Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
20051756 An atypical presentation of visceral leishmaniasis infection in a patient with rheumatoid 2010 Jan Tumor necrosis factor alpha (TNF-alpha) is a cytokine, implicated in the pathogenesis of many inflammatory diseases, as well as in the immune-mediated response to infection, especially against intracellular pathogens. TNF-alpha antagonists have represented a revolution in the management of connective tissue diseases, such as rheumatoid arthritis. However, the use of these agents has been implicated with the emergence of a growing number of opportunistic infections. Here we report the case of a visceral Leishmaniasis in a 77-year-old woman who had been previously treated for rheumatoid arthritis with infliximab. The atypical presentation of this patient, previously treated with an anti-TNF-alpha biologic agent, where no splenomegaly or hepatomegaly was identified, is emphasized.
20863170 Performance in leisure-time physical activities and self-efficacy in females with rheumato 2011 Sep The purpose of this study was to examine leisure-time physical activities (LTPAs) and their association with self-efficacy in females with rheumatoid arthritis (RA) (n = 238). Their self-reported performance in LTPAs was measured by the Interest Checklist and efficacy beliefs by using the Arthritis Self-Efficacy Scales (ASES). LTPAs were classified as active or less active according to how many LTPAs they performed. The participants had reduced their participation in LTPAs by almost one-third during the last year. Active individuals performed the vigorous activities more often, they had a higher level of education, were working to a significantly greater extent, and reported better function, higher scores on the self-efficacy scales, and lower joint pain and fatigue. Multivariate analyses demonstrated that a high level of LTPAs was independently related to less fatigue (OR 0.98, p = 0.004), positive self-efficacy in coping with RA functions (OR 1.03, p = 0.015), and higher employment level (OR 0.42, p = 0.039). Only a quarter of the responders were physically active in their leisure time in the present study. Less active individuals reduced their performance in LTPAs to a much higher degree than active individuals during the last year. Partaking in a high amount of LTPAs was related to less fatigue and higher efficacy beliefs.
20448288 Current evidence for the management of rheumatoid arthritis with glucocorticoids: a system 2010 Jun Glucocorticoids (GCs) rapidly reduce disease activity in early and advanced rheumatoid arthritis (RA). This systematic review on behalf of the task force on recommendations for the management of RA addresses the efficacy of GCs in RA. A literature search was performed in Medline, Embase, the Cochrane database, and the ACR/EULAR abstracts 2007 and 2008 on a set of questions relating to the use of GCs in RA. Eleven publications (including three Cochrane reviews comprising 33 trials) that met the criteria for detailed assessment were found. Robust evidence that GCs are effective as bridging therapy was obtained. The addition of GCs, to either standard synthetic disease-modifying antirheumatic drug (DMARD) monotherapy or combinations of synthetic DMARDs, yields clinical benefits and inhibition of radiographic progression that may extend over many years. In early RA, the addition of low-dose GCs (<7.5 mg/day) to DMARDs leads to a reduction in radiographic progression; in longstanding RA, GCs (up to 15 mg/day) improve disease activity. There is some evidence that appropriate timing of GC administration may result in less morning stiffness. Only indirect information was found on the best tapering strategy, supporting the general view that GCs should be tapered slowly in order to avoid clinical relapses. GCs are effective in relieving signs and symptoms and inhibiting radiographic progression, either as monotherapy or in combination with synthetic DMARD monotherapy or combination therapy.
