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ID PMID Title PublicationDate abstract
20120781 Circulating lipid peroxidation, plasma and erythrocyte antioxidant status in patients with 2009 Aug The aim of the study was to investigate the levels of lipid peroxidation, and both plasma and erythrocyte antioxidant states in patients with rheumatoid arthritis. The population consisted of 60 subjects divided into two groups, 30 subjects had evidence of rheumatoid arthritis and age and sex matched healthy subjects were studied as controls. The level of plasma and erythrocyte thiobarbituric acid reactive substances (TBARS) was markedly increased in both the rheumatoid arthritis patients when compared to control subjects. The activities of plasma and erythrocyte antioxidants were significantly decreased in rheumatoid arthritis. C reactive protein, rheumatoid factor and antistreptolysin-O were significantly higher in rheumatoid arthritis patients than in healthy subjects. In conclusion, on the basis of enhanced lipid peroxidation in rheumatoid arthritis patients with concomitant failure of both the plasma, and erythrocyte antioxidants defense mechanism. These results are consistent with the underlying hypothesis that there is an imbalance between reactive oxygen species production and the antioxidant defense system in inflammatory rheumatoid arthritis disease.
19955045 Identification of cutpoints for acceptable health status and important improvement in pati 2010 Jan OBJECTIVE: To identify cutpoints reflecting Patient Acceptable Symptom State (PASS) and Minimal Clinically Important Improvement (MCII) in patient-reported multi-attribute health status classification systems and health status measurements among patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). METHODS: We identified patients with RA, AS, and PsA from the Norwegian disease-modifying antirheumatic drug (DMARD) register (NOR-DMARD). The patients (n = 4225) had started with DMARD and responded to the PASS and MCII anchoring questions at the 3-month followup examination. Receiver operating characteristics (ROC) curves with 80% specificity and the 75th percentile approach were used to identify PASS and MCII cutpoints in the EuroQol-5 Dimensions (EQ-5D) and the Short-Form-6 Dimensions (SF-6D) indexes, but also in other patient-reported outcomes (joint pain and patient global visual analog scale and Modified Health Assessment Questionnaire). RESULTS: The PASS cutpoints estimated with 80% specificity were around 0.70 in EQ-5D in all diseases and around 0.65 in SF-6D. The cutpoints were around 0.65 and 0.60, respectively, when the 75th percentile approach was used. The MCII cutpoints assessed by 80% specificity varied from 0.10 to 0.19 in EQ-5D and from 0.07 to 0.10 in SF-6D. CONCLUSION: The cutpoints for PASS in EQ-5D and SF-6D indicate that PASS corresponds to a health-related quality of life that is far from perfect health. Somewhat different cutpoints were identified for both PASS and MCII with 80% specificity versus the 75th percentile method.
19034457 Lack of association between interleukin 23 receptor gene polymorphisms and rheumatoid arth 2009 May The recent discovery of interleukin 23 (IL-23), its receptor, and the underlying signal transduction pathway has improved our understanding of cellular immunity. Several studies suggest that IL-23 is an essential promoter of chronic joint inflammation. In this report, we assess the possible association of interleukin 23 receptor (IL23R) polymorphisms and haplotypes with rheumatoid arthritis (RA). The study was conducted on 1,204 RA patients and 979 healthy controls. Seven polymorphisms were selected from previous IBD reports. The seven SNPs (rs1004819, rs7517847, rs10489629, rs2201841, rs1343151, rs11209032 and rs1495965) were genotyped using the TaqMan assay. Comparison of RA and control subjects revealed no statistically significant differences in the distribution of the IL23R genotypes and haplotypes. Our results clearly indicate that IL23R gene polymorphisms do not play a significant role in susceptibility to RA in the Korean population. Accordingly, we conclude that IL23R gene polymorphisms cannot be applied as an effective genetic marker for RA susceptibility.
