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- Volume 55, 2004
Annual Review of Medicine - Volume 55, 2004
Volume 55, 2004
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The Impact of the Completed Human Genome Sequence on the Development of Novel Therapeutics for Human Disease*
Vol. 55 (2004), pp. 1–13More LessWith the official completion of the Human Genome Project in April 2003, we have both the opportunity and the imperative to translate this unprecedented scientific accomplishment into tangible improvements in human health. Medical benefits from the genome will come in stages and can be conceptualized as occurring in three areas: improved understanding of disease causation at the molecular level, improved diagnosis and disease classification based on genetic profiles, and new therapeutics based on targets identified in the genome. These improvements will require increased physician understanding of genetic principles applied to common diseases.
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Toward Alzheimer Therapies Based on Genetic Knowledge *
Vol. 55 (2004), pp. 15–25More LessGenetic analysis has allowed the dissection of the pathogenic pathway that leads to Alzheimer's disease. It has also been integral to the development of earlier and more accurate diagnostic practices. This analysis has identified many potential therapeutic targets, and clinical trials aimed at these targets are now under way. If these approaches are successful, it will be a spectacular validation of genetic-knowledge–based treatment strategies; if they are not, researchers will need to re-evaluate this approach toward understanding and developing strategies for treating complex diseases.
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Inherited Diseases Involving G Proteins and G Protein–Coupled Receptors *
Vol. 55 (2004), pp. 27–39More LessHeterotrimeric G proteins couple seven-transmembrane receptors for diverse extracellular signals to effectors that generate intracellular signals altering cell function. Mutations in the gene encoding the α subunit of the G protein–coupling receptors to stimulation of adenylyl cyclase cause developmental abnormalities of bone, as well as hormone resistance (pseudohypoparathyroidism caused by loss-of-function mutations) and hormone hypersecretion (McCune-Albright syndrome caused by gain-of-function mutations). Loss- and gain-of-function mutations in genes encoding G protein–coupled receptors (GPCRs) have been identified as the cause of an increasing number of retinal, endocrine, metabolic, and developmental disorders. GPCRs comprise an evolutionarily conserved gene superfamily (1). By coupling to heterotrimeric G proteins, GPCRs transduce a wide variety of extracellular signals including monoamine, amino acid, and nucleoside neurotransmitters, as well as photons, chemical odorants, divalent cations, hormones, lipids, peptides and proteins. Following a brief overview of G protein–coupled signal transduction, we review the growing body of evidence that mutations in genes encoding GPCRs and G proteins are an important cause of human disease.
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The Scientific Basis for the Current Treatment of Parkinson's Disease
Vol. 55 (2004), pp. 41–60More LessParkinson's disease (PD) is an age-related neurodegenerative disease that affects approximately one million people in the United States. The introduction of levodopa revolutionized the treatment for this disorder, but the long-term utility of the drug is limited by motor complications, the development of features such as postural instability and dementia that do not respond to treatment, and continued disease progression. Insights into the organization of the basal ganglia in the normal and PD conditions has permitted the design of new treatment strategies that reduce the risk of developing motor complications. Additionally, increased knowledge of the mechanisms responsible for cell death in PD has permitted the development of putative neuroprotective drugs that might slow or stop disease progression. No drug has yet been established to alter the rate of disease progression, but the rapid pace of research offers reason for optimism.
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Progress in Antisense Technology
Vol. 55 (2004), pp. 61–95More LessAntisense technology exploits oligonucleotide analogs to bind to target RNAs via Watson-Crick hybridization. Once bound, the antisense agent either disables or induces the degradation of the target RNA. Antisense agents can also alter splicing. During the past decade, much has been learned about the basic mechanisms of antisense, the medicinal chemistry, and the pharmacologic, pharmacokinetic, and toxicologic properties of antisense molecules. Antisense technology has proven valuable in gene functionalization and target validation. With one drug marketed, Vitravene™, and approximately 20 antisense drugs in clinical development, it appears that antisense drugs may prove important in the treatment of a wide range of diseases.
