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ID PMID Title PublicationDate abstract
12645351 [Early diagnosis of rheumatoid arthritis with a test based upon a specific antigen: cyclic 2003 Feb 1 In patients with rheumatoid arthritis (RA), joint erosions occur at a very early stage of the disease before clinical symptoms can be detected. Early treatment with currently available antirheumatic drugs may stop or delay the development of such erosions. A simple and specific diagnostic test is needed for treatment to be initiated at an early stage. The specificity of the routinely used rheumatoid factor (RF) test is too low for that purpose. A novel autoantibody, directed to citrullinated antigens in the synovium, seems to provide a new starting point. These citrullinated autoantigens (e.g. fibrin) are specifically present in inflamed synovia and the antibodies for these are locally produced. The autoantibodies can be detected in the blood of the patients with RA years before the first clinical signs are manifest, and high titres appear to correlate strongly with erosive disease. The test for cyclic citrullinated peptide, which has recently become available, has a specificity of 98-99% and a sensitivity of 75-80%.
12510349 [The molecular genetics of rheumatoid arthritis disease gene]. 2002 Dec Rheumatoid arthritis(RA) is a chronic polyarthritis of unknown etiology affecting approximately 1% of the population worldwide. Previous studies have shown that the ratio of the risk for siblings of patients with the disease versus the prevalence of that disease in the general population (lambda s) is much greater in RA, suggesting that genetic factors may be involved in familial clustering. Using microsatellite marker analysis and sib-pair linkage study, we have identified three chromosome regions D1S214/253, D8S556 and DXS1232/984 as candidate loci for RA disease genes. In this article, we review the molecular genetic findings on the RA disease genes located respectively at each of the above chromosome regions. We show that the death receptor 3(DR3) gene, a Fas family member, containing nucleotide polymorphism is the candidate disease gene located at D1S214/253. We also identify the mutant forms of angiopoietin-1(Ang-1) and Dbl proto-oncogenes respectively as the candidate genes located at D8S556 and DXS1232/984. We surmise that these mutations are responsible for the impairment of apoptosis induction, angiogenesis and leukocyte function in the patients, which may predispose to autoimmunity.
14620159 Lung involvement in rheumatoid arthritis. 2003 Oct RA is a systemic autoimmune disorder primarily involving the joints. Extra-articular manifestations of RA often include lung involvement with heterogeneous clinical presentation and radiological findings. Autopsy studies reveal that the percentage of RA patients with pathological changes in the lung is significantly higher than that of patients with clinical manifestations. Lung alterations in RA may be primary or secondary to pharmacological treatments and may involve the alveoli, the interstitium, the airways and/or the pleura. These alterations may significantly impair lung function and some of them are potentially life-threatening. Thus, clinical examination and lung function testing should be performed in all patients with RA at the time of diagnosis and during follow-up. Those patients with clinical alterations and/or impaired lung function should undergo a complete radiological study.
14700353 Antioxidant status & lipid peroxidation in patients with rheumatoid arthritis. 2003 Oct BACKGROUND & OBJECTIVES: Rheumatoid arthritis (RA) is a debilitating, chronic multisystem disease with an unknown etiology. Recent findings indicate that increased oxidative stress and/or defective antioxidant status contribute to the etiology of RA. The present study was undertaken to examine the oxidant and antioxidant systems in patients with RA and healthy controls. METHODS: Twenty two patients with RA and 20 healthy volunteers were included in the study. Levels of malondialdehyde (MDA) and antioxidant vitamins (A, E, C) in serum samples were determined by high performance liquid chromatography (HPLC). Spectrophotometric methods were used to determine activity levels of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), in erythrocytes. RESULTS: MDA levels in patients with RA were found to be significantly (P<0.005) higher than controls whereas levels of vitamins A, E, C and activities of GSH-Px, SOD were lower in the patients compared to controls (P<0.005 for SOD and antioxidant vitamins; P<0.05 for GSH-Px). INTERPRETATION & CONCLUSION: There was an increased oxidative stress and a low antioxidant status in patients with RA. These changes are probably due to efforts for reducing lipid peroxidation and hence to lower tissue damage.