20198312 Oral treatment with HE3286 ameliorates disease in rodent models of rheumatoid arthritis. 2010 Apr HE3286 (17alpha-ethynyl-5-androstene-3beta, 7beta, 17beta-triol) is an orally bio-available synthetic derivative of naturally occurring androstene-3beta, 7beta, 17beta-triol. Our present data show that oral treatment with HE3286, favourably influenced the course of arthritis in the rat model of adjuvant-induced arthritis (reduced cumulative disease scores and paw edema), and in the mouse model of collagen antibody-induced arthritis (reduced clinical paw scores). Importantly, HE3286 was not immune suppressive in human mixed lymphocyte reaction or in animals challenged with Coxsackie B3 virus. HE3286 is currently in phase I/II clinical trials in rheumatoid arthritis and ulcerative colitis and these findings further strengthen the possibility that HE3286 may represent an effective anti-inflammatory agent useful for treating chronic inflammation with a more attractive safety profile than glucocorticoids or cyclooxygenase inhibitors.
21287475 A survey of relationship between rheumatoid arthritis and hearing disorders. 2010 Nov RA (rheumatoid arthritis) is a chronic multisystem disease with a variety of systemic manifestations. One of these manifestations, is hearing disorder, so study of the relation between RA and hearing disorders is seem important. This was a case-control study which has done from December 2004 to August 2006. This study compared 50 patients with RA, with age, sex and job-matched as control. Audiometric tests in different frequencies show that hearing threshold in high frequencies specially in 8000 Hz had a significant difference between two groups, also acoustic reflexes were absent in case groups and had significant difference between two groups too. The evaluation of sensory neural hearing loss showed that this hearing loss is sensory not neural. Based on this study, frequent evaluation of audiometric tests is recommended for controlling hearing disorders by therapeutic and rehabilitation procedures in RA patients.
20545211 [Effects of Sanwushaoxie decoction on IL-18, TNF-alpha, IL-4 and IL-10 in patients with rh 2010 Mar OBJECTIVE: To investigate the therapeutic effects of Sanwushaoxie decoction on alternations of serum cytokines in patients with rheumatoid arthritis (RA). METHOD: Sixty-three (63) RA patients were selected and randomly divided into 2 groups, with the treatment group administered with Sanwushaoxie decoction, one prescription, 2 times a day, while patients in the control group were given Common Threewingnut Root polyglycoside 20 mg a time, 3 times a day. The treatment was lasted for 60 days. Serum concentrations of IL-6, TNF-alpha, IL-4, IL-10 were observed during the treatment. RESULT: The clinical effecacy and the experimental indexes were significantly improved in the treatment group than those did in the control group (P < 0.01, P < 0.05). There were significant differences of serum levels of 4 cytokines within the treatment group before and after the treatment (P < 0.01, P < 0.05). The serum levels of IL-4, IL-10 were significantly increased in treatment group compared with those did in the control group (P < 0.01). CONCLUSION: Sanwushaoxie decoction is an effective agent in regulating cytokines, improving symptoms and experimental indexes in patients with RA.
19479706 Association of concomitant fibromyalgia with worse disease activity score in 28 joints, he 2009 Jun 15 OBJECTIVE: To study the association of the presence of fibromyalgia (FM) with the Disease Activity Score in 28 joints (DAS28), the Health Assessment Questionnaire (HAQ), and the Medical Outcomes Study Short Form 36 (SF-36) health survey in patients with rheumatoid arthritis (RA). METHODS: A total of 270 outpatients with RA were enrolled in a prospective cross-sectional study. The patients underwent clinical evaluation and application of the HAQ and SF-36 questionnaires. Disease activity was evaluated using the DAS28 score. FM and RA diagnoses were made according to American College of Rheumatology criteria. RESULTS: The overall prevalence of FM was 13.4%. This group of patients had a higher prevalence of female sex, older mean age, higher functional class, and longer morning stiffness than patients with only RA. Mean +/- SD DAS28 scores were significantly higher in patients with RA and FM (5.36 +/- 0.99) than in patients with RA only (4.03 +/- 1.39; P < 0.001). In a multivariable linear regression analysis, FM was an important predictor of the DAS28 score, even after adjusting for the erythrocyte sedimentation rate, number of swollen joints, functional class, number of disease-modifying antirheumatic drugs currently in use, current dose of steroids, and articular erosions. HAQ and SF-36 scores were also worse in patients with RA and associated FM. CONCLUSION: FM is related to worse scores on the DAS28, HAQ, and SF-36 in patients with RA. The presence of FM may have major implications in the interpretation of the DAS28 score because it is related to higher scores independently of objective evidence of RA activity.
