Sample records for simulating early rheumatoid

  1. New autoantibodies in early rheumatoid arthritis

    PubMed Central

    2013-01-01

    Introduction Rheumatoid arthritis (RA) is a chronic inflammatory joint disease causing articular cartilage and bone destruction. Since irreversible joint destruction can be prevented by intervention at the early stages of disease, early diagnosis of RA is important. In this study, we identified new autoantibodies in the sera of patients with early (less than one year) RA. Methods We screened the sera of 20 RA patients with disease duration less than one year, 19 RA patients with disease duration more than five years and 23 controls on 8,268 human protein arrays. We confirmed the validity of protein array detection by ELISA assays. We then performed epitope mapping with overlapping 15-mers to analyze RA sera reactivity. Results WIBG (within BGCN homolog (Drosophila)), GABARAPL2 (GABA(A) receptor associated protein like 2) and ZNF706 (zinc finger protein 706) proteins are preferentially recognized by autoantibodies from early RA patients. Of interest, autoantibodies to WIBG are very specific for early RA. Indeed, 33% of early RA patients' sera recognize WIBG versus 5% of RA patients with disease duration more than 5 years and 2% of controls. We identified three linear peptides on WIBG GABARAPL2 and ZNF706 that are preferentially recognized by sera of early RA patients. Conclusions We identified new autoantibodies associated with RA with disease duration less than one year. These autoantibodies could be used as diagnosis markers in RA patients. PMID:23886014

  2. Extra-articular features in early rheumatoid disease

    Microsoft Academic Search

    A Fleming; S Dodman; J M Crown; M Corbett

    1976-01-01

    One hundred and two patients who presented with rheumatoid disease within the first year of onset were studied prospectively every four months for a mean 4.5 years to assess the incidence of extra-articular features. The features that seemed to be common in the early stages included hand-muscle wasting, carpal tunnel syndrome, lymphadenopathy, non-specific ankle swelling, and rheumatoid nodules, and to

  3. Modelling the cost-effectiveness of combination therapy for early, rapidly progressing rheumatoid arthritis by simulating the reversible and irreversible effects of the disease

    PubMed Central

    Stephens, Stephanie; Botteman, Marc F; Cifaldi, Mary A; van Hout, Ben A

    2015-01-01

    Objective To estimate the cost-effectiveness of adalimumab plus methotrexate (MTX) versus MTX monotherapy in early, aggressive rheumatoid arthritis (RA) when explicitly modelling short-term (reversible) and long-term (irreversible, ie, joint damage) disease activity and physical function. Methods A microsimulation model was developed to unify, in a single cost-effectiveness model, measures of reversible and irreversible disease activity and physical function based on data from the PREMIER trial. Short term, reversible disease activity was modelled using DAS28 variables, including swollen joint counts, tender joint counts, C reactive protein concentration and pain. The DAS28 variables were then used in a logistic regression to predict short-term American College of Rheumatology (ACR) responses, which informed treatment continuation and switches. Long term, irreversible, radiographically documented joint damage was modelled using modified Total Sharp Score (mTSS). The model then linked both short-term disease activity and mTSS to the Health Assessment Questionnaire score, which was used to calculate direct and indirect costs, and quality adjusted life-years (QALYs). Results When both reversible and irreversible effects of therapy were included, combination therapy was estimated to produce 6-month 50% ACR responses in 75% of patients versus 54% in MTX monotherapy. Compared to MTX monotherapy, combination therapy resulted in 2.68 and 3.04 discounted life years and QALYs gained, respectively. Combination therapy also resulted in a net increase in direct costs of £106?207 for a resulting incremental cost/QALY gain of £32?425. When indirect costs were included in the analysis, the ICER (incremental cost-effectiveness ratio) decreased to £27?238. Disregarding irreversible effects increased the incremental cost-effectiveness ratio to £78?809 (when only direct costs were included). Conclusions Starting with adalimumab plus MTX combination therapy in early, aggressive RA is cost-effective when irreversible damage is adequately considered. PMID:26059521

  4. Treatment strategies in early rheumatoid arthritis and prevention of rheumatoid arthritis.

    PubMed

    Demoruelle, M Kristen; Deane, Kevin D

    2012-10-01

    Data now suggest that current strategies in the treatment of rheumatoid arthritis (RA) should focus on early identification and diagnosis, followed by early initiation of DMARD therapy. Initiation of treatment in early RA-ideally, less than 3-6 months after symptom onset-improves the success of achieving disease remission and reduces joint damage and disability. While the optimal treatment regimen in early RA is unclear, use of initial DMARD mono- or combination therapy with prompt escalation to achieve low disease activity or remission is an appropriate approach. Ultimately, the goal of RA management should be the prevention of inflammatory joint disease and, thereby, prevention of disability. To date, studies have shown that pharmacologic interventions can delay progression from undifferentiated inflammatory arthritis to classifiable RA. However, further investigation is needed to identify asymptomatic individuals at high risk for future RA and to intervene early enough in the pathogenesis of RA to prevent progression to clinical disease. PMID:22773387

  5. Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health

    PubMed Central

    Ahmed, Usman; Anwar, Attia; Savage, Richard S.; Costa, Matthew L.; Mackay, Nicola; Filer, Andrew; Raza, Karim; Watts, Richard A.; Winyard, Paul G.; Tarr, Joanna; Haigh, Richard C.; Thornalley, Paul J.; Rabbani, Naila

    2015-01-01

    There is currently no biochemical test for detection of early-stage osteoarthritis (eOA). Tests for early-stage rheumatoid arthritis (eRA) such as rheumatoid factor (RF) and anti–cyclic citrullinated peptide (CCP) antibodies require refinement to improve clinical utility. We developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline in body fluids. We detected CP in the plasma of healthy subjects and surprisingly found that CP was increased in both patients with eOA and eRA whereas anti–CCP antibodies were predominantly present in eRA. A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases and good skeletal health. This provides a first-in-class plasma/serum-based biochemical assay for diagnosis and type discrimination of early-stage arthritis to facilitate improved treatment and patient outcomes, exploiting citrullinated protein and related differential autoimmunity. PMID:25788417

  6. Hemochromatosis simulating rheumatoid arthritis: a case report.

    PubMed

    Barbosa, Fabíola Brasil; Callegari, Amanda; Sarinho, José Célso; Lucena, Juliana; Casagrande, Renielly; de Souza, Branca Dias Batista

    2014-01-01

    This is a report of a patient who had a previous diagnosis of rheumatoid arthritis, nonerosive, rheumatoid factor negative, that despite the therapeutic approach presented progressive worsening of the articular and general condition. After extensive research, she had a diagnosis of hemochromatosis. Joint symptoms are common manifestations in hemochromatosis. The arthropathy of hemochromatosis may resemble inflammatory arthropathy mimicking RA, particularly in the most common sites as 2nd and 3rd metacarpophalangeal. Radiologically are observed decreased joint space, subchondral sclerosis, cyst formation and chondrocalcinosis. Treatment with disease modifying drugs for rheumatoid arthritis tend to worsen the clinical picture, since the liver is the major site of deposition of iron in hemochromatosis and these medications are known to be hepatotoxic. Phlebotomy treatment for hemochromatosis is apparently ineffective in reversing the articular manifestations, which requires the association with iron chelating drugs. Due to the apparent difficulty in differentiating between the two diseases, a screening profile of iron in patients with rheumatoid arthritis with atypical progression is necessary. PMID:24878794

  7. Early biomarkers of joint damage in rheumatoid and psoriatic arthritis.

    PubMed

    Mc Ardle, Angela; Flatley, Brian; Pennington, Stephen R; FitzGerald, Oliver

    2015-01-01

    Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate biomarkers in rheumatoid and psoriatic arthritis, evaluated the evidence for their potential as biomarkers of bone (joint) damage, and outlined how mass spectrometry-based targeted and multiplexed measurement of candidate biomarker proteins is likely to accelerate their clinical validation and the development of clinical diagnostic tests. PMID:26028339

  8. Combination therapy for early rheumatoid arthritis: a treatment holiday perspective.

    PubMed

    Hirata, Shintaro; Tanaka, Yoshiya

    2015-01-01

    To date, the significance of early intervention with methotrexate and biological disease-modifying anti-rheumatic drugs for rheumatoid arthritis (RA) has not been realized. Longitudinal safety and cost have arisen as new concerns. The concept of a treatment holiday, drug discontinuation after achieving remission, may solve these problems. The authors performed a systematic literature review and identified 13 reports from 10 studies (TNF20, BeSt, OPITMA, HIT-HARD, IMPROVED, PRIZE, IDEA, EMPIRE, tREACH and AVERT) for early RA (?2 years). Eight out of 13 reports (61.5%) were published in 2013 or 2014, indicating emerging interest in recent years. Also, the authors performed a sub-analysis of the HONOR study (n = 51) to compare early (?2 years) and established RA. The proportions of remission (REM) and low disease activity were higher in early RA (REM: 63.0 vs 33.3%, p = 0.0346; low disease activity: 77.8 vs 45.8%, p = 0.0185). In conclusion, early intervention is beneficial for successful treatment holiday, which may lead to risk and cost reduction. However, further investigation is required. PMID:25420554

  9. Clinical endpoint sensitivity in rheumatoid arthritis: modeling and simulation.

    PubMed

    Ma, Lian; Zhao, Liang; Xu, Yun; Yim, Sarah; Doddapaneni, Suresh; Sahajwalla, Chandrahas G; Wang, Yaning; Ji, Ping

    2014-10-01

    The commonly used efficacy endpoints in Rheumatoid Arthritis (RA) clinical trials are American College of Rheumatology 20 % improvement criteria (ACR20), ACR50, and ACR70 response rates, and the 28-joint disease activity score (DAS28). Longitudinal models to quantitate the exposure-response relationships for ACRs and DAS28 score were developed for four biologics used for the management of RA. The models were then used to simulate the clinical outcome at various time points following different treatment regimens. Discriminative sensitivity of these endpoints was assessed using a power analysis. The trial simulation and subsequent power analysis showed that both ACR20 and DAS28 exhibit much lower power in distinguishing between two doses investigated compared with distinguishing treatment effect over placebo/Methotrexate (MTX) control. ACR20 response rate is generally more powerful in detecting treatment effect over placebo/MTX control as compared to DAS28. The findings of current study provide useful information which will help future clinical trial design for the treatment of patients with RA. PMID:25283268

  10. Genetic variants associated with methotrexate efficacy and toxicity in early rheumatoid arthritis: results from the treatment of early aggressive rheumatoid arthritis trial.

    PubMed

    Aslibekyan, S; Brown, E E; Reynolds, R J; Redden, D T; Morgan, S; Baggott, J E; Sha, J; Moreland, L W; O'Dell, J R; Curtis, J R; Mikuls, T R; Bridges, S L; Arnett, D K

    2014-02-01

    Methotrexate (MTX) has emerged as first-line therapy for early moderate-to-severe rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. We tested the associations between 863 known pharmacogenetic variants and MTX response in 471 Treatment of Early Aggressive Rheumatoid Arthritis Trial participants with early RA. Efficacy and toxicity were modeled using multiple regression, adjusted for demographic and clinical covariates. Penalized regression models were used to test joint associations of markers and/or covariates with the outcomes. The strongest genetic associations with efficacy were in CHST11 (five markers with P<0.003), encoding carbohydrate (chondroitin 4) sulfotransferase 11. Top markers associated with MTX toxicity were in the cytochrome p450 genes CYP20A1 and CYP39A1, solute carrier genes SLC22A2 and SLC7A7, and the mitochondrial aldehyde dehydrogenase gene ALDH2. The selected markers explained a consistently higher proportion of variation in toxicity than efficacy. These findings could inform future development of personalized therapeutic approaches. PMID:23545897

  11. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis

    Microsoft Academic Search

    A. C. Verhoeven; H. M. Markusse; Laar van de M. A. F. J; R. Westhovens; Denderen van J. C. M; Zeben van D; B. A. C. Dijkmans; A. J. G. E. Peeters; P. Jacobs; Brink van de H. R; H. J. A. Schouten; Heijde van der M. F. M; A. Boonen; Linden de S. venr

    1997-01-01

    Summary Background The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g\\/day), methotrexate (7·5 mg\\/week), and prednisolone (initially 60 mg\\/day, tapered in 6 weekly steps to 7·5 mg\\/day) with sulphasalazine alone. Methods 155 patients with early rheumatoid arthritis (median duration 4 months) were

  12. Terminal monosaccharide screening of synovial immunoglobulins G and A for the early detection of rheumatoid arthritis

    Microsoft Academic Search

    Ewa Maria Kratz; Krzysztof Borysewicz; Iwona K?tnik-Prastowska

    2010-01-01

    The expressions of some terminal glycotopes of synovial immunoglobulins G, A, and M were analysed in relation to rheumatoid\\u000a arthritis (RA) progression defined according to early and advanced radiological changes in patients’ hands. The relative amounts\\u000a of terminal monosaccharides were determined by lectin-immunoblotting of immunoglobulin preparations using appropriate lectins\\u000a able to recognize ?2,6-linked (Sambucus nigra agglutinin) and ?2,3-linked (Maackia amurensis

  13. Diagnostic value of antibodies to modified citrullinated vimentin in early rheumatoid arthritis.

    PubMed

    Sizova, Lyudmila

    2012-04-01

    The aim of this study was to evaluate the usefulness of antibodies to modified citrullinated vimentin (anti-MCV) for diagnosing early rheumatoid arthritis (RA) and to examine the correlations between anti-MCV and clinical parameters as well as radiographic and ultrasound data. Our results suggest that anti-MCV has a sensitivity and specificity of 53.3 and 83.3%, respectively, and a positive prognostic value of 96% in patients with early RA. Anti-MCV antibodies were observed in 48.5% of rheumatoid factor (RF)-negative RA patients in data from a latex test and in 35.7% of patients with negative results for immunoglobulin (Ig)-M-RF. The positive result for both anti-MCV and IgM-RF has a sensitivity of 42.2% and a specificity of 100%. No significant correlation was observed between anti-MCV and disease activity score using 28 joint counts, radiographic RA stage, number of erosions on ultrasonography of joints, and quality-of-life scores at disease onset. The Spearman correlation was significant in early RA patients with positive results of anti-MCV between the titers of this marker and arthritis duration, level of erythrocyte sedimentation rate, and IgM-RF. The best diagnostic strategy in early RA may be to assay both anti-MCV and IgM-RF. Thus, a question arises regarding the possible inclusion of anti-MCV in future revisions of the classification criteria of RA. PMID:22333689

  14. Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP)

    PubMed Central

    Forslind, K; Ahlmen, M; Eberhardt, K; Hafstrom, I; Svensson, B

    2004-01-01

    Objective: To investigate the role of anti-cyclic citrullinated peptide antibody (anti-CCP) for the prediction of radiological outcome in patients with early rheumatoid arthritis. Methods: Anti-CCP was assessed at baseline in 379 patients with early rheumatoid arthritis (disease duration <1 year). Radiological joint damage and progression were assessed by Larsen score after two years of follow up (end point) and used as outcome variables. The prognostic value of anti-CCP and other demographic and disease related baseline variables were assessed by univariate and multivariate analyses, including calculation of odds ratios (OR), predictive values, and multiple logistic regression models. Results: The presence of anti-CCP was associated with significantly higher Larsen score both at baseline and at end point. Univariate predictor analysis showed that anti-CCP had the highest significant OR for radiological joint damage and progression after baseline Larsen score, followed by rheumatoid factor, erythrocyte sedimentation rate (ESR), C reactive protein, age, smoking status, and sex. In stepwise multiple regression analyses, baseline Larsen score, anti-CCP, and ESR were selected as significant independent predictors of the radiological outcomes. Conclusions: There is good evidence for an association of anti-CCP with radiological joint changes in rheumatoid arthritis. Anti-CCP is an independent predictor of radiological damage and progression. Though prediction in early rheumatoid arthritis is still far from perfect, the use of anti-CCP in clinical practice should make it easier for rheumatologists to reach judicious treatment decisions. PMID:15308518

  15. Genetic Variants Associated with Methotrexate Efficacy and Toxicity in Early Rheumatoid Arthritis: Results from the Treatment of Early Aggressive Rheumatoid Arthritis Trial

    PubMed Central

    Aslibekyan, Stella; Brown, Elizabeth E.; Reynolds, Richard J.; Redden, David T.; Morgan, Sarah; Baggott, Joseph; Sha, Jin; Moreland, Larry W.; O’Dell, James R.; Curtis, Jeffrey R.; Mikuls, Ted R.; Bridges, S. Louis; Arnett, Donna K.

    2013-01-01

    Methotrexate (MTX) has emerged as first-line therapy for early moderate to severe rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. We tested the associations between 863 known pharmacogenetic variants and MTX response in 471 TEAR Trial participants with early RA. Efficacy and toxicity were modeled using multiple regression, adjusted for demographic and clinical covariates. Penalized regression models were used to test joint associations of markers and/or covariates with the outcomes. The strongest genetic associations with efficacy were in CHST11 (five markers with P <0.003), encoding carbohydrate (chondroitin 4) sulfotransferase 11. Top markers associated with MTX toxicity were in the cytochrome p450 genes CYP20A1 and CYP39A1, solute carrier genes SLC22A2 and SLC7A7, and the mitochondrial aldehyde dehydrogenase gene ALDH2. The selected markers explained a consistently higher proportion of variation in toxicity than efficacy. These findings could inform future development of personalized therapeutic approaches. PMID:23545897

  16. Prototype system of laser transillumination computed tomography for early diagnosis of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Sasaki, Yoshiaki; Tanosaki, Shinji; Suzuki, Jota; Emori, Ryota; Inage, Hiroki; Yuasa, Tetsuya; Takagi, Michiaki; Ishikawa, Akira; Taniguchi, Hiroshi; Devaraj, Balasigamani; Akatsuka, Takao

    2003-07-01

    So far we have shown, through various preliminary imaging experiments with small-animal ankle"s and human finger"s joints both healthy and joint-diseased, that early diagnosis for joint disease such as rheumatoid arthritis (RA) is feasible using a transillumination laser CT. For a practical purpose, we have recently proposed and developed a transillumination laser CT imaging system using optical fibers based on the optical heterodyne detection method for a clinical use. In the proposed system, motion-artifact free images can be obtained because measurements can be performed with the object fixed. In addition, use of fiber-optics enables portability, and robustness against environmental changes in a room, such as variable temperature, air-flow shifts, and unexpected vibrations. The imaging system has the following sensing properties: spatial resolution of 500 ?m, a dynamic range of approximately 120 dB, and a minimum-detectable-optical power of 10-14 W as a result of the excellent properties of the heterodyne detection technique. In the present paper, we describe a prototype laser CT imaging system using optical fibers for early diagnosis of joint disease such as rheumatoid arthritis by demonstrating the first in vivo tomographic image of a volunteer"s index finger joint as well as the fundamental imaging properties.

  17. Predictors of Change in Bodily Pain in Early Rheumatoid Arthritis: An Inception Cohort Study

    PubMed Central

    McWilliams, Daniel F; Zhang, Weiya; Mansell, Josephine S; Kiely, Patrick D W; Young, Adam; Walsh, David A

    2012-01-01

    Objective To investigate possible predictors for lack of pain improvement after 1 year of treatment for early rheumatoid arthritis (RA). Methods The Early Rheumatoid Arthritis Network (ERAN) database was used for analysis of baseline and 1-year pain data. The ERAN is a hospital-based inception cohort of 1,189 people. Short Form 36 questionnaire bodily pain scores were used to calculate change in pain at 1 year as the outcome. The proportion of the Disease Activity Score in 28 joints (DAS28) attributable to patient-reported components (joint tenderness and visual analog scale score; DAS28-P) at baseline was derived as a predictor. Predictors of less improvement in pain were investigated using adjusted odds ratios (ORadj) generated by logistic regression, adjusting for 14 additional clinical and demographic covariates. Results Greater pain at baseline was associated with sex, high DAS28, worse mental health, and smoking. Most patients with early RA reported incomplete improvement in bodily pain after 1 year. The DAS28-P index did not significantly change in the patients whose disease remained active. Less improvement in pain was predicted by female sex (ORadj 3.41, 95% confidence interval [95% CI] 1.35–8.64) and a high DAS28-P index at baseline (ORadj for tertiles 2.09, 95% CI 1.24–3.55). Other conventional RA risk factors did not predict pain changes. Conclusion The factors most likely to predict less improvement in pain in early RA are female sex and a high DAS28-P index. A high DAS28-P index may reflect greater contributions of noninflammatory factors, such as central sensitization, to pain. Strategies in addition to inflammatory disease suppression may be required to adequately treat pain. PMID:22556121

  18. Predictors of radiographic joint damage in patients with early rheumatoid arthritis

    PubMed Central

    Jansen, L; van der Horst-Bru..., I E; van Schaardenburg, D; Bezemer, P; Dijkmans, B

    2001-01-01

    OBJECTIVE—To determine factors at diagnosis, associated with radiographic damage at diagnosis and after one year, in patients with early rheumatoid arthritis (RA).?METHODS—New patients with early RA were followed up for one year. Possible prognostic factors were duration of complaints, morning stiffness, disease activity score (DAS28), functional status (Health Assessment Questionnaire (HAQ) score), rheumatoid factor (IgM RF), and C reactive protein (CRP). Outcome was defined as radiographic damage of the hands and feet (Sharp/van der Heijde score). For the statistical analysis, one way analysis of variance and a forward stepwise logistic regression model was used.?RESULTS—130 patients with RA (68% female; median age 64 years, range 21-86) were included. Despite the fact that the median duration of complaints was short (15 weeks, range 2-106) the radiographic damage at diagnosis was significantly correlated with the duration of complaints (p<0.05). Patients with a duration of complaints of >34 weeks had significantly more radiographic joint damage at diagnosis than patients with a shorter duration of complaints. Radiographic progression at one year was correlated with high radiographic joint damage, high CRP level, and a positive IgM RF at entry.?CONCLUSIONS—In early RA, the number of radiographic lesions was correlated with a longer duration of complaints at the first visit. Progression of these lesions was predicted by a high baseline joint damage, high CRP level, and a positive IgM RF. Further reduction of the delay in referral and early treatment may further decrease joint damage in patients with recent onset polyarthritis.?? PMID:11557647

  19. Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis

    PubMed Central

    Lindqvist, E; Jonsson, K; Saxne, T; Eberhardt, K

    2003-01-01

    Objective: To investigate development of radiographic damage in hands and feet of patients with early rheumatoid arthritis (RA) monitored prospectively for 10 years, and to search for prognostic factors. Patients and methods: 181 patients with early RA (mean disease duration one year) were assessed annually with radiographs of hands and feet during years 0–5 and at year 10. Radiographs were evaluated according to Larsen (range 0–200). Predictive factors for progressive disease for years 0–5 and 5–10 were evaluated by logistic regression analyses. Results: 82/168 (49%) patients had erosions at inclusion and almost all became erosive with time (90% after two years and 96% after 10 years). Radiographic progression was most rapid during the first two years and 75% of all damage occurred during the first five years. The median Larsen score increased from 6 at inclusion to 41 after five years and 54 after 10 years. Only 5.3% of all evaluated joints became maximally eroded, the second metacarpophalangeal joint being the most commonly affected. Mean ESR during the first three months and rheumatoid factor status were significant predictors for radiographic progressive disease, it was not possible to predict non-progressive disease. Conclusions: Joint damage in hands and feet developed early and progression was most rapid during the first years of disease. The different rates of progression at different stages should be considered in the design of trials of drugs aimed at retarding joint damage. Disease activity at study start influenced the degree of joint damage during the entire 10 years. PMID:12810421

  20. Mining disease risk patterns from nationwide clinical databases for the assessment of early rheumatoid arthritis risk.

    PubMed

    Chin, Chu Yu; Weng, Meng Yu; Lin, Tzu Chieh; Cheng, Shyr Yuan; Yang, Yea Huei Kao; Tseng, Vincent S

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune rheumatic disease that can cause painful swelling in the joint lining, morning stiffness, and joint deformation/destruction. These symptoms decrease both quality of life and life expectancy. However, if RA can be diagnosed in the early stages, it can be controlled with pharmacotherapy. Although many studies have examined the possibility of early assessment and diagnosis, few have considered the relationship between significant risk factors and the early assessment of RA. In this paper, we present a novel framework for early RA assessment that utilizes data preprocessing, risk pattern mining, validation, and analysis. Under our proposed framework, two risk patterns can be discovered. Type I refers to well-known risk patterns that have been identified by existing studies, whereas Type II denotes unknown relationship risk patterns that have rarely or never been reported in the literature. These Type II patterns are very valuable in supporting novel hypotheses in clinical trials of RA, and constitute the main contribution of this work. To ensure the robustness of our experimental evaluation, we use a nationwide clinical database containing information on 1,314 RA-diagnosed patients over a 12-year follow-up period (1997-2008) and 965,279 non-RA patients. Our proposed framework is employed on this large-scale population-based dataset, and is shown to effectively discover rich RA risk patterns. These patterns may assist physicians in patient assessment, and enhance opportunities for early detection of RA. The proposed framework is broadly applicable to the mining of risk patterns for major disease assessments. This enables the identification of early risk patterns that are significantly associated with a target disease. PMID:25875441

  1. Mining Disease Risk Patterns from Nationwide Clinical Databases for the Assessment of Early Rheumatoid Arthritis Risk

    PubMed Central

    Chin, Chu Yu; Weng, Meng Yu; Lin, Tzu Chieh; Cheng, Shyr Yuan; Yang, Yea Huei Kao; Tseng, Vincent S.

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune rheumatic disease that can cause painful swelling in the joint lining, morning stiffness, and joint deformation/destruction. These symptoms decrease both quality of life and life expectancy. However, if RA can be diagnosed in the early stages, it can be controlled with pharmacotherapy. Although many studies have examined the possibility of early assessment and diagnosis, few have considered the relationship between significant risk factors and the early assessment of RA. In this paper, we present a novel framework for early RA assessment that utilizes data preprocessing, risk pattern mining, validation, and analysis. Under our proposed framework, two risk patterns can be discovered. Type I refers to well-known risk patterns that have been identified by existing studies, whereas Type II denotes unknown relationship risk patterns that have rarely or never been reported in the literature. These Type II patterns are very valuable in supporting novel hypotheses in clinical trials of RA, and constitute the main contribution of this work. To ensure the robustness of our experimental evaluation, we use a nationwide clinical database containing information on 1,314 RA-diagnosed patients over a 12-year follow-up period (1997–2008) and 965,279 non-RA patients. Our proposed framework is employed on this large-scale population-based dataset, and is shown to effectively discover rich RA risk patterns. These patterns may assist physicians in patient assessment, and enhance opportunities for early detection of RA. The proposed framework is broadly applicable to the mining of risk patterns for major disease assessments. This enables the identification of early risk patterns that are significantly associated with a target disease. PMID:25875441

  2. A multicentre trial of bucillamine in the treatment of early rheumatoid arthritis (SNOW study).

    PubMed

    Sagawa, Akira; Fujisaku, Atsushi; Ohnishi, Katsunori; Mukai, Masaya; Yasuda, Izumi; Amasaki, Yoshiharu; Shimizu, Masato; Ichikawa, Kenji; Ohsaki, Hirofumi

    2011-06-01

    In this study, we enrolled early rheumatoid arthritis (RA) patients at multiple institutes who fulfilled the American Rheumatism Association 1987 revised criteria for the classification of RA, and followed the clinical results of disease-modifying anti-rheumatic drug (DMARD) treatment prospectively. With the aim of developing therapeutic guidelines using the disease activity score 28 (DAS28) as disease indices, we investigated the usefulness of bucillamine (BUC), one of the most widely used DMARDs in Japan. Eighty-one patients with early RA who had not previously been treated with DMARDs were suitable for BUC therapy as first-choice treatment. After 24 months of treatment, at least moderate improvement was seen in 87.5% of patients using the DAS28 erythrocyte sedimentation rate (ESR). After 24 months of BUC therapy, 7 patients (43.8%) met the remission criterion of DAS28 (ESR) <2.6. The 24-month BUC continuation rate was 60.5% (49/81, monotherapy + combination therapy), of which 59.2% (29/49) were on BUC monotherapy. From the efficacy and safety viewpoints alike, BUC was useful as first-choice treatment for early RA. PMID:21188453

  3. The performance of a point of care test for detection of anti-mutated citrullinated vimentin and rheumatoid factor in early rheumatoid arthritis.