19380693 Comparison of 1.0-T extremity MR and 1.5-T conventional high-field-Strength MR in patients 2009 Jun PURPOSE: To prospectively determine the comparability of 1.0-T extremity magnetic resonance (MR) imaging and 1.5-T conventional MR for the evaluation of the hand and wrist in assessment of patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: Institutional ethics approval and written informed consent were obtained. Thirty-two patients (30 women, two men; mean age, 52 years) with RA twice underwent MR of either the most symptomatic hand (n = 21) or wrist (n = 11), once performed with a 1.0-T extremity MR system and once with a 1.5-T conventional MR system. The MR examinations were independently assessed by two radiologists blinded to imaging platform and patient clinical information for erosions, synovitis, and bone marrow edema (BME), according to the Rheumatoid Arthritis MR Imaging Score (RAMRIS). One radiologist reevaluated all cases a second time to determine the intraobserver variability for each system. Patient comfort was assessed with a questionnaire. Intraclass correlation coefficients (ICCs) and smallest detectable differences (SDDs) were measured. RESULTS: ICCs for intermachine agreement were 0.97-0.99 for erosions, 0.88-0.97 for synovitis, and 0.98-0.99 for BME for both readers. The SDDs between the two systems, expressed as a percentage of the maximum score, ranged from 3.3% to 12.2% for erosions, from 7.4% to 14.8% for synovitis, and from 5% to 9.9% for BME for both readers. ICCs for interreader agreement ranged from 0.69 to 0.99 and for intrareader agreement, from 0.88 to 0.99. There were substantial differences in the subjective patient assessment of confinement, system noise, and difficulty with immobilization, and 95.8% of patients preferred examinations performed with extremity MR. CONCLUSION: The 1.0-T extremity MR system demonstrates synovial and osseous changes in RA equally as well as a 1.5-T conventional MR system and is preferred by patients.
20217173 Incidence of and risk factors for interstitial pneumonia in patients with rheumatoid arthr 2010 Jun Interstitial lung disease (ILD) is a frequently encountered and sometimes life-threatening complication among patients with rheumatoid arthritis (RA). In this study, we aim to clarify the incidence of and risk factors for ILD using a large observational cohort of RA patients. We analyzed the database from a large observational cohort of Japanese RA patients, the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. We defined as interstitial pneumonia (IP) computed tomography (CT) pattern of nonspecific interstitial pneumonia or diffuse alveolar damage. Newly developed IP was identified from patient reports over 2.5 years (April 2004 to October 2006) and was confirmed by extensive medical record, chest X-ray radiograph, and CT. The raw and age/gender-adjusted incidence of IP were reported. IP risk factors were analyzed using a nested case-control design was employed using conditional logistic regression analysis with a stepwise method. Thirty-seven patients among 5,699 RA patients were diagnosed with newly developed IP, including 18 cases with methotrexate-induced pneumonitis (MTX-IP) and 15 cases with IP associated with RA (RA-IP). The age-adjusted incidence of MTX-IP among total patients, males, and females was 3.775, 6.667, and 1.013 per 1,000 cases, respectively, and of RA-IP among total patients, males, and females was 1.056, 1.452, and 0.677 per 1,000 cases, respectively. Conditional logistic regression analysis after stepwise variable selection identified male gender, increased Japanese version of the Health Assessment Questionnaire (J-HAQ) score, decreased pain visual analog scale (VAS), and elevated erythrocyte sedimentation rate as significant risk factors for MTX-IP, while the only risk factor for RA-IP was male gender. The incidence of and risk factors for IP in RA patients were determined in a large observational cohort of RA patients in Japan.
20722010 Associations of cigarette smoking with rheumatoid arthritis in African Americans. 2010 Dec OBJECTIVE: To examine the associations of cigarette smoking with rheumatoid arthritis (RA) in African Americans, and to determine whether this association is impacted by the HLA-DRB1 shared epitope (SE). METHODS: Smoking status, cumulative smoking exposure, and SE status were determined in African American patients with RA and African American healthy controls. Associations of smoking with RA were examined using age- and sex-adjusted logistic regression analyses. Additive and multiplicative SE-smoking interactions were examined. RESULTS: After adjustment for age and sex, ever smoking (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.07, 1.97) and current smoking (OR 1.56, 95% CI 1.07, 2.26), relative to never smoking, were more common in African American patients with RA (n = 605) than in controls (n = 255). The association of smoking with RA was limited to those with a cumulative exposure exceeding 10 pack-years, associations that were evident both in autoantibody-positive and in autoantibody-negative disease. There was evidence of a significant additive interaction between SE status and heavy smoking (≥10 pack-years) in relation to RA risk (attributable proportion [AP] due to interaction 0.58, P = 0.007), with similar results for the additive interaction between SE status and ever smoking (AP 0.47, P = 0.006). There was no evidence of multiplicative interactions. CONCLUSION: Among African Americans, cigarette smoking is associated not only with the risk of autoantibody-positive RA but also with the risk of autoantibody-negative disease. The risk of RA attributable to smoking is limited to African Americans with more than 10 pack-years of exposure and is more pronounced among individuals positive for the HLA-DRB1 SE.
