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- Volume 1, Issue 2, 2005
Current Rheumatology Reviews - Volume 1, Issue 2, 2005
Volume 1, Issue 2, 2005
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Upgrading a Classic - Bone Scans in Rheumatology
Authors: Robert Pichler and Karl StieglbauerBone scanning is one of the most common procedures performed in the majority of nuclear medicine departments. Radionuclides on 99m-Tc phosphonates initiated the widespread use of bone scintigraphy over 40 years ago. These diagnostic methods exhibit excellent sensitivity in the detection of local abnormalities of bone metabolism, but specificity is lacking. Interpretation using conventional radiological diagnostic methods coupled with a focus on the patients´ history and clinical signs are essential. Bone scintigraphy makes valuable contributions to orthopedics and traumatology; in cancer patients the method is used to detect bone metastasis and target areas for radionuclide therapy in controlling severe osseous pain in both cancer and polyarthritis patients. The development of inflammation scan methods, such as the antibody-labeled granulocyte scan and introduction of methods to detect chronic infectious processes by 67-Ga amplified the diagnostic accuracy. Nuclear medicine today has a broad program for diagnostic and therapeutic approaches to diseases of bone and joints. In a vast spectrum of rheumatological diseases, these methods contribute to early diagnosis, interpretation of extension and are used during follow- up to define both the inflammatory activity in arthritic joints and the therapeutic response in osteoarthritis. Recently the use of 18-FDG by PET camera systems to detect malignancy and infection has provided additional information in the management of rheumatology patients - especially considering differential diagnosis in metastatic diseases. In the future, the excellent properties of 18-F in bone metabolism indices for skeletal PETs may lead to its broader use not only in Paget's disease or SAPHO syndrome, but also in osteoarthritis and the management of patients with osteoporosis.
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The Role of Inflammatory Mediators in Cartilage Degradation
Authors: Kayo Masuko-Hongo and Kazuo YudohMounting evidence points to the importance of the role played by inflammatory mediators, such as cytokines or prostanoids, in the degradation of cartilage, not only in inflammatory arthritis, but also in degenerative joint diseases. In addition to well-known mediators such as interleukin-1, recent investigations have revealed the distinctive roles of a variety of other mediators in the regulation of cartilage matrix turnover. The present review focuses on the roles of inflammatory mediators in cartilage pathology that have been revealed by experimental evidence.
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The Osteoclast as a New Target in the Treatment of Rheumatoid Arthritis: A Role for the Bisphosphonates?
Authors: Jan V. Offel, Evelyne Dombrecht, Wim J. Stevens and Luc De ClerckThere is a lot of evidence that osteoclasts have a pivotal role in the subchondral, periarticular and general bone loss in rheumatoid arthritis. Bisphosphonates have a high affinity for bone where they are strong inhibitors of osteoclast mediated bone resorption. There is no doubt that bisphosphonates are useful in patients with postmenopausal or glucocorticoid induced osteoporosis certainly if these patients also suffer from RA. Bisphosphonates appear to have beneficial effects on subchondral bone loss and joint destruction in animal models of arthritis. However in human studies these effects remain largely unclear although some antiinflammatory influence seems to be confirmed. An explanation for this discrepancy might be the possibility that more potent agents, or higher doses of existing agents, need to be used. Additional research is necessary to reveal if bisphosphonates possess disease-modifying properties in RA.
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The Role of Apoptosis in Arthritis
Authors: Charles J. Malemud and Heather J. GillespieProgrammed cell death (i.e. apoptosis) plays a critical role in the pathogenesis and progression of several arthritic conditions and autoimmune disorders. Apoptosis induction is dependent on the extent to which the initiating apoptotic signal occurs via a receptor-mediated event (i.e. extrinsic pathway) or by changes in mitochondrial membrane permeability (i.e. intrinsic pathway). In this regard, differential activation of downstream caspases that degrade chromatin-containing DNA resulting in internucleosomal DNA fragmentation occurs by one of these apoptosis pathways or by combinations of both. In degenerative joint diseases such as osteoarthritis, interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) as well as nitric oxide (NO) levels are significantly elevated in osteoarthritic joint synovial fluid. Thus, IL-1, TNF-α as well as NO induced human chondrocyte apoptosis in vitro and apoptosis frequency is often elevated in aging and osteoarthritic cartilage compared to young normal subjects or cartilage age-matched to the osteoarthritic specimens, respectively. A decrease in viable chondrocytes which could result from apoptosis induction in articular cartilage probably has significant implications for cartilage repair in osteoarthritis. Synovial hyperplasia with the resultant formation of pannus suggests that apoptosis-resistance pathways are active in rheumatoid arthritis. A resistance to apoptosis induction is pertinent to cartilage and bone destruction as well in rheumatoid arthritis as is the severity and progression of rheumatoid arthritis pathology. It is noteworthy that medical management of rheumatoid or psoriatic arthritis with anti-TNF-α monoclonal antibodies, while limiting lymphocyte infiltration into affected tissues does not induce apoptosis in synovial joint tissue. Systemic lupus erythematosus is an autoimmune disorder in which the failure to delete auto-reactive Tlymphocytes during immune development suggests that dysfunctional T-lymphocyte function may result from defective apoptosis. Defective T lymphocytes are responsible for abnormal B-cell function, autoantibody production as well as synovial joint arthropathy in lupus. In another view, lupus may be characterized by overly aggressive apoptosis leading to increased apoptotic cell load coupled to a deficiency in apoptotic cell clearance. Lymphocyte infiltration of salivary and lacrimal glands characteristic of Sjoren's syndrome causes glagnd destruction by apoptosis with resultant gland dysfunction.