    PubMed

    Rojanasantikul, Preeda; Pattrapornpisut, Prapa; Anuruckparadorn, Kulvara; Katchamart, Wanruchada

    2014-07-01

    The purpose of this study was to determine the diagnostic performance of a point-of-care test (POCT) for detection of anti-mutated citrullinated vimentin (anti-MCV) and rheumatoid factor (RF) in early rheumatoid arthritis (RA) with 2 years of disease duration or less. Additionally, we evaluated the agreement of these tests when using EDTA whole blood and capillary blood. Patients with RA and other rheumatic disorders were consecutively recruited from the rheumatology outpatient clinic. The POCT for detection of anti-MCV and RF using capillary blood and EDTA whole blood was performed in 78 patients with early RA, 55 patients with other rheumatic disorders, and 55 healthy blood donors. The sensitivity and specificity of anti-MCV POCT in patients with early RA were 64 and 97 %, respectively, while the sensitivity and specificity of RF POCT were 51 and 95 %, respectively. The positive likelihood ratio of the POCT for anti-MCV was higher than those for RF (23.5 vs 9.4). The negative likelihood was 0.37 for anti-MCV and 0.52 for RF. There were three cases with false positive for anti-MCV including a patient with psoriatic arthritis and the other two with systemic sclerosis. The agreement between capillary blood and EDTA whole blood testing for anti-MCV and RF was low to moderate with Cohen's kappa of 0.58 and 0.49, respectively. This POCT for detection of anti-MCV and RF yielded high specificity and may be a valuable tool for the diagnosis of early RA. Using this POCT with EDTA whole blood instead of capillary blood is not recommended. PMID:24577818

  4. Effect of steroid treatment on the migration behaviour of neutrophils in patients with early rheumatoid arthritis.

    PubMed

    Aglas, F; Rainer, F; Lipp, R W; Schnedl, W J; Horn, S; Egger, G

    1997-01-01

    The influence of methylprednisolone on the migratory characteristics of neutrophil granulocytes was investigated in 10 patients with early rheumatoid arthritis (RA) and compared to 12 controls. The migration of neutrophils was measured with a whole-blood membrane filter assay with and without stimulation by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP). Total migration index (TMI), distribution characteristics (DC) and the product of TMI and DC (neutrophil migratory activity; NMA) served to characterize the migratory behaviour of neutrophils. The data demonstrated an increased polymorphonuclear leucocyte (PMN) migration in patients with early RA, indicating a bystander role of PMNs in inflammatory joint injury. Treatment with methylprednisolone reduced significantly the penetration depth (DC) of neutrophils, but did not influence the number of migrating cells (TMI). The unstimulated NMA was significantly reduced due to the marked DC reduction, whereas steroids did not influence the stimulated NMA of neutrophils. A significant reduction in PMN penetration depth was demonstrated only after a steroid therapy of at least 10 days, suggesting that a longer period of steroid therapy is necessary to provide effective inflammatory control. PMID:9440143

  5. Terminal monosaccharide screening of synovial immunoglobulins G and A for the early detection of rheumatoid arthritis.

    PubMed

    Kratz, Ewa Maria; Borysewicz, Krzysztof; Katnik-Prastowska, Iwona

    2010-08-01

    The expressions of some terminal glycotopes of synovial immunoglobulins G, A, and M were analysed in relation to rheumatoid arthritis (RA) progression defined according to early and advanced radiological changes in patients' hands. The relative amounts of terminal monosaccharides were determined by lectin-immunoblotting of immunoglobulin preparations using appropriate lectins able to recognize alpha2,6-linked (Sambucus nigra agglutinin) and alpha2,3-linked (Maackia amurensis agglutinin) sialic acid, galactose (Ricinus communis agglutinin I), N-acetylglucosamine (Griffonia simplicifolia agglutinin II) as well as alpha1,6-linked (Aleuria aurantia lectin), alpha1,3-linked (Lotus tetragonolobus agglutinin), and alpha1,2-linked (Ulex europaeus agglutinin) fucose. The results indicate differences between early and advanced RA stages in the terminal sugar exposition of synovial IgG and IgA, but not IgM. The galactose-deficient glycotope with exposed N-acetylglucosamine of the synovial 33.1-kDa IgG fragment appeared exclusively in the early stage of RA. In contrast, this glycotope of intact synovial IgG and IgA was present in both groups, although with higher proportions in advanced RA. The proportions of the sialyl and fucosyl determinants of intact synovial A and G immunoglobulins were clearly lower in the early RA group than in the advanced. The analysis of terminal oligosaccharide exposition in IgG, IgG fragments, and IgA present in the synovial fluid of RA patients might be applicable as a stage-specific marker in the diagnosis and therapy of RA patients. PMID:19816690

  6. Circulating surfactant protein -D is low and correlates negatively with systemic inflammation in early, untreated rheumatoid arthritis

    Microsoft Academic Search

    Anne Friesgaard Christensen; Grith Lykke Sørensen; Kim Hørslev-Petersen; Uffe Holmskov; Hanne Merete Lindegaard; Kirsten Junker; Merete Lund Hetland; Kristian Stengaard-Pedersen; Søren Jacobsen; Tine Lottenburger; Torkell Ellingsen; Lis Smedegaard Andersen; Ib Hansen; Henrik Skjødt; Jens Kristian Pedersen; Ulrik Birk Lauridsen; Anders Svendsen; Ulrik Tarp; Jan Pødenphant; Aage Vestergaard; Anne Grethe Jurik; Mikkel Østergaard; Peter Junker

    2010-01-01

    INTRODUCTION: Surfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial

  7. Rheumatoid arthritis.

    PubMed

    Grainger, Andrew J; Rowbotham, Emma L

    2013-02-01

    Since the advent of disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis, there has been an increasing emphasis on the early diagnosis and monitoring of this condition. This has led to the greater involvement of advanced imaging techniques such as ultrasound and MRI. Ultrasound appearances of common findings in rheumatoid arthritis are discussed in this review. Comparison of ultrasound in terms of sensitivity and specificity with other imaging modalities and with clinical examination is also made. Quantification is also discussed as a tool to allow assessment of response to drug therapy, an area that is likely to progress further as techniques become increasingly reproducible. Finally, as ultrasound techniques continue to develop, its involvement in the management of patients with rheumatoid arthritis is increasing. New techniques such as fusion imaging and sonoelastography, while at present still largely research-based entities, may offer increasingly improved diagnostic benefits in the field of inflammatory arthropathy. PMID:23487337

  8. A qualitative interview study: patient accounts of medication use in early rheumatoid arthritis from symptom onset to early postdiagnosis

    PubMed Central

    Townsend, Anne; Backman, Catherine L; Adam, Paul; Li, Linda C

    2013-01-01

    Objective To examine accounts of medication use in participants with early rheumatoid arthritis (RA) from symptom onset to early postdiagnosis. Design Qualitative study with in-depth, personal interviews. Participants 37 women and one man, aged 30–70s, with a diagnosis of RA <12?months. Main outcome measure Participants’ experiences and feelings of medication use in early RA. Setting British Columbia, Canada. Results Medications were central to how people managed symptoms and disease. Two main themes were identified, showing that optimum medication use was hampered, and how this related to delayed diagnosis and effective care. The first theme, ‘paradox of prediagnosis reliance on over the counter (OTC) medications’, describes how people's self-management with OTC medications was ‘effective’. Participants relied extensively on OTC medications for pain relief and to maintain ‘normal life’. However, as this contributed to delayed medical consultation, diagnosis and effective treatment, OTC medication was also potentially detrimental to disease outcome. The second theme, ‘ambivalence around prescription medications post diagnosis’, describes how adherence was hindered by patient beliefs, priorities and ambivalence towards medications. Conclusions This study highlights how people use medications in early RA and contributes to a better understanding of medication use that may transfer to other conditions. Given the drive towards active self-management in healthcare and patients’ ambivalence about using strong medications, an in-depth understanding of how these combined factors impact patient experiences will help healthcare providers to support effective medication practices. The reported extensive reliance on OTC medications may speak to a care gap needing further investigation in the context of health behaviours and outcomes of patient self-management. PMID:23408077

  9. Markers of B-lymphocyte activation are elevated in patients with early rheumatoid arthritis and correlated with disease activity in the ESPOIR cohort

    Microsoft Academic Search

    Jacques-Eric Gottenberg; Corinne Miceli-Richard; Béatrice Ducot; Philippe Goupille; Bernard Combe; Xavier Mariette

    2009-01-01

    INTRODUCTION: Little is known about systemic B-cell activation in early rheumatoid arthritis (RA). We therefore evaluated the serum levels of markers of B-cell activation in patients included in the ESPOIR early arthritis cohort. METHODS: In the ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks but less than 6 months), 710 patients were assessed at

  10. Spontaneous expression of immediately-early response genes c-fos and egr-1 in collagenase-producing rheumatoid synovial fibroblasts

    Microsoft Academic Search

    A. Trabandt; W. K. Aicher; R. E. Gay; V. P. Sukhatme; H.-G. Fassbender; S. Gay

    1992-01-01

    In view of the important role of interstitial collagenase in the pathogenesis of rheumatoid arthritis (RA), we studied the expression of fibroblast-type collagenase in rheumatoid synovium and searched for its potential transcription factors, namely the oncoprotein c-fos and the early-growth-response gene-1 (egr-1), an inducible zinc-finger encoding gene. Elevated levels of RNA sequences complimentary to c-fos and egr-1 cDNA probes could

  11. Candidate autoantigens identified by mass spectrometry in early rheumatoid arthritis are chaperones and citrullinated glycolytic enzymes

    PubMed Central

    Goëb, Vincent; Thomas-L'Otellier, Marlène; Daveau, Romain; Charlionet, Roland; Fardellone, Patrice; Le Loët, Xavier; Tron, François; Gilbert, Danièle; Vittecoq, Olivier

    2009-01-01

    Introduction The aim of our study was to identify new early rheumatoid arthritis (RA) autoantibodies. Methods Sera obtained from 110 early untreated RA patients (<6 months) were analyzed by western blot using HL-60 cell extract, separated on one-dimensional and two-dimensional gel electrophoresis (1-DE, 2-DE). Sera from 50 healthy blood donors and 20 patients with non-RA rheumatisms were used as controls for 1-DE and 2-DE, respectively. The immunoreactive proteins were identified by MALDI-TOF mass spectrometric analysis and the presence of potential sites of citrullination in each of these proteins was evaluated. FT-ICR mass spectrometry was used to verify experimentally the effect of citrullination upon the mass profile observed by MALDI-TOF analysis. Results The 110 1-DE patterns allowed detection of 10 recurrent immunoreactive bands of 33, 39, 43, 46, 51, 54, 58, 62, 67 and 70 kDa, which were further characterized by 2-DE and proteomic analysis. Six proteins were already described RA antigens: heterogeneous nuclear ribonucleoprotein A2/B1, aldolase, ?-enolase, calreticulin, 60 kDa heat shock protein (HSP60) and BiP. Phosphoglycerate kinase 1 (PGK1), stress-induced phosphoprotein 1 and the far upstream element-binding proteins (FUSE-BP) 1 and 2 were identified as new antigens. Post-translational protein modifications were analyzed and potentially deiminated peptides were found on aldolase, ?-enolase, PGK1, calreticulin, HSP60 and the FUSE-BPs. We compared the reactivity of RA sera with citrullinated and noncitrullinated ?-enolase and FUSE-BP linear peptides, and showed that antigenicity of the FUSE-BP peptide was highly dependent on citrullination. Interestingly, the anti-cyclic citrullinated peptide antibody (anti-CCP2) status in RA serum at inclusion was not correlated to the reactivity directed against FUSE-BP citrullinated peptide. Conclusions Two categories of antigens, enzymes of the glycolytic family and molecular chaperones are also targeted by the early untreated RA autoantibody response. For some of them, and notably the FUSE-BPs, citrullination is involved in the immunological tolerance breakdown observed earlier in RA patients. Autoantibodies recognizing a citrullinated peptide from FUSE-BP may enhance the sensibility for RA of the currently available anti-CCP2 test. PMID:19284558

  12. Anti-type II collagen antibodies are associated with early radiographic destruction in rheumatoid arthritis

    PubMed Central

    2012-01-01

    Introduction We have previously reported that high levels of antibodies specific for native human type II collagen (anti-CII) at the time of RA diagnosis were associated with concurrent but not later signs of inflammation. This was associated with CII/anti-CII immune complex (IC)-induced production of pro-inflammatory cytokines in vitro. In contrast, anti-cyclic citrullinated peptide antibodies (anti-CCP) were associated both with late inflammation and late radiological destruction in the same RA cohort. We therefore hypothesized that anti-CII are also associated with early erosions. Methods Two-hundred-and-fifty-six patients from an early RA cohort were included. Baseline levels of anti-CII, anti-CCP and anti-mutated citrullinated vimentin were analyzed with ELISA, and rheumatoid factor levels were determined by nephelometry. Radiographs of hands and feet at baseline, after one and after two years were quantified using the 32-joints Larsen erosion score. Results Levels of anti-CII were bimodally distributed in the RA cohort, with a small (3.1%, 8/256) group of very high outliers with a median level 87 times higher than the median for the healthy control group. Using a cut-off discriminating the outlier group that was associated with anti-CII IC-induced production of proinflammatory cytokines in vitro, baseline anti-CII antibodies were significantly (p = 0.0486) associated with increased radiographic damage at the time of diagnosis. Anti-CII-positive patient had also significantly increased HAQ score (p = 0.0303), CRP (p = 0.0026) and ESR (p = 0.0396) at the time of diagnosis but not during follow-up. The median age among anti-CII-positive subjects was 12 years higher than among the anti-CII-negative patients. Conclusion In contrary to anti-CCP, anti-CII-positive patients with RA have increased joint destruction and HAQ score at baseline. Anti-CII thus characterizes an early inflammatory/destructive phenotype, in contrast to the late appearance of an inflammatory/destructive phenotype in anti-CCP positive RA patients. The anti-CII phenotype might account for part of the elderly acute onset RA phenotype with rather good prognosis. PMID:22548748

  13. Detection of bone erosions in early rheumatoid arthritis: 3D ultrasonography versus computed tomography.

    PubMed

    Peluso, G; Bosello, S L; Gremese, E; Mirone, L; Di Gregorio, F; Di Molfetta, V; Pirronti, T; Ferraccioli, G

    2015-07-01

    Three-dimensional (3D) volumetric ultrasonography (US) is an interesting tool that could improve the traditional approach to musculoskeletal US in rheumatology, due to its virtual operator independence and reduced examination time. The aim of this study was to investigate the performance of 3DUS in the detection of bone erosions in hand and wrist joints of early rheumatoid arthritis (ERA) patients, with computed tomography (CT) as the reference method. Twenty ERA patients without erosions on standard radiography of hands and wrists underwent 3DUS and CT evaluation of eleven joints: radiocarpal, intercarpal, ulnocarpal, second to fifth metacarpo-phalangeal (MCP), and second to fifth proximal interphalangeal (PIP) joints of dominant hand. Eleven (55.0 %) patients were erosive with CT and ten of them were erosive also at 3DUS evaluation. In five patients, 3DUS identified cortical breaks that were not erosions at CT evaluation. Considering CT as the gold standard to identify erosive patients, the 3DUS sensitivity, specificity, PPV, and NPV were 0.9, 0.55, 0.71, and 0.83, respectively. A total of 32 erosions were detected with CT, 15 of them were also observed at the same sites with 3DUS, whereas 17 were not seen on 3DUS evaluation. The majority of these 3DUS false-negative erosions were in the wrist joints. Furthermore, 18 erosions recorded by 3DUS were false positive. The majority of these 3DUS false-positive erosions were located at PIP joints. This study underlines the limits of 3DUS in detecting individual bone erosion, mostly at the wrist, despite the good sensitivity in identifying erosive patients. PMID:26091903

  14. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset

    Microsoft Academic Search

    Fiona M McQueen; Neal Stewart; Jeff Crabbe; Elizabeth Robinson; Sue Yeoman; Paul L J Tan; Lachy McLean

    1998-01-01

    OBJECTIVESTo evaluate the role of magnetic resonance imaging (MRI) of the wrist in detecting early joint damage in patients with rheumatoid arthritis (RA).METHODSMRI was performed on 42 patients with early RA (median symptom duration of four months). Scans were scored separately by two musculoskeletal radiologists using a newly devised scoring system, which was validated. MRI findings were compared with plain

  15. The ratio of circulating osteoprotegerin to RANKL in early rheumatoid arthritis predicts later joint destruction

    Microsoft Academic Search

    P. P. Geusens; R. B. M. Landewé; P. Garnero; D. Chen; C. R. Dunstan; W. F. Lems; P. Stinissen; D. M. F. M. van der Heijde; S. van der Linden; M. Boers

    2006-01-01

    Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease that may result in debilitating joint deformities with destruction of bone and cartilage. Inflammation is still considered the pivotal inducer of both components of joint damage. Results of recent animal studies suggested a prominent contribution of osteoclastic bone resorption that could be dissociated from inflammation. RANKL and its natural decoy re-

  16. Prediction of erosiveness and rate of development of new erosions in early rheumatoid arthritis

    Microsoft Academic Search

    T T Möttönen

    1988-01-01

    Fifty eight patients suffering from a recent onset of rheumatoid arthritis (RA) were studied. Fifty six patients were followed up for 24 months and two for 18 months. Erosions were detected in 17 patients at the onset and at the end of the follow up period the number of patients with erosions was 44. The erosiveness in the joint groups

  17. Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analyses from the PREMIER study

    Microsoft Academic Search

    M Hoff; T K Kvien; J Kalvesten; A Elden; G Haugeberg

    2009-01-01

    Objective: The effect of adalimumab on hand osteo- porosis was examined and related to radiographic joint damage in the three treatment arms of the PREMIER study: adalimumab plus methotrexate, adalimumab and methotrexate monotherapy. Predictors of hand bone loss were also searched for. Methods: 768 patients (537 fulfilled 2 years) with rheumatoid arthritis (RA) for less than 3 years, never treated

  18. Serum Levels of Asymmetric Dimethylarginine and Apelin as Potential Markers of Vascular Endothelial Dysfunction in Early Rheumatoid Arthritis

    PubMed Central

    Di Franco, Manuela; Spinelli, Francesca Romana; Metere, Alessio; Gerardi, Maria Chiara; Conti, Virginia; Boccalini, Francesca; Iannuccelli, Cristina; Ciciarello, Francesco; Agati, Luciano; Valesini, Guido

    2012-01-01

    Objectives. Impaired endothelial function represents the early stage of atherosclerosis, which is typically associated with systemic inflammatory diseases like rheumatoid arthritis (RA). As modulators of endothelial nitric oxide synthase expression, asymmetric-dimethylarginine (ADMA) and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes. We conducted a prospective, case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA (ERA) before and after disease-modifying antirheumatic drug (DMARD) therapy. Methods. We enrolled 20 consecutively diagnosed, treatment-naïve patients with ERA and 20 matched healthy controls. Serum ADMA and apelin levels and the 28-joint disease activity scores (DAS28) were assessed before and after 12 months of DMARDs treatment. All patients underwent ultrasonographic assessment for intima-media tickness (IMT) evaluation. Results. In the ERA group, ADMA serum levels were significantly higher than controls at baseline (P = 0.007) and significantly decreased after treatment (P = 0.012 versus controls). Baseline serum apelin levels were significantly decreased in this group (P = 0.0001 versus controls), but they were not significantly altered by treatment. IMT did not show significant changes. Conclusions. ERA is associated with alterations of serum ADMA and apelin levels, which might be used as biomarkers to detect early endothelial dysfunction in these patients. PMID:22927708

  19. Challenges and opportunities in the early diagnosis and optimal management of rheumatoid arthritis in Africa and the Middle East.

    PubMed

    Halabi, Hussein; Alarfaj, Abdurhman; Alawneh, Khaldoon; Alballa, Soliman; Alsaeid, Khalid; Badsha, Humeira; Benitha, Romela; Bouajina, Elyes; Al Emadi, Samar; El Garf, Ayman; El Hadidi, Khaled; Laatar, Ahmed; Makhloufi, Chafia D; Masri, Abdel F; Menassa, Jeanine; Al Shaikh, Ahmed; Swailem, Ramiz Al; Dougados, Maxime

    2015-03-01

    Early diagnosis and early initiation of disease-modifying antirheumatic drug (DMARD) therapy slow the progression of joint damage and decrease the morbidity and mortality associated with rheumatoid arthritis (RA). According to the European League Against Rheumatism (EULAR) guidelines, treatment should be initiated with methotrexate and addition of biological DMARDs such as tumour necrosis factor (TNF) inhibitors should be considered for RA patients who respond insufficiently to methotrexate and/or other synthetic DMARDs and have poor prognostic factors. Africa and the Middle East is a large geographical region with varying treatment practices and standards of care in RA. Existing data show that patients with RA in the region are often diagnosed late, present with active disease and often do not receive DMARDs early in the course of the disease. In this review, we discuss the value of early diagnosis and remission-targeted treatment for limiting joint damage and improving disease outcomes in RA, and the challenges in adopting these strategies in Africa and the Middle East. In addition, we propose an action plan to improve the overall long-term outlook for RA patients in the region. PMID:24620997

  20. Decreased Circulating Visfatin Is Associated with Improved Disease Activity in Early Rheumatoid Arthritis: Data from the PERAC Cohort

    PubMed Central

    Sglunda, Ond?ej; Mann, He?man; Hulejová, Hana; Kuklová, Markéta; Pecha, Ond?ej; Pleštilová, Lenka; Filková, Mária; Pavelka, Karel; Vencovský, Ji?í; Šenolt, Ladislav

    2014-01-01

    Objective To evaluate circulating visfatin and its relationship with disease activity and serum lipids in patients with early, treatment-naïve rheumatoid arthritis (RA). Methods Serum visfatin was measured in 40 patients with early RA before and after three months of treatment and in 30 age- and sex-matched healthy individuals. Disease activity was assessed using the Disease Activity Score for 28 joints (DAS28) at baseline and at three and 12 months. Multivariate linear regression analysis was performed to evaluate whether improved disease activity is related to serum visfatin or a change in visfatin level. Results Serum visfatin was significantly elevated in early RA patients compared to healthy controls (1.92±1.17 vs. 1.36±0.93 ng/ml; p?=?0.034) and significantly decreased after three months of treatment (to 0.99±0.67 ng/ml; p<0.001). Circulating visfatin and a change in visfatin level correlated with disease activity and improved disease activity over time, respectively. A decrease in visfatin after three months predicted a DAS28 improvement after 12 months. In addition, decreased serum visfatin was not associated with an improved atherogenic index but was associated with an increase in total cholesterol level. Conclusion A short-term decrease in circulating visfatin may represent an independent predictor of long-term disease activity improvement in patients with early RA. PMID:25068448

  1. Prediction of erosiveness and rate of development of new erosions in early rheumatoid arthritis.

    PubMed

    Möttönen, T T

    1988-08-01

    Fifty eight patients suffering from a recent onset of rheumatoid arthritis (RA) were studied. Fifty six patients were followed up for 24 months and two for 18 months. Erosions were detected in 17 patients at the onset and at the end of the follow up period the number of patients with erosions was 44. The erosiveness in the joint groups studied was as follows: metatarsophalangeal (MTP) (36 patients), metacarpophalangeal (MCP) (22), proximal interphalangeal (PIP) (21), interphalangeal (IP) joints of first toes and wrists (13), elbows and knees (two), and shoulders, ankles, and hips (one). Erosiveness in the feet was twice that in the fingers, and the erosions in the feet appeared at an earlier phase of disease. Destructions favoured the dominant hand. Swelling in the PIP joints appeared to be a better predictor of erosiveness than joint tenderness. The number of joints to become eroded was significantly increased in the patients with flexor tenosynovitis in the hands. Erythrocyte sedimentation rate (ESR) was more closely related to progression of joint damage than C reactive protein (CRP) or haemoglobin. The rate of development of new erosions was the same in seronegative and seropositive patients. In addition, HLA-DR4 allele did not correlate either with seropositivity or with erosiveness. Adequate antirheumatic drug treatment (gold in most instances) was not able to restrain the erosive process despite decreased rheumatoid disease activity. PMID:3137902

  2. Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project)

    PubMed Central

    Kastbom, A; Strandberg, G; Lindroos, A; Skogh, T

    2004-01-01

    Objectives: To evaluate the diagnostic sensitivity of antibodies to cyclic citrullinated peptide (CCP) in recent onset rheumatoid arthritis (RA) at diagnosis and 3 years later, and to evaluate anti-CCP antibody as a predictor of the disease course during 3 years. Methods: 242 patients with recent onset (?1 year) RA were followed up regularly during 3 years after inclusion in the Swedish multicentre study "TIRA" 1996–98. Anti-CCP antibodies were analysed by an enzyme immunoassay (EIA). Rheumatoid factors (RFs) were analysed by latex agglutination and two isotype-specific (IgM and IgA) EIAs. Disease activity was assessed by plasma CRP, ESR, 28 joint disease activity score, and the physician's global assessment of disease activity. Functional ability was evaluated by the Health Assessment Questionnaire. Results: Overall, the diagnostic sensitivity of anti-CCP antibodies was 64% and the proportion of positive tests increased with the number of fulfilled classification criteria according to the American College of Rheumatology. The anti-CCP antibody results correlated with RF, but were better than RF as predictor of a more aggressive disease course. After 3 years 5/97 patients had changed anti-CCP status: 2 from negative to positive and 3 from positive to negative. The mean level of anti-CCP antibodies declined by 131 U/ml during the 3 year follow up (95% CI 34 to 228 U/ml). Conclusion: The anti-CCP antibody assay has a similar diagnostic sensitivity to that of RF in early RA, but is better as a predictor of the disease course over 3 years. Although the mean serum level declines, anti-CCP antibody positivity remains essentially unaltered 3 years after diagnosis and start of antirheumatic treatment. PMID:15308517

  3. Rheumatoid Arthritis

    MedlinePLUS

    ... Arthritis Overview What is rheumatoid arthritis? Rheumatoid (say: "roo-mah-toyd") arthritis (RA) is an autoimmune disease ... bone thinning, cataracts and diabetes. Antirheumatic (say: "anti-roo-mat-ick") medicines can help fight RA. If ...

  4. Early activation of invariant natural killer T cells in a rheumatoid arthritis model and application to disease treatment

    PubMed Central

    Miellot-Gafsou, Aurore; Biton, Jérôme; Bourgeois, Elvire; Herbelin, André; Boissier, Marie-Christophe; Bessis, Natacha

    2010-01-01

    Invariant NKT (iNKT) cells are a distinctive subtype of CD1d-restricted T cells involved in regulating autoimmunity and capable of producing various T helper type 1 (Th1), Th2 and Th17 cytokines. Activation of iNKT cells by their exogenous ligand ?-galactosylceramide (?-GalCer) exerts therapeutic effects in autoimmune diseases such as rheumatoid arthritis (RA). However, the pathophysiological role of iNKT cells in RA, in the absence of exogenous stimulation, is incompletely understood. We investigated the potential pathophysiological effects of iNKT cells in mice with collagen-induced arthritis (CIA), a model of RA. We found that iNKT cells underwent activation only in the early phases of the disease (6 days post-induction). In the liver, but not the spleen or lymph nodes, this early activation led to the release of interleukins -4, -17A and -10 and of interferon-?; and an increased CD69 expression. Importantly, clinical and histological signs of arthritis were improved by the functional blockade of iNKT cells by a monoclonal antibody to CD1d at the early phase of the disease. This improvement was associated on day 6 post-induction with decreased expression of co-stimulatory molecules (CD80, CD86, CD40) on splenic dendritic cells and macrophages, whereas regulatory T-cell suppressive effects and proportions were not modified. Taken in concert, these findings suggest that iNKT cells are activated early in the course of CIA and contribute to the pathogenesis of arthritis. Therefore, iNKT-cell activation may be a valid treatment target in RA. PMID:20113367

  5. Circadian Relationships between Interleukin (IL)-6 and Hypothalamic-Pituitary-Adrenal Axis Hormones: Failure of IL6 to Cause Sustained Hypercortisolism in Patients with Early Untreated Rheumatoid Arthritis

    Microsoft Academic Search

    LESLIE J. CROFFORD; KONSTANTINE T. KALOGERAS; GEORGE MASTORAKOS; MARIA-ALEXANDRA MAGIAKOU; JANA WELLS; KEITH S. KANIK; PHILIP W. GOLD; GEORGE P. CHROUSOS; RONALD L. WILDER

    Systemic symptoms in rheumatoid arthritis (RA) are mediated, at least in part, by elevated levels of circulating interleukin (IL)-6, and this cytokine is also a potent stimulus of the hypothalamic-pituitary- adrenal axis. To evaluate the 24-h circadian secretory dynamics of ACTH, cortisol, and IL-6 and their interactions in patients with early untreated RA, we recruited and studied five newly diagnosed,

  6. Variability in depression prevalence in early rheumatoid arthritis: a comparison of the CES-D and HAD-D Scales

    PubMed Central

    Covic, Tanya; Pallant, Julie F; Tennant, Alan; Cox, Sally; Emery, Paul; Conaghan, Philip G

    2009-01-01

    Background Depression is common in rheumatoid arthritis (RA), however reported prevalence varies considerably. Two frequently used instruments to identify depression are the Center for Epidemiological Studies Depression (CES-D) scale, and the Hospital Anxiety and Depression Scale (HADS). The objectives of this study were to test if the CES-D and HADS-D (a) satisfy current modern psychometric standards for unidimensional measurement in an early RA sample; (b) measure the same construct (i.e. depression); and (c) identify similar levels of depression. Methods Data from the two scales completed by patients with early RA were fitted to the Rasch measurement model to show that (a) each scale satisfies the criteria of fit to the model, including strict unidimensionality; (b) that the scales can be co-calibrated onto a single underlying continuum of depression and to (c) examine the location of the cut points on the underlying continuum as indication of the prevalence of depression. Results Ninety-two patients with early RA (62% female; mean age = 56.3, SD = 13.7) gave 141 sets of paired CES-D and HAD-D data. Fit of the data from the CES-D was found to be poor, and the scale had to be reduced to 13 items to satisfy Rasch measurement criteria whereas the HADS-D met model expectations from the outset. The 20 items combined (CES-D13 and HADS-D) satisfied Rasch model expectations. The CES-D gave a much higher prevalence of depression than the HADS-D. Conclusion The CES-D in its present form is unsuitable for use in patients with early RA, and needs to be reduced to a 13-item scale. The HADS-D is valid for early RA and the two scales measure the same underlying construct but their cut points lead to different estimates of the level of depression. Revised cut points on the CES-D13 provide comparative prevalence rates. PMID:19200388

  7. High variability in glucocorticoid starting doses in patients with rheumatoid arthritis: observational data from an early arthritis cohort.