19377402 [Portuguese recommendations for the use of methotrexate in the treatment of rheumatoid art 2009 Jan OBJECTIVES: To develop Portuguese evidence-based recommendations for the use of methotrexate (MTX) in daily clinical practice in rheumatic disorders. METHODS: The Portuguese project was integrated in the multinational 3E Initiative (Evidence, Expertise, Exchange) 2007-2008 where a total of 751 rheumatologists from 17 countries have participated. Ten clinical questions concerning the use of MTX in rheumatic diseases were formulated and the Portuguese group added three more questions. A systematic literature search in Medline, Embase, Cochrane Library and 2005-2007 ACR/EULAR meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford Levels of Evidence. In Portugal, a national meeting was held in Obidos on February 15th and 16th, 2008, involving 50 rheumatologists who discussed and voted by Dephi method the recommendations. Finally, the agreement among the rheumatologists and the potential impact on their clinical practice was assessed. RESULTS: Thirteen national key recommendations on the use of MTX were formulated: work-up before starting MTX, optimal dosage and route of administration, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy, management in the peri-operative period, during infections, before/during pregnancy and after clinical remission, screening and treatment of tuberculosis and the role of MTX as a steroid-sparing agent in rheumatic diseases. DISCUSSION: The Portuguese recommendations for the use of MTX in daily clinical practice were developed, which are evidence-based and supported by a panel of 50 rheumatologists, enhancing their validity and practical use. This project was integrated in a multinational initiative that led to the recent publication of ten multinational recommendations which differ from ours in some specific aspects.
20378656 Cost-effectiveness of cognitive-behavioral group therapy for dysfunctional fear of progres 2010 Dec BACKGROUND: Anxiety disorders are widespread in patients with chronic diseases such as rheumatoid arthritis (RA). This paper targets the cost-effectiveness analysis of a cognitive-behavioral group therapy (CBT) in comparison to a client-centered, supportive-experiential group therapy (SET) in arthritis patients with dysfunctional fear of progression. METHODS: From the societal perspective, direct costs were compared with the reduction of fear of progression over time. Means, their 95% confidence intervals (95% CI), the incremental cost-effectiveness graphic and the acceptability curve were obtained using 1000 non-parametric bootstrap replications. RESULTS: A total of 174 RA patients were included in the economic evaluation. The estimated means (95% CI) of direct costs and reduction of fear of progression were, respectively, €7945.34 (5075.59; 11335.08) and 0.25 (-0.48; 0.99) for patients in the SET and 5619.25 € (3950.67; 7708.52) and 0.94 (0.29; 1.62) for patients in the CBT. As the majority of the cost-effect pairs after bootstrap analysis were located in the southeast quadrant of the cost-effectiveness plane, the CBT can be considered a dominant intervention. CONCLUSION: The main result of our study is the higher cost-effectiveness of CBT in comparison to SET in RA patients with dysfunctional fear of progression.