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Serum Proteomics in Cancer Diagnosis and Management *
Vol. 55 (2004), pp. 97–112More LessMass spectrometry–based diagnostics has the potential to revolutionize molecular medicine. Using modern mass-spectrometer technologies, clinical tests can be developed that are practical, robust, accurate, and inexpensive. Serum proteomic pattern profiling couples mass spectrometry with adaptive artificial-intelligence–based bioinformatics, which can now be employed to detect pathological states reflected in the serum proteome. With this approach, rapid and cost-effective tests with exquisite clinical sensitivity and specificity are emerging. These tools may dramatically change how disease is detected, monitored, and managed.
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Molecular Neurobiology of Drug Addiction
Vol. 55 (2004), pp. 113–132More LessAddiction can be viewed as a form of drug-induced neural plasticity. One of the best-established molecular mechanisms of addiction is upregulation of the cAMP second messenger pathway, which occurs in many neuronal cell types in response to chronic administration of opiates or other drugs of abuse. This upregulation and the resulting activation of the transcription factor CREB appear to mediate aspects of tolerance and dependence. In contrast, induction of another transcription factor, termed ΔFosB, exerts the opposite effect and may contribute to sensitized responses to drug exposure. Knowledge of these mechanisms could lead to more effective treatments for addictive disorders.
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Beta-Cell Replacement for Type I Diabetes
Vol. 55 (2004), pp. 133–156More LessThe ability to achieve insulin independence with either solid-organ pancreas or islet transplantation has increased the number of patients seeking beta-cell replacement as an alternative to insulin therapy. Despite dramatic improvements in the ability to achieve insulin independence following solid-organ pancreas transplantation, the secondary complications of long-standing diabetes are frequently irreversible by the time surgical intervention is justified based on the risk of this procedure. Pancreatic islet transplantation provides a safer and less invasive alternative for beta-cell replacement that could be justified earlier in the course of diabetes to prevent the development of secondary complications. Recent advances in the technology of islet isolation, as well as the ability to prevent the alloimmune and recurrent autoimmune response following islet transplantation with immunosuppressive regimens that are not toxic to beta cells, have rekindled an interest in this field. Widespread application of islet transplantation will depend on further improvements in selective immunosuppression, development of immunologic tolerance, and finding new sources of beta cells.
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Cochlear Implantation for the Treatment of Deafness
Vol. 55 (2004), pp. 157–167More LessCochlear implants have dramatically changed the treatment and prognosis for patients with profound sensorineural hearing loss. Deaf adults and children can be successfully (re)integrated into the hearing world through a multidisciplinary approach involving otolaryngologists, audiologists, and speech/language pathologists. As the technology of the cochlear prosthesis advances, the candidacy for these devices continues to broaden. This review addresses the basic technology, candidacy criteria, and important issues in the fields of adult and pediatric cochlear implantation. Cost utility and future directions in the treatment of the profoundly hearing impaired are discussed.
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Drug-Eluting Stents
Vol. 55 (2004), pp. 169–178More LessAdvances in catheter and stent design have made stent implantation the standard coronary angioplasty procedure. Unfortunately, in-stent restenosis continues to plague this procedure, with the optimum binary restenosis rates reaching ∼10% to 20%. In the past few years, it has become clear that in-stent restenosis is largely due to the migration and proliferation of vascular smooth muscle cells to form a neointima. To address this issue, stents coated with drug-delivery vehicles have been developed to deliver antiproliferative therapeutics. Two drugs, rapamycin and taxol, have been the lead compounds for testing the idea of a drug-eluting stent. These drugs have been successful largely because of the solid mechanistic understanding of their effects and extensive preclinical examination. The result of these years of work is that the rapamycin-coated stent entered the US market in April of 2003, and the taxol-coated stent appears poised to follow soon.