    PubMed

    Albrecht, Katinka; Callhoff, Johanna; Schneider, Matthias; Zink, Angela

    2015-08-01

    To evaluate initial glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA). Six hundred sixty-nine patients with early RA were followed for 2 years in the multicenter "Course And Prognosis of Early Arthritis" cohort. Treatment was applied according to routine care. Assessments included disease activity (DAS28), disability Hannover Functional Status Questionnaire (FFbH), and treatment details. Mixed models, ANCOVA, and logistic regression models were used for statistical analysis. In total, 518 patients (77 %) received oral GCs at baseline; 20 % received a low dose (<7.5 mg prednisolone/day), 22 % received a moderate (7.5-19 mg), and 35 % received a high dose (?20 mg). In a multivariate logistic regression analysis, higher DAS28 values (OR 1.3) were associated with the use of higher GC doses at baseline (p < 0.001). After adjusting for age, sex, and baseline DAS28 and DMARDs, the patients who started with high-dose GCs had a greater improvement in DAS28 (month 3) and FFbH (month 6, p < 0.001 each). At 2 years, the mean DAS28 remission rates and FFbH values were similar. In all GC groups, the mean dose was tapered to 4 mg/day within 6 months. The reported comorbidities were not increased in patients with high-dose GC therapy. Starting treatment with high-dose GCs led to a better clinical response within 3 to 6 months compared to starting patients on lower dosages. Irrespective of the starting approach, rheumatologists tapered GCs down to a low dose within 6 months. With this strategy, clinical outcomes at 2 years did not differ relevantly. PMID:25663291

  8. Multiparameter Phospho-Flow Analysis of Lymphocytes in Early Rheumatoid Arthritis: Implications for Diagnosis and Monitoring Drug Therapy

    PubMed Central

    Galligan, Carole L.; Siebert, Janet C.; Siminovitch, Katherine A.; Keystone, Edward C.; Bykerk, Vivian; Perez, Omar D.; Fish, Eleanor N.

    2009-01-01

    Background The precise mechanisms involved in the initiation and progression of rheumatoid arthritis (RA) are not known. Early stages of RA often have non-specific symptoms, delaying diagnosis and therapy. Additionally, there are currently no established means to predict clinical responsiveness to therapy. Immune cell activation is a critical component therefore we examined the cellular activation of peripheral blood mononuclear cells (PBMCs) in the early stages of RA, in order to develop a novel diagnostic modality. Methods and Findings PBMCs were isolated from individuals diagnosed with early RA (ERA) (n?=?38), longstanding RA (n?=?10), osteoarthritis (OA) (n?=?19) and from healthy individuals (n?=?10). PBMCs were examined for activation of 15 signaling effectors, using phosphorylation status as a measure of activation in immunophenotyped cells, by flow cytometry (phospho-flow). CD3+CD4+, CD3+CD8+ and CD20+ cells isolated from patients with ERA, RA and OA exhibited activation of multiple phospho-epitopes. ERA patient PBMCs showed a bias towards phosphorylation-activation in the CD4+ and CD20+ compartments compared to OA PBMCs, where phospho-activation was primarily observed in CD8+ cells. The ratio of phospho (p)-AKT/p-p38 was significantly elevated in patients with ERA and may have diagnostic potential. The mean fluorescent intensity (MFI) levels for p-AKT and p-H3 in CD4+, CD8+ and CD20+ T cells correlated directly with physician global assessment scores (MDGA) and DAS (disease activity score). Stratification by medications revealed that patients receiving leflunomide, systemic steroids or anti-TNF therapy had significant reductions in phospho-specific activation compared with patients not receiving these therapies. Correlative trends between medication-associated reductions in the levels of phosphorylation of specific signaling effectors and lower disease activity were observed. Conclusions Phospho-flow analysis identified phosphorylation-activation of specific signaling effectors in the PB from patients with ERA. Notably, phosphorylation of these signaling effectors did not distinguish ERA from late RA, suggesting that the activation status of discrete cell populations is already established early in disease. However, when the ratio of MFI values for p-AKT and p-p38 is >1.5, there is a high likelihood of having a diagnosis of RA. Our results suggest that longitudinal sampling of patients undergoing therapy may result in phospho-signatures that are predictive of drug responsiveness. PMID:19693272

  9. The clinical effectiveness of static resting splints in early rheumatoid arthritis: a randomized controlled trial

    Microsoft Academic Search

    J. Adams; J. Burridge; M. Mullee; A. Hammond; C. Cooper

    2008-01-01

    Objective. To evaluate the effectiveness of static resting splints in early RA. Methods. A multicentre, randomized, trial was conducted. Patients (n ¼ 120) received either static resting splints (positioned with the wrist in neutral, MCP joint (MCPJ) and IP joint (IPJ) in a maximum of 608 and 308 of flexion, respectively) plus standardized occupational therapy or standardized occupational therapy alone.

  10. Circulating surfactant protein -D is low and correlates negatively with systemic inflammation in early, untreated rheumatoid arthritis

    PubMed Central

    2010-01-01

    Introduction Surfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA. Methods One-hundred-and-sixty disease-modifying antirheumatic drug (DMARD) naïve RA patients with disease duration less than six months were studied prospectively for four years (CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) trial) including disease activity measures (C-reactive protein, joint counts and Health Assessment Questionnaire (HAQ) score), autoantibodies, x-ray findings and SP-D. SP-D was quantified by enzyme-linked immunosorbent assay (ELISA) and molecular size distribution was assessed by gel filtration chromatography. Further, SP-D Met11Thr single nucleotide polymorphism (SNP) analysis was performed. Results Serum SP-D was significantly lower in RA patients at baseline compared with healthy controls (P < 0.001). SP-D increased slightly during follow-up (P < 0.001), but was still subnormal at four years after adjustment for confounders (P < 0.001). SP-D in synovial fluid was up to 2.5-fold lower than in serum. While multimeric variants were detected in serum, SP-D in synovial fluid comprised trimeric subunits only. There were no significant associations between genotype distribution and SP-D. Baseline SP-D was inversely associated to CRP and HAQ score. A similar relationship was observed regarding temporal changes in SP-D and CRP (zero to four years). SP-D was not associated to x-ray findings. Conclusions This study confirms that circulating SP-D is persistently subnormal in early and untreated RA despite a favourable therapeutic response obtained during four years of follow-up. SP-D correlated negatively to disease activity measures, but was not correlated with x-ray progression or SP-D genotype. These observations suggest that SP-D is implicated in RA pathogenesis at the protein level. The exclusive presence of trimeric SP-D in affected joints may contribute to the maintenance of joint inflammation. Trial registration (j.nr NCT00209859). PMID:20211020

  11. Cervical Myelopathy in Rheumatoid Arthritis

    PubMed Central

    Mukerji, N.; Todd, N. V.

    2011-01-01

    Involvement of the cervical spine is common in rheumatoid arthritis. Clinical presentation can be variable, and symptoms may be due to neck pain or compressive myeloradiculopathy. We discuss the pathology, grading systems, clinical presentation, indications for surgery and surgical management of cervical myelopathy related to rheumatoid arthritis in this paper. We describe our surgical technique and results. We recommend early consultation for surgical management when involvement of the cervical spine is suspected in rheumatoid arthritis. Even patients with advanced cervical myelopathy should be discussed for surgical treatment, since in our experience improvement in function after surgery is common. PMID:22203899

  12. Cost-effectiveness of infliximab versus conventional combination treatment in methotrexate-refractory early rheumatoid arthritis: 2-year results of the register-enriched randomised controlled SWEFOT trial

    PubMed Central

    Eriksson, Jonas K; Karlsson, Johan A; Bratt, Johan; Petersson, Ingemar F; van Vollenhoven, Ronald F; Ernestam, Sofia; Geborek, Pierre; Neovius, Martin

    2015-01-01

    Objective To estimate the incremental cost-effectiveness of infliximab versus conventional combination treatment over 21?months in patients with methotrexate-refractory early rheumatoid arthritis. Methods In this multicentre, two-arm, parallel, randomised, active-controlled, open-label trial, rheumatoid arthritis patients with <1?year symptom duration were recruited from 15 rheumatology clinics in Sweden between October 2002 and December 2005. After 3–4?months of methotrexate monotherapy, patients not achieving low disease activity were randomised to addition of infliximab or sulfasalazine+hydroxychloroquine (conventional treatment group). Costs of drugs, healthcare use, and productivity losses were retrieved from nationwide registers, while EuroQol 5-Dimensions utility was collected quarterly. Results Of 487 patients initially enrolled, 128 and 130 were randomised to infliximab and conventional treatment, respectively. The infliximab group accumulated higher drug and healthcare costs (€27?487 vs €10?364; adjusted mean difference €16?956 (95% CI 14?647 to 19?162)), while productivity losses did not differ (€33?804 vs €29?220; €3961 (95% CI ?3986 to 11?850)), resulting in higher societal cost compared to the conventional group (€61?291 vs €39?584; €20?916 (95% CI 12?800 to 28?660)). Mean accumulated quality-adjusted life-years (QALYs) did not differ (1.10 vs 1.12; adjusted mean difference favouring infliximab treatment 0.01 (95% CI ?0.07 to 0.08)). The incremental cost-effectiveness ratios for the infliximab versus conventional treatment strategy were €2?404?197/QALY from the societal perspective and €1?948?919/QALY from the healthcare perspective. Conclusions In early, methotrexate-refractory rheumatoid arthritis, a treatment strategy commencing with addition of infliximab, as compared to sulfasalazine+hydroxychloroquine, was not cost-effective over 21?months at willingness to pay levels generally considered acceptable. Trial registration number: NCT00764725. PMID:24737786

  13. COBRA combination therapy in patients with early rheumatoid arthritis: Long-term structural benefits of a brief intervention

    Microsoft Academic Search

    Maarten Boers; Arco C. Verhoeven; Rene Westhovens; Mart A. F. J. van de Laar; Harry M. Markusse; J. Christiaan van Denderen; Marie Louise Westedt; Andre J. Peeters; Ben A. C. Dijkmans; Piet Jacobs; Annelies Boonen; Sjef van der Linden

    2002-01-01

    Objective. The Combinatietherapie Bij Reuma- toide Artritis (COBRA) trial demonstrated that step- down combination therapy with prednisolone, metho- trexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radio- logic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which

  14. Causal Modeling Using Network Ensemble Simulations of Genetic and Gene Expression Data Predicts Genes Involved in Rheumatoid Arthritis

    Microsoft Academic Search

    Heming Xing; Paul D. McDonagh; Jadwiga Bienkowska; Tanya Cashorali; Karl Runge; Robert E. Miller; Dave Decaprio; Bruce Church; Ronenn Roubenoff; Iya G. Khalil; John Carulli; Edmund J. Crampin

    2011-01-01

    Tumor necrosis factor ? (TNF-?) is a key regulator of inflammation and rheumatoid arthritis (RA). TNF-? blocker therapies can be very effective for a substantial number of patients, but fail to work in one third of patients who show no or minimal response. It is therefore necessary to discover new molecular intervention points involved in TNF-? blocker treatment of rheumatoid

  15. Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals a high prevalence of erosions at four months after symptom onset

    PubMed Central

    McQueen, F.; Stewart, N.; Crabbe, J.; Robinson, E.; Yeoman, S.; Tan, P.; McLean, L.

    1998-01-01

    OBJECTIVES—To evaluate the role of magnetic resonance imaging (MRI) of the wrist in detecting early joint damage in patients with rheumatoid arthritis (RA).?METHODS—MRI was performed on 42 patients with early RA (median symptom duration of four months). Scans were scored separately by two musculoskeletal radiologists using a newly devised scoring system, which was validated. MRI findings were compared with plain radiography, clinical measures, and HLA-DRB*01/04 genotyping.?RESULTS—Interobserver reliability for the overall MRI score was high (r = 0.81) as was intraobserver reliability (r = 0.94 for observer 1 and 0.81 for observer 2). There was more variation in scoring synovitis (interobserver reliability: r = 0.74). Erosions were detected in 45% of scans (19 of 42), compared with 15% of plain radiographs. The most common site for erosions was the capitate (39%), for synovitis the ulnar aspect of the radiocarpal joint, and for tendonitis, the extensor carpi ulnaris tendon. The total MRI score and MRI synovitis score correlated most significantly with C reactive protein (r = 0.40 and 0.42 respectively, p<0.01). The MRI erosion score was highly correlated with MRI bone marrow oedema (r = 0.83) as well as the Ritchie score and disease activity score (r = 0.32, p<0.05). HLA-DRB1*04 or *01 (shared epitope +ve) was found in 76% of patients; 84% of those with MRI erosions and 69% of those without (NS, p = 0.3).?CONCLUSIONS—A high proportion of RA patients develop MRI erosions very early in their disease, when plain radiography is frequently normal. MRI of the dominant wrist may identify those requiring early aggressive treatment.?? Keywords: magnetic resonance imaging; carpus; rheumatoid arthritis PMID:9771209

  16. A rare association of early-onset inclusion body myositis, rheumatoid arthritis and autoimmune thyroiditis: a case report and literature review

    PubMed Central

    Clerici, Angelo Maurizio; Bono, Giorgio; Delodovici, Maria Luisa; Azan, Gaetano; Cafasso, Giuseppina; Micieli, Giuseppe

    2013-01-01

    Summary Sporadic inclusion body myositis (sIBM) is a slowly progressive, red-rimmed vacuolar myopathy leading to muscular atrophy and progressive weakness; it predominantly affects males older than fifty years, and is resistant to immunotherapy. It has been described in association with immuno-mediated thrombocytopenic purpura, multiple sclerosis, connective tissue disorders and, occasionally, rheumatoid arthritis. A 37-year-old man with longstanding rheumatoid arthritis and autoimmune thyroiditis with hypothyroidism was referred to us with slowly progressive, diffuse muscle weakness and wasting, which had initially involved the volar finger flexors, and subsequently also the ankle dorsiflexors and knee extensors. Needle electromyography showed typical myopathic motor unit potentials, fibrillation and positive sharp waves with normal nerve conduction studies. Quadriceps muscle biopsy was suggestive of sIBM. Considering data published in the literature, this case may be classified as an early-onset form. The patient was treated with long-term intravenous immunoglobulin and obtained a substantial stabilization of his muscle strength. PMID:24125563

  17. Clinical and radiological dissociation of anti-TNF plus methotrexate treatment in early rheumatoid arthritis in routine care: Results from the ABRAB study

    PubMed Central

    2014-01-01

    Background Rheumatoid arthritis (RA) is a chronic autoinflammatory joint disease which leads to the destruction of joints and disability of the patients. Anti-tumour necrosis factor (anti-TNF) drugs can halt radiological progression better than conventional DMARDs even in clinical non-responders. Methods The efficacy of anti-TNF plus methotrexate (MTX) treatment versus MTX monotherapy on clinical and radiological outcomes were compared in early rheumatoid arthritis (RA) patients in clinical practice by retrospective analysis of an observational cohort. 49 early RA patients (group A) on first-line MTX monotherapy and 35 early RA patients (group B) on anti-TNF plus MTX treatment were selected from an observational cohort and evaluated retrospectively focusing on their first twelve months of treatment. Data on disease activity (DAS28) and functional status (HAQ-DI) were collected three monthly. One-yearly radiological progression was calculated according to the van der Heijde modified Sharp method (vdHS). Clinical non-responder patients in both groups were selectively investigated from a radiological point of view. Results Disease activity was decreased and functional status was improved significantly in both groups. One-yearly radiological progression was significantly lower in group B than in group A. The percentage of patients showing radiological non-progression or rapid radiological progression demonstrated a significant advantage for group B patients. In addition non-responder patients in group B showed similar radiological results as responders, while a similar phenomenon was not observed in patients in group A. Conclusions Clinical efficacy within our study was similar for tight-controlled MTX monotherapy as well as for combination treatment with anti-TNF and MTX. However MTX monotherapy was accompanied by more rapid radiological progression and less radiological non-progression. Anti-TNF plus MTX decreased radiological progression even in clinical non-responders supporting the advantage of anti-TNF plus MTX combination in dissociating clinical and radiological effects. PMID:25059769

  18. Validating IC early-failure simulation

    NASA Astrophysics Data System (ADS)

    Moosa, Mohamod S.; Poole, Kelvin F.; Grams, Michael L.

    1995-09-01

    Early failures are the dominant concern as integrated circuit technology matures into consistently producing systems of high reliability. These failures are attributed to the presence of randomly occurring defects in elementary objects (contacts, vias, metal runs, gate oxides, bonds etc.) that result in extrinsic rather than intrinsic (wearout-related) mortality. A model relating system failure to failure at the elementary objective level has been developed. Reliability is modeled as a function of circuit architecture, mask layout, material properties, life-test data, worst-case use-conditions and the processing environment. The effects of competing failure mechanisms and the presence of redundant sub-systems are accounted for. Hierarchy is exploited in the analysis, allowing large scale designs to be simulated. Experimental validation of the modeling of oxide leakage related failure, based on correlation between actual failures reported for a production integrated circuit and Monte Carlo simulations that incorporate wafer-level test results and process defect monitor data, is presented. The state of the art in IC reliability simulation is advanced in that a methodology that provides the capability to design-in reliability while accounting for early failures has been developed; applications include process qualification, design assessment and fabrication monitoring.

  19. ACPA fine-specificity profiles in early rheumatoid arthritis patients do not correlate with clinical features at baseline or with disease progression

    PubMed Central

    2013-01-01

    Introduction Autoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA). The RA-specific ACPA are frequently present prior to disease onset and their presence associates with a more erosive disease course. ACPA can therefore be used to aid the diagnosis and prognosis of RA. Recently, it became clear that ACPA are very heterogeneous, both in an individual patient and among different patients. The aim of this study was to investigate whether clinically meaningful ACPA profiles exist in early RA patients. Methods Twenty citrullinated peptides and the corresponding non-citrullinated control peptides were immobilized on microarray sensor chips. Sera from 374 early arthritis patients were analyzed by surface plasmon resonance imaging (iSPR) of biomolecular interactions on the sensor chip. Results Cluster analysis of the reactivities with the citrullinated peptides, after subtraction of the reactivities with the corresponding control peptides confirmed the heterogeneity of the ACPA response in RA and revealed 12 distinct ACPA profiles. The association of the 5 most frequent profiles with clinical features at diagnosis and during the disease course was examined, showing no statistically significant associations. Conclusions Compared to the detection of ACPA in RA sera by CCP-based assays, ACPA profiling in early arthritis patients did not reveal associations with disease activity and progression scores. PMID:24286543

  20. Early Metacarpal Bone Mineral Density Loss Using Digital X-Ray Radiogrammetry and 3-Tesla Wrist MRI in Established Rheumatoid Arthritis: A Longitudinal One-Year Observational Study

    PubMed Central

    Algulin, Jakob; Mangat, Pamela; Lim, Adrian K. P.; Satchithananda, Keshthra; Hajnal, Joseph V.; Taylor, Peter C.

    2015-01-01

    Objectives. Early change in rheumatoid arthritis (RA) is characterised by periarticular osteopenia. We investigated the relationship of early metacarpal digital X-ray radiogrammetry bone mineral density (DXR-BMD) change rate (RC-BMD, mg/cm2/month) to longitudinal changes in hand and feet radiographic and wrist MRI scores over 1 year. Materials and Methods. 10 RA patients completed the study and had wrist 3T-MRI and hand and feet X-rays at various time points over 1 year. MRI was scored by RAMRIS, X-ray was done by van der Heijde modified Sharp scoring, and RC-BMD was analysed using dxr-online. Results. There was good correlation amongst the two scorers for MRI measures and ICC for erosions: 0.984, BME: 0.943, and synovitis: 0.657. Strong relationships were observed between RC-BMD at 12-week and 1-year change in wrist marrow oedema (BME) (r = 0.78, P = 0.035) but not with erosion, synovitis, or radiographic scores. Conclusion. Early RC-BMD correlates with 1-year wrist BME change, which is a known predictor of future erosion and joint damage. However, in our pilot study, early RC-BMD did not show relationships to MRI erosion or radiographic changes over 1 year. This may reflect a slower kinetic in the appearance of MRI/radiographic erosions, generating the hypothesis that RC-BMD may be a more sensitive and early structural prognostic marker in RA follow-up. PMID:25785197

  1. Maintenance of remission following 2?years of standard treatment then dose reduction with abatacept in patients with early rheumatoid arthritis and poor prognosis

    PubMed Central

    Westhovens, Rene; Robles, Manuel; Ximenes, Antonio Carlos; Wollenhaupt, Jurgen; Durez, Patrick; Gomez-Reino, Juan; Grassi, Walter; Haraoui, Boulos; Shergy, William; Park, Sung-Hwan; Genant, Harry; Peterfy, Charles; Becker, Jean-Claude; Murthy, Bindu

    2015-01-01

    Objectives To evaluate maintenance of response while reducing intravenous abatacept dose from ?10?mg/kg to ?5?mg/kg in patients with early rheumatoid arthritis (RA) who achieved disease activity score (DAS)28 (erythrocyte sedimentation rate, ESR) <2.6. Methods This 1-year, multinational, randomised, double-blind substudy evaluated the efficacy and safety of ?10?mg/kg and ?5?mg/kg abatacept in patients with early RA with poor prognosis who had reached DAS28 (ESR) <2.6 at year 2 of the AGREE study. The primary outcome was time to disease relapse (defined as additional disease-modifying antirheumatic drugs, ?2 courses high-dose steroids, return to open-label abatacept ?10?mg/kg, or DAS28 (C reactive protein) ?3.2 at two consecutive visits). Results 108 patients were randomised (?10?mg/kg, n=58; ?5?mg/kg, n=50). Three and five patients, respectively, discontinued, and four per group returned to open-label abatacept. Relapse over time and the proportion of patients relapsing were similar in both groups (31% (?10?mg/kg) vs 34% (?5?mg/kg); HR: 0.87 (95% CI 0.45 to 1.69)). Mean steady-state trough serum concentration for the ?10?mg/kg group was 20.3–24.1?µg/mL, compared with 8.8–12.0?µg/mL for the ?5?mg/kg group. Conclusions This exploratory study suggests that abatacept dose reduction may be an option in patients with poor prognosis early RA who achieve DAS28 (ESR) <2.6 after ?1?year on abatacept (?10?mg/kg). Trial registration number NCT00989235. PMID:25550337

  2. My Treatment Approach to Rheumatoid Arthritis

    PubMed Central

    Davis, John M.; Matteson, Eric L.

    2012-01-01

    The past decade has brought important advances in the understanding of rheumatoid arthritis and its management and treatment. New classification criteria for rheumatoid arthritis, better definitions of treatment outcome and remission, and the introduction of biologic response-modifying drugs designed to inhibit the inflammatory process have greatly altered the approach to managing this disease. More aggressive management of rheumatoid arthritis early after diagnosis and throughout the course of the disease has resulted in improvement in patient functioning and quality of life, reduction in comorbid conditions, and enhanced survival. PMID:22766086

  3. Identification of Urinary Peptide Biomarkers Associated with Rheumatoid Arthritis

    PubMed Central

    McInnes, Iain B.; Husi, Holger; Klein, Julie; Dakna, Mohammed; Mullen, William; Mischak, Harald

    2014-01-01

    Early diagnosis and treatment of rheumatoid arthritis are associated with improved outcomes but current diagnostic tools such as rheumatoid factor or anti-citrullinated protein antibodies have shown limited sensitivity. In this pilot study we set out to establish a panel of urinary biomarkers associated with rheumatoid arthritis using capillary electrophoresis coupled to mass spectrometry. We compared the urinary proteome of 33 participants of the Scottish Early Rheumatoid Arthritis inception cohort study with 30 healthy controls and identified 292 potential rheumatoid arthritis-specific peptides. Amongst them, 39 were used to create a classifier model using support vector machine algorithms. Specific peptidic fragments were differentially excreted between groups; fragments of protein S100-A9 and gelsolin were less abundant in rheumatoid arthritis while fragments of uromodulin, complement C3 and fibrinogen were all increasingly excreted. The model generated was subsequently tested in an independent test-set of 31 samples. The classifier demonstrated a sensitivity of 88% and a specificity of 93% in diagnosing the condition, with an area under the receiver operating characteristic curve of 0.93 (p<0.0001). These preliminary results suggest that urinary biomarkers could be useful in the early diagnosis of rheumatoid arthritis. Further studies are currently being undertaken in larger cohorts of patients with rheumatoid arthritis and other athridities to assess the potential of the urinary peptide based classifier in the early detection of rheumatoid arthritis. PMID:25144639

  4. Hand bone loss in early undifferentiated arthritis: evaluating bone mineral density loss before the development of rheumatoid arthritis

    Microsoft Academic Search

    G Haugeberg; M J Green; M A Quinn; H Marzo-Ortega; S Proudman; Z Karim; R J Wakefield; P G Conaghan; S Stewart; P Emery

    2006-01-01

    Objectives: (1) To examine the change in regional bone mineral density (BMD), including the hands, and assess its role as a predictor of outcome in patients presenting with an early undifferentiated inflammatory arthritis; (2) to examine for associations with the changes in hand BMD.Methods: 74 patients with undifferentiated hand arthritis of less than 12 months’ duration were examined at baseline

  5. Evaluating drug-free remission with abatacept in early rheumatoid arthritis: results from the phase 3b, multicentre, randomised, active-controlled AVERT study of 24?months, with a 12-month, double-blind treatment period

    PubMed Central

    Emery, Paul; Burmester, Gerd R; Bykerk, Vivian P; Combe, Bernard G; Furst, Daniel E; Barré, Emilie; Karyekar, Chetan S; Wong, Dennis A; Huizinga, Tom W J

    2015-01-01

    Objectives To evaluate clinical remission with subcutaneous abatacept plus methotrexate (MTX) and abatacept monotherapy at 12?months in patients with early rheumatoid arthritis (RA), and maintenance of remission following the rapid withdrawal of all RA treatment. Methods In the Assessing Very Early Rheumatoid arthritis Treatment phase 3b trial, patients with early active RA were randomised to double-blind, weekly, subcutaneous abatacept 125?mg plus MTX, abatacept 125?mg monotherapy, or MTX for 12?months. Patients with low disease activity (Disease Activity Score (DAS)28 (C reactive protein (CRP)) <3.2) at month 12 entered a 12-month period of withdrawal of all RA therapy. The coprimary endpoints were the proportion of patients with DAS28 (CRP) <2.6 at month 12 and both months 12 and 18, for abatacept plus MTX versus MTX. Results Patients had <2?years of RA symptoms, DAS28 (CRP) ?3.2, anticitrullinated peptide-2 antibody positivity and 95.2% were rheumatoid factor positive. For abatacept plus MTX versus MTX, DAS28 (CRP) <2.6 was achieved in 60.9% versus 45.2% (p=0.010) at 12?months, and following treatment withdrawal, in 14.8% versus 7.8% (p=0.045) at both 12 and 18?months. DAS28 (CRP) <2.6 was achieved for abatacept monotherapy in 42.5% (month 12) and 12.4% (both months 12 and 18). Both abatacept arms had a safety profile comparable with MTX alone. Conclusions Abatacept plus MTX demonstrated robust efficacy compared with MTX alone in early RA, with a good safety profile. The achievement of sustained remission following withdrawal of all RA therapy suggests an effect of abatacept's mechanism on autoimmune processes. Trial registration number NCT01142726. PMID:25367713

  6. Influence of gender on assessments of disease activity and function in early rheumatoid arthritis in relation to radiographic joint damage

    Microsoft Academic Search

    M Ahlmén; B Svensson; K Albertsson; K Forslind; I Hafström

    2010-01-01

    Objective:To evaluate gender differences in score on 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) and Signals Of Functional Impairment (SOFI) and to relate these scores to radiographic joint destruction.Methods:In all, 549 patients with early RA (62% women) from the BARFOT (for “Better Anti-Rheumatic FarmacOTherapy”) study were included. At baseline, 1, 2 and 5 years DAS28, HAQ and SOFI

  7. The rheumatoid forefoot.

    PubMed

    Brooks, Francis; Hariharan, Kartik

    2013-12-01

    Rheumatoid arthritis (RA) manifests itself in a variety of ways, with its effect being seen in around 90 % of sufferers' feet. The foot has been found to be the most common reason for incapacity in patients with RA, with the forefoot the most common area. The foot is second, behind only the hand, as the most common place for manifestation of RA. Pain in the foot is commonly the most debilitating condition, which causes the patient to seek specialist help. As well as pain, foot deformities such as hallux valgus and claw toes are common complaints. These symptoms often arise as a result of continued walking on an unstable foot, leading to painful callosities and dislocation of the metatarsophalangeal joints. Other conditions, such as pannus formation and Morton's neuroma, can be related to RA. This review sets out what we believe to be a successful approach to the rheumatoid forefoot, which aims at the relief of pain and the preservation of ambulation. Key to a successful outcome is appropriate medical control with a multidisciplinary approach that enables close liaison between orthopaedic surgeons, orthotists, and rheumatologists. Combined clinics provide this multidisciplinary care. Those treating RA need to be aware of the high incidence of foot involvement and how early intervention may benefit the patient. The aim of this article is to present current evidence to enable people to develop a treatment algorithm for this condition. PMID:23943297

  8. Which patients stop working because of rheumatoid arthritis? Results of five years' follow up in 732 patients from the Early RA Study (ERAS)

    PubMed Central

    Young, A; Dixey, J; Kulinskaya, E; Cox, N; Davies, P; Devlin, J; Emery, P; Gough, A; James, D; Prouse, P; Williams, P; Winfield, J

    2002-01-01

    Objectives: To assess the occurrence and prognostic factors for the ability to maintain paid work in patients with rheumatoid arthritis (RA). Setting: Inception cohort of patients with RA recruited from rheumatology departments in nine NHS Hospital Trusts in England. Patients: All consecutive patients with RA of less than two years' duration, before any second line (disease modifying) drug treatment, and followed up for five years. Methods: Clinical, laboratory, and radiological assessments, and all treatments were recorded prospectively using a standardised format at presentation and yearly. Outcome measures: Changes in, and loss of paid work by five years' follow up. Results: 732 patients completed the five year follow up. 353/721 (49%) were gainfully employed at the onset of RA, 211 (60%) were still working at five years, 104 (29%) stopped because of the disease, and 31 (9%) retired for reasons other than RA. Work disability at five years was more likely in manual workers (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.4 to 3.8) and worse baseline Health Assessment Questionnaire (HAQ>1.5, OR 2.26, 95% CI 1.38 to 3.7). In combination with other baseline variables (erythrocyte sedimentation rate, sex, age of onset, and radiological erosions), employment outcome was predicted in 78% using multivariate analysis. Conclusions: Nearly half of the patients with RA were in paid employment at onset, work disability was an adverse outcome for a third of these patients by five years, and manual work and high baseline HAQ were important predictors for this. These details are likely to be useful to clinicians, health professionals, and patients in order to plan medical, orthopaedic, and remedial treatments in early RA. Future disease modifying treatments could be compared with this cohort of patients who were treated with conventional second line drugs. PMID:11874837

  9. Simulation models of early visual processes

    NASA Technical Reports Server (NTRS)

    Ahumada, Albert J., Jr.; Watson, Andrew B.