19832990 Increased levels of circulating microparticles in primary Sjögren's syndrome, systemic lu 2009 INTRODUCTION: Cell stimulation leads to the shedding of phosphatidylserine (PS)-rich microparticles (MPs). Because autoimmune diseases (AIDs) are characterized by cell activation, we investigated level of circulating MPs as a possible biomarker in primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: We measured plasma levels of total, platelet and leukocyte MPs by prothrombinase capture assay and flow cytometry in 43 patients with pSS, 20 with SLE and 24 with RA and in 44 healthy controls (HCs). Secretory phospholipase A2 (sPLA2) activity was assessed by fluorometry. Soluble CD40 ligand (sCD40L) and soluble P-selectin (sCD62P), reflecting platelet activation, were measured by ELISA. RESULTS: Patients with pSS showed increased plasma level of total MPs (mean +/- SEM 8.49 +/- 1.14 nM PS equivalent (Eq), P < 0.0001), as did patients with RA (7.23 +/- 1.05 n PS Eq, P = 0.004) and SLE (7.3 +/- 1.25 nM PS Eq, P = 0.0004), as compared with HCs (4.13 +/- 0.2 nM PS Eq). Patients with AIDs all showed increased level of platelet MPs (P < 0.0001), but only those with pSS showed increased level of leukocyte MPs (P < 0.0001). Results by capture assay and flow cytometry were correlated. In patients with high disease activity according to extra-glandular complications (pSS), DAS28 (RA) or SLEDAI (SLE) compared with low-activity patients, the MP level was only slightly increased in comparison with those having a low disease activity. Platelet MP level was inversely correlated with anti-DNA antibody level in SLE (r = -0.65; P = 0.003) and serum beta2 microglobulin level in pSS (r = -0.37; P < 0.03). The levels of total and platelet MPs were inversely correlated with sPLA2 activity (r = -0.37, P = 0.0007; r = -0.36, P = 0.002, respectively). sCD40L and sCD62P concentrations were significantly higher in pSS than in HC (P < or = 0.006). CONCLUSIONS: Plasma MP level is elevated in pSS, as well as in SLE and RA, and could be used as a biomarker reflecting systemic cell activation. Level of leukocyte-derived MPs is increased in pSS only. The MP level is low in case of more severe AID, probably because of high secretory phospholipase A2 (sPLA2) activity, which leads to consumption of MPs. Increase of platelet-derived MPs, sCD40L and sCD62P, highlights platelet activation in pSS.
18635596 Anti-inflammatory therapy with tumour necrosis factor alpha inhibitors improves high-densi 2009 Jun OBJECTIVE: High-density lipoprotein (HDL) antiatherogenic functions seem to be diminished during inflammatory conditions such as rheumatoid arthritis (RA). The aim of this study was to investigate the effects of tumour necrosis factor (TNF) inhibition on the antioxidative capacity of HDL in RA. METHODS: Plasma lipids and paraoxonase (PON-1) activity were investigated in 45 RA patients, before and during 6 months of anti-TNF therapy. In addition, HDL was isolated and tested for its ability to inhibit copper-induced oxidation of low-density lipoprotein in vitro. RESULTS: Plasma HDL concentrations did not change considerably after 6 months of therapy. However, stable increases of PON-1 activities were observed throughout the same period (p<0.03). The increases were more obvious when related to HDL or apolipoprotein AI concentrations. HDL total antioxidative capacity significantly improved 6 months after the initiation of anti-TNF therapy (p = 0.015). The initial improvement of PON-1 activity paralleled a decrease in the inflammatory status, whereas specific TNF blockade was likely to be responsible for the long-term effects. CONCLUSIONS: Anti-TNF therapy with infliximab has beneficial effects on lipids through changes in HDL antioxidative capacity, which might be clinically relevant and contribute to the reported protective effect of anti-TNF on cardiovascular morbidity in RA. This emphasises the importance of HDL antiatherogenic capacity for cardiovascular risk in chronic inflammatory conditions.
