ISSN:1040-8711    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Tumor necrosis factor-&agr; (TNF-&agr;) antagonists have rapidly emerged as a valuable class of antirheumatic agents. Etanercept, a dimerized version of the soluble tumor necrosis factor receptor II, and infliximab, a chimeric anti–TNF-&agr; monoclonal antibody, are currently approved for the treatment of rheumatoid arthritis (RA) based on their proven beneficial effects in clinical trials. New insights into the role of TNF-&agr; in disease pathogenesis have expanded our understanding about the possible mechanisms by which these agents reduce synovial inflammation and inhibit bone and cartilage degradation. The enlarging safety experience has revealed growing concerns about TNF-&agr; inhibition and increased risk for opportunistic infection, most notably the reactivation of latentMycobacterium tuberculosisinfection. Recent recommendations have addressed this risk by calling for pretreatment screening for previous exposure to tuberculosis. The success of etanercept and infliximab therapy for RA has prompted the development of other TNF-&agr; antagonists and extended the investigation of this therapeutic approach to other inflammatory diseases. TNF-&agr; antagonists promise to shape the care of RA and other rheumatic diseases for many years to come.

ISSN:1040-8711    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

This article reviews and cites only publications relating to the management of lupus that have appeared since 1999. The data in these publications demonstrate that preventive and proactive strategies are as important as medication in improving the quality of life and life span of the patient with lupus. The use of lasers and thalidomide represents major advances in cutaneous lupus. The first major study over 25 years using nonsteroidal anti-inflammatory drugs to manage lupus suggests benefits. Further evidence was presented showing that dehydroepiandrosterone, leflunomide, and methotrexate are effective in treating mild to moderate disease. Various iterations and modifications of traditional cyclophosphamide therapy with or without mycophenolate mofetil, cyclosporine, and azathioprine continue to be studied for treating organ-threatening disease. Intravenous gamma globulin and selective apheresis are niche therapies appropriate in a few, highly selected patients. Immunoablative doses of cyclophosphamide appear to be as effective as stem cell transplantation for serious disease resistant to conventional doses of cyclophosphamide. Twelve biologic agents have been studied in lupus since 1999, with only LJP-394 showing clear-cut, convincing efficacy.

ISSN:1040-8711    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The current status of stem cell transplantation in rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus, and systemic sclerosis are reviewed. From a large European bone marrow transplant registry, a birds' eye view of stem cell transplantation for autoimmune disease can be obtained. Among 43 rheumatoid arthritis patients, 35 juvenile chronic arthritis patients, 34 systemic lupus erythematosus patients, and 58 systemic sclerosis patients who underwent stem cell transplantation, initial responses in most patients were good to excellent. Although initial transplant related mortality was low for rheumatoid arthritis, somewhat higher rates for juvenile chronic arthritis, systemic lupus erythematosus, and systemic sclerosis may be falling with modifications in the stem cell transplantation regimens. In rheumatoid arthritis and systemic lupus erythematosus treatment, the criteria for patient selection are still not clear and the therapeutic regimens for stem cell transplantation (and whether follow-up treatment is necessary) are not fully defined. In juvenile chronic arthritis, responses are encouraging although little fully published data beyond that from the European Bone Marrow Transplant Registry exist. In systemic sclerosis, criteria for patient selection and a limited number of stem cell transplantation regimens have been agreed on and controlled trials are underway.

ISSN:1040-8711    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Specific inhibitors of cyclooxygenase-2 were introduced into widespread clinical use in 1999. Since that time, celecoxib and rofecoxib have become two of the most commonly prescribed medications in the United States. Clinical trials using these medications for arthritis and pain have uniformly demonstrated efficacy superior to that of placebo and similar to that of nonsteroidal anti-inflammatory drugs. However, controversy surrounding the proper place of cyclooxygenase-2 inhibitors in the hierarchy of treatment for arthritis continues, based primarily on their higher cost compared with that of acetaminophen and nonsteroidal anti-inflammatory drugs. A decreased risk of gastrointestinal toxicity remains the primary justification for using the more expensive cyclooxygenase-2 inhibitors in preference to nonsteroidal anti-inflammatory drugs. The renal and cardiovascular effects of rofecoxib and celecoxib have been investigated in relation to nonsteroidal anti-inflammatory drugs and to one another. The data with respect to alteration in renal function, lower extremity edema, and hypertension indicates that cyclooxygenase-2 inhibitors affect the kidney in a manner similar to that of nonsteroidal anti-inflammatory drugs. The data comparing the cyclooxygenase-2 inhibitors is difficult to interpret because it is not clear that comparable doses have been used in clinical trials. The potential thrombogenic risk of cyclooxygenase-2 inhibitors remains controversial, and conflicting data exist. It remains important to increase our understanding of the place of these agents in clinical practice from the perspective of efficacy, toxicity, and cost.