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New Approaches to Hemodialysis
Vol. 55 (2004), pp. 179–189More LessTreatment of end-stage renal disease with dialysis is characterized by high mortality rate, low quality of life, and high cost. Recent randomized controlled studies showed that increasing the dialysis dose above the currently recommended levels in thrice-weekly hemodialysis does not decrease the patient mortality rate. Short daily hemodialysis or daily home nocturnal hemodialysis are promising alternatives. Both improve quality of life and control blood pressure and anemia; nocturnal hemodialysis additionally controls serum phosphates without phosphate binders, allows a free diet, and corrects sleep apnea. Although the direct cost of daily hemodialysis is higher than that of conventional hemodialysis, the cost of total care, especially when delivered at home, seems to be lower. Further confirmation of these results is important. Restructuring of the dialysis reimbursement system is necessary to make the use of daily hemodialysis possible. Hemofiltration techniques, sorbents, and the renal tubular assist device may also help change the current grim statistics.
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Emerging Infectious Threats to the Blood Supply
Vol. 55 (2004), pp. 191–207More LessDuring the past 15 years, it has become clear that new agents and new strains of existing agents continue to emerge worldwide as protagonists of infectious disease. These emerging agents pose threats not only to the general human population but also to recipients of blood transfusions. Indeed, the modern era of blood safety perhaps began with the recognition of HIV as an emerging agent transmissible by blood transfusion. Today, emerging infectious agents that pose a threat to the blood supply are not limited to viruses, but include bacterial, protozoan, and prion agents. Preventing the transmission of these new agents by blood transfusion is often problematic, as the available tools may be inadequate. It is certain, however, that new agents will continue to emerge as threats to blood safety and these agents are likely to require novel approaches to prevent their transmission.
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Lead Poisoning
Vol. 55 (2004), pp. 209–222More LessUnderstanding of lead toxicity has advanced substantially over the past three decades, and focus has shifted from high-dose effects in clinically symptomatic individuals to the consequences of exposure at lower doses that cause no symptoms, particularly in children and fetuses. The availability of more sensitive analytic methods has made it possible to measure lead at much lower concentrations. This advance, along with more refined epidemiological techniques and better outcome measures, has lowered the least observable effect level until it approaches zero. As a consequence, the segment of the population who are diagnosed with exposure to toxic levels has expanded. At the same time, environmental efforts, most importantly the removal of lead from gasoline, have dramatically reduced the amount of lead in the biosphere. The remaining major source of lead is older housing stock. Although the cost of lead paint abatement is measured in billions of dollars, the monetized benefits of such a Herculean task have been shown to far outweigh the costs.
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The Impact of Minimally Invasive Surgical Techniques
Sir Ara Darzi, and Yaron MunzVol. 55 (2004), pp. 223–237More LessThe use of minimally invasive techniques (MIT) in patient care is well documented in ancient history; however, it was not until the 1990s that advancements in technology enabled surgeons to realize the true potential of this approach. The minimally invasive approach has revolutionized surgical care, significantly reducing postoperative pain, recovery time, and hospital stays with marked improvements in cosmetic outcome and overall cost-effectiveness. It is now used around the world and in all major fields of surgery, compelling changes in training programs in order to assure quality control and patient safety. The bond between surgeons practicing minimally invasive surgery (MIS) and the high-tech industry is of utmost importance to future developments. Surgical robotic systems represent the most technologically advanced product of this collaboration, and their potential application in MIS shows much promise. As technology advances, additional developments in MIT are likely.
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Implementing A Research Agenda for Complementary and Alternative Medicine *
Vol. 55 (2004), pp. 239–254More LessComplementary and alternative medicine (CAM) consists of diverse clinical interventions that are practiced because of their popularity rather than the prior demonstration of safety and efficacy required for conventional agents. CAM therapies can be grouped into five categories: biologically based therapies, manipulative and body-based interventions, mind-body interventions, “energy” therapies, and alternative medical systems. The present evidence that individual CAM interventions are efficacious is largely anecdotal, but hundreds of small trials have yielded positive results. For a few modalities, existing data are either very encouraging or else sufficient to conclude that they are ineffective. CAM interventions are presumed to be safe, yet they may not be, particularly in the case of botanical agents with inherent toxicities, significant drug interactions, or potent adulterants. The public health questions regarding CAM can only be addressed through a research agenda that defines which interventions have favorable therapeutic indices. Implementation of this agenda involves adequate characterization and standardization of the product or practice, with rigorous investigation to demonstrate its safety, mechanism of action, and efficacy.