20507945 Characterization of connective tissue disease-associated pulmonary arterial hypertension f 2010 Dec BACKGROUND: REVEAL (the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) is the largest US cohort of patients with pulmonary arterial hypertension (PAH) confirmed by right-sided heart catheterization (RHC), providing a more comprehensive subgroup characterization than previously possible. We used REVEAL to analyze the clinical features of patients with connective tissue disease-associated PAH (CTD-APAH). METHODS: All newly and previously diagnosed patients with World Health Organization (WHO) group 1 PAH meeting RHC criteria at 54 US centers were consecutively enrolled. Cross-sectional and 1-year mortality and hospitalization analyses from time of enrollment compared CTD-APAH to idiopathic disease and systemic sclerosis (SSc) to systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). RESULTS: Compared with patients with idiopathic disease (n = 1,251), patients with CTD-APAH (n = 641) had better hemodynamics and favorable right ventricular echocardiographic findings but a higher prevalence of pericardial effusions, lower 6-min walk distance (300.5 ± 118.0 vs 329.4 ± 134.7 m, P = .01), higher B-type natriuretic peptide (BNP) levels (432.8 ± 789.1 vs 245.6 ± 427.2 pg/mL, P < .0001), and lower diffusing capacity of carbon monoxide (Dlco) (44.9% ± 18.0% vs 63.6% ± 22.1% predicted, P < .0001). One-year survival and freedom from hospitalization were lower in the CTD-APAH group (86% vs 93%, P < .0001; 67% vs 73%, P = .03). Compared with patients with SSc-APAH (n = 399), those with other CTDs (SLE, n = 110; MCTD, n = 52; RA, n = 28) had similar hemodynamics; however, patients with SSc-APAH had the highest BNP levels (552.2 ± 977.8 pg/mL), lowest Dlco (41.2% ± 16.3% predicted), and poorest 1-year survival (82% vs 94% in SLE-APAH, 88% in MCTD-APAH, and 96% in RA-APAH). CONCLUSIONS: Patients with SSc-APAH demonstrate a unique phenotype with the highest BNP levels, lowest Dlco, and poorest survival of all CTD-APAH subgroups. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL: clinicaltrials.gov.
20112363 The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic 2010 Feb OBJECTIVE: Genome-wide association (GWA) studies in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Caucasian populations have independently identified risk variants in and near the tumor necrosis factor alpha (TNFalpha)-induced protein 3 gene (TNFAIP3), which is crucial for the regulation of TNF-mediated signaling and Toll-like receptor signaling. The aim of this study was to assess the role of TNFAIP3 in the development of SLE and RA in Japanese subjects. METHODS: We selected 2 single-nucleotide polymorphisms (SNPs) from previous GWA studies. Rs2230926 is a nonsynonymous SNP in TNFAIP3 and is associated with SLE, while rs10499194 is an intergenic SNP associated with RA. We then performed 2 independent sets of SLE case-control comparisons (717 patients and 1,362 control subjects) and 3 sets of RA case-control comparisons (3,446 patients and 2,344 control subjects) using Japanese subjects. We genotyped SNPs using TaqMan assays. RESULTS: We observed a significant association between rs2230926 and an increased risk of SLE and RA in the Japanese population (for SLE, odds ratio [OR] 1.92, 95% confidence interval [95% CI] 1.53-2.41, P = 1.9 x 10(-8); for RA, OR 1.35, 95% CI 1.18-1.56, P = 2.6 x 10(-5)). The intergenic SNP rs10499194 was also associated with SLE and RA, while the risk allele for RA in Caucasians was protective against the diseases in our population. CONCLUSION: We demonstrated a significant association between the nonsynonymous variant in TNFAIP3 and the risk for SLE and RA in the Japanese population. TNFAIP3, similar to STAT4 and IRF5, may be a common genetic risk factor for SLE and RA that is shared between the Caucasian and Japanese populations.
20937848 The neuroimmune semaphorin-3A reduces inflammation and progression of experimental autoimm 2010 Nov 15 Semaphorin-3A (Sema3A), a member of a large family of conserved proteins originally implicated in axon guidance, is expressed by activated T cells and downmodulates T cell activation in vitro. This study examined the effect and mechanism of action of Sema3A overexpression in a mouse model of collagen-induced arthritis. Prophylactic i.p. administration of plasmid DNA encoding Sema3A markedly reduced the incidence, disease severity, and articular inflammation compared with control plasmid without insert. Treatment of Sema3A reduced anticollagen IgG levels and suppressed collagen-specific proinflammatory cytokine (IFN-γ and IL-17) release, but increased IL-10 concentration in the serum. In line with results in arthritic mice, Sema3A expression is defective in CD4(+) T cells derived from patients with rheumatoid arthritis. In contrast, increased expression of the Sema3A receptor neuropilin-1 (NP-1) is detected in the same cells. The CD4(+)NP-1(+) T cells are a T cell subset involved in the control of the immune responses. They express greater amounts of IL-10 and show suppressive activities on autologous CD4(+) T cells. Sema3A acted directly on CD4(+)NP-1(+) T cells, because it could increase IL-10 production and influence the regulatory function on CD4(+) T cell growth. Therefore, I propose that Sema3A increases the CD4(+)NP-1(+) T cell ability to suppress alloresponses, that its transient expression is altered in rheumatoid inflammation, and that reintroduction of Sema3A is sufficient to attenuate collagen-induced arthritis, supporting its therapeutic potential in the treatment of autoimmune disorders.