    1988-01-01

    Several areas of early visual processes are studied using computer models. These models include retinal cone placement, cone color arrangement, development of geniculate receptive fields, cortical simple cells, and motion field extraction. The receptive field of a model cortical unit is indicated schematically.

  10. Validating IC early-failure simulation

    Microsoft Academic Search

    Mohamed S. Moosa; Kelvin F. Poole; Michael L. Grams

    1995-01-01

    Early failures are the dominant concern as integrated circuit technology matures into consistently producing systems of high reliability. These failures are attributed to the presence of randomly occurring defects in elementary objects (contacts, vias, metal runs, gate oxides, bonds etc.) that result in extrinsic rather than intrinsic (wearout-related) mortality. A model relating system failure to failure at the elementary objective

  11. How citrullination invaded rheumatoid arthritis research

    PubMed Central

    2014-01-01

    Citrullination and the immune response to citrullinated proteins have been fundamental for the early recognition of rheumatoid arthritis by serological tests and a better understanding of its pathophysiology. In the first years after the initial publications, the focus was on the antibodies directed to citrullinated proteins. It is now realized that citrullinating enzymes and citrullinated proteins may have important roles in the maintenance of the inflammatory processes in the joints. There is also accumulating evidence for a direct role of citrullination in tissue destruction in the rheumatoid synovium. Here we will discuss the development and importance of anti-citrullinated protein antibodies in rheumatoid arthritis as well as recent findings implicating citrullination in the pathophysiology of rheumatoid arthritis. PMID:24472574

  12. Early development of Xenopus embryos is affected by simulated gravity

    NASA Technical Reports Server (NTRS)

    Yokota, Hiroki; Neff, Anton W.; Malacinski, George M.

    1994-01-01

    Early amphibian (Xenopus laevis) development under clinostat-simulated weightlessness and centrifuge-simulated hypergravity was studied. The results revealed significant effects on (i) 'morphological patterning' such as the cleavage furrow pattern in the vegetal hemisphere at the eight-cell stage and the shape of the dorsal lip in early gastrulae and (ii) 'the timing of embryonic events' such as the third cleavage furrow completion and the dorsal lip appearance. Substantial variations in sensitivity to simulated force fields were observed, which should be considered in interpreting spaceflight data.

  13. Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension

    PubMed Central

    Kvien, T; Zeidler, H; Hannonen, P; Wollheim, F; Forre, O; Hafstrom, I; Kaltwasser, J; Leirisalo-Repo, M; Manger, B; Laasonen, L; Prestele, H; Kurki, P

    2002-01-01

    Objective: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. Methods: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. Results: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. Conclusion: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients. PMID:12006323

  14. Insulin-like growth factor I receptor density on CD4+T-lymphocytes from active early steroid- and DMARD-naïve rheumatoid arthritis patients is up-regulated and not influenced by 1 year of clinically effective treatment.

    PubMed

    Laurberg, Trine Bay; Ellingsen, Torkell; Thorsen, Jonas; Møller, Bjarne Kuno; Hansen, Ib; Tarp, Ulrik; Hetland, Merete Lund; Hørslev-Petersen, Kim; Flyvbjerg, Allan; Frystyk, Jan; Stengaard-Pedersen, Kristian

    2012-02-01

    The IGF-IR density on CD4+T-lymphocytes was studied using flow cytometry in 40 early steroid- and DMARD-naïve rheumatoid arthritis (RA) patients before and after 52 weeks of treatment with methotrexate+placebo or methotrexate+cyclosporine A and in 15 controls. RA patients had increased IGF-IR density on CD4+T-lymphocytes at week 0 and week 52, irrespective of treatment. IGF-IR-positive CD4+T-lymphocytes fraction decreased during treatment, but neither at week 0 nor at week 52 did it differ from healthy controls. No correlations were found to disease activity parameters. PMID:21246373

  15. Quasars, the early universe, and plasma simulations

    SciTech Connect

    Ferland, Gary J.; Verner, Dmitri A. [Physics Department, University of Kentucky, Lexington, Kentucky 40506 (United States)

    1998-09-28

    Quasars are among the most luminous objects in the universe, and the most distant for which we can obtain good spectroscopy. These spectra carry with them information about the formation of the first large structures in the universe and the first generations of star formation in newly born galaxies. The spectrum of a quasar has strong broad emission lines, formed by a non-equilibrium low-density photoionized gas. This spectrum can best be interpreted by reference to large-scale simulations of the full environment. This in turn is strongly coupled to many basic plasma physics questions. Here we discuss the current status of quasar research, numerical plasma simulations, and the atomic database.

  16. Diagnosis and classification of rheumatoid arthritis.

    PubMed

    Kourilovitch, Maria; Galarza-Maldonado, Claudio; Ortiz-Prado, Esteban

    2014-01-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease of unclear etiology that is manifested in by a progressive and destructive polyarthritis in association with serological evidence of autoreactivity. Its diagnosis is based on the classification criteria that involve four parameters: joint involvement, serology (rheumatoid factor and anti-cyclic citrullinated peptide--anti-CCP), levels of acute phase reactants and the duration of the symptoms Aletaha, et al. [1]. This classification simplifies the categorization of the patients with early RA; however, the diagnosis requires highly trained specialists who are able to differentiate early symptoms of RA from other pathologies. PMID:24568777

  17. Frequency of Th17 CD4+ T Cells in Early Rheumatoid Arthritis: A Marker of Anti-CCP Seropositivity

    PubMed Central

    Arroyo-Villa, Irene; Bautista-Caro, María-Belén; Balsa, Alejandro; Aguado-Acín, Pilar; Nuño, Laura; Bonilla-Hernán, María-Gema; Puig-Kröger, Amaya; Martín-Mola, Emilio; Miranda-Carús, María-Eugenia

    2012-01-01

    Objective To examine the frequency and phenotype of Th17 cells in the peripheral blood of early RA (eRA) patients. Methods CD4+ T cells were isolated from the peripheral blood of 33 eRA patients, 20 established RA patients and 53 healthy controls (HC), and from the synovial fluid of 20 established RA patients (RASF), by ficoll-hypaque gradient and magnetical negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells was determined by flow cytometry and concentrations of IL-17, IFN-?, TNF-? and IL-10 were measured by ELISA in cell-free supernatants. Results When all of our eRA patients were analyzed together, a significantly lower percentage of circulating Th17 cells and a lower CD4-derived IL-17 secretion were observed in comparison with HC. However, after stratifying by anti-CCP antibody status, circulating Th17 cells were decreased in anti-CCP(+) but not in anti-CCP(-)-eRA. All Th17 cells were CD45RO+CD45RA- and CCR6+. Dual Th17/Th1 cells were also exclusively decreased in anti-CCP(+)-eRA. Circulating Th17 and Th17/Th1 cells were negatively correlated with anti-CCP titres. When anti-CCP(+)-eRA patients were retested one year after initiating treatment with oral methotrexate, their circulating Th17 frequency was no longer different from HC. Of note, the percentage of circulating Th1 cells and the secretion of CD4-derived IFN-?, TNF-? and IL-10 were not different between eRA patients and HC. In established RA patients, circulating Th17 and T17/Th1 cell frequencies were comparable to HC. In RASF, both Th17 and Th1 cells were increased when compared with blood of eRA patients, established RA patients and HC. Conclusion Decreased circulating Th17 levels in eRA seem to be a marker of anti-CCP seropositivity, and return to levels observed in healthy controls after treatment with methotrexate. PMID:22870298

  18. Assessment of the utility of visual feedback in the treatment of early rheumatoid arthritis patients: a pilot study.

    PubMed

    El Miedany, Y; El Gaafary, M; Palmer, D

    2012-10-01

    Earlier studies revealed that visual feedback has contributed in the management of neuromuscular as well as psychiatric disorders; however, it has not yet been applied in rheumatology. Visual feedback is a relatively new tool that enables the patient to visualize as well as monitor a real-time change of their disease activity parameters as well as the patient's reported outcome measures. Integrating electronic data recording in the standard rheumatology clinical practice made visual feedback possible. To evaluate the feasibility of using the visual feedback in patients with early inflammatory arthritis (EA) and how ubiquitous computing technology can improve the patients' compliance and adherence to therapy, this was a double-blind randomized controlled study, which included 111 patients diagnosed to have EA according to the new ACR/EULAR criteria. All patients received disease-modifying antirheumatic drugs (DMARDs) therapy and monitored regularly over the period of 1 year. By the 6th month of treatment, the patients were randomly allocated to an active group (55 patients) to whom the visual feedback (visualization of charts showing the progression of disease activity parameters) was added to their management protocol, and a control group (56 patients) who continued their standard management protocols. The patients were monitored for another 6-months period. All the patient's disease activity parameters, patient reported outcome measures (PROMs), medications, scores of falls, and cardiovascular risks were recorded electronically. Primary outcome was the change in the patients' adherence to their medications, disease activity score (DAS-28), and PROMs: pain score, patient global assessment, functional disability, and quality of life. Secondary outcome was the answers to a questionnaire completed by every patient in both the active group and control group (using Visual Analogue Scale) by the end of 1 year of management, to rate from the patient's perspective the impact of the management protocol, whether using the standard or visual feedback approach, on them and their disease. The visual feedback provided a significant greater reduction in disease activity parameters as well as improvement of the patients' adherence to antirheumatic therapy (P < 0.01). Also stopping the DMARDs therapy because of intolerance was significantly less in the active group. Concerns about the future was significantly less in the active group whereas inability to coup with daily life and disease stress were significantly more among the control group. The improvement of disease activity parameters was associated with improvement in functional disability and quality of life scores. Mean changes in disease parameters showed no significant differences at 3-6 months of therapy but differences were statistically significant at 12-months follow-up (P < 0.01). Medication compliance was significantly correlated with changes in all measured disease parameters. By recording and monitoring disease activity parameters electronically and incorporating the visual feedback approach into clinical practice, a new experience can be created. Visual feedback enabled the patients to see how they are doing regarding their disease activity and helps to optimize their adherence to their treatment. Visual feedback had a positive and significant impact on the disease activity control. PMID:21909946

  19. Early morphea simulating patch-stage mycosis fungoides.

    PubMed

    Fujimoto, Masakazu; Basko-Plluska, Juliana L; Petronic-Rosic, Vesna; Shea, Christopher R

    2015-05-01

    Morphea is a rare fibrosing condition of the skin and underlying tissues characterized histopathologically by thickened collagen bundles throughout the dermis, loss of adnexal structures, and "fat trapping." In the early stages of morphea, the absence of the fully developed characteristic findings may cause diagnostic confusion for the practicing pathologist. The authors report an unusual case of early morphea misdiagnosed as patch-stage poikilodermatous mycosis fungoides (MF) based on the initial clinical, histopathologic, and molecular findings. However, as time elapsed, well-developed lesions revealed clinical and histopathologic features diagnostic of morphea. The authors report this case to illustrate that lesions of early morphea may simulate MF. Given the similarities in clinicopathologic presentation, dermatologists and dermatopathologists should be cautious not to inadvertently misinterpret early morphea as MF. PMID:25768945

  20. Treatment of rheumatoid arthritis using photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hendrich, Christian; Diddens, Heyke C.; Nosir, Hany R.; Siebert, Werner E.

    1995-03-01

    The only early therapy of rheumatoid arthritis in orthopedic surgery is a synovectomy, which is restricted to more or less big joints. A laser-synovectomy of small joints is ineffective yet. An alternative method may be photodynamic therapy. In our study we describe the photodynamic effect of Photosan 3 in a cell culture study.

  1. Surgery of the rheumatoid elbow.

    PubMed Central

    Souter, W A

    1990-01-01

    I suggest that for too long the problem of the rheumatoid elbow, particularly the need for surgical intervention, has been underestimated. Where the latter has been advocated the philosophy has been adopted that synovectomy and debridement with excision of the head of the radius is probably all that is required, or that in the late case excision arthroplasty may yield an adequate result. I suggest that these approaches are no longer tenable. Synovectomy and debridement with or without excision of the head of the radius does indeed retain an extremely valuable place in the management of stage 1, 2, and early stage 3 disease. In the later stages of the disease, however, serious consideration must now be given to total joint replacement, the results of which can be remarkably successful and durable, and the complications from which can now be contained within acceptable limits provided that the operating team is fully experienced. It must also be stressed how necessary it is in the medical or combined clinic to pursue careful clinical and radiological monitoring of the rheumatoid elbow so that signs of dangerous deterioration can be recognised early, and surgery applied at a time when optimal conditions for the particular surgical weapons to be used still exist. Images PMID:2241304

  2. Quantum Simulations in Ion Traps -- Towards Simulating the Early Expanding Universe

    E-print Network

    Lutz Petersen

    2007-05-07

    This thesis provides an overview of an approach to quantum simulations using magnesium-25 ions stored in a linear Paul trap as the carriers of quantum information. Their quantum state is manipulated and read out using ultraviolet laser beams. Several important steps towards realising the first experiments have been undertaken, the most striking of which is cooling the ions to their motional ground state. We describe a first experiment simulating cosmological particle creation in the Early Universe and discuss the expected results.

  3. Rheumatoid Arthritis Educational Video Series

    MedlinePLUS Videos and Cool Tools

    ... treatments are available, what is happening in the immune system and what other conditions are associated with RA. ... Rheumatologist Rheumatoid Arthritis: Additional Conditions Rheumatoid Arthritis: The Immune System Don’t have SilverLight? Get it here. Updated: ...

  4. Handout on Health: Rheumatoid Arthritis

    MedlinePLUS

    ... Genetic variation increases risk of rheumatoid arthritis and lupus: Separate research found a SNP in a large ... both rheumatoid arthritis and another autoimmune disease, systemic lupus erythematosus (lupus). The STAT4 gene encodes a protein ...

  5. A Simulation Environment for Early Lifecycle Software Reliability Research and Prediction

    Microsoft Academic Search

    Anneliese Von Mayrhauser; James Keables

    1992-01-01

    It is important to apply models of software reliability early in the development lifecycle. This paper describes a software reliability simulation environment that will allow us to investigate early application of software reliablity models. The simulation environment uses information available during the design and coding phases to assist an model selection and early software reliability prediction. While we have just

  6. Rheumatoid arthritis in a military aviator.

    PubMed

    Moszyk, Danielle J; Sulit, Daryl J

    2007-01-01

    Rheumatoid arthritis is a chronic inflammatory condition whose pathogenesis is determined partially by genetic and environmental factors. Without treatment, 20 to 30% of individuals with this condition will become permanently disabled in a few years. Rheumatoid arthritis and its potential complications can cause significant disability and could seriously affect the performance of an aviator. Traditionally, disease-modifying anti-rheumatic drugs (DMARD) and biologics have not been used until disease progression occurs, but they recently have been added earlier in the course of disease for a more aggressive approach to treatment. It has been shown to significantly reduce the number of affected joints, pain, and disability. This newer treatment regimen has helped a military pilot continue his aviation career. We present the case of an experienced designated military pilot who was diagnosed with rheumatoid arthritis. He was initially treated early with a DMARD and biologic medication. He has remained in remission and currently only uses etanercept (biologic medication) and a non-steriodal anti-inflammatory drug to control his disease. He has responded favorably to therapy and has few limitations. Due to his positive response to treatment, the aviator was granted military aeromedical waivers for rheumatoid arthritis and chronic medication use. PMID:17225486

  7. Laryngeal Manifestations of Rheumatoid Arthritis

    PubMed Central

    Hamdan, A. L.; Sarieddine, D.

    2013-01-01

    Rheumatoid arthritis is a destructive autoimmune disease that affects 3% of the adult population. It is characterized by the formation of both articular and extra-articular lesions with predilection for small joints. There are ubiquitous reports on the head and neck manifestations of RA with emphasis on the larynx. The laryngeal presenting features of this systemic disease may mimic a plethora of medical conditions, inflammatory and neoplastic. The main phonatory and respiratory symptoms are often subtle and misleading. This paper represents a literature review of the laryngeal manifestations of RA with emphasis on the clinical symptoms, laryngeal findings, diagnosis, and treatment. An early diagnosis of laryngeal involvement may prevent drastic complications. PMID:23864939

  8. Oxidation in rheumatoid arthritis

    Microsoft Academic Search

    Carol A Hitchon; Hani S El-Gabalawy

    2004-01-01

    Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) produced in the course of cellular oxidative phosphorylation, and by activated phagocytic cells during oxidative bursts, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. They also serve as

  9. Treating the Rheumatoid Hand

    PubMed Central

    Hastings, D. E.; Welsh, R. P.

    1978-01-01

    Deformities in the rheumatoid hand will vary according to whether the joints or the tendons are involved. Frequently both will be involved and several different deformities will be present in the same hand. However, a logical approach to examination and treatment, as outlined in this article, will simplify decision making and ensure prompt, appropriate treatment. PMID:21304805

  10. MicroRNAs in Rheumatoid Arthritis

    PubMed Central

    Ceribelli, Angela; Nahid, Md A.; Satoh, Minoru; Chan, Edward K.L.

    2011-01-01

    Rheumatoid arthritis (RA) is a chronic and severe autoimmune disease that affects joint tissues, bone, and cartilage. However, the pathogenesis of RA is still unclear. Autoantibodies such as rheumatoid factor and anti-cyclic citrullinated peptide are useful tools for early diagnosis, monitoring disease activity, and predicting prognosis. Recently, many groups have focused their attention on the role of microRNAs in the pathogenesis of RA, as well as a potential biomarker to monitor RA. In fact, the expression of some microRNAs, such as miR-146a, is upregulated in different cell types and tissues in RA patients. MicroRNAs in RA could also be considered as possible future targets for new therapeutic approaches. PMID:21600203

  11. Rheumatoid arthritis in Lesotho.

    PubMed Central

    Moolenburgh, J D; Moore, S; Valkenburg, H A; Erasmus, M G

    1984-01-01

    Thirty-nine black African patients were seen with probable, definite or classical rheumatoid arthritis (RA); 32 of these were seen in a prospective study out of a total of 15 834 new patients 15 years and older at presentation seen in a 12-month period. The diagnosis was based on the American Rheumatism Association criteria for RA or the Rome criteria for inactive RA. The high incidence of severe disease as well as the occurrence of advanced disease in young patients is notable. 80% of the patients came from rural areas. Radiological lesions were found in 74% and serological abnormalities in 92%. Rheumatoid factor (RF) was found to be positive in 12% of an age and sex matched control group and in 19% of a group of patients suffering from tuberculosis. PMID:6696515

  12. Rheumatoid arthritis in greece

    Microsoft Academic Search

    A. P. Andonopoulos; V. Galanopoulou; A. A. Drosos; H. M. Moutsopoulos

    1987-01-01

    A high frequency of anti-Ro (SSA) circulating antibodies and lack of HLA-DR4 association described recently in Greek rheumatoid arthritis (RA) patients, prompted us to study their clinical and laboratory picture and compare it with that described in the literature. One hundred and ninety seven patients with definite or classical RA were divided into three groups A, B, and C with

  13. Pericarditis in rheumatoid arthritis

    Microsoft Academic Search

    A. G. Jurik; H. Graudal

    1986-01-01

    The annual incidence of clinically manifest pericarditis was found to be 0.34% in 157 females and 0.44% in 77 males with rheumatoid arthritis, observed for a mean time of 5.7 years. The development of pericarditis was independent of disease duration, but was related to extensive joint involvement, subcutaneous nodules, and a high Waaler Rose titre. Concomitant pleural effusion was present

  14. Anglo-French contributions to the recognition of rheumatoid arthritis

    PubMed Central

    Fraser, Kevin J.

    1982-01-01

    Early descriptions of rheumatoid arthritis in the English and French literature are reviewed. Charcot pointed out that the disease was recognised as distinct from gout in eighteenth century England, and pictorial evidence for this is presented. His own work on arthritis led to a series of noteworthy interactions with Alfred Baring Garrod, which are discussed. Images PMID:7051988

  15. The clinical features of rheumatoid arthritis.

    PubMed

    Grassi, W; De Angelis, R; Lamanna, G; Cervini, C

    1998-05-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive damage of synovial-lined joints and variable extra-articular manifestations. Tendon and bursal involvement are frequent and often clinically dominant in early disease. RA can affect any joint, but it is usually found in metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints, as well as in the wrists and knee. Articular and periarticular manifestations include joint swelling and tenderness to palpation, with morning stiffness and severe motion impairment in the involved joints. The clinical presentation of RA varies, but an insidious onset of pain with symmetric swelling of small joints is the most frequent finding. RA onset is acute or subacute in about 25% of patients, but its patterns of presentation also include palindromic onset, monoarticular presentation (both slow and acute forms), extra-articular synovitis (tenosynovitis, bursitis), polymyalgic-like onset, and general symptoms (malaise, fatigue, weight loss, fever). The palindromic onset is characterized by recurrent episodes of oligoarthritis with no residual radiologic damage, while the polymyalgic-like onset may be clinically indistinguishable from polymyalgia rheumatica in elderly subjects. RA is characteristically a symmetric erosive disease. Although any joint, including the cricoarytenoid joint, can be affected, the distal interphalangeal, the sacroiliac, and the lumbar spine joints are rarely involved. The clinical features of synovitis are particularly apparent in the morning. Morning stiffness in and around the joints, lasting at least 1 h before maximal improvement is a typical sign of RA. It is a subjective sign and the patient needs to be carefully informed as to the difference between pain and stiffness. Morning stiffness duration is related to disease activity. Hand involvement is the typical early manifestation of rheumatoid arthritis. Synovitis involving the metacarpophalangeal, proximal interphalangeal and wrist joints causes a characteristic tender swelling on palpation with early severe motion impairment and no radiologic evidence of bone damage. Fatigue, feveret, weight loss, and malaise are frequent clinical signs which can be associated with variable manifestations of extra-articular involvement such as rheumatoid nodules, vasculitis, hematologic abnormalities, Felty's syndrome, and visceral involvement. Although there is no laboratory test to exclude or prove the diagnosis of rheumatoid arthritis, several laboratory abnormalities can be detected. Abnormal values of the tests for evaluation of systemic inflammation are the most typical humoral features of RA. These include: erythrocyte sedimentation rate, acute phase proteins and plasma viscosity. Erythrocyte sedimentation rate and C-reactive protein provide the best information about the acute phase response. The C-reactive protein is strictly correlated with clinical assessment and radiographic changes. Plain film radiography is the standard investigation to assess the extent of anatomic changes in rheumatoid arthritis patients. The radiographic features of the hand joints in early disease are characterized by soft tissue swelling and mild juxtaarticular osteoporosis. In the the past 10 years, ultrasonography has gained acceptance for studying joint, tendon and bursal involvement in RA. It may improve the early clinical assessment and the follow-up of these patients, showing such details as synovial thickening even within finger joints. Other imaging techniques, such as magnetic resonance, computed tomography and scintigraphy may provide useful information about both the features and the extent for anatomic damage in selected rheumatoid arthritis patients. The natural history of the disease is poorly defined; its clinical course is fluctuating and the prognosis unpredictable. RA is an epidemiologically relevant cause of disability. An adequate early treatment of RA may alter the diseas PMID:9652497

  16. Early treatment in early undifferentiated arthritis

    Microsoft Academic Search

    Ignazio Olivieri; Piercarlo Sarzi-Puttini; Serena Bugatti; Fabiola Atzeni; Salvatore d'Angelo; Roberto Caporali

    The early diagnosis of new-onset rheumatoid arthritis (RA) has become a major objective for rheumatologists in order to identify a management strategy able to change the natural history of the disease and to prevent joint damage and functional impairment. Emergent evidence emphasizes the benefits of early aggressive therapy of RA. By the nineties, early arthritis cohorts have been collected throughout

  17. Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs

    PubMed Central

    2012-01-01

    Introduction Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA. Methods The study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ? 1) at 12 months. Results Baseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ? 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01). Conclusions CXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments. PMID:22336440

  18. [The role of biomarkers in diagnostics and forecasting of effectiveness of modern therapy of rheumatoid arthritis].