20490569 [Validation of the German version of the Regional Pain Scale for the diagnosis of fibromya 2010 Jun OBJECTIVE: Use of the American College of Rheumatology classification criteria for the clinical diagnosis of fibromyalgia syndrome (FMS) is under debate. The Regional Pain Scale (RPS) had been developed for the diagnosis of FMS in clinical practice and in survey settings (survey criteria of FMS). So far a German version has not been validated. METHODS: A total of 216 patients with FMS, 53 with active rheumatoid arthritis (RA) and 60 with depressive disorder, recruited from clinical institutions completed the RPS. Forty-three patients with FMS filled in the RPS within 8 weeks a second time. RESULTS: The intraclass coefficient of FMS diagnosis after 8 weeks was 0.78 (test-retest reliability). The 7-day interval of pain was criticized by physicians. The absence of some articular pain regions was criticized by patients (face validity). The concordance of FMS diagnoses to survey and ACR criteria was 84.7% (+/-1.1); 45.3% of the patients with RA and 38.3% of the patients with depressive disorder met the survey criteria of FMS (discriminant validity). CONCLUSION: The RPS has good reliability and convergent validity, but limited discriminant validity. The RPS is suited as a screening instrument for the diagnosis of FMS in clinical practice.
20828279 RAPID and FAST4WARD trials: certolizumab pegol for rheumatoid arthritis. 2010 Sep In the last decade, biological therapies have dramatically changed the treatment for rheumatoid arthritis (RA) in such a way that remission is currently an achievable goal. The armamentarium of therapeutic options for RA has recently been enriched with another approved anti-TNF-alpha agent, certolizumab pegol (CZP). This article reviews the trials conducted with CZP in RA, the Rheumatoid Arthritis PreventIon of structural Damage (RAPID 1 and 2) and the EFficAcy and Safety of cerTolizumab pegol - 4 Weekly dosAge in RheumatoiD arthritis (FAST4WARD). These trials have demonstrated that this new biological agent significantly improves the clinical signs and symptoms of RA, inhibits progression of structural damage, and improves physical function and quality of life in patients with active RA who have failed treatment with methotrexate. The safety profile of CZP is acceptable and similar to that of other anti-TNF-alpha agents.
20398006 The immunomodulatory effects of estrogens: clinical relevance in immune-mediated rheumatic 2010 Apr Immunological, epidemiological, and clinical evidence suggest that female sex hormones play an important role in the etiology and pathophysiology of chronic immune/inflammatory diseases. Several significant factors generate confusion and opposite conclusions in evaluating the role of estrogens in these diseases, including relatively superficial translational studies from animals to the human condition, the different effects of estrogens on their different receptors or on different target cells, the different estrogen concentrations employed, and opposite effects (especially on cell proliferation) exerted by different peripheral estrogen metabolites. A preponderance of 16alpha-hydroxylated estrogens, as observed in rheumatoid arthritis synovial fluids, is an unfavorable sign in synovial inflammation. Since 17beta-estradiol administered during hormone replacement therapy will rapidly increase estrone sulfate after conversion in adipose tissue by aromatases, hormone replacement therapy can have proinflammatory effects by providing estrone sulfate to the inflamed synovial tissue. In addition, it appears that the use of combined oral contraceptives is associated with an increased risk of at least systemic lupus erythematosus. In conclusion, estrogens are generally considered as enhancers of cell proliferation and humoral immune response.