20298547 Development of proteoglycan-induced arthritis depends on T cell-supported autoantibody pro 2010 INTRODUCTION: Inflammatory joint destruction in rheumatoid arthritis (RA) may be triggered by autoantibodies, the production of which is supported by autoreactive T cells. Studies on RA and animal models of the disease suggest that T cells recruited in the joints can locally initiate or propagate arthritis. Herein, we investigated the role of joint-homing versus lymphoid organ-homing T cells in the development of proteoglycan-induced arthritis (PGIA), an autoimmune model of RA. METHODS: To identify T cells migrating to the joints before and during development of autoimmune arthritis, we transferred fluorescence-labeled T cells, along with antigen-presenting cells, from BALB/c mice with PGIA to naïve syngeneic severe combined immunodeficient (SCID) mice. We then monitored the recruitment of donor T cells in the ankle joints and joint-draining lymph nodes of the recipients using in vivo two-photon microscopy and ex vivo detection methods. To limit T-cell access to the joints, we selectively depleted T cells in the blood circulation by treatment with FTY720, an inhibitor of lymphocyte egress from lymphoid organs. Reduction of T cell presence in both lymphoid organs and blood was achieved by injection of donor cells from which T cells were removed prior to transfer. T and B cells were quantitated by flow cytometry, and antigen (PG)-specific responses were assessed by cell proliferation and serum antibody assays. RESULTS: Despite development of adoptively transferred arthritis in the recipient SCID mice, we found very few donor T cells in their joints after cell transfer. Treatment of recipient mice with FTY720 left the T-cell pool in the lymphoid organs intact, but reduced T cells in both peripheral blood and joints. However, FTY720 treatment failed to inhibit PGIA development. In contrast, arthritis was not seen in recipient mice after transfer of T cell-depleted cells from arthritic donors, and serum autoantibodies to PG were not detected in this group of mice. CONCLUSIONS: Our results suggest that antigen-specific T cells, which home to lymphoid organs and provide help to B cells for systemic autoantibody production, play a greater role in the development and progression of autoimmune arthritis than the small population of T cells that migrate to the joints.
20080904 Role of circulating endothelial progenitor cells in patients with rheumatoid arthritis wit 2010 Mar OBJECTIVE: Patients with rheumatoid arthritis (RA) are prone to premature atherosclerosis. We hypothesize that depletion of circulating endothelial progenitor cells (EPC) related to RA can contribute to the development of atherosclerosis. METHODS: We studied coronary calcifications by multidetector computed tomography and their relationship with different subtypes of circulating EPC in 70 patients with RA and 35 age- and sex-matched controls (mean age 54.1 +/- 10.2 yrs, 87% were women). The presence of coronary atherosclerosis was defined as an Agatston score > or = 10. Four subpopulations of EPC were determined by flow cytometry on the basis of surface expression of CD34, CD133, and KDR antigen: CD34+, CD34/KDR+, CD133+, and CD133/KDR+ EPC, respectively. RESULTS: Among those with RA, 15 patients (21%) had coronary atherosclerosis. The mean Agatston score was higher (61.8 +/- 201.7 vs 0.14 +/- 0.69; p = 0.01) and coronary atherosclerosis was more prevalent (21.4% vs 0%; p < 0.01) in patients with RA compared to controls. RA patients with coronary atherosclerosis were older (66.2 +/- 6.9 vs 51.5 +/- 16.2 yrs; p < 0.01), had higher prevalence of hypertension (46.7% vs 14.5%; p = 0.01), and had lower CD133/KDR+ (0.45% +/- 0.28% vs 0.89% +/- 0.81%; p < 0.01) and CD133+ EPC levels (0.74% +/- 0.39% vs 1.22% +/- 0.83%; p < 0.01), but similar CD34/KDR+ and CD34+ EPC levels (all p > 0.05) compared to those without. Multiple logistic regression revealed that older age (OR 1.25, 95% CI 1.10-1.41, p < 0.01) and lower CD133/KDR+ EPC (OR 0.07, 95% CI 0.00-0.97, p < 0.01) were independent predictors for coronary atherosclerosis in patients with RA. CONCLUSION: Our results demonstrated that RA patients with coronary atherosclerosis have significantly lower levels of CD133/KDR+ and CD133+ EPC than those without. In addition to older age, lower levels of circulating CD133/KDR+ EPC also predicted occurrence of coronary atherosclerosis in RA patients.