    PubMed

    Aleksandrova, E N; Novikov, A A; Nasonov, E L

    2013-08-01

    The rheumatoid arthritis is one of the most severe and widespread systemic inflammatory autoimmune diseases. The modern laboratory diagnostic of rheumatoid arthritis includes detection of large spectrum of biomarkers (autoantibodies, indicators of acute phase of inflammation, cytokines, markers of activation of endothelium, subpopulations of lymphocytes, products of metabolism of bone and cartilaginous tissue, genetic markers) in blood, synovial fluid, and synovial tissue. Alongside with common techniques of immunodiagnostics, the multiplex analysis of biomarkers based on genetic, transcript and proteomic technologies is applied. The results of identification of biomarkers are an important instrument of early diagnostics, activity evaluation, severity of disease course and disease prognosis and effectiveness of applied therapy. Among biomarkers associated with rheumatoid arthritis the most clinical value have antibodies (rheumatoid factor class IgM, antibodies to citrullinized proteins) and acute phase indicators (erythrocyte sedimentation rate, C-reactive protein) which are diagnostic criteria of rheumatoid arthritis and can be used in evaluation of prognosis of this disease. On basis of multi-parametric analysis of 12 key proteins of blood serum the new index of activity of rheumatoid arthritis (Vectra DA) is developed Nowadays, the potential biomarkers are detected providing to implement immunologic monitoring and prognosis of effectiveness of therapy of rheumatoid arthritis with genetic engineering biologic preparations. The laboratory tests are developed to evaluate immunogenicity of genetic engineering biologic preparations and diagnostic of latent tuberculosis infection in patients with rheumatoid arthritis against the background of therapy with using this group of pharmaceuticals. PMID:24340741

  19. Stochastic Joint Simulation of Facies and Diagenesis: A Case Study on Early Diagenesis

    E-print Network

    Boyer, Edmond

    Stochastic Joint Simulation of Facies and Diagenesis: A Case Study on Early Diagenesis of Facies and Diagenesis: A Case Study on Early Diagenesis of the Madison Formation (Wyoming, USA) -- The aim of this paper is to propose an integrated approach to reproduce both facies and diagenetic trends

  20. Cytodiagnosis of rheumatoid pleural effusions

    PubMed Central

    Boddington, M. M.; Spriggs, A. I.; Morton, J. A.; Mowat, A. G.

    1971-01-01

    The stained smears of the deposits from one pericardial and 19 pleural effusions complicating rheumatoid arthritis were examined. On the basis of clinical and biochemical evidence it was considered that in six cases the effusions were due to the rheumatoid disease while in a further nine cases the association was considered likely. In the remaining five cases the association was considered to be due to chance as other causes for the effusions were diagnosed. On cytological examination, seven cases showed a characteristic picture of degenerating polymorphs with amorphous extracellular material and epithelioid cells many of which were multinucleate. Five others contained similar amorphous material without epithelioid cells; of these two had many plasma cells and a third numerous macrophages probably containing `droplets' of rheumatoid factor complex. Thus in 12 of 15 cases a definite diagnosis of rheumatoid effusion could be made. In the remaining five cases cytological examination confirmed that the effusions were unrelated to the rheumatoid disease. The extracellular material gave a non-specific fluorescence with labelled anti-? globulin antisera, and since this reaction was not seen in control pleural fluid deposits, or with preparations of fibrin, it may have a confirmatory value. It is concluded that in many cases reliable cytological evidence can be found to confirm or refute a diagnosis of rheumatoid pleural or pericardial effusion. This may be helpful in the management of the rheumatoid disease. Images PMID:4101492

  1. From early virtual garment simulation to interactive fashion design

    Microsoft Academic Search

    Pascal Volino; Frederic Cordier; Nadia Magnenat-thalmann

    2005-01-01

    Virtual garment design and simulation involves a combination of a large range of techniques, involving mechanical simulation, collision detection, and user interface techniques for creating garments. Here, we perform an extensive review of the evolution of these techniques made in the last decade to bring virtual garments to the reach of computer applications not only aimed at graphics, but also

  2. Automated Multi-Agent Simulation Generation and Validation (Early Innovation)

    E-print Network

    Paris-Sud XI, Université de

    positive and normative investigations of phenomena out of reach when one uses analytical studies[2, 14: the tool reads and write parameter files, starts the simulation program and analyzes result logs. One

  3. [Autoantibodies, diagnostic and prognostic markers of rheumatoid polyarthritis].

    PubMed

    Sibilia, J

    2000-10-21

    AN IMPORTANT CLINICAL TOOL: A sensitive and specific marker allowing the diagnosis of rheumatoid arthritis, and even more importantly an early assessment of severity, would be a highly valuable clinical tool. Autoantibodies have been found to be quite useful in clinical practice for diagnosis and assessing prognosis. EARLY-STAGE RHEUMATOID ARTHRITIS: Ideally, the marker should be sensitive and specific when the first signs of the disease develop. To date, only the rheumatoid factor and anti-filaggrin antibodies (including anti-stratum comeum or "anti-keratin" and anti-perinuclear factors) have been used with sufficiently acceptable standards. IgM rheumatoid factors can be detected in about 80% of patients with rheumatoid arthritis but they lack specificity since they are also found in other auto-immune conditions (lupus, Sjögren's syndrome), in chronic infections, and in certain lymphoproliferative syndromes (with or without cryoglobulinemia). Anti-filaggrin antibodies are more specific (70 to 100% depending on the study) but can only be detected in 30 to 50% of the patients. High titers of rheumatoid factors (IgM and/or IgA) and anti-filiggrin antibodies are factors of poor prognosis because they are associated with destructive polyarthritis, sometimes complicated with extra-articular signs (nodules, vasculitis). Among the new autoantibodies being studied, only anti-Sa appears to have real diagnostic and prognostic value. The recent data must be confirmed. STRATEGIES FOR OVERT DISEASE: Systematic and repeated assay of autoantibody levels is not warranted in patients with overt disease. Anti-Ro-SS/A, ANCA can however, in some cases, detect unusual complications. THREE STRATEGIES WOULD BE PARTICULARLY INTERESTING: The first is to search for highly specific markers with the aim of identifying a subgroup of rheumatoid arthritis patients as early as possible who have specifically defined clinical, biological and disease-progression criteria. The second is to validate composite scores integrating autoantibodies to achieve early definition of disease severity. The third is to search for markers of progression, particularly autoantibodies, that could modulate inflammatory processes and osteo-cartilaginous degeneration. PMID:11094620

  4. Quality of Life After TKA for Patients With Juvenile Rheumatoid Arthritis

    Microsoft Academic Search

    Brigitte M. Jolles; Earl R. Bogoch

    2008-01-01

    Total knee arthroplasty frequently is required during early adulthood in patients with advanced juvenile rheumatoid arthritis.\\u000a We queried patients on issues of importance to them, asked whether they were satisfied with surgical outcomes, and ascertained\\u000a their postoperative status. We retrospectively reviewed 14 adult patients (22 knees) with severe juvenile rheumatoid arthritis\\u000a who were treated with primary total knee arthroplasty between

  5. Smoking and rheumatoid arthritis.

    PubMed

    Chang, Kathleen; Yang, So Min; Kim, Seong Heon; Han, Kyoung Hee; Park, Se Jin; Shin, Jae Il

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by both genetic and environmental factors. Smoking has been implicated as one of the most important extrinsic risk factors for its development and severity. Recent developments have shed light on the pathophysiology of RA in smokers, including oxidative stress, inflammation, autoantibody formation and epigenetic changes. The association of smoking and the development of RA have been demonstrated through epidemiologic studies, as well as through in vivo and animal models of RA. With increased use of biological agents in addition to standard disease-modifying antirheumatic drugs (DMARDs), there has been interest in how smoking affects drug response in RA treatment. Recent evidence suggests the response and drug survival in people treated with anti-tumour necrosis factor (anti-TNF) therapy is poorer in heavy smokers, and possible immunological mechanisms for this effect are presented in the current paper. PMID:25479074

  6. Pathogenesis of rheumatoid arthritis.

    PubMed

    Kolarz, G

    1988-01-01

    This report gives a review on recent results of investigations of cellular aspects of inflammation. The role of macrophages and T-helper-cells with particular focus to the effects of the various mediators on their target cells will be discussed. Interleukin 1, Tumor Necrosis Factor, Interleukin 2, and Interferon as well as arachidonic acid metabolites contribute to the clinical findings of inflammation. We have to admit that the whole process of inflammation in rheumatic arthritis (RA) is not yet clear. For example we do not know in detail why RA is self perpetuating, why and when rheumatoid pannus occurs or under which circumstances immune complexes may cause the various organ manifestations. Recent findings are discussed. PMID:2464266

  7. Autoantibodies in rheumatoid arthritis: a review.

    PubMed

    Mewar, D; Wilson, A G

    2006-12-01

    Emerging insights into the importance of B cells in the pathogenesis of rheumatoid arthritis (RA) as highlighted by the efficacy of B cell depletion is one factor that has contributed to the upsurge of interest in the potential role of autoantibodies both as disease markers and with respect to a pathogenic role. Since the initial description of rheumatoid factor (RF), a large number of both disease-specific and non-specific autoantibodies have been described in patients with RA including antibodies to type II collagen (CII), immunoglobulin binding protein (BiP) and antibodies directed at citrullinated peptides (anti-CCP) and other citrullinated proteins such as vimentin (anti-Sa) . Despite some overlap the serological profile of RA does appear to be distinct from other diseases such as SLE . Although the precise mechanisms responsible for the formation of these antibodies have not been well defined their presence must reflect the interaction between T and B cells believed to be relevant to the pathogenesis of RA. The specificity of the association of such factors as anti-CCP and anti-BiP with RA may reflect unique pathogenic events leading to the processing and presentation of the "cryptic self" . Ease of measurement and stability make autoantibodies attractive diagnostic and prognostic markers particularly in early disease when it may be difficult to distinguish self-limiting synovitis from persistent disease . The purpose of this article is to provide an overview of the current state of knowledge of the spectrum of autoantibodies thus far characterised in individuals with rheumatoid arthritis, and discuss their diagnostic, prognostic and pathogenetic relevance. PMID:17064873

  8. Rheumatoid nodule presenting as Morton's neuroma.

    PubMed

    Chaganti, S; Joshy, S; Hariharan, K; Rashid, M

    2013-09-01

    Among 101 feet that presented with symptoms and signs similar to Morton's neuroma, intermetatarsal rheumatoid nodules were found in five feet (three patients). Two patients had bilateral involvement. Histology of the excised tissue showed the presence of a rheumatoid nodule and Morton's neuroma in four feet and a rheumatoid nodule with unremarkable nerve bundles in one. A rheumatoid nodule can coexist with Morton's neuroma, as seen in our patients, and the presentation is often similar to that of a Morton's neuroma. Our patients were rendered asymptomatic with surgical treatment and went on to have appropriate management of rheumatoid arthritis. Rheumatoid nodule should be considered in the differential diagnosis of Morton's neuroma in not only rheumatoid arthritis patients but also asymptomatic patients who have never been tested for rheumatoid antibodies. PMID:23135058

  9. Rheumatoid Arthritis - Multiple Languages: MedlinePlus

    MedlinePLUS

    ... Are Here: Home ? Multiple Languages ? All Health Topics ? Rheumatoid Arthritis URL of this page: http://www.nlm.nih. ... V W XYZ List of All Topics All Rheumatoid Arthritis - Multiple Languages To use the sharing features on ...

  10. Genetic Analysis Workshop 15: simulation of a complex genetic model for rheumatoid arthritis in nuclear families including a dense SNP map with linkage disequilibrium between marker loci and trait loci.

    PubMed

    Miller, Michael B; Lind, Gregg R; Li, Na; Jang, Soon-Young

    2007-01-01

    Data for Problem 3 of the Genetic Analysis Workshop 15 were generated by computer simulation in an attempt to mimic some of the genetic and epidemiological features of rheumatoid arthritis (RA) such as its population prevalence, sex ratio, risk to siblings of affected individuals, association with cigarette smoking, the strong effect of genotype in the HLA region and other genetic effects. A complex genetic model including epistasis and genotype-by-environment interaction was applied to a population of 1.9 million nuclear families of size four from which we selected 1500 families with both offspring affected and 2000 unrelated, unaffected individuals all of whose first-degree relatives were unaffected. This process was repeated to produce 100 replicate data sets. In addition, we generated marker data for 22 autosomes consisting of a genome-wide set of 730 simulated STRP markers, 9187 SNP markers and an additional 17,820 SNP markers on chromosome 6. Appropriate linkage disequilibrium between markers and between trait loci and markers was modelled using HapMap Phase 1 data http://www.hapmap.org/downloads/phasing/2005-03_phaseI/. The code base for this project was written primarily in the Octave programming language, but it is being ported to the R language and developed into a larger project for general genetic simulation called GenetSim http://genetsim.org/. All of the source code that was used to generate the GAW 15 Problem 3 data is freely available for download at http://genetsim.org/gaw15/. PMID:18466538

  11. Can Rheumatoid Arthritis Be Prevented?

    PubMed Central

    Deane, Kevin

    2013-01-01

    The discovery of elevations of rheumatoid arthritis (RA)-related biomarkers prior to the onset of clinically apparent RA raises hopes that individuals who are at risk for future RA can be identified in a preclinical phase of disease that is defined as abnormalities of RA-related immune activity prior to the clinically apparent onset of joint disease. Additionally, there is a growing understanding of the immunologic processes that are occurring in preclinical RA, as well as a growing understanding of risk factors that may be mechanistically related to RA development. Furthermore, there are data supporting that treatment of early RA can lead to drug free remission. Taken as a whole, these findings suggest that it may be possible to use biomarkers and other factors to accurately identify the likelihood and timing of onset of future RA, and intervene with immunomodulatory therapies and/or risk factor modification to prevent the future onset of RA in at-risk individuals. Importantly, several clinical prevention trials for RA have already been tried, and one is underway. However, while our understanding of the growing understanding of the mechanisms and natural history of RA development may be leading us to the implementation of prevention strategies for RA, there are still several challenges to be met. These include developing sufficiently accurate methods of predicting those at high risk for future RA so that clinical trials can be developed based on accurate rates of development of arthritis and subjects can be adequately informed of their risk for disease, identifying the appropriate interventions and biologic targets for optimal prevention, and addressing the psychosocial and economic aspects that are crucial to developing broadly applicable prevention measures for RA. These issues notwithstanding, prevention of RA may be within reach in the near future. PMID:24315049

  12. Anti-Sa antibodies: prognostic and pathogenetic significance to rheumatoid arthritis.

    PubMed

    El-Gabalawy, Hani S; Wilkins, John A

    2004-01-01

    Anti-Sa antibodies are detected in the serum of 20-47% of patients with rheumatoid arthritis. These antibodies have a high degree of specificity for the disease, and appear to identify a subset of early rheumatoid arthritis patients destined to have aggressive and destructive disease. It has recently been confirmed that anti-Sa antibodies are directed to citrullinated vimentin, thus placing them in the anti-citrulline family of autoantibodies. The Sa antigen has previously been shown to be present in synovium. This, along with the demonstration of citrullinated proteins in rheumatoid synovium, suggests that anti-Sa antibodies may play a pathogenetic role in the initiation and/or persistence of rheumatoid synovitis. PMID:15059270

  13. Prostaglandins and Rheumatoid Arthritis

    PubMed Central

    Fattahi, Mohammad Javad; Mirshafiey, Abbas

    2012-01-01

    Rheumatoid arthritis (RA) is a chronic, autoimmune, and complex inflammatory disease leading to bone and cartilage destruction, whose cause remains obscure. Accumulation of genetic susceptibility, environmental factors, and dysregulated immune responses are necessary for mounting this self-reacting disease. Inflamed joints are infiltrated by a heterogeneous population of cellular and soluble mediators of the immune system, such as T cells, B cells, macrophages, cytokines, and prostaglandins (PGs). Prostaglandins are lipid inflammatory mediators derived from the arachidonic acid by multienzymatic reactions. They both sustain homeostatic mechanisms and mediate pathogenic processes, including the inflammatory reaction. They play both beneficial and harmful roles during inflammation, according to their site of action and the etiology of the inflammatory response. With respect to the role of PGs in inflammation, they can be effective mediators in the pathophysiology of RA. Thus the use of agonists or antagonists of PG receptors may be considered as a new therapeutic protocol in RA. In this paper, we try to elucidate the role of PGs in the immunopathology of RA. PMID:23193470

  14. Dietary intervention in rheumatoid arthritis

    PubMed Central

    Jamison, Jennifer R

    1987-01-01

    Rheumatoid arthritis is a disabling disease prevalent in modern society. Dietary prevention may be possible in a subgroup of individuals who appear to suffer food intolerance; dietary intervention, as an adjunct to other management strategies, may be useful in modifying the inflammatory response. The former suggestion is supported by anecdotal evidence; the latter by some in vitro experimentation which implicates arachidonic acid metabolism in the pathogenesis of rheumatoid tissue inflammation. While the value of dietary modification in the prevention and control of rheumatoid arthritis remains unproven, the potential benefits are significant. Further clinical investigation is justified. In the interim dietary modification which takes congnisance of arachidonic acid metabolism can be justified provided this falls within general dietary recommendations for modern society.

  15. Some Remarks on Modeling of the Early Stage of Cloud Formation in a Simulation Chamber

    Microsoft Academic Search

    Adel N. Saad; Josef Podzimek; John C. Carstens

    1976-01-01

    A numerical model has been developed to describe the early stage of cloud formation in a relatively small simulation chamber. The results for adiabatic expansion show a tendency for the cloud droplet spectrum to narrow, similar to the results obtained by other authors. The influence of updraft fluctuations is not as important as the fluctuation of temperature which depends upon

  16. Racial and ethnic disparities in rheumatoid arthritis.

    PubMed

    McBurney, Christine A; Vina, Ernest R

    2012-10-01

    Racial and ethnic health disparities are a national health issue. They are well described in other chronic diseases, but in rheumatoid arthritis (RA), research into their causes, outcomes, and elimination is in its early stages. Health disparities occur in a complex milieu, with system-level, provider-level, and individual-level factors playing roles. Dissecting the overlapping aspects of race/ethnicity, socioeconomic variables, and how their individual components combine to explain the magnitude of disparities in RA can be challenging. Recent research has focused on the extent to which treatment preferences, adherence, trust in physicians, patient-physician communication, health literacy, and depression have contributed to observed disparities in RA. Practicing evidence-based medicine, improving patient-physician communication skills, reducing language and literacy barriers, improving adherence to therapies, raising awareness of racial/ethnic disparities, and recognizing comorbidities such as depression are steps clinicians may take to help eliminate racial/ethnic disparities in RA. PMID:22773376

  17. Prognostic laboratory markers of joint damage in rheumatoid arthritis

    PubMed Central

    Lindqvist, E; Eberhardt, K; Bendtzen, K; Heinegard, D; Saxne, T

    2005-01-01

    Objective: To investigate whether determination of a set of laboratory markers at baseline provides prognostic information on joint damage in hands and feet in rheumatoid arthritis. Methods: 183 patients with early rheumatoid arthritis included in a prospective study were examined. Radiographic changes in hands and feet at 5 and 10 years after inclusion were evaluated (Larsen). The markers analysed were: erythrocyte sedimentation rate (ESR); HLA-DRB alleles typed by restriction fragment length polymorphism; and C reactive protein, cartilage oligomeric matrix protein (COMP), rheumatoid factor (RF) (IgG, IgA, and IgM subtypes), antibodies against cyclic citrullinated peptide (anti-CCP), and antibodies against interleukin 1? (anti-IL1?), analysed by immunoassays. Multiple linear regression with backward elimination was used to determine the prognostic value of the variables. Results: 117/176 patients were positive for IgG RF, 138/176 for IgA RF, 139/176 for IgM RF, 140/176 for anti-CCP, and 40/182 for anti-IL1?. After five years, ESR, the presence of IgA RF, serum COMP, and the presence of anti-CCP were significantly associated with more severe joint damage, and the presence of anti-IL1? with less severe joint damage. Baseline C reactive protein and anti-CCP predicted radiographic outcome after 10 years. A stronger prediction was obtained by combining the prognostic factors. Conclusions: Early determination of anti-CCP, IgA RF, anti-IL-1?, ESR, C reactive protein, and COMP predicted the development of joint damage in hands and feet in this cohort. A combination of these measures reflecting different aspects of the disease process should be useful for evaluating prognosis in individual patients with early rheumatoid arthritis. PMID:15458956

  18. Assessing the value of rheumatoid arthritis treatment alternatives: the potential effect of tumor necrosis factor inhibitors.

    PubMed

    Mizutani, Wesley

    2003-03-01

    Early intervention with drugs that delay structural damage from rheumatoid arthritis may limit disability and reduce the high costs associated with advancing disease. However, conventional agents have a potential for significant toxicities, which require monitoring that confers additional treatment costs. A new class of drugs has been developed: biologic response modifiers, two of which--etanercept and infliximab--inhibit tumor necrosis factor, a pivotal regulator of inflammation, and delay arthritic progression. Managed care organizations should encourage early diagnosis of rheumatoid arthritis, referral to a rheumatologist, and treatment with agents that reduce the overall costs of this debilitating disease. PMID:12715413

  19. Recent advances in rheumatoid arthritis

    Microsoft Academic Search

    Ernest Suresh

    2010-01-01

    Management of rheumatoid arthritis (RA) has radically changed over the last decade. Diagnostic methods have improved with availability of highly specific tests such as antibody to cyclic citrullinated peptide (specificity ?96%), and introduction of advanced imaging modalities such as ultrasound and magnetic resonance imaging to facilitate earlier diagnosis. The current aim of management is to achieve remission and prevent joint

  20. Climate model simulations of the observed early-2000s hiatus of global warming

    NASA Astrophysics Data System (ADS)

    Meehl, Gerald A.; Teng, Haiyan; Arblaster, Julie M.

    2014-10-01

    The slowdown in the rate of global warming in the early 2000s is not evident in the multi-model ensemble average of traditional climate change projection simulations. However, a number of individual ensemble members from that set of models successfully simulate the early-2000s hiatus when naturally-occurring climate variability involving the Interdecadal Pacific Oscillation (IPO) coincided, by chance, with the observed negative phase of the IPO that contributed to the early-2000s hiatus. If the recent methodology of initialized decadal climate prediction could have been applied in the mid-1990s using the Coupled Model Intercomparison Project Phase 5 multi-models, both the negative phase of the IPO in the early 2000s as well as the hiatus could have been simulated, with the multi-model average performing better than most of the individual models. The loss of predictive skill for six initial years before the mid-1990s points to the need for consistent hindcast skill to establish reliability of an operational decadal climate prediction system.

  1. The Early Jurassic climate: General circulation model simulations and the paleoclimate record

    SciTech Connect

    Chandler, M.A.

    1992-01-01

    This thesis presents the results of several general circulation model simulations of the Early Jurassic climate. The general circulation model employed was developed at the Goddard Institute for Space Studies while most paleoclimate data were provided by the Paleographic Atlas Project of the University of Chicago. The first chapter presents an Early Jurassic base simulation, which uses detailed reconstructions of paleogeography, vegetation, and sea surface temperature as boundary condition data sets. The resulting climatology reveals an Earth 5.2[degrees]C warmer, globally, than at present and a latitudinal temperature gradient dominated by high-latitude warming (+20[degrees]C) and little tropical change (+1[degrees]C). Comparisons show a good correlation between simulated results and paleoclimate data. Sensitivity experiments are used to investigate any model-data mismatches. Chapters two and three discuss two important aspects of Early Jurassic climate, continental aridity and global warming. Chapter two focuses on the hydrological capabilities of the general circulation model. The general circulation model's hydrologic diagnostics are evaluated, using the distribution of modern deserts and Early Jurassic paleoclimate data as validating constraints. A new method, based on general circulation model diagnostics and empirical formulae, is proposed for evaluating moisture balance. Chapter three investigates the cause of past global warming, concentrating on the role of increased ocean heat transport. Early Jurassic simulations show that increased ocean heat transports may have been a major factor in past climates. Increased ocean heat transports create latitudinal temperature gradients that closely approximate paleoclimate data and solve the problem of tropical overheating that results from elevated atmospheric carbon dioxide. Increased carbon dioxide cannot duplicate the Jurassic climate without also including increased ocean heat transports.

  2. Combination Therapy for Rheumatoid Arthritis in the Era of Biologicals

    PubMed Central

    2006-01-01

    Early, aggressive disease management is critical for halting disease progression and joint destruction in patients with rheumatoid arthritis. Combination therapy with at least two disease-modifying antirheumatic drugs, such as methotrexate (MTX), sulfasalazine, or hydroxychloroquine, is often more effective than monotherapy in reducing disease activity. Biologic therapies represent more effective and tolerable treatment options that, when combined with MTX, have been shown to dramatically reduce inflammation, inhibit radiographic progression, and induce remission. Although several types of treatment strategies are used in clinical practice, the most aggressive approaches that target early disease have shown the most promise in reversing disease progression and reducing disease-related costs. PMID:18751844

  3. Treatment in juvenile rheumatoid arthritis and new treatment options

    PubMed Central

    Kasapçopur, Özgür; Barut, Kenan

    2015-01-01

    Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of the childhood with the highest risk of disability. Active disease persists in the adulthood in a significant portion of children with juvenile rheumatoid arthritis despite many developments in the diagnosis and treatment. Therefore, initiation of efficient treatment in the early period of the disease may provide faster control of the inflammation and prevention of long-term harms. In recent years, treatment options have also increased in children with juvenile idiopathic arthritis owing to biological medications. All biological medications used in children have been produced to target the etiopathogenesis leading to disease including anti-tumor necrosis factor, anti-interleukin 1 and anti-interleukin 6 drugs. In this review, scientific data about biological medications used in the treatment of rheumatoid arthritis and new treatment options will be discussed.

  4. Insights into the early Eocene hydrological cycle from an ensemble of atmosphere-ocean GCM simulations

    NASA Astrophysics Data System (ADS)

    Carmichael, Matthew; Lunt, Daniel; Pancost, Richard

    2015-04-01

    Recent studies utilising a range of geochemical proxies have indicated that a significant perturbation to global hydrology occurred at the Paleocene-Eocene Thermal Maximum (PETM; ~56 Ma). An enhanced hydrological cycle for the warm early Eocene is also suggested to have played a key role in maintaining high-latitude warmth during this interval. Comparisons of proxy data to General Circulation Model (GCM) simulated hydrology have not widely been made however, and inter-model variability remains poorly characterised despite significant differences in simulated surface temperatures. In this work, we address this by undertaking an intercomparison of GCM-derived precipitation distributions within the EoMIP ensemble (Lunt et al., 2012), which includes previously-published early Eocene simulations performed using five GCMs differing in boundary conditions, model structure and precipitation-relevant parameterisation schemes. We show that an intensified hydrological cycle is simulated for all Eocene simulations relative to preindustrial. This is primarily due to elevated atmospheric paleo-CO2, although the effects of differences in paleogeography/ice sheets are also of importance in some models. For a given CO2 level, globally-averaged precipitation rates vary widely between models, largely as a result of different climate sensitivities (dT/dCO2) and differing parameterisation schemes. Despite this, models with similar global precipitation sensitivities (dP/dT) display different regional responses for a given temperature change. Regions which are particularly model sensitive include the South Pacific, tropical Africa and the Tethys and may represent targets for future proxy acquisition. A comparison of leaf-fossil-derived precipitation estimates with GCM data illustrates that models tend to unanimously underestimate early Eocene precipitation rates at high latitudes. Models which warm these regions via elevated CO2 or by utilising alternative parameterisations are most successful in simulating a match with geologic data. Further data from low-latitude regions and better constraints on early Eocene CO2 are required to discriminate between these model simulations, given the large error bars on paleoprecipitation estimates. Given the clear differences apparent between simulated precipitation distributions within the ensemble, further interrogation of paleohydrological data may offer an independent means by which to evaluate model skill for warm climates.

  5. Autoantibodies in rheumatoid arthritis: rheumatoid factors and anticitrullinated protein antibodies

    PubMed Central

    Kang, E.H.

    2010-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease, characterized by chronic, erosive polyarthritis and by the presence of various autoantibodies in serum and synovial fluid. Since rheumatoid factor (RF) was first described, a number of other autoantibodies have been discovered in RA patients. The autoantigens recognized by these autoantibodies include cartilage components, chaperones, enzymes, nuclear proteins and citrullinated proteins. However, the clinical significances and pathogenic roles of these antibodies are largely unknown except for RF and anticitrullinated protein antibodies (ACPAs), whose clinical usefulness has been acknowledged due to their acceptable sensitivities and specificities, and prognostic values. This review presents and discusses the current state of the art regarding RF and ACPA in RA. PMID:19926660

  6. From early virtual garment simulation to interactive fashion design Pascal Volino*, Frederic Cordier, Nadia Magnenat-Thalmann

    E-print Network

    Cordier, Frederic

    From early virtual garment simulation to interactive fashion design Pascal Volino*, Frederic simulation; Virtual garments; Fashion design; Pattern prototyping 1. Introduction The challenges of virtual Accepted 15 September 2004 Abstract Virtual garment design and simulation involves a combination of a large

  7. Immune modulation of rheumatoid arthritis.

    PubMed

    Pappas, Dimitrios A; Geraldino-Pardilla, Laura; Bathon, Joan M

    2011-12-01

    The approval - several years ago - of the first tumour necrosis factor-? (TNF-?) inhibitor for the management of rheumatoid arthritis launched a new era in the therapeutics of rheumatology. Since then an almost cataclysmic discovery of new treatment targets and corresponding biologic agents ensued. Nowadays, the rheumatologist and the rheumatologic patient have the luxury of several immune modulators available to successfully treat the majority of patients with RA or other inflammatory arthritides and conditions. In this review we focus on a discussion of the approved immune modulators/biologic agents available for the treatment of rheumatoid arthritis. We also present an overview of agents under development. For the immune modulators discussed, we describe their mechanism of action and summarise initial data and recent updates on efficacy and safety. PMID:22265267

  8. Use of computer simulations for the early introduction of nuclear engineering concepts

    SciTech Connect

    Ougouag, A.M.; Zerguini, T.H.