19228144 Abatacept, a novel CD80/86-CD28 T cell co-stimulation modulator, in the treatment of rheum 2009 Apr Rheumatoid arthritis is a chronic systemic inflammatory disease with major articular manifestations. While its aetiology still remains to be resolved, our understanding on the pathogenesis of rheumatoid arthritis has become clearer during two decades enlightening the role of adaptative immunity in the development of the symptoms and signs as well as in the progression of the pathological articular changes taking place in inadequately controlled disease. T lymphocytes are considered to be an important cell type in the pathogenesis of rheumatoid arthritis through production of proinflammatory cytokines, promotion of formation of ectopic lymphoid structures and neovascularization in synovial tissue, promotion autoantibody production by B cells, and activation of synoviocytes and osteoclasts. Abatacept, a CTLA4-Ig fusion protein, represents a new therapeutic approach in rheumatoid arthritis. Abatacept attenuates T cell activation as it regulates the activation of T cells by inhibiting the CD80/86:CD28 co-stimulatory pathway that is required for the proper T cell activation. This MiniReview gives an overview on the mechanism of action of abatacept and summarizes the published clinical data on abatacept in the treatment of rheumatoid arthritis.
20691091 Survival dimensionality reduction (SDR): development and clinical application of an innova 2010 Aug 6 BACKGROUND: Epistasis is recognized as a fundamental part of the genetic architecture of individuals. Several computational approaches have been developed to model gene-gene interactions in case-control studies, however, none of them is suitable for time-dependent analysis. Herein we introduce the Survival Dimensionality Reduction (SDR) algorithm, a non-parametric method specifically designed to detect epistasis in lifetime datasets. RESULTS: The algorithm requires neither specification about the underlying survival distribution nor about the underlying interaction model and proved satisfactorily powerful to detect a set of causative genes in synthetic epistatic lifetime datasets with a limited number of samples and high degree of right-censorship (up to 70%). The SDR method was then applied to a series of 386 Dutch patients with active rheumatoid arthritis that were treated with anti-TNF biological agents. Among a set of 39 candidate genes, none of which showed a detectable marginal effect on anti-TNF responses, the SDR algorithm did find that the rs1801274 SNP in the Fc gamma RIIa gene and the rs10954213 SNP in the IRF5 gene non-linearly interact to predict clinical remission after anti-TNF biologicals. CONCLUSIONS: Simulation studies and application in a real-world setting support the capability of the SDR algorithm to model epistatic interactions in candidate-genes studies in presence of right-censored data. AVAILABILITY: http://sourceforge.net/projects/sdrproject/.
19910794 Update on rheumatic manifestations of infectious diseases. 2010 Jan PURPOSE OF REVIEW: As infectious diseases continue to emerge, and as molecular techniques advance, the rheumatic manifestations of infectious diseases are increasingly recognized and better understood. Herein, we review important recent clinical, epidemiologic, and basic science advances within this area of rheumatology. RECENT FINDINGS: We searched the U.S. National Library of Medicine PubMed database for relevant articles published since 1 January 2008. We identified a number of studies suggesting a potentially greater role for persistent viral and bacterial infections in the development of rheumatoid arthritis or rheumatoid arthritis-like syndromes. These include emerging pathogens like Chikungunya virus, as well as historically important pathogens like measles. New literature furthers the idea that antecedent infections with Chlamydia sp. could be causative in some cases of undifferentiated spondyloarthritis. Other studies document diagnostic methods capable of distinguishing between Hepatitis C virus and auto-immune driven arthritis allowing clinicians to better target therapy. SUMMARY: Infectious pathogens are increasingly recognized in association with rheumatic disease. Rheumatologists should be aware of this trend as such recognition may alter the diagnosis and management of rheumatic symptoms, as well as trigger new research opportunities to better understand the causes of rheumatic disease.