12934956 Treatment of rheumatoid arthritis with electromagnetic millimeter waves applied to acupunc 2003 The aim of the study was to evaluate the efficacy and safety of electromagnetic millimeter waves (MW) applied to acupuncture points in patients with rheumatoid arthritis (RA). Twelve patients with RA were exposed to MW with power 2.5 mW and band frequency 54-64 GHz. MW were applied to the acupuncture points of the affected joints in a double blind manner. At least 2 and maximum 4 points were consecutively exposed to MW during one session. Total exposure time consisted of 40 minutes. According to the study design, group I received only real millimeter wave therapy (MWT) sessions, group II only sham sessions. Group III was exposed to MW in a random cross-over manner. Pain intensity, joint stiffness and laboratory parameters were recorded before, during and immediately after the treatment. The study was discontinued because of beneficial therapeutic effects of MWT. Patients from group I (n=4) reported significant pain relief and reduced joint stiffness during and after the course of therapy. Patients from group II (n=4) revealed no improvement during the study. Patients from group III reported the changes of pain and joint stiffness only after real MW sessions. After further large-scale clinical investigations MWT may become a non-invasive adjunct in therapy of patients with RA.
15478165 Anti-tumor necrosis factor agents for rheumatoid arthritis in the setting of chronic hepat 2004 Oct 15 OBJECTIVE: To examine the safety of using anti-tumor necrosis factor (TNF) therapy in patients with rheumatoid arthritis (RA) in the setting of hepatitis C virus (HCV) infection. METHODS: The charts of 5 patients known to have RA requiring anti-TNF therapy as well as established HCV infection were reviewed retrospectively for laboratory data of hepatic parenchymal inflammation and viral proliferation while taking these agents. RESULTS: In a mean +/- SD followup period of 41 months (+/- 28.2 months), no patient displayed evidence of sustained elevation of serum aminotransferases during therapy with anti-TNF. Additionally, 1 patient was observed to have a decreased HCV viral load after extended treatment with only anti-TNF (no therapy for HCV). CONCLUSION: Anti-TNF therapy for RA in the setting of HCV appears to be safe and well tolerated without apparent influence on the underlying HCV infection. Therefore, this approach should be further evaluated prospectively for longterm safety.
11840694 Gene therapy for rheumatoid arthritis. Lessons from animal models, including studies on in 2002 Feb Evidence from animal models convincingly supports the fact that gene therapy can be an advantageous strategy in the treatment of chronic destructive RA. In this article, we review the state of the art in anticytokine gene transfer into the synovial arthritic joint with the emphasis on IL-1Ra, IL-4, and IL-10 effects on CIA in mice. In CIA, only high and continuous release of IL-1Ra protein systemically by mini-osmotic pumps could prevent disease onset and was curative in mice. Local gene transfer seemed to be the obvious way to reach the high local levels that are demanded for protection. It was shown that local IL-1Ra overexpression reduced arthritis incidence and severity as well as tissue destruction. In line with observations about neutralizing antibodies and soluble receptors, gene therapy with TNF soluble receptors provided anti-inflammatory activity in early arthritis but not in advanced arthritis. The limited efficacy at later stages and poor protection against destruction imply that the combination of gene constructs for TNF and IL-1 inhibitors is the obvious direction for future therapy. Apart from targeting of proinflammatory cytokines, adenoviral overexpression of IL-10 and IL-4 may have therapeutic applicability. Local injection of AdIL-10 in the knee joint was effective at the site, but also highly reduced spreading to ipsilateral sites. High local dosages caused suppression in contralateral sites as well. The reports on the anti-inflammatory effect of AdIL-4 are conflicting; however, all present data showed that IL-4 overexpression provides impressive protection against cartilage and bone erosion. Apart from the local effects in the injected joint, it is becoming more and more clear that local treatment also affects arthritis in nearby joints. This is an intriguing general finding, which may enlarge the therapeutic applicability of gene transfer in human arthritis. Proving the feasibility of gene therapy in experimental arthritis, most research efforts are now focused on improving local gene delivery by enhanced viral infection of synovial cells, using RGD-modified adenovirus, or achieving prolonged persistence and regulated expression with AAV. Elegant future alternatives are the application of in vitro engineered T cells as a vehicle capable of specific homing to joint tissues. The feasibility of viral transduction of chondrocytes to obtain a tissue-specific approach to treat articular cartilage damage in arthritis needs further attention.