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Basic Advances and New Avenues in Therapy of Spinal Cord Injury
Vol. 55 (2004), pp. 255–282More LessThe prospects for successful clinical trials of neuroprotective and neurorestorative interventions for patients with acute and chronic myelopathies depend on preclinical animal models of injury and repair that reflect the human condition. Remarkable progress continues in the attempt to promote connections between the brain and the sensory and motor neurons below a spinal cord lesion. Recent experiments demonstrate the potential for biological therapies to regenerate or remyelinate axons and to incorporate new neural cells into the milieu of a traumatic spinal cord injury. The computational flexibility and plasticity of the sensorimotor systems of the brain, spinal cord, and motor unit make functional use of new circuitry feasible in patients. To incorporate residual and new pathways, neural repair strategies must be coupled to rehabilitation therapies that drive activity-dependent plasticity for walking, for reaching and grasping, and for bowel and bladder control. Prevention of pain and dysautonomia are also clinical targets. Research aims to define the temporal windows of opportunity for interventions, test the safety and efficacy of delivery systems of agents and cells, and provide a better understanding of the cascades of gene expression and cell interactions both acutely and chronically after injury. These bench-to-bedside studies are defining the neurobiology of spinal cord injury rehabilitation.
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Clinical Management of Tuberculosis in the Context of HIV Infection
Vol. 55 (2004), pp. 283–301More LessGlobally, the HIV and tuberculosis epidemics are stoking each other, creating a public health crisis of enormous proportions. At the level of individuals, contemporaneous infection with M. tuberculosis and HIV poses great challenges to clinical management. This chapter provides an overview of active and latent tuberculosis treatment in HIV-infected and -uninfected individuals. The discussion focuses on medication issues, including interactions between antitubercular drugs, antiretroviral drugs, and medicines used for opportunistic infections and treatment in the face of comorbidities. Clinical questions specific to coinfection are discussed, including duration and timing initiation of therapy and immune reconstitution. Most of the data presented were generated in industrialized settings and are presented to assist patient management in such settings. However, given the disproportionate amount of TB/HIV in less-developed nations and the increasing availability of antiretroviral therapy in resource-limited settings, the issues presented will become increasingly relevant globally.
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HIV–Associated Lipodystrophy: Pathogenesis, Prognosis, Treatment, and Controversies
Vol. 55 (2004), pp. 303–317More LessPotent antiretroviral agents markedly suppress HIV and have dramatically improved the clinical course, prognosis, and survival of HIV-infected patients. Unfortunately, highly active antiretroviral therapy is often compromised by metabolic complications, including insulin resistance, dyslipidemia, and fat redistribution. Together these changes have been termed the HIV-lipodystrophy syndrome, which is estimated to affect a majority of patients treated with potent combination antiretroviral therapy. Routine testing of fasting glucose is recommended for all HIV-infected patients, particularly those who are obese, have a family history of diabetes mellitus, or are receiving protease inhibitor therapy. Preliminary investigations have demonstrated the potential utility of insulin-sensitizing agents and lipid-lowering therapies to ameliorate these metabolic disturbances. Patients with HIV infection who demonstrate fat redistribution and develop hyperinsulinemia and dyslipidemia may be at increased risk of cardiovascular disease. However, the long-term effects on cardiovascular disease have not yet been determined.