20507292 The impact of Rituximab therapy on the chromosomes of patients with Rheumatoid arthritis. 2010 May The open prospective combined cytogenetic and clinical study investigated the impact of biological therapy Rituximab on number and structure of chromosomes in Rheumatoid arthritis patients. The purpose of this study was to investigate safety of Rituximab on chromosomes as well as cytotoxic therapy Methotrexate. A total of 8 seropositive Rheumatoid arthritis patients were analyzed for primary end point of eventual cytotoxic effect of Rituximab. Assessment was done before and 1 month later, actually 2 weeks after the administration of full course of Rituximab in infusion. Patients suffering from active Rheumatoid arthritis were randomly assigned according to established protocol to receive infusion of Rituximab in a full dose of 2.0 grams divided in a two doses of 1.0 gram on days 1 and 15. The lymphocytes from peripheral blood were cultured according to Moorhead method. The results obtained from this investigation showed that normal male and female karyogram was found after the full therapy of Rituximab. The results from this study, that was done on a rather small number of subjects, indicate that Rituximab does not express either clastogenic or aneugenic effects. But, co-finding of this study was that Methotrexate had a side effect on chromosomal aberration in one female RA patient, and after discontinuation of this treatment the normal karyogram was observed.
19506910 Pathogenic antibody recognition of cartilage. 2010 Jan Antibodies against cartilage proteins are highly prevalent in the sera and synovial fluids of rheumatoid arthritis (RA) patients and also precede disease induction in various spontaneous and induced animal models of arthritis. These antibodies play an important role in the induction and perpetuation of the clinical disease. Antibodies binding to cartilage protein(s), especially the major articular cartilage protein, collagen type II (CII) can induce, in naive mice, an acute form of arthritis that can substantially destroy the cartilage and bone architecture. More importantly, these anti-CII antibodies can also directly cause the destruction of the target tissue preceding and independently of disease development and in the absence of any other pathogenic inflammatory factors or the action of immune cells. Alternatively, antibodies to citrullinated protein antigens and rheumatoid factor are well-validated prognostic and diagnostic markers of severe erosive RA, although their arthritogenic potential is questioned. Recently, we have found that the monoclonal antibodies to citrulline-modified cartilage protein can bind cartilage and synovial tissue and mediate arthritis in mice. Similarly, one of the pathogenic anti-CII monoclonal antibodies has rheumatoid-factor-like activity, suggesting a disease-inducing role for these commonly prevalent antibodies in RA patients. Interestingly, recent findings have also shown that the enzymatic cleavage or modification of pathogenic IgG antibodies protects the cartilage surface, thereby opening up new therapeutic possibilities for protecting the cartilage from inflammatory damage.
19822065 Disease-modifying anti-rheumatic drugs in rheumatoid arthritis and ankylosing spondylitis. 2009 Jul Disease modifying antirheumatic drugs (DMARDs) are widely used and well accepted for the treatment of patients with rheumatoid arthritis (RA). Many studies have been performed with monotherapy and combinations of DMARDs showing their efficacy and safety. In ankylosing spondylitis (AS) DMARDs, sulfasalazine especially, are recommended only for the peripheral involvement and not for the axial symptoms. For this disease there is a lack of clinical trials and most of the trials did not show efficacy on the axial symptoms of the disease. In this paper, the differences and similarities of DMARDs in the treatment of RA and AS patients will be discussed.
20193006 Transcriptional regulation of bone and joint remodeling by NFAT. 2010 Jan Osteoporosis and arthritis are highly prevalent diseases and a significant cause of morbidity and mortality worldwide. These diseases result from aberrant tissue remodeling leading to weak, fracture-prone bones or painful, dysfunctional joints. The nuclear factor of activated T cells (NFAT) transcription factor family controls diverse biologic processes in vertebrates. Here, we review the scientific evidence that links NFAT-regulated gene transcription to bone and joint pathology. A particular emphasis is placed on the role of NFATs in bone resorption and formation by osteoclasts and osteoblasts, respectively. In addition, emerging data that connect NFATs with cartilage biology, angiogenesis, nociception, and neurogenic inflammation are explored. The goal of this article is to highlight the importance of tissue remodeling in musculoskeletal disease and situate NFAT-driven cellular responses within this context to inspire future research endeavors.