    1985-11-01

    A sophomore level nuclear engineering (NE) course is being introduced at the University of Illinois. Via computer simulations, this course presents materials covering the most important aspects of the field. It is noted that computer simulations in nuclear engineering are cheaper and safer than experiments yet they provide an effective teaching tool for the early introduction of advanced concepts. The new course material can be used as a tutorial and for remedial learning. The use of computer simulation motivates learning since students associate computer activities with games. Such a course can help in the dissemination of the proper information to students from different fields, including liberal arts, and eventually increase undergraduate student enrollment in nuclear engineering.

  9. The Argo simulation - II. The early build-up of the Hubble sequence

    NASA Astrophysics Data System (ADS)

    Fiacconi, Davide; Feldmann, Robert; Mayer, Lucio

    2015-01-01

    The Hubble sequence is a common classification scheme for the structure of galaxies. Despite the tremendous usefulness of this diagnostic, we still do not fully understand when, where, and how this morphological ordering was put in place. Here, we investigate the morphological evolution of a sample of 22 high-redshift (z ? 3) galaxies extracted from the Argo simulation. Argo is a cosmological zoom-in simulation of a group-sized halo and its environment. It adopts the same high-resolution (˜104 M?, ˜100 pc) and sub-grid physical model that was used in the Eris simulation but probes a sub-volume almost 10 times bigger with as many as 45 million gas and star particles in the zoom-in region. Argo follows the early assembly of galaxies with a broad range of stellar masses (log M?/M? ˜ 8-11 at z ? 3), while resolving properly their structural properties. We recover a diversity of morphologies, including late-type/irregular disc galaxies with flat rotation curves, spheroid dominated early-type discs, and a massive elliptical galaxy, already established at z ˜ 3. We identify major mergers as the main trigger for the formation of bulges and the steepening of the circular velocity curves. Minor mergers and non-axisymmetric perturbations (stellar bars) drive the bulge growth in some cases. The specific angular momenta of the simulated disc components fairly match the values inferred from nearby galaxies of similar M? once the expected redshift evolution of disc sizes is accounted for. We conclude that morphological transformations of high-redshift galaxies of intermediate mass are likely triggered by processes similar to those at low redshift and result in an early build-up of the Hubble sequence.

  10. A Systematic Review of Serum Biomarkers Anti-Cyclic Citrullinated Peptide and Rheumatoid Factor as Tests for Rheumatoid Arthritis

    PubMed Central

    Taylor, Peter; Gartemann, Juliane; Hsieh, Jeanie; Creeden, James

    2011-01-01

    This systematic review assesses the current status of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) tests in the diagnosis and prognosis of rheumatoid arthritis (RA). We reviewed publications on tests and biomarkers for early diagnosis of RA from English-language MEDLINE-indexed journals and non-MEDLINE-indexed sources. 85 publications were identified and reviewed, including 68 studies from MEDLINE and 17 non-MEDLINE sources. Anti-CCP2 assays provide improved sensitivity over anti-CCP assays and RF, but anti-CCP2 and RF assays in combination demonstrate a positive predictive value (PPV) nearing 100%, greater than the PPV of either of the tests alone. The combination also appears to be able to distinguish between patients whose disease course is expected to be more severe and both tests are incorporated in the 2010 ACR Rheumatoid Arthritis Classification Criteria. While the clinical value of anti-CCP tests has been established, differences in cut-off values, sensitivities and specificities exist between first-, second- and third-generation tests and harmonization efforts are under way. Anti-CCP and RF are clinically valuable biomarkers for the diagnosis and prognosis of RA patients. The combination of the two biomarkers in conjunction with other clinical measures is an important tool for the diagnosis and management of RA patients. PMID:21915375

  11. Autoimmune correlation of rheumatoid arthritis and periodontitis.

    PubMed

    Arunachalam, Lalitha Tanjore

    2014-09-01

    Rheumatoid arthritis and periodontitis, both, chronic inflammatory diseases share certain common diagnostic, pathological, immunogenetic and therapeutic features. A recently discovered enzymatic mimicry between human and bacterial species is novel and it opens up a new terrain for therapeutic blockade in the management of rheumatoid arthritis. PMID:25425834

  12. Cytokines in the pathogenesis of rheumatoid arthritis

    Microsoft Academic Search

    Georg Schett; Iain B. McInnes

    2007-01-01

    Cytokines regulate a broad range of inflammatory processes that are implicated in the pathogenesis of rheumatoid arthritis. In rheumatoid joints, it is well known that an imbalance between pro- and anti-inflammatory cytokine activities favours the induction of autoimmunity, chronic inflammation and thereby joint damage. However, it remains less clear how cytokines are organized within a hierarchical regulatory network, and therefore

  13. Autoimmune correlation of rheumatoid arthritis and periodontitis

    PubMed Central

    Arunachalam, Lalitha Tanjore

    2014-01-01

    Rheumatoid arthritis and periodontitis, both, chronic inflammatory diseases share certain common diagnostic, pathological, immunogenetic and therapeutic features. A recently discovered enzymatic mimicry between human and bacterial species is novel and it opens up a new terrain for therapeutic blockade in the management of rheumatoid arthritis. PMID:25425834

  14. Direct Simulation of Early-Stage Sec-Facilitated Protein Translocation

    PubMed Central

    Zhang, Bin; Miller, Thomas F.

    2012-01-01

    Direct simulations reveal key mechanistic features of early-stage protein translocation and membrane integration via the Sec-translocon channel. We present a novel computational protocol that combines non-equilibrium growth of the nascent protein with microsecond-timescale molecular dynamics trajectories. Analysis of multiple, long-timescale simulations elucidates molecular features of protein insertion into the translocon, including signal-peptide docking at the translocon lateral gate (LG), large-lengthscale conformational rearrangement of the translocon LG helices, and partial membrane integration of hydrophobic nascent-protein sequences. Furthermore, the simulations demonstrate the role of specific molecular interactions in the regulation of protein secretion, membrane integration, and integral membrane protein topology. Salt-bridge contacts between the nascent-protein N-terminus, cytosolic translocon residues, and phospholipid head groups are shown to favor conformations of the nascent protein upon early-stage insertion that are consistent with the Type II (Ncyt/Cexo) integral membrane protein topology; and extended hydrophobic contacts between the nascent protein and the membrane lipid bilayer are shown to stabilize configurations that are consistent with the Type III (Nexo/Ccyt) topology. These results provide a detailed, mechanistic basis for understanding experimentally observed correlations between integral membrane protein topology, translocon mutagenesis, and nascent-protein sequence. PMID:22852862

  15. Treatment of rheumatoid arthritis with traditional chinese medicine.

    PubMed

    Lee, Wen-Yuan; Chen, Hsin-Yi; Chen, Kuan-Chung; Chen, Calvin Yu-Chian

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease that will affect quality of life and, working efficiency, and produce negative thoughts for patients. Current therapy of RA is treated with disease-modifying antirheumatic drugs (DMARDs). Although most of these treatment methods are effective, most patients still have a pleasant experience either due to poor efficacy or side effects or both. Interleukin-6 receptor (IL6R) is important in the pathogenesis of RA. In this study, we would like to detect the potential candidates which inhibit IL6R against RA from traditional Chinese medicine (TCM). We use TCM compounds from the TCM Database@Taiwan for virtually screening the potential IL6R inhibitors. The TCM candidate compound, calycosin, has potent binding affinity with IL6R protein. The molecular dynamics simulation was employed to validate the stability of interaction in the protein complex with calycosin. The analysis indicates that protein complex with calycosin is more stable. In addition, calycosin is known to be one of the components of Angelica sinensis, which has been indicated to have an important role in the treatment of rheumatoid arthritis. Therefore, calycosin is a potential candidate as lead compounds for further study in drug development process with IL6R protein against rheumatoid arthritis. PMID:24991562

  16. Randomized controlled trial design in rheumatoid arthritis: the past decade

    PubMed Central

    Strand, Vibeke; Sokolove, Jeremy

    2009-01-01

    Much progress has occurred over the past decade in rheumatoid arthritis trial design. Recognized challenges have led to the establishment of a clear regulatory pathway to demonstrate efficacy of a new therapeutic. The use of pure placebo beyond 12 to 16 weeks has been demonstrated to be unethical and thus background therapy and/or early rescue has become regular practice. Goals of remission and 'treating to targets' may prove more relevant to identify real-world use of new and existing therapeutics. Identification of rare adverse events associated with new therapies has resulted in intensive safety evaluation during randomized controlled trials and emphasis on postmarketing surveillance and use of registries. PMID:19232061

  17. Inflammation, endothelial function and atherosclerosis in rheumatoid arthritis

    PubMed Central

    2012-01-01

    Different techniques have proven to be useful in determining the presence of subclinical cardiovascular disease in patients with rheumatoid arthritis (RA). Doppler imaging with iontophoresis of acetylcholine and flow-mediated, endothelium-dependent vasodilation give information on endothelial dysfunction, an early step in the atherogenesis process. However, there is no good correlation between these two surrogate markers of cardiovascular disease in RA. A single determination of routine laboratory markers of inflammation does not seem to relate to endothelial function in RA. Further research is needed to determine whether microvascular endothelial function is a better predictor of cardiovascular outcome than macrovascular endothelial function in patients with RA. PMID:22808986

  18. Miscarriage but not fecundity is associated with progression of joint destruction in rheumatoid arthritis

    PubMed Central

    van Dunne, F M; Lard, L; Rook, D; Helmerhorst, F; Huizinga, T

    2004-01-01

    Objective: To determine whether reproductive history before disease onset is associated with severity of joint destruction in rheumatoid arthritis. Methods: A special early arthritis clinic (EAC) was established at the department of rheumatology of Leiden University Medical Centre. General practitioners were encouraged to refer patients with joint complaints to this clinic, where the diagnosis of rheumatoid arthritis was made by a rheumatologist. In all, 113 female patients with definite rheumatoid arthritis were included in this study. A structured questionnaire was administered and joint damage was assessed by sequential x rays of the hands and feet, using the modified Sharp score. Results: The length of time of unprotected intercourse until first pregnancy (fecundity) was comparable with data from earlier studies, with 16% of the patients reporting a time to first pregnancy of more than 12 months. Fecundity did not reflect the extent of joint damage over time. The miscarriage rate was 15% per pregnancy, comparable to population figures (12–15%). A significant increase in joint damage over a two year follow up was found in patients with rheumatoid arthritis who had experienced at least one miscarriage compared with those who had never had a miscarriage (mean modified Sharp scores at 2 years, 24 (95% confidence interval, 15 to 32) and 16 (10 to 23), respectively; p<0.05). At baseline, the Sharp scores were similar in the two subgroups. Conclusions: Miscarriage before disease onset but not fecundity is associated with the progression of joint damage in rheumatoid arthritis. PMID:15249322

  19. Managed care implications in managing rheumatoid arthritis.

    PubMed

    Owens, Gary M

    2014-05-01

    Rheumatoid arthritis (RA) is a systemic inflammatory form of arthritis characterized by joint inflammation, pain, swelling, and stiffness. While contemporary treatment strategies based on early diagnosis, aggressive treatment, and regular monitoring have helped a significant number of patients achieve evidence-based treatment goals, RA still presents substantial management challenges to both clinicians and patients, and has the potential to lead to severe disability over time. In addition to its significant clinical consequences, RA has important economic implications. Both direct and indirect medical costs associated with RA are significant, including costs of medications, ambulatory and office-based care, and quality-of-life and productivity costs. In addition, a significant proportion of patients with prevalent RA have associated cardiovascular disease and other comorbidities, further compounding healthcare costs and complicating management of this disorder. Clinically favorable and cost-effective management must focus on prevention of disease progression and the improved patient health status and productivity than can result from optimal disease control. With the myriad of treatment options both available and emerging, managed care organizations are faced with difficult decisions surrounding the most clinically and cost-effective allocation of treatments designed to improve disease outcomes for patients with RA. It is vital that managed care clinicians and providers analyze both the overall burden and the specific costs of RA. This will allow a better understanding of how costs and issues relating to healthcare utilization affect the treatment of patients with RA and impact individualized therapy, care coordination, and outcomes. PMID:25180623

  20. Synthesis of underpolymerized hyaluronic acid by fibroblasts cultured from rheumatoid and non-rheumatoid synovitis

    Microsoft Academic Search

    E. Vuorio; S. Einola; S. Hakkaralnen; R. Penttinen

    1982-01-01

    Fibroblast cultures were started from synovial tissue of normal controls and patients with seronegative and seropositive rheumatoid arthritis, juvenile rheumatoid arthritis and chronic non-rheumatoid synovitis. Glycosaminoglycan synthesis of the cultures was studied by metabolic labeling with 3H-glucosamine. Molecular weight of hyaluronic acid produced and secreted into culture medium by these fibroblast strains was studied by gel filtration in a Sepharose

  1. A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early clinical response of brodalumab, a human anti-IL-17R antibody, in methotrexate-resistant rheumatoid arthritis

    PubMed Central

    2013-01-01

    Introduction The aim of this study was to evaluate the safety, pharmacokinetics, and clinical response of brodalumab (AMG 827), a human, anti-IL-17 receptor A (IL-17RA) monoclonal antibody in subjects with moderate-to-severe rheumatoid arthritis (RA). Methods This phase Ib, randomized, placebo-controlled, double-blind multiple ascending dose study enrolled subjects with moderate to severe RA (?6/66 swollen and ?8/68 tender joints). Subjects were randomized 3:1 to receive brodalumab (50 mg, 140 mg, or 210 mg subcutaneously every two weeks for 6 doses per group; or 420 mg or 700 mg intravenously every 4 weeks for two doses per group) or placebo. Endpoints included incidence of adverse events (AEs) and pharmacokinetics. Exploratory endpoints included pharmacodynamics, and improvements in RA clinical metrics. Results Forty subjects were randomized to investigational product; one subject discontinued due to worsening of RA (placebo). The study was not designed to assess efficacy. AEs were reported by 70% (7/10) of placebo subjects and 77% (22/30) of brodalumab subjects. Three serious AEs were reported in two subjects; there were no opportunistic infections. Brodalumab treatment resulted in inhibition of IL-17 receptor signaling and receptor occupancy on circulating leukocytes. No treatment effects were observed with individual measures of RA disease activity. On day 85 (week 13) 37% (11/30) of brodalumab subjects and 22% (2/9) of placebo subjects achieved ACR20; 7% (2/30) brodalumab subjects and 11% (1/9) of placebo subjects achieved ACR50; and 0% (0/30) brodalumab subjects and 0% (0/9) of placebo subjects achieved ACR70. Conclusions Multiple dose administration of brodalumab was tolerated in subjects with active RA. There was no evidence of a clinical response to brodalumab in subjects with RA. Trial registration ClinicalTrials.gov, NCT00771030 PMID:24286136

  2. STAT4 and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus

    PubMed Central

    Remmers, Elaine F.; Plenge, Robert M.; Lee, Annette T.; Graham, Robert R.; Hom, Geoffrey; Behrens, Timothy W.; de Bakker, Paul I.W.; Le, Julie M.; Lee, Hye-Soon; Batliwalla, Franak; Li, Wentian; Masters, Seth L.; Booty, Matthew G.; Carulli, John P.; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Chen, Wei V.; Amos, Christopher I.; Criswell, Lindsey A.; Seldin, Michael F.; Kastner, Daniel L.

    2009-01-01

    BACKGROUND Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q. METHODS We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus. RESULTS A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P = 2.81×10-7; odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P = 0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P = 1.87×10-9; odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis. CONCLUSIONS A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses. PMID:17804842

  3. MHD Simulations of the Solar Corona in Early August 2010 Using the HMI Magnetic Field Data

    NASA Astrophysics Data System (ADS)

    Hayashi, Keiji; Zhao, X.; Liu, Y.; Sun, X.; Hoeksema, J.; HMI Team

    2011-05-01

    The HMI is observing the line-of-sight magnetic field, vector field and the Doppler plasma velocity. The full-disk magnetogram observation with high temporal and spatial resolution provides better global solar magnetic field map, in that the data gap is minimized and the noise level is quite low. To utilize the benefit of the HMI's magnetogram observation, we conducted the MHD simulation of the global solar corona using the HMI data. We chose a period around August 1st, 2010, to see how the magnetic field connectivity in the global scale had changed around the period: In early August period, the changes of the global coronal magnetic field seen at the entire Earth-side hemisphere seem to be well related with the emergence of the sunspot at the north-east part of the full disk images, though the dynamics involving both magnetic field and plasma will be retrieved by means of the MHD simulation models. We used the synchronic frame format to make the global solar surface magnetic field maps so that the magnetic field distribution at the time of interest will be better specified thus the simulated situation will be more realistic. In addition, we used the daily-updated global maps that are made by regularly replacing the portion of the global map with the meridional slip of the full-disk data on regular (daily) basis as well as the standard ones that are well low-nose dataset made with better-calibrated data.

  4. Early structural development in melt-quenched polymer PTT from atomistic molecular dynamic simulations

    NASA Astrophysics Data System (ADS)

    Hsieh, Min-Kang; Lin, Shiang-Tai

    2009-12-01

    Molecular dynamics simulations are performed to study the initial structural development in poly(trimethylene terephthalate) (PTT) when quenched below its melting point. The development of local ordering has been observed in our simulations. The thermal properties, such as the glass transition temperature (Tg) and the melting temperature (Tm), determined from our simulations are in reasonable agreement with experimental values. It is found that, between these two temperatures, the number of local structures quickly increases during the thermal relaxation period soon after the system is quenched and starts to fluctuate afterwards. The formation and development of local structures is found to be driven mainly by the torsional and van der Waals forces and follows the classical nucleation-growth mechanism. The variation of local structures' fraction with temperature exhibits a maximum between Tg and Tm, resembling the temperature dependence of the crystallization rate for most polymers. In addition, the backbone torsion distribution for segments within the local structures preferentially reorganizes to the trans-gauche-gauche-trans (t-g-g-t) conformation, the same as that in the crystalline state. As a consequence, we believe that such local structural ordering could be the baby nuclei that have been suggested to form in the early stage of polymer crystallization.

  5. Gene Discoveries Could Help Rheumatoid Arthritis Treatment

    MedlinePLUS

    ... HealthDay . All rights reserved. More Health News on: Genes and Gene Therapy Recent Health News Related MedlinePlus Health Topics Genes and Gene Therapy Rheumatoid Arthritis About MedlinePlus Site Map FAQs Contact ...

  6. Leprosy and rheumatoid arthritis: consequence or association?

    PubMed

    Henriques, Celia Coelho; Lopéz, Begoña; Mestre, Tiago; Grima, Bruno; Panarra, António; Riso, Nuno

    2012-01-01

    Leprosy or Hansen's disease is a chronic granulomatous infectious disease caused by Mycobacterium leprae with a high prevalence in some developing countries however, it is rarely seen in non-endemic regions. Arthritis has been described in all types of Hansen's disease. Chronic arthritis is known to exist even in paucibacillary forms, resolved or treated disease and in patients without reaction, suggesting a perpetuated inflammatory process. In these cases leprosy can mimic some autoimmune diseases such as rheumatoid arthritis. When a patient with a history of leprosy presents with a symmetric, distal, polyarthritis the diagnosis may not be linear. Possibly it is a rheumatoid-like leprous arthritis with M leprae acting as the trigger element for the chronic process or it is an overlap condition, with a concomitant rheumatoid arthritis? A case report of a patient with a chronic inflammatory arthritis with 10 years of evolution is presented. The differential diagnosis between leprous and rheumatoid arthritis is discussed. PMID:22891014

  7. Paraproteins in rheumatoid arthritis and related disorders

    Microsoft Academic Search

    Clive Anthony Kelly

    1992-01-01

    Summary  There is evidence that the prevalence of monoclonal parparoteinaemia is slightly increased in patients with rheumatoid arthritis.\\u000a The possibility that this may be a marker of the development of later malignancy in such patients is explored. Mortality rates\\u000a in rheumatoid arthritis are increased although the development of lymphoreticular malignancy contributes only a small percentage\\u000a of this increase. However, it does

  8. The Biology of the Rheumatoid Synovial Cell

    PubMed Central

    Haselwood, Douglas M.; Castles, James J.

    1977-01-01

    Over the past 15 years, many of the elaborate research techniques of cell biology and biochemistry have been applied toward discovering the cause of rheumatoid arthritis. Consequently, it is valuable to review the morphological, physiological and biochemical alterations that have been observed in rheumatoid synovial cells. All of the changes observed suggest that a viral agent may form the basis for these alterations. However, studies to date have failed to isolate or identify the putative causative virus and the search continues. PMID:198974

  9. Computation models simulating notochordal cell extinction during early ageing of an intervertebral disc.

    PubMed

    Louman-Gardiner, K M; Coombe, D; Hunter, C J

    2011-12-01

    Lower back pain due to intervertebral disc (IVD) degeneration is a prevalent problem which drastically affects the quality of life of millions of sufferers. Healthy IVDs begin with high populations of notochordal cells in the nucleus pulposus, while by the second stage of degeneration, these cells will be replaced by chondrocyte-like cells. Because the IVD is avascular, these cells rely on passive diffusion of nutrients to survive. It is thought that this transition in cell phenotype causes the shift of the IVD's physical properties, which impede the flow of nutrients. Our computational model of the IVD illustrates its ability to simulate the evolving chemical and mechanical environments occurring during the early ageing process. We demonstrate that, due to the insufficient nutrient supply and accompanying changes in physical properties of the IVD, there was a resultant exponential decay in the number of notochordal cells over time. PMID:21424951

  10. Understanding the early stages of growth of Ge on Si(001) from lattice based simulations

    NASA Astrophysics Data System (ADS)

    Ghosh, Paramita; Nath, Pinku; Ranganathan, Madhav

    2015-09-01

    A modified lattice model is developed to study the growth of Ge on Si(001). In addition to the usual bond energies, surface reconstruction and elastic strain are explicitly taken into account in this study. We introduce an additional rebonding energy for formation of vacancies in the dimer chains. Kinetic Monte Carlo simulations of growth and annealing successfully reproduce several important features in the range of growth from a small fraction of a monolayer to about one monolayer thick. These include the formation of dimer chains, formation and alignment of vacancies in the dimer chains and the peak in the dimer chain length distribution. We carefully analyze separately the role of mismatch strain and surface reconstruction on this behavior. Through this work, we show a significantly simplified, but nevertheless quantitatively accurate model for the early stages of growth of Ge on Si(001).

  11. The surgical management of the rheumatoid spine: Has the evolution of surgical intervention changed outcomes?

    PubMed Central

    Bhatia, Robin; Haliasos, Nikolas; Vergara, Pierluigi; Anderson, Caroline; Casey, Adrian

    2014-01-01

    Context: Surgery for the rheumatoid cervical spine has been shown to stabilize the unstable spine; arrest/improve the progression of neurological deficit, help neck pain, and possibly decelerate the degenerative disease process. Operative intervention for the rheumatoid spine has significantly changed over the last 30 years. Aims: The purpose of this study was to review all cases of cervical rheumatoid spine requiring surgical intervention in a single unit over the last 30 years. Materials and Methods: A prospectively-maintained spine database was retrospectively searched for all cases of rheumatoid spine, leading to a review of indications, imaging, Ranawat and Myelopathy Disability Index measures, surgical morbidity, and survival curve analysis. Results: A total of 224 cases were identified between 1981 and 2011. Dividing the data into three time-epochs, there has been a significant increase in the ratio of segment-saving Goel-Harms C1-C2: Occipitocervical fixation (OCF) surgery and survival has increased between 1981 and 2011 from 30% to 51%. Patients undergoing C1-C2 fixation were comparatively less myelopathic and in a better Ranawat class preoperatively, but postoperative outcome measures were well-preserved with favorable mortality rates over mean 39.6 months of follow-up. However, 11% of cases required OCF at mean 28 months post-C1-C2 fixation, largely due to instrumentation failure (80%). Conclusion: We present the largest series of surgically managed rheumatoid spines, revealing comparative data on OCF and C1-C2 fixation. Although survival has improved over the last 30 years, there have been changes in medical, surgical and perioperative management over that period of time too confounding the interpretation; however, the analysis presented suggests that rheumatoid patients presenting early in the disease process may benefit from C1 to C2 fixation, albeit with a proportion requiring OCF at a later time. PMID:25013346

  12. [Pulmonary changes in rheumatoid arthritis].

    PubMed

    Kohout, A; Resl, M; Bácová, M

    2001-07-01

    A 78-year-old smoker with a medical history of rheumatoid arthritis (RA) diagnosed 23 years before death and treated for 10 years by sulfasalazine followed by 7 years of therapy by purine antimetabolite (AZAMUN, Leiras Co.). Two years before his death chemotherapy was added to treat a low grade malignant lymphoma. Pulmonary changes revealed during autopsy consisted of diffuse interstitial fibrosis, diffuse alveolar damage in its acute to subacute phase, and massive multiple bilateral ossifications. The possible side effect of RA treatment on pulmonary tissue is discussed. Post mortem low-voltage X-ray examination appears as a method which may contribute to the accurate distribution and correct diagnosis of multiple pulmonary ossification. PMID:11669018

  13. Psychosocial Concepts in Rheumatoid Arthritis

    PubMed Central

    McGillivray, Donald C.

    1973-01-01

    This article reviews and tabulates some of the current concepts of the role of psychosocial factors in rheumatoid arthritis (RA). Concepts prevalent during the 1950's are listed followed by discussion of some of the variable factors that complicate studies in this field. Studies are then cited which lead to the following conclusions: 1. Patients with RA tend to have certain personality characteristics, such as depression, rigidity, dependency, neurotic response patterns, emotional instability, feelings of guilt and low ego strength. 2. These are not specific to RA. 3. They may well be sequelae of the disease rather than pre-morbid features. 4. There is no clear evidence as to the role of psychological stress in causing or activating RA. 5. Personality factors have an influence on the course of the disease. PMID:20468900

  14. Microbial Infection and Rheumatoid Arthritis

    PubMed Central

    Li, Song; Yu, Yangsheng; Yue, Yinshi; Zhang, Zhixin; Su, Kaihong

    2014-01-01

    Rheumatoid arthritis (RA) is a complex autoimmune disease affecting 1–2% of general worldwide population. The etiopathogenesis of RA involves the interplay of multiple genetic risk factors and environmental triggers. Microbial infections are believed to play an important role in the initiation and perpetuation of RA. Recent clinical studies have shown the association of microbial infections with RA. Accumulated studies using animal models have also found that microbial infections can induce and/or exaggerate the symptoms of experimental arthritis. In this review, we have identified the most common microbial infections associated with RA in the literature and summarized the current evidence supporting their pathogenic role in RA. We also discussed the potential mechanisms whereby infection may promote the development of RA, such as generation of neo-autoantigens, induction of loss of tolerance by molecular mimicry, and bystander activation of the immune system. PMID:25133066

  15. Numerical simulations of the early stages of high-speed droplet breakup

    NASA Astrophysics Data System (ADS)

    Meng, J. C.; Colonius, T.

    2015-07-01

    Experiments reported in the literature are reproduced using numerical simulations to investigate the early stages of the breakup of water cylinders in the flow behind normal shocks. Qualitative features of breakup observed in the numerical results, such as the initial streamwise flattening of the cylinder and the formation of tips at its periphery, support previous experimental observations of stripping breakup. Additionally, the presence of a transitory recirculation region at the cylinder's equator and a persistent upstream jet in the wake is noted and discussed. Within the uncertainties inherent to the different methods used to extract measurements from experimental and numerical results, comparisons with experimental data of various cylinder deformation metrics show good agreement. To study the effects of the transition between subsonic and supersonic post-shock flow, we extend the range of incident shock Mach numbers beyond those investigated by the experiments. Supersonic post-shock flow velocities are not observed to significantly alter the cylinder's behavior, i.e., we are able to effectively collapse the drift, acceleration, and drag curves for all simulated shock Mach numbers. Using a new method that minimizes noise errors, the cylinder's acceleration is calculated; acceleration curves for all shock Mach numbers are subsequently collapsed by scaling with the pressure ratio across the incident shock. Furthermore, we find that accounting for the cylinder's deformed diameter in the calculation of its unsteady drag coefficient allows the drag coefficient to be approximated as a constant over the initial breakup period.