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Human Papillomavirus Vaccines and Prevention of Cervical Cancer
Vol. 55 (2004), pp. 319–331More LessCervical cancer and precancerous cervical lesions constitute a major problem in women's health. Every year 470,000 cases of cervical cancer are diagnosed worldwide, and about half the women afflicted will die. In the United States alone, ∼14,000 cases of cervical cancer are diagnosed each year despite the availability of screening and access to high-quality gynecological care. With the confirmation that cervical cancer is caused by an infectious agent, human papillomavirus, the possibility of fighting this disease with either prophylactic or therapeutic vaccination arose. This review describes advances in vaccine development and very promising first results for prophylactic vaccination against cervical cancer.
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Opportunities for Control of Meningococcal Disease in the United States *
Vol. 55 (2004), pp. 333–353More LessThe United States currently has relatively low rates of meningococcal disease caused by Neisseria meningitidis. Serogroups Y, C, and B are most common. Although most cases are sporadic, a minority are associated with outbreaks. Pediatric populations have disproportionately higher rates of disease, but nearly two thirds of all cases occur in persons aged 15 years and older. The major challenge to control of domestic meningococcal disease is the absence of a vaccine to prevent sporadic cases spanning many age groups. The quadrivalent A/C/Y/W-135 meningococcal polysaccharide vaccine is licensed in the United States, but because of its limited efficacy in children under two years of age, it is recommended for high-risk groups and outbreak response rather than routine childhood immunization. New conjugate meningococcal vaccines have successfully reduced endemic disease in the United Kingdom, and similar vaccines promise to have a dramatic impact on the burden of meningococcal disease in the United States.
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Recent Advances in the Development of HIV-1 Vaccines Using Replication-Incompetent Adenovirus Vectors
Vol. 55 (2004), pp. 355–372More LessAn increasing body of evidence suggests that a vaccine that elicits anti-HIV-1 cellular immunity could provide the basis for an effective AIDS vaccine. Comparative immunization experiments testing a variety of vaccine approaches have demonstrated that replication-incompetent adenovirus vectors are an effective means for eliciting cytotoxic T-lymphocyte (CTL) immune responses against HIV-1 antigens. These immune responses effectively control viremia in nonhuman primates following challenge with simian AIDS viruses. Such data, coupled with epidemiology studies that identify HIV-1 gag, pol, and nef as the best antigens for broadly directed cellular immune responses, provide guidance for the development of a potential AIDS vaccine.
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Left Ventricular Diastolic Dysfunction and Diastolic Heart Failure
Vol. 55 (2004), pp. 373–394More LessThirty to fifty percent of patients presenting with signs and symptoms of heart failure have a normal left ventricular (LV) systolic ejection fraction. The clinical examination cannot distinguish these patients (diastolic heart failure) from those with a depressed ejection fraction (systolic heart failure), but echocardiography can. The management of diastolic heart failure has two major objectives. The first is to reverse the consequences of diastolic dysfunction (e.g., venous congestion), and the second is to eliminate or reduce the factors responsible for diastolic dysfunction (e.g., myocardial hypertrophy, fibrosis, and ischemia).
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Mechanisms of Pulmonary Fibrosis
Vol. 55 (2004), pp. 395–417More LessTissue injury evokes highly conserved, tightly regulated inflammatory responses and less well-understood host repair responses. Both inflammation and repair involve the recruitment, activation, apoptosis, and eventual clearance of key effector cells. In this review, we propose the concept of pulmonary fibrosis as a dysregulated repair process that is perpetually “turned on” even though classical inflammatory pathways may be dampened or “switched off.” Significant regional heterogeneity, with varied histopathological patterns of inflammation and fibrosis, has been observed in individual patients with idiopathic pulmonary fibrosis. We discuss environmental factors and host response factors, such as genetic susceptibility and age, that may influence these varied manifestations. Better understanding of the mechanisms of lung repair, which include alveolar reepithelialization, myofibroblast differentiation/activation, and apoptosis, should offer more effective therapeutic options for progressive pulmonary fibrosis.