19644872 Value of anti-modified citrullinated vimentin and third-generation anti-cyclic citrullinat 2009 Aug OBJECTIVE: Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPAs) determined by testing with second-generation anti-cyclic citrullinated peptide (anti-CCP-2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third-generation anti-CCP (anti-CCP-3) and anti-modified citrullinated vimentin (anti-MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease-modifying antirheumatic drug (DMARD)-free remission in RA. METHODS: Patients with UA (n=625) were studied for whether UA progressed to RA after 1 year. Patients with RA (n=687) were studied for whether sustained DMARD-free remission was achieved and for the rate of joint destruction during a median followup of 5 years. Positive predictive values (PPVs) for RA development and for associations with the disease course in RA were compared between single tests (anti-CCP-2, anti-CCP-3, anti-MCV, and RF) and between combinations of these tests. RESULTS: Among the single tests performed in patients with UA, anti-CCP-2 tended to have the highest PPV for RA development (67.1%), but the 95% confidence intervals of the other tests overlapped. Among the single tests in patients with RA, all 4 tests showed comparable associations with the rate of joint destruction and with the achievement of remission. In both ACPA-positive and ACPA-negative RA, the presence of RF was not associated with more joint destruction. For all outcome measures, performing combinations of 2 or 3 autoantibody tests did not increase the predictive accuracy compared with performing a single test. CONCLUSION: For clinical practice, a single autoantibody test is sufficient for risk estimation in UA and RA.
21063826 [Biologics during pregnancy and breast--feeding]. 2010 Nov Over the past years, biological therapies, especially anti-TNF-α antibody therapy has emerged as a treatment approach in patients who have failed to achieve or maintain remission with tradional DMARDs. Women suffering from inflammatory arthritis may need to continue therapy throughout pregnancy and/or in the lactation period, hence the increased concern over the safety of antirheumatic drugs during pregnancy. Anti-TNF agents fall within the US FDA category B concerning fetal risk, indicating that no adequate and well-controlled studies have been conducted in pregnant or lactating women. However, in the last decade, numerous case series and registry data of pregnancies exposed to anti-TNF therapy have accumulated in the literature. According to these data, TNF inhibitor therapies appear to be safe in pregnancy, since no increased risk of malformations has been demonstrated. Ceasing therapy after conception should be considered, but treatment may be continued during pregnancy when indicated.The use of these agents is likely compatible with breast-feeding. The extent of fetal risk is not clarified for exposure to other biologics, such as Rituximab.
19217946 Angiogenesis and its targeting in rheumatoid arthritis. 2009 Jul Angiogenesis, the development of new capillaries, is involved in leukocyte ingress into the synovium during the development and progression of rheumatoid arthritis. Several soluble and cell surface-bound mediators including growth factors, cytokines, chemokines, proteolytic matrix-degrading enzymes, cell adhesion molecules and others may promote synovial neovascularization. On the other hand, endogenous angiostatic factors, such as angiostatin, endostatin, interleukin-4 (IL-4), IL-13, interferons and some angiostatic chemokines are also produced within the rheumatoid synovium, however, their effects are insufficient to control synovial angiogenesis and inflammation. Several specific and non-specific strategies have been developed to block the action of angiogenic mediators. The first line of angiostatic agents include vascular endothelial growth factor (VEGF), angiopoietin, alpha(V)beta(3) integrin antagonist, as well as non-specific angiogenesis inhibitors including traditional disease-modifying agents (DMARDs), anti-tumor necrosis factor biologics, angiostatin, endostatin, fumagillin analogues or thalidomide. Potentially any angiostatic compound could be introduced to studies using animal models of arthritis or even to human rheumatoid arthritis trials.