15464079 Anti-inflammatory drugs and tumor necrosis factor-alpha production from monocytes: role of 2004 Oct 6 Inhibition of tumor necrosis factor-alpha (TNF-alpha) represents a relevant target in rheumatoid arthritis therapy. Besides inhibiting cyclooxygenase, anti-inflammatory drugs can affect the activation of transcription factors. We investigated the ability of dexamethasone, indomethacin, and rofecoxib to modulate nuclear factor-kappaB (NF-kappaB) activation and TNF-alpha release from human monocytes challenged with lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA). Both stimuli induced NF-kappaB nuclear translocation and TNF-alpha secretion. Dexamethasone potently inhibited TNF-alpha release, indomethacin inhibited only PMA-evoked release, while rofecoxib had no effect. In the electrophoretic mobility shift assay, dexamethasone and rofecoxib dose-dependently inhibited the DNA binding activity of NF-kappaB in stimulated monocytes, whereas indomethacin failed to inhibit the LPS-evoked one. These results were further confirmed by evaluating the drugs' ability to reduce nuclear NF-kappaB subunits, as well as the amount of phosphorylated IkappaBalpha in cytosolic fractions. In conclusion, these results indicate that anti-inflammatory drugs differ largely in their ability to inhibit NF-kappaB activity and/or TNF-alpha release from human monocytes. These effects can be relevant to rheumatoid arthritis therapy.
16136957 [Effect of bizhongxiao decotion on TNF-alpha and interleukin-1beta in plasma of rats with 2004 Jun OBJECTIVE: To observe the influence of bizhongxiao decotion (BZXD) on the plasma TNF-alpha and IL-1beta in rats with C II-induced arthritis (CIA) and to explore the mechanism of BZXD in the treatment of rheumatoid arthritis. METHODS: We divided 75 rats into 4 groups randomly. The rat experimented arthritis model was established by subcutaneous injection with collagen II. The plasma TNF-alpha and IL-1beta levels were detected with the radio-immunity assay at different time spots. RESULTS: The incidence of arthritis in the rats immunized with C II was approximately 88%. The plasma TNF-alpha and IL-1beta levels of the model group, BZXD group and methotrexate (MTX) group were notably higher than those of the normal group (P < 0.05). The plasma TNF-alpha and IL-1beta levels of the model group were higher than those of the MTX control group and BZXD treatment group at different time spots (P < 0. 01). The plasma TNF-alpha and IL-1beta levels rose step by step, but those of the BZXD group and MTX group decreased gradually. Moreover, the plasma TNF-alpha and IL-1beta levels of the rats of BZXD group were lower than those of the MTX group (P < 0. 05). CONCLUSION: TNF-alpha and IL-1beta play a very important role in the formation and development of rheumatoid arthritis. Both BZXD and MTX can notably decrease the plasma TNF-alpha and IL-1beta levels, but the effect of BZXD is better than that of MTX.