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Systemic Mastocytosis *
Cem Akin, and Dean D. MetcalfeVol. 55 (2004), pp. 419–432More LessSystemic mastocytosis is a clonal disorder of the mast cell and its progenitor. The symptoms of systemic mastocytosis are due to the pathologic accumulation and activation of mast cells in various tissues such as bone marrow, skin, gastrointestinal tract, liver, and spleen. Recent studies revealed striking differences between the molecular and cellular biology of mast cells in patients with mastocytosis and those of healthy individuals. These findings are being used in formulating diagnostic criteria as well as designing novel treatment approaches to the disease.
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The erbB Family: Targets for Therapeutic Development Against Cancer and Therapeutic Strategies Using Monoclonal Antibodies and Tyrosine Kinase Inhibitors
Vol. 55 (2004), pp. 433–457More LessThe overexpression and aberrant function of members of the erbB family of receptors, particularly erbB1 (also known as epidermal growth factor receptor), and its ligands in many human cancers have provided a rationale for targeting this signaling network with novel approaches. erbB1 is a selective target for inhibiting cancers because its activation often confers a proliferative advantage. Activation of the erbB1 tyrosine kinase provides signals that drive dysregulated proliferation, invasion, metastasis, angiogenesis, and cell survival, and its inhibition has potential in both the treatment and prevention of these malignancies. Based on the structure and function of erbB1, two therapeutic strategies have been developed. The first uses human monoclonal antibodies (MAbs) generated against the receptor's ligand-binding extracellular domain. These MAbs block binding of receptor-activating ligands, and, in some cases, can induce receptor endocytosis and downregulation. The second uses small molecules that compete with adenosine triphosphate (ATP) for binding to the receptor's kinase pocket, thereby blocking receptor activation and the transduction of postreceptor signals. Early clinical studies suggest that both approaches are well tolerated and can induce clinical activity in many common malignancies.
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Nonmyeloablative Allogeneic Immunotherapy for Solid Tumors *
Vol. 55 (2004), pp. 459–475More LessOver the past decade, considerable advances have been made in the field of allogeneic hematopoietic stem cell transplantation. Recognition that transplanted donor immune cells can cure patients with leukemia has led to the development of nonmyeloablative or “low-intensity” conditioning regimens, which have expanded the application of allogeneic transplantation to a growing number of hematological malignancies. The improved safety and preliminary success of this transplant approach have justified applying allogeneic immunotherapy to patients with treatment-refractory solid tumors.
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Rituximab: Expanding Role in Therapy for Lymphomas and Autoimmune Diseases
Vol. 55 (2004), pp. 477–503More LessRituximab (Rituxan®) is a human-mouse chimeric monoclonal antibody that targets the B-cell CD20 antigen and causes rapid and specific B-cell depletion. Rituximab was approved in the United States in 1997 to treat low-grade or follicular, relapsed or refractory, CD20-positive B-cell non-Hodgkin's lymphoma (NHL). Since then, further clinical experience with rituximab has been incorporated into the prescribing information, which now stipulates an extended eight-week schedule, treatment of patients with refractory or relapsed bulky disease measuring >10 cm, and retreatment of patients who responded to rituximab previously. In 1998, the European Union approved rituximab (MabThera®) to treat stage III/IV, follicular, chemotherapy-resistant, or relapsed NHL. Recently, the European Union also approved the use of rituximab in combination with standard chemotherapy for aggressive NHL. Many clinical trials have evaluated rituximab, alone or with other therapies, in indolent and aggressive NHL as well as other B-cell lymphoproliferative disorders. New studies are evaluating rituximab's role in first-line therapy, maintenance therapy, and stem-cell transplantation procedures. The use of rituximab against autoimmune disorders, such as rheumatoid arthritis, immune thrombocytopenic purpura, autoimmune hemolytic anemia, systemic lupus erythematosus, and multiple sclerosis, is also under investigation.