  16. Simulation models for European corn borer postdiapause morphogenesis and early infestation of maize in Missouri, USA

    NASA Astrophysics Data System (ADS)

    Magai, Robert N.; Decker, W. L.; Keaster, Armon J.

    The European corn borer is one of the most damaging insect pests to maize in the United States. Different methods exist for the estimation of time of damage to corn by first generation European corn borer. The most commonly used method is the linear thermal constant concept of phenology which by convention calculates cumulative thermal units from January 1 or another arbitrary date. Linear and nonlinear models based on the thermal units concept developed were to predict and simulate postdiapause development of the European corn borer and subsequent infestation of the maize crop using early spring temperatures (May 1-15) in central Missouri. The developmental rates of European corn borer were obtained from growth chamber investigations that simulated those temperatures, the operational temperatures being selected from a compilation of archival meteorological data from 1948 to 1989. The linear and polynomial regression models were developed to predict phenological stages of the European corn borer using thermal units as developmental rates. The models were compared against each other to determine the better predictor of estimation values: each explained 94 and 98% of the variation in developmental stages, respectively. In addition, the models were tested against independent field data and both models gave good predictions of developmental stages, indicating that either model would be a good predictor.

  17. Rheumatoid nodules in the thyroid bed following total thyroidectomy: a case report

    PubMed Central

    2013-01-01

    Introduction Rheumatoid nodules occur in 30 percent of patients with active rheumatoid arthritis. Common sites include the buttocks or the extensor surface of the forearm, with one group documenting their presence in the thyrohyoid membrane. To the best of our knowledge, rheumatoid nodules have not been described in the thyroid bed. Case presentation We present the case of a 46-year-old Caucasian woman with active rheumatoid arthritis and Hashimoto's thyroiditis who presented with compressive neck symptoms. An ultrasound scan revealed that both lobes of her thyroid were enlarged. The right lobe measured 7.9×3.4×3.3cm and the left 8.3×3.3×3.1cm. A solitary 1.0×0.6×0.8cm nodule was seen in the right lower lobe. Her thyroid-stimulating hormone level was 4.22uU/mL (0.34 to 5.60). A total thyroidectomy was performed due to her symptoms and the possible growth of a nodule when on levothyroxine. A postoperative ultrasound scan showed no remaining thyroid tissue. The pathology revealed several small neoplasms ranging from a well-encapsulated adenoma to highly atypical follicular and papillary Hurthle cell lesions in the setting of Hashimoto’s thyroiditis. Low-dose radioactive iodine (33.4mCi) was given. Four months later, our patient complained of a feeling of fullness in her neck. A solid nodule of mixed echogenicity (5.6×3.3×2.3cm) was seen in the right level VI of the neck, and solid tissue of mixed echogenicity (2.9×2.3×1.7cm) on the left. Following repeat surgery, the pathology from the right specimen showed Hashimoto’s thyroiditis. The left specimen had areas of granuloma formation with fibrinoid necrosis and palisading histiocytes, consistent with the histology of rheumatoid nodules. No evidence of malignancy was seen. The patient continues to do well and remains disease-free. Conclusions Rheumatoid nodules have not been reported in the thyroid bed. Their pathogenesis is not clear. Postoperative release of tumor necrosis factor alpha and local vascular damage may have triggered the nodule formation in this case. Rheumatoid nodules must be kept in the differential diagnosis of an enlarging thyroid in the setting of active rheumatoid arthritis. A fine-needle aspiration biopsy may show granuloma formation and be the most cost-effective initial diagnostic step, especially if there is a concern for malignancy. Early identification of these nodules will help decrease morbidity from unnecessary interventions and result in treatment that is both timely and appropriate. PMID:24168730

  18. Reconciling reconstructed and simulated features of the winter Pacific/North American pattern in the early 19th century

    NASA Astrophysics Data System (ADS)

    Zanchettin, D.; Bothe, O.; Lehner, F.; Ortega, P.; Raible, C. C.; Swingedouw, D.

    2015-06-01

    Reconstructions of past climate behavior often describe prominent anomalous periods that are not necessarily captured in climate simulations. Here, we illustrate the contrast between an interdecadal strong positive phase of the winter Pacific/North American pattern (PNA) in the early 19th century that is described by a PNA reconstruction based on tree rings from northwestern North America, and a slight tendency towards negative winter PNA anomalies during the same period in an ensemble of state-of-the-art coupled climate simulations. Additionally, a pseudo-proxy investigation with the same simulation ensemble allows for assessing the robustness of PNA reconstructions using solely geophysical predictors from northwestern North America for the last millennium. The reconstructed early 19th-century positive PNA anomaly emerges as a potentially reliable feature, although the pseudo-reconstructions are subject to a number of sources of uncertainty and deficiencies highlighted especially at multidecadal and centennial timescales. The pseudo-reconstructions demonstrate that the early 19th-century discrepancy between reconstructed and simulated PNA does not stem from the reconstruction process. Instead, reconstructed and simulated features of the early 19th-century PNA can be reconciled by interpreting the reconstructed evolution during this time as an expression of internal climate variability, which is unlikely to be reproduced in its exact temporal occurrence by a small ensemble of climate simulations. However, firm attribution of the reconstructed PNA anomaly is hampered by known limitations and deficiencies of coupled climate models and uncertainties in the early 19th-century external forcing and background climate state.

  19. Circadian use of glucocorticoids in rheumatoid arthritis.

    PubMed

    Cutolo, Maurizio; Sulli, Alberto; Pincus, Theodore

    2015-01-01

    A clear temporal relationship exists in rheumatoid arthritis (RA) patients between increased nocturnal levels of pro-in?ammatory cytokines, such as TNF-? and interleukin (IL)-6, pro-inflammatory hormones (i.e. melatonin, prolactin) and insufficient night production of the anti-in?ammatory cortisol (circadian rhythm). Under long-standing chronic stress of disease, insufficient cortisol is available to inhibit an ongoing nocturnal immune/inflammatory reaction. Clinical RA symptoms follow the same circadian rhythm with highest morning severity. Chronotherapy with nighttime glucocorticoid (GC) availability optimizes the treatment of RA patients with low-dose GCs through more efficient targeting of mediators of the immune/inflammatory reaction during the night to be available on arising. Circadian use of low-dose, long-term prednisone, by using night-release formulations (ingested at 10 to 11 p.m.) especially in early RA patients, appears characterized by a significantly superior efficacy on decreasing morning stiffness and IL-6 serum levels, compared to conventional daytime immediate-release prednisone. Shift from medium-dose, immediate-release prednisone (over 7.5-10 mg/day) to night-release formulations GC low-dose, long-term chronotherapy requires a gradual passage, since the hypothalamic-pituitary-adrenal axis of the treated RA patients, potentially altered by a negative feedback induced by the medium/high daily exogenous GC administration, needs time to re-synchronize control of endogenous GC production into a circadian and more physiological nocturnal hormone availability/optimized efficacy. PMID:25227591

  20. Preliminary clinical results: an analyzing tool for 2D optical imaging in detection of active inflammation in rheumatoid arthritis

    Microsoft Academic Search

    Radin Adi Aizudin Bin Radin Nasirudin; Reinhard Meier; Carmen Ahari; Matti Sievert; Martin Fiebich; Ernst J. Rummeny; Peter B. Noël

    2011-01-01

    Optical imaging (OI) is a relatively new method in detecting active inflammation of hand joints of patients suffering from rheumatoid arthritis (RA). With the high number of people affected by this disease especially in western countries, the availability of OI as an early diagnostic imaging method is clinically highly relevant. In this paper, we present a newly in-house developed OI

  1. Laboratory biomarkers or imaging in the diagnostics of rheumatoid arthritis?

    PubMed

    Šenolt, Ladislav; Grassi, Walter; Szodoray, Peter

    2014-01-01

    Rheumatoid arthritis (RA) is a common autoimmune disease in which a heterogeneous course and different pathogenic mechanisms are implicated in chronic inflammation and joint destruction. Despite the diagnostic contribution of anti-citrullinated protein/peptide antibodies (ACPAs) and rheumatoid factors, about one-third of RA patients remain seronegative. ACPAs belong to a heterogeneous family of autoantibodies targeting citrullinated proteins, including myelin-basic protein, several histone proteins, filaggrin and fibrin, fibrinogen or vimentin. In addition to ACPAs, antibodies directed against other post-translationally modified-carbamylated proteins (anti-CarP) were detected in up to 30% of ACPA-negative patients. Using phage display technology, further autoantibodies were recently discovered as candidate biomarkers for seronegative RA patients. Furthermore, in clinical practice, ultrasound may reveal subclinical synovitis and radiographically undetected bone erosions. To improve diagnostic certainty in undifferentiated arthritis and seronegative patients, ultrasound imaging and several new biomarkers may help to identify at risk patients and those with early disease. In this commentary we summarize recent advances in joint ultrasound and future potential of serological biomarkers to improve diagnosis of RA. PMID:24642071

  2. The Multifaceted Aspects of Interstitial Lung Disease in Rheumatoid Arthritis

    PubMed Central

    Grosso, Vittorio; Scorletti, Eva; Crepaldi, Gloria; Caporali, Roberto

    2013-01-01

    Interstitial lung disease (ILD) is a relevant extra-articular manifestation of rheumatoid arthritis (RA) that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD) significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP) is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP); other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation. PMID:24205507

  3. Asporin repeat polymorphism in rheumatoid arthritis

    PubMed Central

    Torres, B; Orozco, G; García?Lozano, J R; Oliver, J; Fernández, O; González?Gay, M A; Balsa, A; García, A; Pascual?Salcedo, D; López?Nevot, M A; Núñez?Roldán, A; Martín, J

    2007-01-01

    Background Asporin belongs to a family of proteins associated with the cartilage matrix. Objective To investigate the role of the functional polymorphism consisting of an aspartic acid (D) repeat polymorphism located in the ASPN gene in the susceptibility to and clinical outcome of rheumatoid arthritis. Methods A total of 803 Spanish Caucasian patients with rheumatoid arthritis and 904 controls of the same ethnic origin and matched for age and sex were included in the study. The asporin D repeat polymorphism was genotyped using polymerase chain reaction with a fluorescent primer. Results No significant differences were detected in the distribution of the 10 alleles found in our population on comparing patients with rheumatoid arthritis with control groups. Nevertheless, individuals bearing D14 produced rheumatoid factor more often than the rest (85.7% v 72.1%, p?=?0.006, odds ratio (OR) ?=?2.35, 95% confidence interval 1.21 to 4.50), and the mean (SD) onset age was higher in the group of individuals bearing D13 (50.09 (13.94)) compared with the rest (47.21 (14.31)), although the difference did not reach significance (p?=?0.06). Conclusion The results do not support a major role for asporin D repeat polymorphism in the susceptibility to rheumatoid arthritis. Nevertheless, they support the influence of this gene on the outcome of the disease. PMID:16707531

  4. Early Metal Enrichment by Pregalactic Outflows. II. Three-dimensional Simulations of Blow-Away

    NASA Astrophysics Data System (ADS)

    Mori, Masao; Ferrara, Andrea; Madau, Piero

    2002-05-01

    Supernova (SN)-driven pregalactic outflows may be an efficient mechanism for distributing the product of stellar nucleosynthesis over large cosmological volumes prior to the reionization epoch. Here, we present results from three-dimensional numerical simulations of the dynamics of SN-driven bubbles as they propagate through and escape the grasp of subgalactic halos with masses M=108h-1 Msolar at redshift z=9. Halos in this mass range are characterized by very short dynamical timescales (and even shorter gas cooling times) and may therefore form stars in a rapid but intense burst before SN ``feedback'' quenches further star formation. The hydrodynamic simulations use a nested grid method to follow the evolution of explosive multi-SN events operating on the characteristic timescale of a few times 107 yr, the lifetime of massive stars. The results confirm that if the star formation efficiency of subgalactic halos is <~10%, a significant fraction of the halo gas will be lifted out of the potential well (``blow-away''), shock the intergalactic medium, and pollute it with metal-enriched material, a scenario recently advocated by Madau, Ferrara, & Rees. The volume filling factor of the ejecta is of order unity. Depending on the stellar distribution, we find that less than 30% of the available SN energy gets converted into kinetic energy of the blown-away material, the remainder being radiated away. It appears that mechanical feedback is less efficient than expected from simple energetic arguments, as off-nuclear SN explosions drive inward-propagating shocks that tend to collect and pile up cold gas in the central regions of the host halo. Low-mass galaxies at early epochs may survive multiple SN events and continue forming stars.

  5. Hybrid 18 F-FDG PET–MRI of the hand in rheumatoid arthritis: initial results

    Microsoft Academic Search

    Falk Miese; Axel Scherer; Benedikt Ostendorf; Alexander Heinzel; Rotem S. Lanzman; Patric Kröpil; Dirk Blondin; Hubertus Hautzel; Hans-Jörg Wittsack; Matthias Schneider; Gerald Antoch; Hans Herzog; N. Jon Shah

    18F-fluorodeoxyglucose PET (18F-FDG PET) is highly sensitive to inflammatory changes within the synovial tissue in rheumatoid\\u000a arthritis (RA). However, the highest spatial resolution for soft tissue can be achieved with MRI. Here, we report on the first\\u000a true hybrid PET–MRI examination of the hand in early RA exploiting the advantages of both modalities. PET–MRI was performed\\u000a with a prototype of

  6. The microbiome and rheumatoid arthritis

    PubMed Central

    Scher, Jose U.; Abramson, Steven B.

    2012-01-01

    Humans are not (and have never been) alone. From the moment we are born, millions of micro-organisms populate our bodies and coexist with us rather peacefully for the rest of our lives. This microbiome represents the totality of micro-organisms (and their genomes) that we necessarily acquire from the environment. Micro-organisms living in or on us have evolved to extract the energy they require to survive, and in exchange they support the physiological, metabolic and immune capacities that have contributed to our evolutionary success. Although currently categorized as an autoimmune disorder and regarded as a complex genetic disease, the ultimate cause of rheumatoid arthritis (RA) remains elusive. It seems that interplay between predisposing genetic factors and environmental triggers is required for disease manifestation. New insights from DNA sequence-based analyses of gut microbial communities and a renewed interest in mucosal immunology suggest that the microbiome represents an important environmental factor that can influence autoimmune disease manifestation. This Review summarizes the historical clues that suggest a possible role for the microbiota in the pathogenesis of RA, and will focus on new technologies that might provide scientific evidence to support this hypothesis. PMID:21862983

  7. Isolated Rheumatoid Nodules: A Diagnostic Dilemma

    PubMed Central

    Gale, Michael; Gilbert, Erin; Blumenthal, David

    2015-01-01

    We present a 27-year-old male with multiple nonpainful soft tissue masses over several metacarpals, bilateral elbows, the left wrist, and both knees since the age of 4. Physical exam was significant for firm, nonmobile, nodular growths over the extensor surfaces of bilateral elbows and knees and on the 2nd and 5th metacarpal phalangeal joints. Laboratory studies revealed an unremarkable rheumatoid factor, negative ANA screening and normal joint radiographs. Differential diagnosis included subcutaneous granuloma annulare (SGA), seronegative rheumatoid nodule, and calcinosis cutis. Biopsy is the only method to distinguish benign rheumatoid nodules from SGA. This case illustrates the importance of biopsy in diagnosis, an awareness of the potential complications, and the need for good follow-up. PMID:25802526

  8. Late Onset Takayasu Arteritis and Rheumatoid Arthritis

    PubMed Central

    Verweij, K. E.; van Well, A. M. E.; vd Sluijs, J. W.; Dees, A.

    2012-01-01

    We encountered the rare case of a 48-year-old Caucasian woman who developed Takayasu arteritis (TA) while suffering from seropositive rheumatoid arthritis (RA). Several studies have reported an association between TA and various autoimmune disorders, however, the concurrent presence of Takayasu arteritis and rheumatoid arthritis is described in only few cases in the literature to date. The exact nature of the relationship between TA and RA remains unknown. Perhaps the development of these two diseases represents non-specific systemic inflammatory changes in the presence of a hereditary background predisposing to both RA and TA. PMID:22844294

  9. Transcript profiling towards personalised medicine in rheumatoid arthritis.

    PubMed

    Verweij, C L

    2009-12-01

    Rheumatoid arthritis (RA ) is a chronic inflammatory joint disease that is heterogeneous in nature. The heterogeneity is reflected by the variation in responsiveness to virtually any treatment modality. Since our understanding of the molecular complexity is incomplete and criteria for categorisation are limited, we mainly consider the disease RA as group average. A powerful way to gain insight into the complexity of RA has arisen from DNA microarray technology, which allows an open-ended survey to comprehensively identify the genes and biological pathways that are associated with clinically defined conditions. During the last decade encouraging results have been generated towards the molecular description of complex diseases in general. Here, I describe developments in genomics research that provide a framework to increase our understanding of the pathogenesis and the identification of biomarkers for early diagnosis, prognosis and stratification, aimed at a personal medicine approach in RA . PMID:20009112

  10. Autoimmunity to Citrullinated Proteins and the Initiation of Rheumatoid Arthritis

    PubMed Central

    Holers, V. Michael

    2014-01-01

    Clinical manifestations of rheumatoid arthritis (RA), the second most common human autoimmune disease, are primarily focused on the joints, causing disability and requiring life-long treatment to ameliorate signs and symptoms. The etiology of RA is unknown; however, important discoveries in two areas have been made which provide hope that the causal mechanisms can be identified. First, the most severe form of this disease is associated with the presence of humoral and cellular autoimmunity to citrullinated proteins and peptides. Second, in the natural history of RA, autoimmunity to citrullinated antigens appears years prior to the onset of clinically apparent disease. Herein is described a model in which to consider how these two features are linked during very early disease development. PMID:24215742

  11. Treat to target strategy in rheumatoid arthritis: real benefits.

    PubMed

    Cardiel, Mario H

    2013-01-01

    Treating rheumatoid arthritis (RA) with a goal or «Treat to target» strategy is a therapeutic proposal taken from cardiovascular and endocrine literature. It proposes that the therapeutic target in RA should be a state of remission, or an alternative goal could be a low disease activity. Rheumatologists should measure and register disease activity in every clinical visit and if the goal has not been reached, therapeutic adjustments should be made. Current evidence from clinical trials and a meta-analysis supports the notion that this strategy has important clinical benefits in patients with early RA when compared with routine care. It is also described that using protocolized treatment offers greater benefits. Recent data from Dutch cohorts is presented showing its successful implementation. A discussion is offered on the need of more studies in established RA. PMID:22985804

  12. Glucocorticoids in rheumatoid arthritis: lessons from the Utrecht study.

    PubMed

    Jacobs, J W G; Bijlsma, J W J

    2011-01-01

    The lessons from the Utrecht study on glucocorticoid therapy in early rheumatoid arthritis and of the spin-off and follow-up studies are reviewed. The data indicate that: glucocorticoids are DMARDs, the joint-sparing effect is predominantly on erosions, glucocorticoids do not influence the percentage of patients developing erosive disease, and the gain in joint-sparing effect persists after the stop of treatment. Further lessons are that the size of the joint-sparing effect and the (presumed) size of the symptomatic effect of glucocorticoids depend on co-therapies. Additional DMARDs must be added to glucocorticoids for maximum effect on radiographic progression. Finally, low-dose glucocorticoids are safer than often thought. PMID:22018185

  13. Rheumatoid Cachexia Revisited: A Metabolic Co-Morbidity in Rheumatoid Arthritis

    PubMed Central

    Masuko, Kayo

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease in which pro-inflammatory cytokines, including tumor necrosis factor (TNF)-?, play a crucial role. The chronic inflammation, combined with reduced physical activity, leads to muscle wasting whereas fat mass would be maintained; the resulting abnormal metabolic state is described as rheumatoid cachexia. Since the loss of muscle volume would be compensated by the increased fat mass, body mass index (BMI) is reported not to reflect the nutritional status in RA patients. The implication of rheumatoid cachexia for cardiovascular risk and clinical prognosis is not clearly understood, however, adequate control of disease activity in combination with appropriate physical exercise could be the most important strategy to control rheumatoid cachexia and related metabolic problems. PMID:25988122

  14. Early warnings of the potential for malaria transmission in Rural Africa using the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS)

    NASA Astrophysics Data System (ADS)

    Yamana, T. K.; Eltahir, E. A.

    2010-12-01

    Early warnings of malaria transmission allow health officials to better prepare for future epidemics. Monitoring rainfall is recognized as an important part of malaria early warning systems, as outlined by the Roll Back Malaria Initiative. The Hydrology, Entomology and Malaria Simulator (HYDREMATS) is a mechanistic model that relates rainfall to malaria transmission, and could be used to provide early warnings of malaria epidemics. HYDREMATS is used to make predictions of mosquito populations and vectorial capacity for 2005, 2006, and 2007 in Banizoumbou village in western Niger. HYDREMATS is forced by observed rainfall, followed by a rainfall prediction based on the seasonal mean rainfall for a period two or four weeks into the future. Predictions made using this method provided reasonable estimates of mosquito populations and vectorial capacity, two to four weeks in advance. The predictions were significantly improved compared to those made when HYDREMATS was forced with seasonal mean rainfall alone.

  15. Leprosy and rheumatoid arthritis: consequence or association?

    PubMed Central

    Henriques, Celia Coelho; Lopéz, Begoña; Mestre, Tiago; Grima, Bruno; Panarra, António; Riso, Nuno

    2012-01-01

    Leprosy or Hansen’s disease is a chronic granulomatous infectious disease caused by Mycobacterium leprae with a high prevalence in some developing countries however, it is rarely seen in non-endemic regions. Arthritis has been described in all types of Hansen’s disease. Chronic arthritis is known to exist even in paucibacillary forms, resolved or treated disease and in patients without reaction, suggesting a perpetuated inflammatory process. In these cases leprosy can mimic some autoimmune diseases such as rheumatoid arthritis. When a patient with a history of leprosy presents with a symmetric, distal, polyarthritis the diagnosis may not be linear. Possibly it is a rheumatoid-like leprous arthritis with M leprae acting as the trigger element for the chronic process or it is an overlap condition, with a concomitant rheumatoid arthritis? A case report of a patient with a chronic inflammatory arthritis with 10 years of evolution is presented. The differential diagnosis between leprous and rheumatoid arthritis is discussed. PMID:22891014

  16. State-of-the-art: rheumatoid arthritis

    Microsoft Academic Search

    Iain B McInnes; James R ODell

    2010-01-01

    The understanding of the pathogenesis and optimal therapeutics for rheumatoid arthritis (RA) has advanced remarkably over the last decade. This review highlights these key advances, particularly the outcomes of genome-wide scans which have provided an increasingly robust appraisal of the complex genetics that underpin RA. Such observations are placed in pathogenetic context, particularly concerning the breach of tolerance that presages

  17. Hard Metal Alveolitis Accompanied by Rheumatoid Arthritis

    Microsoft Academic Search

    Paula A. Hahtola; Ritva E. Järvenpää; Kari Lounatmaa; Jorma J. Mattila; Immo Rantala; Jukka A. Uitti; Seppo Sutinen

    2000-01-01

    Hard metal lung diseases (HML) are rare, and complex to diagnose. We describe the case of a patient with allergic alveolitis accompanied by rheumatoid arthritis. A sharpener of hard metal by trade, our patient was a 45-year-old, nonsmoking Caucasian female who experienced symptoms of cough and phlegm, and dyspnea on exertion. Preliminary lung findings were inspiratory rales in both basal

  18. North African vegetation-precipitation feedback in early and mid-Holocene climate simulations with CCSM3-DGVM

    NASA Astrophysics Data System (ADS)

    Rachmayani, R.; Prange, M.; Schulz, M.

    2015-02-01

    The present study analyses the sign, strength, and working mechanism of the vegetation-precipitation feedback over North Africa in middle (6 ka BP) and early Holocene (9 ka BP) simulations using the comprehensive coupled climate-vegetation model CCSM3-DGVM (Community Climate System Model version 3 and a dynamic global vegetation model). The coupled model simulates enhanced summer rainfall and a northward migration of the West African monsoon trough along with an expansion of the vegetation cover for the early and middle Holocene compared to the pre-industrial period. It is shown that dynamic vegetation enhances the orbitally triggered summer precipitation anomaly by approximately 20% in the Sahara-Sahel region (10-25° N, 20° W-30° E) in both the early and mid-Holocene experiments compared to their fixed-vegetation counterparts. The primary vegetation-rainfall feedback identified here operates through surface latent heat flux anomalies by canopy evaporation and transpiration and their effect on the mid-tropospheric African easterly jet, whereas the effects of vegetation changes on surface albedo and local water recycling play a negligible role. Even though CCSM3-DGVM simulates a positive vegetation-precipitation feedback in the North African region, this feedback is not strong enough to produce multiple equilibrium climate-ecosystem states on a regional scale.

  19. Prediction and evaluation method of wind environment in the early design stage using BIM-based CFD simulation

    NASA Astrophysics Data System (ADS)

    Lee, Sumi; Song, Doosam

    2010-06-01

    Drastic urbanization and manhattanization are causing various problems in wind environment. This study suggests a CFD simulation method to evaluate wind environment in the early design stage of high-rise buildings. The CFD simulation of this study is not a traditional in-depth simulation, but a method to immediately evaluate wind environment for each design alternative and provide guidelines for design modification. Thus, the CFD simulation of this study to evaluate wind environments uses BIM-based CFD tools to utilize building models in the design stage. This study examined previous criteria to evaluate wind environment for pedestrians around buildings and selected evaluation criteria applicable to the CFD simulation method of this study. Furthermore, proper mesh generation method and CPU time were reviewed to find a meaningful CFD simulation result for determining optimal design alternative from the perspective of wind environment in the design stage. In addition, this study is to suggest a wind environment evaluation method through a BIM-based CFD simulation.

  20. [Diet, nutrition and rheumatoid arthritis].

    PubMed

    Miggiano, G A D; Gagliardi, L

    2005-01-01

    Rheumatoid Arthritis (RA) is a chronic inflammatory disease resulting in diarthrodial joints inflammation (particularly joints of hands, wrists, feet, knees, cubitus, ankles, shoulder, etc.) that is manifested by swelling and functional impairment. The associated complications, osteoporosis and cardiovascular disease, make RA important in public health terms. During the active phase of disease, elevated plasma concentrations of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and acute-phase proteins, lead to reduction of fat free body mass (FFM) with a loss mean of 15% of cell body mass (CM) and consequent reduction of muscle strength. The pharmacological therapy (non steroidal anti inflammatory drugs (NSAIDs), slow acting antirheumatic drugs and corticosteroids), have the potential to cause side-effects, such as gastrointestinal bleeding, bone loss beyond to increase the requirement of some nutrients and reduce their absorption. The diet may play role in the management of RA, particularly in alleviating the symptoms of the disease, combating the side-effects of therapy and reducing the risk of complications. The increase of the caloric and proteic intake is not sufficient to offset a increased metabolic rhythm and important proteic catabolism but a diet balanced may warrant an adequate intake of nutrients. The carbohydrates of the diet provide 55-60% of the caloric intake, the diet is normo-proteinic or hyper-proteinic in the active phase of disease, and lipids represent 25-30% of the caloric intake (saturated, monounsaturated, polyunsaturated fatty acids in the ratio 1:1:1). omega-3 fatty acids supplementation, in combination with reduction of fatty acids omega-6 and adequate intake of monounsaturated fatty acids induce improvement in symptoms and sometimes a reduction in NSAIDs usage. Proper antioxidant nutrients (Vitamin A, Vitamin C, selenium) may provide an important defence against the increased oxidant stress and a supplementation of folate and vitamin B12, in patients treated with methotrexate (MTX), reduce the incidence of side effects and offset the elevation in plasma homocysteine frequent in these patients. Calcium and vitamin D, in patients treated with corticosteroids, reduce the bone loss, while a supplementation with iron may prevent anaemia. Finally, elimination diets may be feasible therapy only in patients with positive skin prick test. PMID:16048032

  1. Role of anti-citrullinated protein antibodies in diagnosis and prognosis of rheumatoid arthritis

    PubMed Central

    Puszczewicz, Mariusz; Iwaszkiewicz, Cezary

    2011-01-01

    Antibodies to citrullinated proteins/peptides (ACPAs) are the second serological marker to have recently been included in the 2010 ACR/EULAR Rheumatoid Arthritis (RA) Classification Criteria, which are focused on early diagnosis and therapy. This review discusses their history and some clinical aspects of ACPAs, focusing on the diagnostic utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies as a marker of RA as compared to the widely used rheumatoid factor (RF). Simultaneously, this review aims to raise physician awareness and interest in anti-citrullinated vimentin antibody (anti-Sa/anti-MCV), another member of the ACPA family, which appears to have a better predictive value as a marker of RA than anti-CCP or RF and correlates closely with disease activity and therapeutic response among patients with RA. PMID:22291756

  2. Role of anti-citrullinated protein antibodies in diagnosis and prognosis of rheumatoid arthritis.

    PubMed

    Puszczewicz, Mariusz; Iwaszkiewicz, Cezary

    2011-04-01

    Antibodies to citrullinated proteins/peptides (ACPAs) are the second serological marker to have recently been included in the 2010 ACR/EULAR Rheumatoid Arthritis (RA) Classification Criteria, which are focused on early diagnosis and therapy. This review discusses their history and some clinical aspects of ACPAs, focusing on the diagnostic utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies as a marker of RA as compared to the widely used rheumatoid factor (RF). Simultaneously, this review aims to raise physician awareness and interest in anti-citrullinated vimentin antibody (anti-Sa/anti-MCV), another member of the ACPA family, which appears to have a better predictive value as a marker of RA than anti-CCP or RF and correlates closely with disease activity and therapeutic response among patients with RA. PMID:22291756

  3. Modeling Temporal Processes in Early Spacecraft Design: Application of Discrete-Event Simulations for Darpa's F6 Program

    NASA Technical Reports Server (NTRS)

    Dubos, Gregory F.; Cornford, Steven

    2012-01-01

    While the ability to model the state of a space system over time is essential during spacecraft operations, the use of time-based simulations remains rare in preliminary design. The absence of the time dimension in most traditional early design tools can however become a hurdle when designing complex systems whose development and operations can be disrupted by various events, such as delays or failures. As the value delivered by a space system is highly affected by such events, exploring the trade space for designs that yield the maximum value calls for the explicit modeling of time.This paper discusses the use of discrete-event models to simulate spacecraft development schedule as well as operational scenarios and on-orbit resources in the presence of uncertainty. It illustrates how such simulations can be utilized to support trade studies, through the example of a tool developed for DARPA's F6 program to assist the design of "fractionated spacecraft".