12468957 The prevalence of coeliac disease in rheumatoid arthritis. 2002 Dec OBJECTIVE: To determine the prevalence of coeliac disease in rheumatoid arthritis. METHODS: One hundred and sixty patients with seropositive rheumatoid arthritis were tested for the endomysial antibody. Those found positive were studied further with endoscopic small bowel biopsy. RESULTS: Only one patient was found to have coeliac disease, and that had already been diagnosed. Thus the prevalence of previously undiagnosed coeliac disease in rheumatoid arthritis is 0 (95% CI 0-0.24%) and the overall prevalence of coeliac disease is 0.63% (95% CI 0.1-3.5%). These prevalences are not significantly different from the reported prevalences of coeliac disease in the general population. CONCLUSIONS: This study does not support an association between coeliac disease and seropositive rheumatoid arthritis or the screening of such patients for coeliac disease.
15301246 Renal function in rheumatoid arthritis patients treated with methotrexate and infliximab. 2004 Jul OBJECTIVE: This study was aimed at monitoring the early and late effects of infliximab on renal proximal function in RA patients treated with methotrexate. N-acetyl-3-D-glucosaminidase (NAG) activity in urine served as an indicator of proximal tubular damage METHODS: NAG activity was estimated in 21 patients during the course of treatment with infliximab and methotrexate. In every patient NAG-enzymuria was estimated directly before and 60 min after infliximab infusions and 62 weeks after starting the therapy. RESULTS: The total of mean NAG activities observed before each infusion of infliximab was significantly lower (p < 0.02) than NAG-enzymuria before the start of infliximab treatment (7.4 UI/g vs 11.8 UI/g). The proportion of patients in whom NAG activity rose by more than 50% during treatment ranged from 5.3% to 25%. Administration of infliximab did not significantly change the mean serum creatinine levels or creatinine clearance. No significant differences were observed in the mean values of NAG values before and 60 min after infliximab infusion. Patients who demonstrated elevated NAG activities during the course of the whole treatment demonstrated significantly more pronounced NAG enzymuria before treatment and one hour after the first infusion (p < 0.0005), as well as higher RA activity (p < 0.05). There was no observed influence of NSAIDs or prednisone on the frequency of elevated NAG activities. Raised creatinine concentrations (> 1.3 mg/dL) were noted before and during the course of infliximab treatment in 3 patients. In 16 patients abdominal fat aspiration biopsy was performed and in 3 the presence of amyloid deposits was demonstrated. In these patients NAG activity exceeded twice the upper normal limit. CONCLUSION: The introduction of infliximab during methotrexate therapy demonstrated no early or delayed nephrotoxicity of the drug in patients with rheumatoid arthritis.
15689049 Skeletal benefit after one year of risedronate therapy in patients with rheumatoid arthrit 2004 Glucocorticoid therapy is an important risk factor for osteoporosis in rheumatoid arthritis. Reduction in fracture risk is the most important endpoint for osteoporosis treatments. The aim of this study was to evaluate whether skeletal benefit (increases in osteosonogrammetry parameters, reduction in bone turnover and fracture incidence) are maintained during a follow-up of 1 year with risedronate therapy (5 mg/day). During the study period osteosonogrammetry parameters showed a significant increase and no new osteoporotic fractures were reported, suggesting an antifracture effect of risedronate therapy. Urine crosslinks (as a bone resorption marker) significantly decreased during the follow-up, suggesting a positive balance in the bone remodeling process. The tolerability of risedronate was good and only seven out of 51 patients presented minimal adverse effects. In summary, risedronate significantly decreased new osteoporotic fractures in patients with rheumatoid arthritis and glucocorticoid-induced osteoporosis and is an effective and well-tolerated treatment.
15208869 [Effect of low intensity helium-neon laser and decimeter electromagnetic irradiation on fu 2004 Mar Clinical, laboratory, and immunoassay of 58 patients with rheumatoid arthritis, first and second degree of activity was carried out. Low-energy helium-neon laser exposure and decimeter electromagnetic radiation (DMEM) of peripheral blood was given along with the use of non-steroidal antiinflammatory drugs and methotrexate. Peculiarities of this magnetic-laser effect on proliferation response and apoptosis of mononuclear leucocytes in vitro and in vivo have been revealed. It was also established that the application of DMEM-therapy brought patients with RA in shorter period of time to clinical improvement evaluated by ACR criteria.