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Botulinum Toxin and Other New Approaches to Migraine Therapy
Vol. 55 (2004), pp. 505–518More LessThe number of migraine treatments and our understanding of migraine pathophysiology are both increasing. Newer treatments focus on migraine prevention. Botulinum toxin (BTX) is a potent neurotoxin used primarily to treat diseases associated with increased muscle activity. Recently, BTX was found to have antinociceptive effects that are probably independent of its muscle-relaxant action. Clinical trials support the efficacy of BTX type A (and possibly also type B) in the treatment of migraine. The anticonvulsant topiramate was recently shown to be effective for migraine prevention. At the low doses used for this indication, cognitive side effects are not a major concern. Another new approach to migraine prevention is angiotensin type 1 (AT1) receptor blockade. The high tolerability of the AT1 receptor blocker candesartan warrants further studies to assess its role in migraine prevention.
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Management of Infections in the Neutropenic Patient
Vol. 55 (2004), pp. 519–526More LessNeutropenic patients continue to be at increased risk for developing serious infections despite substantial advances in supportive care. Epidemiologic shifts occur periodically and need to be detected early because they influence prophylactic, empiric, and specific therapy strategies. Although effective in preventing bacterial and some fungal infections, prophylaxis must be used with caution because it is associated with the emergence of resistance. The choices for empiric therapy include combination regimens and monotherapy. Specific choices depend on local factors (epidemiology, susceptibility/resistance patterns, availability). Various treatment settings (hospital-based, early discharge, outpatient) are also available, and the choice depends on the patient's risk category. Early diagnosis and treatment of many fungal and viral infections remains suboptimal. Infection control and prevention are important strategies, especially with the emergence of multidrug-resistant organisms.
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Previous Volumes
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Volume 75 (2024)
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Volume 74 (2023)
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Volume 73 (2022)
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Volume 72 (2021)
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Volume 71 (2020)
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Volume 70 (2019)
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Volume 69 (2018)
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Volume 68 (2017)
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Volume 67 (2016)
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Volume 66 (2015)
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Volume 65 (2014)
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Volume 64 (2013)
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Volume 63 (2012)
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Volume 62 (2011)
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Volume 61 (2010)
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Volume 60 (2009)
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Volume 59 (2008)
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Volume 58 (2007)
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Volume 57 (2006)
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Volume 56 (2005)
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Volume 55 (2004)
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Volume 54 (2003)
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Volume 53 (2002)
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Volume 52 (2001)
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Volume 51 (2000)
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Volume 50 (1999)
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Volume 49 (1998)
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Volume 48 (1997)
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Volume 47 (1996)
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Volume 46 (1995)
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Volume 45 (1994)
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Volume 44 (1993)
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Volume 43 (1992)
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Volume 42 (1991)
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Volume 41 (1990)
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Volume 40 (1989)
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Volume 39 (1988)
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Volume 38 (1987)
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Volume 37 (1986)
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Volume 36 (1985)
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Volume 35 (1984)
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Volume 34 (1983)
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Volume 33 (1982)
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Volume 32 (1981)
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Volume 31 (1980)
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Volume 30 (1979)
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Volume 29 (1978)
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Volume 28 (1977)
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Volume 27 (1976)
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Volume 26 (1975)
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Volume 25 (1974)
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Volume 24 (1973)
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Volume 23 (1972)
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Volume 22 (1971)
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Volume 21 (1970)
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Volume 20 (1969)
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Volume 19 (1968)
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Volume 18 (1967)
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Volume 17 (1966)
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Volume 16 (1965)
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Volume 15 (1964)
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Volume 14 (1963)
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Volume 13 (1962)
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Volume 12 (1961)
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Volume 11 (1960)
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Volume 10 (1959)
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Volume 9 (1958)
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Volume 8 (1957)
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Volume 7 (1956)
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Volume 6 (1955)
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Volume 5 (1954)
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Volume 4 (1953)
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Volume 3 (1952)
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Volume 2 (1951)
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Volume 1 (1950)
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Volume 0 (1932)