the past few years, and many others are under investigation. Strategies that enhance the normal tolerance mechanisms of the immune system are being developed. In particular, strategies to block T(H)1-type responses or enhance T(H)2/3-type responses have generated interest.

The largest lymphoid organ in the body is the gut and the gut-associated lymphoid tissue. The mucosal immune system faces many challenges in protecting the body from microbial invasion. Its chief function is to maintain a diverse population of mature lymphocytes capable of responding to foreign antigens. This task is accomplished with a variety of unique features that distinguish the mucosal from the systemic immune system. In addition, the mucosal immune system plays a role in inflammatory bowel disease, Whipple disease, autoimmune gastritis, Helicobacter pylori infection, immunoproliferative small intestinal disease, hepatitis A, B, C, D, E, F, and G, autoimmune hepatitis, primary biliary cirrhosis, progressive sclerosing cholangitis, and vanishing bile duct syndrome.

The kidney can become involved in immune-mediated diseases through 3 mechanisms. It can be the primary target of antibody-mediated injury. Good-pasture syndrome, with antibodies directed at the glomerular basement membrane, is an example of this type. The kidney can be injured by immune complexes that are trapped in the kidney and cause local inflammation. Examples include systemic lupus erythematosus and IgA nephropathies. Finally, the kidney can be injured by immune responses initiated in other organs. In Wegener granulomatosis, inflammation begins in the airway but results in glomerulonephritis. Currently available therapies lack efficacy and specificity. New therapies based on pathophysiology are being developed in animal models.