12010605 Cytokines in rheumatoid arthritis. 2002 Jun Rheumatoid arthritis (RA) is a chronic disease characterized by synovial inflammation that leads to the destruction of cartilage and bone. In the last decade, there was a lot of successful research in the field of cytokine expression and regulation. It has become clear that pro- and anti-inflammatory cytokines, derived predominantely from cells of macrophage lineage, play a major role in the initiation and perpetuation of the chronic inflammatory process in the RA synovial membrane. Monokines are abundant in rheumatoid synovial tissue, whereas low amounts of lymphokines are found. The involvement of pro-inflammatory cytokines, particularly interleukin (IL)-1 and tumor necrosis factor-alpha, in the pathogenesis of RA is well accepted. Recent data provide evidence that the pro-inflammatory cytokine IL-18 plays a crucial role in the development and sustenance of inflammatory joint diseases. There also appears to be a compensatory anti-inflammatory response in RA synovial membrane. It has become clear in the last few years that T cell-derived cytokines expressed preferentially by Th1 cells contribute to joint destruction and inflammation in RA. However, products from Th2 cells may be protective.
12440938 Erythropoietin and interleukin-1beta modulate nitrite production in a Swiss 3T3 cell model 2002 Nov Erythropoietin (EPO), a haemopoietic growth factor and a primary regulator of erythropoiesis, is widely used to treat anaemia in various chronic complications of rheumatoid arthritis (RA). Fibroblast-like cells, found in the pannus tissue of joints, are thought to contribute to the inflammatory pathology of RA. Thus for the current study we investigated the effects of recombinant human EPO (rHuEPO) on NO metabolism, using an interleukin-1beta (IL-1beta)-stimulated Swiss 3T3 fibroblast monolayer as a model for fibroblast activity in RA. The results show that, over 3 days, both alone and in combination with the pro-inflammatory cytokine IL-1beta (10 ng/ml), rHuEPO (25 micro-units/ml) induced significant production of nitrite in cell culture supernatants. This is an indicator of NO production by nitric oxide synthase (NOS), which is a well-documented mediator of metalloproteinase-mediated tissue remodelling in RA. It therefore appears that, through modulation of NOS-dependent NO production, rHuEPO may influence remodelling of connective tissue in RA, independently of its established erythropoietic role.
14994386 Polymorphisms in the mannose binding lectin (MBL) gene are not associated with radiographi 2004 Mar OBJECTIVE: To investigate the association between the mannose binding lectin gene (MBL) promoter and structural single nucleotide polymorphisms (SNP) with development of erosions in a primary care inception cohort of patients with inflammatory polyarthritis (IP). METHODS: DNA was available from 438 patients with IP and radiographic data were available for all patients at 5 years. Four SNP [MBL-550*C/G (H/L), MBL-221*G/C (Y/X), MBL codon 52*C/T, and MBL codon 54*G/A] mapping to the MBL gene were genotyped using primer extension techniques. Allele frequencies were compared between IP cases with erosions by 5 years and those without. RESULTS: None of the SNP were associated with erosive outcomes by 5 years. Furthermore there was no association with Larsen score by 1 or 5 years or with the change in Larsen score between 1 and 5 years. Similarly, the genotype combinations known to encode for low MBL protein production were not associated with erosive outcome in the IP cohort as a whole or in those with rheumatoid arthritis (RA) by 5 years. CONCLUSION: Polymorphism within the MBL gene is not associated with presence or extent of erosions by 5 years in patients with RA or IP.