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The Role of Chemokines in the Pathogenesis of Rheumatoid Arthritis
Authors: Kenji Tani, Keiko Sato and Saburo SoneRheumatoid arthritis (RA) is a chronic, multisystem autoimmune disease characterized by persistent accumulation of leukocytes in the synovial compartment. The influx of the leukocytes is important as a critical step in the pathogenesis of RA. Chemotactic cytokines (chemokines) play a critical role in the pathogenesis of RA not only by inducing the migration of inflammatory cells but also by enhancing the production of inflammatory mediators and angiogenesis. The production of chemokines is regulated by proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6 produced in the inflamed joint suggesting that the efficacy of anti-cytokine therapy is mediated at least partly by the reduction of chemokine production. Th1- type T cells have a role in the joint inflammation of RA because Th1-related chemokine receptors are predominantly expressed on RA synovial tissue T cells. The present review summarizes current knowledge on the role of chemokines and their receptors in the pathogenesis of RA. The authors also review the important relevance of chemokines for therapeutic intervention.
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The Long-Term Outcome of Juvenile Idiopathic Arthritis
Authors: Angelo Ravelli and Alberto MartiniOver the past decades, a number of studies have evaluated the long-term outcome of juvenile idiopathic arthritis (JIA) and some of them have also attempted to identify early prognostic factors. The available data indicate that JIA is not a benign disease because a substantial number of patients still enter adulthood with persistently active disease and may develop severe physical disability. Although a great deal of data are accumulating on prognostic factors in JIA, prediction of long-term outcome early after disease presentation is still difficult because comparisons among existing studies are hindered by a number of reasons. To increase comparability of future analyses and obtain generalizable information on the prognosis of JIA and its prediction, a great deal of effort should be directed toward standardizing the study design and the measurement of predictors and outcomes.
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Specific Biologic Therapy with Tumor Necrosis Factor Inhibitors in Patients with Inflammatory Myopathy
Authors: Albert Selva-O'Callaghan, Moises Labrador-Horrillo and Miquel V. TarresTumor necrosis factor (TNF) and TNF receptors are members of a family of molecules with important regulatory functions that include cellular activation and apoptosis. Neutralization of TNFa has proven to be effective in a variety of inflammatory disorders and autoimmune diseases such as rheumatoid arthritis and Crohn's disease. Treatment of inflammatory myopathies remains a challenge, especially in the case of refractory disease. Elevation of soluble tumor necrosis factor observed in patients with polymyositis/dermatomyositis has led to the suggestion that biologic therapies may be useful in these patients, although experience with anti-TNF agents is still limited. The aim of this mini-review is to summarize the biological bases for treatment of these patients with TNFα inhibitors, to look at the risks and benefits of this therapy -malignancy in patients with a recognized paraneoplastic association and infection versus therapeutic response in refractory myositisand to review the results of the currently reported cases.
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Nociceptive Pathway and Pathology of Low Back Pain
By Shinji ImaiDespite the various classical works, the mechanism of chronic low back pain has not been fully understood. Recent improvement of neuroanatomical techniques has enabled discrimination of fine neural elements as well as exact tracing of the neural projection. Use of these techniques to elucidate the fine innervation of the vertebral column has provided numerous original findings. The present article reviews those studies that contributed to the improvement of our understanding on the mechanism of chronic low back pain. Meanwhile, recent development of molecular biological techniques has also elucidated participation of cellular mediators in the local and central sensitization of nociceptors. The cellular components as well as their chemical mediators may represent an attractive therapeutic target of near future.