18825571 Implementing arthritis clinical practice guidelines in primary care. 2009 Mar BACKGROUND: Multi-faceted interventions are among the strongest methods for changing provider behavior. AIMS: This paper reports the design, implementation and process evaluation of an educational program to disseminate clinical practice guidelines (CPGs) on the management of rheumatoid arthritis (RA) and osteoarthritis (OA) in primary care. METHODS: Organizations were invited to participate in inter-professional workshops on OA and RA followed by six months of activities to support the delivery of care in the community. Confidence in ability to manage arthritis was assessed at baseline using a 10 point numerical rating scale. Qualitative assessments were done immediately and 3-12 months post workshop. RESULTS: 646 multidisciplinary providers from 216 organizations attended one of 30 workshops. Providers (n = 584) reported moderate confidence in managing arthritis: family physicians: mean: SD = 7.46(1.42), n = 145; nurse practitioners: 6.10(1.84), n = 73; other health care professionals: 5.23(2.83), n = 389. Participants identified team learning, the opportunity to network and the involvement of trained patient educators as strong features of the workshops. At follow-up, participants indicated the greatest impact of the program was on collaborative care (83%) and patient self-management (79%). CONCLUSIONS: Qualitative results suggest that inter-professional learning may be a successful strategy for improving the delivery of collaborative arthritis care and supporting patient self-management.
19248090 The DERAA HLA-DR alleles in patients with early polyarthritis: protection against severe d 2009 Mar OBJECTIVE: To define the association of alleles encoding the HLA-DR rheumatoid arthritis (RA) protective epitope (DERAA) with the presence of RA-associated antibodies at study inclusion and with severe outcome in patients with early polyarthritis (EPA). METHODS: Consecutive EPA patients (n = 210) were evaluated early (mean of 4.8 months after diagnosis) and prospectively (for 30 months). HLA class II typing was performed by polymerase chain reaction using sequence-specific primers, and HLA-DR alleles DERAA, RA-associated shared epitope (SE), and non-SE/non-DERAA (neither SE nor DERAA) were identified. RA-associated antibodies identified were anti-Sa/citrullinated vimentin, anti-cyclic citrullinated peptide 2, and IgM rheumatoid factor. Severe disease was defined according to a preset threshold of joint destruction and/or functional limitation. RESULTS: DERAA and SE alleles were present in 62 and 110 of the 210 EPA patients, respectively. At 30 months, severe disease was present in 78 patients (37%). In contrast to SE alleles, DERAA alleles were not associated with the production of RA-associated antibodies, but were strongly protective against severe disease at 30 months (odds ratio 0.30, P < 0.001). DERAA alleles emerged as a strong, independent protective marker on multivariate analysis. The protective effect of DERAA was seen only in patients who did not already have erosions at study inclusion, was independent of the presence of antibodies, but was not associated with spontaneous remission. CONCLUSION: In our EPA cohort, the presence of a DERAA sequence was a strong independent predictor of a better prognosis, but only in the absence of erosive disease that was already present at inclusion. Identification of DERAA alleles may help in managing the large subgroup of EPA patients who do not have erosions at baseline.