11922198 Evaluation of lipid profile, macular toxicity and clinical manifestations according to APO 2002 OBJECTIVE: To investigate the effect of APO E gene polymorphism over lipid profile, macular toxicity and clinical manifestations in RA and SLE patients treated with chloroquine. MATERIALS AND METHODS: We studied 45 RA and 29 SLE patients treated with chloroquine who were classified based on the therapeutic regime of chloroquine into three groups: A) Cumulative dose of 100-300 g, B) >300 g and C) Never received chloroquine. Clinical evaluation, fasting lipid profile, visual field testing and stereoscopic photos of the retina were performed. APO E genotype was determined by PCR-RFLP. RESULTS: Reduced apo B levels in RA and SLE according to the cumulative dose of chloroquine 2/3 APO E genotype in a subset of SLE patients were observed. Macular toxicity was independent of both APO E genotype and cumulative chloroquine dose. CONCLUSIONS: Reduced apo B levels were observed associated to chloroquine treatment and 2/3 APO E genotype.
12835414 Impaired inflammatory and pain responses in mice lacking an inducible prostaglandin E synt 2003 Jul 22 Prostaglandin (PG)E2 is a potent mediator of pain and inflammation, and high levels of this lipid mediator are observed in numerous disease states. The inhibition of PGE2 production to control pain and to treat diseases such as rheumatoid arthritis to date has depended on nonsteroidal antiinflammatory agents such as aspirin. However, these agents inhibit the synthesis of all prostanoids. To produce biologically active PGE2, PGE synthases catalyze the isomerization of PGH2 into PGE2. Recently, several PGE synthases have been identified and cloned, but their role in inflammation is not clear. To study the physiological role of the individual PGE synthases, we have generated by targeted homologous recombination a mouse line deficient in microsomal PGE synthase 1 (mPGES1) on the inbred DBA/1lacJ background. mPGES1-deficient (mPGES1-/-) mice are viable and fertile and develop normally compared with wild-type controls. However, mPGES1-/- mice displayed a marked reduction in inflammatory responses compared with mPGES1+/+ mice in multiple assays. Here, we identify mPGES1 as the PGE synthase that contributes to the pathogenesis of collagen-induced arthritis, a disease model of human rheumatoid arthritis. We also show that mPGES1 is responsible for the production of PGE2 that mediates acute pain during an inflammatory response. These findings suggest that mPGES1 provides a target for the treatment of inflammatory diseases and pain associated with inflammatory states.
12969322 Past, present and future drug treatment for rheumatoid arthritis and systemic lupus erythe 2003 Oct Historically, treatment of complex autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus has aimed to relieve symptoms, and in severe cases, use broad-spectrum immunosuppressive treatments in attempts to induce permanent remission. Recent research into the causes of chronic autoimmune inflammatory activation have not only explored the mechanism of action of known therapies, but also provided a number of new targets for therapy, by identifying the cells, cytokines and signalling pathways activated during autoimmune antibody mediated processes. This review briefly outlines progress in the understanding of the autoimmune nature of rheumatoid diseases and the expansion of treatment options, from broad to specific immunotherapies for these closely related diseases.
12477293 The evolving therapy of rheumatic diseases, the future is now. 2002 Apr There are two main ways in which physicians will be urged to improve the outcome for their patients suffering from rheumatic diseases in the coming era, these are, early diagnosis and timely effective therapy. Current reserch suggests that in rheumatoid arthritis joint damage occurs early, often within the first 2 years and even in the absence of associating severe symptoms, is a call for action for primary care physicians as well as rheumatologists. Similarly in SLE patients, sometimes the treatments are ineffective or too toxic with sepsis or opportunistic infections often limiting their use or resulting in the death of the patient. As primary care physicians are the clinicians most frequently visited by patients with initial symptoms of the disease, they first need to learn when to suspect it as well as its complications, and when to refer the patient appropriately. Rheumatologists need to determine when and how to prescribe the most appropriate treatment, as well as how to incorporate the new drugs which are emerging on the scene. At the same time, earlier initiation of combination therapy with the disease modifying anti-rheumatic therapy holds an area of continued exploration. This new information has modified our approach to patients' management. The age of "wait and see" is over.