ISSN:1040-8711    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Mixed cryoglobulinemia is characterized by a wide spectrum of manifestations that may vary from mild symptoms (such as purpura, arthralgias, and Raynaud phenomenon) to life-threatening conditions (such as acute abdomen, hyperviscosity syndrome, and renal involvement). Hepatitis C virus infection is considered the principal trigger of the disease. Therefore, the treatment not only should be tailored to the prevailing symptom but also take into account the presence of a chronic, often smoldering infection. Symptomatic therapies are to be used in cases of minor clinical manifestations and aggressive modalities in cases of life-threatening conditions. The use of aggressive cytotoxic regimens should actually be stopped and every potentially immunosuppressive drug should be used with caution. Antiviral medications are used with growing frequency. To date, a few small trials with interferon-&agr; alone or in combination with ribavirin in mixed cryoglobulinemia have been conducted. This overview deals with the current approach to the management of mixed cryoglobulinemia, focusing in particular on antiviral treatment in hepatitis C virus infection with or without mixed cryoglobulinemia.

ISSN:1040-8711    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Despite increasing knowledge of the immunology and pathophysiology of the antiphospholipid syndrome, treating this condition remains challenging. Because of a paucity of randomized controlled trials, many of the treatment recommendations are not evidence-based. Retrospective case series suggest that a high level of oral anticoagulation is needed to prevent recurrent thrombosis. The combination of heparin and low-dose aspirin is effective in significantly increasing the chances of a successful pregnancy in woman with recurrent pregnancy failure associated with antiphospholipid antibodies. Primary prevention with aspirin is justified in patients with antiphospholipid antibodies but without a prior history of thrombosis. Interesting and controversial issues in the treatment of the antiphospholipid syndrome include the use of less intensive anticoagulation or antiplatelet agents in some patient subsets, anticoagulation for certain nonstroke neurologic conditions, the role of other agents (hydroxychloroquine, antioxidants), and novel immunomodulatory strategies.

ISSN:1040-8711    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:1040-8711    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Perhaps one of the most elusive areas of study in autoimmunity has been identifying the self-antigens that initially trigger the development of autoimmune responses. Recent work in this area has demonstrated that a number of biochemical modifications that arise in proteins after their translation induce autoimmune responses to otherwise ignored self-proteins. This article will describe those autoimmune diseases in which posttranslational modifications may play a role in initiation of disease, as well as identify how these modifications arise and contribute to the breakdown of immune tolerance. Lastly, we will address how posttranslational modifications in self-antigens affect current diagnostic techniques and the development of immunotherapies for autoimmune diseases.

ISSN:1040-8711    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

There are many posttranslational modifications of proteins of which all are homeostatically important either to carry out a particular structural or functional role or to allow efficient recycling of the amino acid constituents. An important feature of the modified proteins is the acquisition of autoantigenicity. That notion should have been recognized for years with the modifications of immunoglobulin G that constitute new targets for rheumatoid factors. Citrullination or the deimination of arginine residues in proteins creates epitopes that are targeted by rheumatoid autoantibodies with a diagnostic sensitivity and specificity of 40% to 70% and 92% to 99%, respectively. The how, when, and why of the responsible break in tolerance are largely speculative but apoptosis, multiple genetic and environmental influences are likely required. Identifying citrullinated proteins as autoantigens has resulted in new diagnostic and prognostic autoantibody markers for RA and studying the citrullination process and its nature and role in cell biology has provided new insights into its pathogenesis.

ISSN:1040-8711    

出版商:OVID    

年代:2002

数据来源: OVID