20890820 [Retrospective study of the first metatarsophalangeal joint arthrodesis: 39 cases]. 2010 Oct BACKGROUND: The first metatarsophalangeal joint arthrodesis is a fusion with optimal alignment of the first metatarsal and first phalanx which conferring indolence, strength and stability. AIM: The goal of this study was to evaluate the place of arthrodesis of the first metatarsophalangeal joint in surgery of the fore foot. METHODS: This work is based on analysis of records of 35 patients between 1995 and 2006. 39 first metatarsophalangeal joint arthrodesis were practice (3 were bilateral). They had a follow up of from three to ten years. All patients were called for a complete exploration radiographic and clinical evaluation according to the criteria of KITAOKA. The average age of patients was 54 years. RESULTS: They were 28 women and 7 men. The indications were hallux rigidus in 51% cases and rheumatoid arthritis in 41% cases. The procedure used mostly a stable fixation with a compressive screw. The dorsal flexion recommended is between 20 and 30°. Ankylosis of the ankle or the inter-phalangeal joint was an against indication for the first metatarsophalangeal joint arthrodesis. The study found a patient subjective satisfaction rate of 92 per cent, there was no pain for 89 per cent of cases. It was noted 4 non-fusion cases paradoxically with satisfactory functional result. There was no pain of inter-phalangeal joint in all cases when X-rays showed arthritis in 4 cases. CONCLUSION: The first metatarsophalangeal joint arthrodesis, provided we respect a few simple principles, restores painless and satisfying function of foot.
20459811 Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patien 2010 INTRODUCTION: Increasing evidence indicates that microRNAs (miRNAs) play a critical role in the pathogenesis of inflammatory diseases. The aim of the study was to investigate the expression pattern and function of miRNAs in CD4+ T cells from patients with rheumatoid arthritis (RA). METHODS: The expression profile of miRNAs in CD4+ T cells from synovial fluid (SF) and peripheral blood of 33 RA patients was determined by microarray assay and validated by qRT-PCR analysis. The correlation between altered expression of miRNAs and cytokine levels was determined by linear regression analysis. The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry. A genome-wide gene expression analysis was further performed to identify miR-146a-regulated genes in T cells. RESULTS: miRNA expression profile analysis revealed that miR-146a expression was significantly upregulated while miR-363 and miR-498 were downregulated in CD4+ T cells of RA patients. The level of miR-146a expression was positively correlated with levels of tumor necrosis factor-alpha (TNF-alpha), and in vitro studies showed TNF-alpha upregulated miR-146a expression in T cells. Moreover, miR-146a overexpression was found to suppress Jurkat T cell apoptosis. Finally, transcriptome analysis of miR-146a overexpression in T cells identified Fas associated factor 1 (FAF1) as a miR-146a-regulated gene, which was critically involved in modulating T cell apoptosis. CONCLUSIONS: We have detected increased miR-146a in CD4+ T cells of RA patients and its close correlation with TNF-alpha levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets.
19351498 [The expression of Toll-like receptor 8 and cytokines in rheumatoid arthritis mice induced 2009 Apr AIM: To explore the expression of Toll-like receptor 8(TLR8)in rheumatoid arthritis induced by chicken II collogen in mice and analyze the relation of TLR8 to IL-10, IL-17A and IL-1beta. METHODS: Twelve DBA/1J mice were randomly divided into model group(T) and negative group(NC). The paw swelling was seen at the day of 27 post the first immunization with chicken II collogen. The serum TNF-alpha was detected by ELISA and inflammatory cell infiltration was examined by HE. Real-time PCR was used to analysis the expression of IL-10, IL-17A, IL-1beta and TLR8 in spleen mononuclear cells. RESULTS: Severe inflammation was detected in model group mice by histological analysis, which was not seen in negative group. The serum TNF-alpha in model group was enhanced compared with that in negative group(P<0.01). The expression levels of IL-10, IL-17A, TLR8 and IL-1beta in spleen mononuclear cells from model group were increased compared with those from negative group(P<0.01, P<0.05). Statistical analysis showed that there was negative correlation between the expression of TLR8 and IL-10(P<0.01), and there was no correlation between the expression of TLR8 and IL-17A or IL-1beta(P>0.05). CONCLUSION: The expression of TLR8 was increased in rheumatoid arthritis-mice induced by chicken II collogen, and there was negative correlation between the expression of TLR8 and the expression of IL-10.