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Antigen Specificity and Clinical Relevance of Antiphospholipid Syndrome- Related Autoantibodies
Authors: Ricardo R. Forastiero and Marta E. MartinuzzoThe presence of antiphospholipid antibodies (aPL) combined with venous or arterial thrombosis, and/or obstetric complications defines the antiphospholipid syndrome (APS). Lupus anticoagulants (LA) and anticardiolipin antibodies (aCL) were the first described aPL. It has been shown that aPL, despite their name, are not directed against anionic phospholipids, as had previously thought, but are a part of a large family of autoantibodies against phospholipid-binding plasma proteins. The most important and relevant antigenic targets involved in APS are β2 glycoprotein I (β2GPI) and prothrombin. However, an increasing number of other phospholipid-binding proteins with crucial functions in the regulation of blood coagulation and fibrinolysis are also targeted by APS-related autoantibodies. For clinical purposes, it is important to find which aPL markers has the best prognostic value. While it has been clearly demonstrated that LA and, to a lesser extent, aCL represent a risk for thrombosis, the role of antibodies directed against β2GPI, prothrombin as well as other targets is still uncertain and controversial. Data from a prospective study showed the presence of antibodies to prothrombin and/or β2GPI is a predictor of first or recurrent thromboembolic events in patients with LA and/or aCL. This review intends to highlight the antigen specificity and clinical relevance of APSrelated aPL.
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Cyclophosphamide: Time to Say Goodnight and Goodbye?
Authors: Catherine Edwards and David IsenbergFor over 20 years cyclophosphamide, either intravenous or oral, has been widely used in the treatment of patients with lupus nephritis, cerebritis and vasculitis. Although clearly beneficial for many patients, its propensity to cause haematological complications and reduced fertility has made it unpopular with both patients and physicians. The introduction of mycophenalate mofetil, and the exciting potential for other forms of therapy including B cell depletion, the B cell toleragen LJP394 and anti-BlyS antibodies, now makes it possible to consider the future of the treatment of patients with lupus without resorting to cyclophosphamide. This review considers how close we are to achieving this goal.
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Hyperuricemia and Coronary Artery Disease
Authors: Christine Halligan and Eric L. MattesonHyperuricemia is strongly associated with several known risk factors for cardiac disease including hypertension, diabetes mellitus, hypercholesterolemia and obesity. Despite this association between hyperuricemia and these coronary artery disease risk indicators, most studies have failed to demonstrate a direct causal relationship between hyperuricemia itself and cardiovascular disease. It has been suggested that insulin resistance and endothelial dysfunction may be a common denominator in linking cardiovascular disease and hyperuricemia.
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Syphilis: Its History and World Impact
More LessThe history of syphilis is one of irresponsibility, mythology and more recently, scientific insight. Pseudo-Descartian (defined as 'I think, therefore I publish') mythology has until now precluded any cogent discussion of where the disease originated and who was responsible for its spread. Evidence-based research now allows clear separation of syphilis from others in its class of treponematosis. Examination of skeletons from populations with clinically diagnosed bejel and yaws revealed bone alterations distinctive to those diseases and clearly separating them from syphilis. These insights allowed confident identification, for the first time, of the New World origin of syphilis and indeed, the 'smoking gun' in the Dominican Republic. Thus, the role of Columbus' crew in transmitting syphilis from the New World to the Old is confirmed. Finally, the impact of syphilis on history is explored, ranging from character assassination to potential effect on artistic expression and on the madness that enveloped the third to fifth decades of the last century.
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Volumes & issues
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Volume 20 (2024)
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Volume 19 (2023)
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Volume 18 (2022)
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Volume 17 (2021)
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Volume 16 (2020)
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Volume 15 (2019)
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Volume 14 (2018)
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Volume 13 (2017)
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Volume 12 (2016)
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Volume 11 (2015)
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Volume 10 (2014)
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Volume 9 (2013)
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Volume 8 (2012)
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Volume 7 (2011)
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Volume 6 (2010)
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Volume 5 (2009)
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Volume 4 (2008)
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Volume 3 (2007)
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Volume 2 (2006)
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Volume 1 (2005)
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Metabolic Syndrome in Behçets Disease Patients: Keep an Eye on the Eye
Authors: Suzan S. ElAdle, Eiman A. Latif, Yousra H. Abdel-Fattah, Emad El Shebini, Iman I. El-Gazzar, Hanan M. El-Saadany, Nermeen Samy, Reem El-Mallah, Mohamed N. Salem, Nahla Eesa, Rawhya El Shereef, Marwa El Khalifa, Samar Tharwat, Samah I. Nasef, Maha Emad Ibrahim, Noha M. Khalil, Ahmed M. Abdalla, Mervat I. Abd Elazeem, Rasha Abdel Noor, Rehab Sallam, Amany El-Bahnasawy, Amira El Shanawany, Soha Senara, Hanan M. Fathi, Samah A. El Bakry, Ahmed Elsaman, Amany El Najjar, Usama Ragab, Esraa A. Talaat, Nevin Hammam, Aya K. El-Hindawy, Tamer A. Gheita and Faten Ismail
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