  4. Current Concepts in the Management of the Rheumatoid Hand

    PubMed Central

    Chung, Kevin C; Pushman, Allison G

    2011-01-01

    Hand surgeons are an integral part of the management team for patients with rheumatoid arthritis. There is now a greater understanding of the national utilization of rheumatoid hand surgery, which highlights the differences between hand surgeons and rheumatologists regarding the treatment of the rheumatoid hand. Advances in medical treatments have also decreased the prevalence of hand deformities caused by this disease. Hand surgeons today have less exposure to treating rheumatoid hand, but despite more effective medical options, surgery may still offer patients hope for improvement of hand function and appearance. This article will summarize the current state of rheumatoid hand surgery and discuss the surgical treatment strategies for optimizing outcomes for patients suffering from rheumatoid arthritis. PMID:21463736

  5. Myocardial dysfunction in rheumatoid arthritis: epidemiology and pathogenesis

    PubMed Central

    Giles, Jon T; Fernandes, Verônica; Lima, Joao AC; Bathon, Joan M

    2005-01-01

    Data from population- and clinic-based epidemiologic studies of rheumatoid arthritis patients suggest that individuals with rheumatoid arthritis are at risk for developing clinically evident congestive heart failure. Many established risk factors for congestive heart failure are over-represented in rheumatoid arthritis and likely account for some of the increased risk observed. In particular, data from animal models of cytokine-induced congestive heart failure have implicated the same inflammatory cytokines produced in abundance by rheumatoid synovium as the driving force behind maladaptive processes in the myocardium leading to congestive heart failure. At present, however, the direct effects of inflammatory cytokines (and rheumatoid arthritis therapies) on the myocardia of rheumatoid arthritis patients are incompletely understood. PMID:16207349

  6. The effect of etanercept on anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatoid arthritis

    Microsoft Academic Search

    H A Chen; K C Lin; C H Chen; H T Liao; H P Wang; H N Chang; C Y Tsai; C T Chou

    2006-01-01

    Objective: To evaluate the changes in anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) following etanercept treatment in patients with rheumatoid arthritis.Methods: The study included 90 patients with rheumatoid arthritis who failed treatment with disease modifying antirheumatic drugs (DMARDs). All patients were allowed to continue treatment with DMARDs; 52 of them received etanercept as a twice weekly 25 mg

  7. Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

    PubMed Central

    Burska, Agata N.; Hunt, Laura; Strollo, Rocky; Ryan, Brent J.; Vital, Ed; Nissim, Ahuva; Winyard, Paul G.; Emery, Paul; Ponchel, Frederique

    2014-01-01

    Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential. PMID:24782594

  8. Preclinical Rheumatoid Arthritis (Autoantibodies): An Updated Review

    PubMed Central

    Deane, Kevin D.

    2014-01-01

    Multiple studies demonstrate that there is a period of development of rheumatoid arthritis (RA) during which there are elevations of disease-related biomarkers, including autoantibodies, in the absence of and prior to the development of RA; this period can be termed ‘preclinical RA’. These ‘preclinical’ autoantibodies including rheumatoid factor and antibodies to citrullinated protein antigens, and more recent studies have also identified a wider variety of autoantibodies and a wide range of inflammatory biomarkers. These findings in conjunction with established and emerging data about genetic and environmental risk factors for RA support a model of disease development where certain factors lead to an initial triggering of RA-related autoimmunity that expands over time to the point where symptomatic arthritis classifiable as RA develops. Herein will be reviewed updates in the field, as well as a discussion of current limitations of our understanding of preclinical RA, and potential future directions for study. PMID:24643396

  9. Nanomedicine delivers promising treatments for rheumatoid arthritis.

    PubMed

    Prasad, Leena Kumari; O'Mary, Hannah; Cui, Zhengrong

    2015-07-01

    An increased understanding in the pathophysiology of chronic inflammatory diseases, such as rheumatoid arthritis, reveals that the diseased tissue and the increased presence of macrophages and other overexpressed molecules within the tissue can be exploited to enhance the delivery of nanomedicine. Nanomedicine can passively accumulate into chronic inflammatory tissues via the enhanced permeability and retention phenomenon, or be surface conjugated with a ligand to actively bind to receptors overexpressed by cells within chronic inflammatory tissues, leading to increased efficacy and reduced systemic side-effects. This review highlights the research conducted over the past decade on using nanomedicine for potential treatment of rheumatoid arthritis and summarizes some of the major findings and promising opportunities on using nanomedicine to treat this prevalent and chronic disease. PMID:26084368

  10. Leucocyte superoxide dismutase in rheumatoid arthritis.

    PubMed Central

    Youssef, A A; Baron, D N

    1983-01-01

    Superoxide dismutase (SOD) activity was measured in polymorphonuclear leucocytes (PMNLs) and mononuclear cells (MNCs) from 60 patients with rheumatoid arthritis (RA) and in 15 controls. In all patients and controls SOD activity (U/mg protein) in MNCs was twice that in PMNLs. SOD activity in PMNLs and in MNCs from patients with RA was significantly higher than that in controls. SOD activity in PMNLs (but not in MNCs) from patients treated with corticosteroids was significantly higher than that from patients treated with nonsteroidal anti-inflammatory drugs. There was no relation between SOD activity in both PMNLs and MNCs and either the patients' age, sex, duration of disease, serum immunoglobulin concentration, IgM rheumatoid factor, and copper level, or the degree of disease activity. PMID:6625704

  11. HLA in Singapore Chinese with rheumatoid arthritis.

    PubMed

    Boey, M L; Wee, G B; Mohan, C; Howe, H S; Chan, S H; Feng, P H

    1992-10-01

    The HLA-A, B, C, DR and DQ antigens were determined in 50 Singapore Chinese patients with rheumatoid arthritis (RA). There was a significant increase in the prevalence of HLA-Bw46, DRw53 and DQ3 in patients with RA. The linkage disequilibrium between Bw46 and DRw53 explains this association. This major histocompatibility complex association differs from the HLA-DR4 link in Caucasian populations and suggests that RA is an immunogenetically heterogeneous disease. PMID:1464861

  12. Longitudinal immunomonitoring following tocilizumab in rheumatoid arthritis

    Microsoft Academic Search

    Pascale Louis-Plence; Yves-Marie Pers; Pierre Portales; Julie Quentin; Sylvie Fabre; Jean-François Eliaou; Christian Jorgensen

    2011-01-01

    IntroductionTocilizumab is a humanised anti-interleukin (IL)-6 receptor monoclonal antibody, which binds to circulating soluble IL-6 receptor and membrane-expressed IL-6 receptor, inhibiting IL-6 binding to both forms of IL-6 receptor. Tocilizumab is an efficient therapy for adults with moderate to severe rheumatoid arthritis (RA) in whom disease-modifying antirheumatic drugs or a tumour necrosis factor (TNF) inhibitor has failed. However, the impact

  13. The burden of illness of rheumatoid arthritis

    Microsoft Academic Search

    Annelies Boonen; Johan L. Severens

    2011-01-01

    It is necessary to understand the full burden of illness of a disease before the value of interventions can be assessed. Rheumatoid\\u000a arthritis (RA) has an impact on a variety of stakeholders, including patients, healthcare systems, and society as a whole.\\u000a This overview discusses the societal and patient perspectives, distinguishing several domains of impact. Epidemiology is important from a societal

  14. Advances in the treatment of rheumatoid arthritis

    PubMed Central

    Vivar, Nancy

    2014-01-01

    The intense pursuit of novel therapies in rheumatoid arthritis has provided physicians with an assorted set of biologic drugs to treat patients with moderate to severe disease activity. Nine different biologic therapies are currently available: seven inhibitors of pro-inflammatory cytokines (five targeting tumor necrosis factor [TNF], one interleukin [IL]-1 and one IL-6), as well as a T- and a B-lymphocyte targeting agent. All these drugs have roughly similar efficacy profiles and are approved as first- or second-line therapy in patients who failed to respond to conventional disease-modifying anti-rheumatic drugs (DMARDs) and in most cases for first line use in rheumatoid arthritis as well. Despite the irrefutable clinical and radiological benefits of biologic therapies, there are still low rates of patients achieving stable remission. Therefore, the quest for new and more effective biologic therapies continues and every year new drugs are tested. Simultaneously, optimal use of established agents is being studied in different ways. Recently, the approval of the first small molecule targeting intracellular pathways has opened a new chapter in the treatment of rheumatoid arthritis. Other emerging treatment strategies include the activation of regulatory T cells as well as new cytokine-targeting therapies. PMID:24860653

  15. Immunodiagnostic Significance of Anti-RA33 Autoantibodies in Saudi Patients with Rheumatoid Arthritis

    PubMed Central

    Al-Mughales, Jamil A.

    2015-01-01

    The primary objective of this study was to evaluate and compare the immunodiagnostic significance and utility of anti-RA33 with anti-CCP, RF, and CRP in Saudi patients with rheumatoid arthritis. Methods. This was a prospective controlled clinical study conducted at King Abdul Aziz University Tertiary Medical Centre. The sera of 41 RA patients, 31 non-RA patients, and 29 healthy controls were collected. Anti-RA33 and anti-CCP were measured using commercially available ELISA principle kits. RF and CRP were measured using nephelometry. Results. Anti-RA33 antibodies had the lowest positive and negative predictive values and showed a sensitivity of 7.32% with 95.12% specificity. Of the other three markers (including anti-CCP antibodies, CRP, and RF), only anti-CCP showed specificity of 90.46% with sensitivity of 63.41% compared to non-RA patients + healthy control. There was a significant correlation with rheumatoid factor positivity with anti-CCP. With respect to CRP, a notable correlation was seen only with anti-RA33. Conclusion. Compared to rheumatoid factor, anti-CCP antibodies, and C-reactive proteins, the anti-RA33 autoantibodies seem to be not representing as an important additional immunodiagnostic marker in Saudi patients with established RA. RA33 may have more interest in early RA or less severe RA and other systemic connective tissue disorders. PMID:25883991

  16. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis.

    PubMed

    Khandpur, Ritika; Carmona-Rivera, Carmelo; Vivekanandan-Giri, Anuradha; Gizinski, Alison; Yalavarthi, Srilakshmi; Knight, Jason S; Friday, Sean; Li, Sam; Patel, Rajiv M; Subramanian, Venkataraman; Thompson, Paul; Chen, Pojen; Fox, David A; Pennathur, Subramaniam; Kaplan, Mariana J

    2013-03-27

    The early events leading to the development of rheumatoid arthritis (RA) remain unclear, but formation of autoantibodies to citrullinated protein antigens (ACPAs) is considered a key pathogenic event. Neutrophils isolated from patients with various autoimmune diseases display enhanced neutrophil extracellular trap (NET) formation, a phenomenon that exposes autoantigens in the context of immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers, and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and RA synovial fluid neutrophils compared to neutrophils from healthy controls and from patients with osteoarthritis (OA). Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules, and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. Indeed, during NETosis, neutrophils externalized the citrullinated autoantigens implicated in RA pathogenesis, and anti-citrullinated vimentin antibodies potently induced NET formation. Moreover, the inflammatory cytokines interleukin-17A (IL-17A) and tumor necrosis factor-? (TNF-?) induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines, and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease. PMID:23536012

  17. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis

    PubMed Central

    Khandpur, Ritika; Carmona-Rivera, Carmelo; Vivekanandan-Giri, Anuradha; Gizinski, Alison; Yalavarthi, Srilakshmi; Knight, Jason S.; Friday, Sean; Li, Sam; Patel, Rajiv M.; Subramanian, Venkataraman; Thompson, Paul; Chen, Pojen; Fox, David A.; Pennathur, Subramaniam; Kaplan, Mariana J.

    2013-01-01

    The early events leading to the development of rheumatoid arthritis (RA) remain unclear but formation of autoantibodies to citrullinated antigens (ACPA) is considered a key pathogenic phenomenon. Neutrophils isolated from patients with various autoimmune diseases display enhanced extracellular trap formation (NETs), a phenomenon that externalizes autoantigens and immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and synovial fluid RA neutrophils, compared to neutrophils from healthy controls and from patients with osteoarthritis. Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. During NETosis, neutrophils externalized citrullinated autoantigens implicated in RA pathogenesis, whereas anti-citrullinated vimentin antibodies potently induced NET formation. The inflammatory cytokines IL-17A and TNF-? induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease. PMID:23536012

  18. Current therapies in rheumatoid arthritis: a Latin American perspective.

    PubMed

    Burgos-Vargas, Rubén; Catoggio, Luis Jose; Galarza-Maldonado, Claudio; Ostojich, Kasmir; Cardiel, Mario H

    2013-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting the synovium of joints, tendons, and some extra-articular sites. RA prevalence in Latin America ranges from 0.4 to 1.6%. Early treatment of RA translates into a substantial reduction in the cost to society. In light of this, early disease clinics are being established in some countries. Barriers to RA management, such as delay in referral to rheumatologists and limited access to therapy, have been identified. Evidence-based treatment guidelines have been adapted by countries according to their own situations. The need for keeping accurate records of biologics prescribed has been addressed by biologic registries, thereby contributing toward a better understanding of rheumatic diseases and their treatment. Current biologics include the tumor necrosis factor (TNF)-? inhibitors (etanercept, infliximab, and adalimumab), B-cell depletion agent (rituximab), interleukin-6 receptor blocker (tocilizumab), and T-cell co-stimulatory blocker (abatacept). Future therapies include kinase inhibitors (tofacitinib and fostamatinib), alternative TNF-? inhibitors (golimumab and certolizumab), and biosimilars. PMID:23337169

  19. Autoantibodies to PAD4 and BRAF in rheumatoid arthritis.

    PubMed

    Auger, Isabelle; Charpin, Caroline; Balandraud, Nathalie; Martin, Marielle; Roudier, Jean

    2012-09-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes cartilage and bone destruction. The mechanisms leading to RA are unknown. There is currently no reliable cure for RA. Early treatment can reduce inflammation, joint damage and bone destruction. Thus, early diagnosis of RA is critical. However, definitive diagnosis of RA can be difficult. Immunologic tests that can be performed for the diagnosis of RA include detection of anti citrullinated protein antibodies (ACPAs). However, one third of RA patients have no ACPAs. To identify new autoantibodies in RA, we used the sera of RA patients to screen protein arrays containing 8000 human proteins. We found and validated two major autoantigens: PAD4 (peptidyl arginine deiminase 4) and BRAF (v raf murine sarcoma viral oncogene homolog B1) catalytic domain. We identified peptide targets of anti PAD4 and BRAF autoantibodies. We observed that anti PAD4 are inhibitory whereas anti BRAF stimulate BRAF activity. Anti PAD4 and anti BRAF antibodies may be used to diagnose RA, particularly in the absence of anti citrullinated protein antibodies. PMID:22349616

  20. Differentiated services with multiple random early detection algorithm using ns2 simulator

    Microsoft Academic Search

    Mohammed A. Qadeer; Vikas Sharma; Ankit Agarwal; S. S. Husain

    2009-01-01

    This paper presents an overview of random early detection algorithm and differentiated services on ns2. In the present scenario of computer networks the traffic is increasing exponentially due to which packet losses are also increasing at a great rate. An active queue management in routers and gateways can potentially reduce packet loss rates in the Internet. In this paper we

  1. Early stage of critical clusters growth in phenomenological and molecular dynamics simulation models

    Microsoft Academic Search

    Romuald Puzyrewski; Jaroslaw Rybicki; Micha? Bia?oskórski

    2006-01-01

    The growth of critical clusters is discussed in the paper according to the classical and molecular dynamics (MD) approaches. A new formula for molecule numbers in critical clusters has been derived within the framework of the classical approach. A set of equations controlling the early stage of growth in a neighborhood of a critical size is presented. As far as

  2. Observation of early shell-dopant mix in OMEGA direct-drive implosions and comparisons with radiation-hydrodynamic simulations

    SciTech Connect

    Baumgaertel, J. A.; Bradley, P. A.; Hsu, S. C.; Cobble, J. A.; Hakel, P.; Tregillis, I. L.; Krasheninnikova, N. S.; Murphy, T. J.; Schmitt, M. J.; Shah, R. C.; Obrey, K. D.; Batha, S. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Johns, H.; Joshi, T.; Mayes, D.; Mancini, R. C.; Nagayama, T. [Physics Department, University of Nevada, Reno, Nevada 89557 (United States)

    2014-05-15

    Temporally, spatially, and spectrally resolved x-ray image data from direct-drive implosions on OMEGA were interpreted with the aid of radiation-hydrodynamic simulations. Neither clean calculations nor those using a turbulent mix model can explain fully the observed migration of shell-dopant material (titanium) into the core. Shell-dopant migration was observed via time-dependent, spatially integrated spectra, and spatially and spectrally resolved x-ray images of capsule implosions and resultant dopant emissions. The titanium emission was centrally peaked in narrowband x-ray images. In post-processed clean simulations, the peak titanium emission forms in a ring in self-emission images as the capsule implodes. Post-processed simulations with mix reproduce trends in time-dependent, spatially integrated spectra, as well having centrally peaked Ti emission in synthetic multiple monochromatic imager. However, mix simulations still do not transport Ti to the core as is observed in the experiment. This suggests that phenomena in addition to the turbulent mix must be responsible for the transport of Ti. Simple diffusion estimates are unable to explain the early Ti mix into the core. Mechanisms suggested for further study are capsule surface roughness, illumination non-uniformity, and shock entrainment.

  3. Synovial fibroblasts spread rheumatoid arthritis to unaffected joints

    Microsoft Academic Search

    Stephanie Lefèvre; Anette Knedla; Christoph Tennie; Andreas Kampmann; Christina Wunrau; Robert Dinser; Adelheid Korb; Eva-Maria Schnäker; Ingo H Tarner; Paul D Robbins; Christopher H Evans; Henning Stürz; Jürgen Steinmeyer; Steffen Gay; Jürgen Schölmerich; Thomas Pap; Ulf Müller-Ladner; Elena Neumann

    2009-01-01

    Active rheumatoid arthritis originates from few joints but subsequently affects the majority of joints. Thus far, the pathways of the progression of the disease are largely unknown. As rheumatoid arthritis synovial fibroblasts (RASFs) which can be found in RA synovium are key players in joint destruction and are able to migrate in vitro, we evaluated the potential of RASFs to

  4. Cells of the synovium in rheumatoid arthritis. Macrophages

    Microsoft Academic Search

    Raimund W Kinne; Bruno Stuhlmüller; Gerd-R Burmester

    2007-01-01

    The multitude and abundance of macrophage-derived mediators in rheumatoid arthritis and their paracrine\\/autocrine effects identify macrophages as local and systemic amplifiers of disease. Although uncovering the etiology of rheumatoid arthritis remains the ultimate means to silence the pathogenetic process, efforts in understanding how activated macrophages influence disease have led to optimization strategies to selectively target macrophages by agents tailored to

  5. Rheumatoid meningitis: an autopsy report and review of the literature

    Microsoft Academic Search

    Takashi Kato; Ken-ichi Hoshi; Yoshiki Sekijima; Masayuki Matsuda; Takao Hashimoto; Masako Otani; Akio Suzuki; Shu-ichi Ikeda

    2003-01-01

    We report the clinical and autopsy findings of a 71-year-old Japanese woman with rheumatoid meningitis. This patient developed subacute meningitis during an inactive stage of rheumatoid arthritis (RA), and despite intensive examinations no causative agents or underlying disease could be identified except for RA. Based on persistent hypocomplementaemia and increased serum levels of immune complexes she was suspected of having

  6. Clinical associations of dual-energy X-ray absorptiometry measurement of hand bone mass in rheumatoid arthritis

    Microsoft Academic Search

    J. DEVLIN; J. LHJLEY; A. HUISSOON; R. HOLDER; R. REECE; P. PERKINS; P. EMERY

    1996-01-01

    SUMMARY Hand bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) has potential as a marker of progression in early rheumatoid arthritis (RA). We examined a DXA methodology and studied in a cross-sectional manner 202 patients with RA. Hand BMD correlated inversely with age and was higher in males. Hand BMD correlated with lumbar and femoral sites. In females,

  7. Quantification of joint inflammation in rheumatoid arthritis by time-resolved diffuse optical spectroscopy and tracer kinetic modeling

    NASA Astrophysics Data System (ADS)

    Ioussoufovitch, Seva; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith; Diop, Mamadou

    2015-03-01

    Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation, which can cause progressive joint damage and disability. Diffuse optical spectroscopy (DOS) and imaging have the potential to become potent monitoring tools for RA. We devised a method that combined time-resolved DOS and tracer kinetics modeling to rapidly and reliably quantify blood flow in the joint. Preliminary results obtained from two animals show that the technique can detect joint inflammation as early as 5 days after onset.

  8. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology\\/European League Against Rheumatism collaborative initiative

    Microsoft Academic Search

    Daniel Aletaha; Tuhina Neogi; Alan J. Silman; Julia Funovits; David T. Felson; Clifton O Bingham III; Neal S. Birnbaum; Gerd R. Burmester; Vivian P. Bykerk; Marc D. Cohen; Bernard Combe; Karen H. Costenbader; Maxime Dougados; Paul Emery; Gianfranco Ferraccioli; Johanna M. W. Hazes; Kathryn Hobbs; Tom W. J. Huizinga; Arthur Kavanaugh; Jonathan Kay; Tore K Kvien; Timothy Laing; Philip Mease; Henri A Ménard; Larry W. Moreland; Raymond L. Naden; Theodore Pincus; Josef S Smolen; Ewa Stanislawska-Biernat; Deborah Symmons; Paul P. Tak; Katherine S. Upchurch; Ji?í Vencovský; Frederick Wolfe; Gillian Hawker

    2010-01-01

    ObjectiveThe 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA.MethodsA joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to

  9. Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis

    Microsoft Academic Search

    Cees J Haagsma; Henk J Blom; Piet L C M van Riel; Martin A van’t Hof; Belinda A J Giesendorf; Dinny van Oppenraaij-Emmerzaal; Levinus B A van de Putte

    1999-01-01

    OBJECTIVETo study the influence of sulphasalazine (SSZ), methotrexate (MTX), and the combination (COMBI) of both on plasma homocysteine and to study the relation between plasma homocysteine and their clinical effects.METHODS105 patients with early rheumatoid arthritis (RA) were randomised between SSZ (2–3 g\\/day), MTX (7.5–15 mg\\/week), and the COMBI (same dose range) and evaluated double blindly during 52 weeks. Plasma homocysteine,

  10. Mechanisms of action of cyclosporin a in animal models of rheumatoid arthritis

    Microsoft Academic Search

    R. L. Wong

    1993-01-01

    Animal models of rheumatoid arthritis have been used to study the effects of numerous immunosuppressive agents in order to\\u000a provide therapies for human rheumatoid arthritis. This review summarizes the use of cyclosporin A in several models of rheumatoid\\u000a arthritis and supports the rationale for its use in the treatment of rheumatoid arthritis.

  11. The computer BESK and an early attempt to simulate galactic dynamics

    E-print Network

    Lindblad, Per Olof

    2015-01-01

    The first N-body simulation of interacting galaxies, even producing spiral arms, was performed by Erik Holmberg in Lund (1941), not with a numerical computer, but by his arrangement of movable light-bulbs and photocells to measure the luminosity at each bulb and thereby estimate the gravitational force. A decade later, and with the arrival of the first programable computers, computations of galactic dynamics were performed, which were later transferred into a N-body simulation movie. I present here the background details for this work with a description of the important elements to note in the movie which may be retrieved at http://ttt.astro.su.se/~po .

  12. The winter Pacific-North-American pattern in the early 19th century in proxy-based reconstructions and climate simulations

    NASA Astrophysics Data System (ADS)

    Zanchettin, Davide; Bothe, Oliver; Lehner, Flavio; Ortega, Pablo; Raible, Christoph C.; Swingedouw, Didier

    2015-04-01

    Reconstructions of past climate behavior often describe prominent anomalous periods that are not necessarily captured in climate simulations. In this contribution, we illustrate the case of the winter Pacific/North American pattern (PNA) in the early 19th century. During this period, the interdecadal strong positive PNA phase described by a PNA reconstruction based on tree-rings from northwestern North America contrasts with the slight tendency towards negative winter PNA anomalies in an ensemble of state-of-the-art coupled climate simulations. In an attempt to reconcile the simulated and reconstructed behaviors, the robustness of PNA reconstructions based exclusively on geophysical predictors from northwestern North America is investigated following a pseudo-proxy analysis in the same simulation ensemble. The reconstructed early-19th-century positive PNA anomaly emerges as a potentially reliable feature, although it is subject to a number of sources of uncertainty and potential deficiencies. The pseudo-reconstructions demonstrate that the early-19th-century discrepancy between reconstructed and simulated PNA does not stem from the reconstruction process. Instead, reconstructed and simulated features of the early-19th-century PNA can be reconciled by interpreting the reconstructed evolution during this time as an expression of internal climate variability, hence distinguished from the externally-forced signal described by the ensemble mean and unlikely to be reproduced in its exact temporal occurrence by a small ensemble of climate simulations.

  13. Early containment of high-alkaline solution simulating low-level radioactive waste stream in clay-bearing blended cement

    SciTech Connect

    Kruger, A.A. [Westinghouse Hanford Co., Richland, WA (United States); Olson, R.A.; Tennis, P.D. [Northwestern Univ., Evanston, IL (United States). Center for Advanced Cement-Based Materials] [and others

    1995-04-01

    Portland cement blended with fly ash and attapulgite clay was mixed with high-alkaline solution simulating low-level radioactive waste stream at a one-to-one weight ratio. Mixtures were adiabatically and isothermally cured at various temperatures and analyzed for phase composition, total alkalinity, pore solution chemistry, and transport properties as measured by impedance spectroscopy. Total alkalinity is characterized by two main drops. The early one corresponds to a rapid removal of phosphorous, aluminum, sodium, and to a lesser extent potassium solution. The second drop from about 10 h to 3 days is mainly associated with the removal of aluminum, silicon, and sodium. Thereafter, the total alkalinity continues descending, but at a lower rate. All pastes display a rapid flow loss that is attributed to an early precipitation of hydrated products. Hemicarbonate appears as early as one hour after mixing and is probably followed by apatite precipitation. However, the former is unstable and decomposes at a rate that is inversely related to the curing temperature. At high temperatures, zeolite appears at about 10 h after mixing. At 30 days, the stabilized crystalline composition Includes zeolite, apatite and other minor amounts of CaCO{sub 3}, quartz, and monosulfate Impedance spectra conform with the chemical and mineralogical data. The normalized conductivity of the pastes shows an early drop, which is followed by a main decrease from about 12 h to three days. At three days, the permeability of the cement-based waste as calculated by Katz-Thompson equation is over three orders of magnitude lower than that of ordinary portland cement paste. However, a further decrease in the calculated permeability is questionable. Chemical stabilization is favorable through incorporation of waste species into apatite and zeolite.

  14. Depression in Rheumatoid Arthritis and its relation to disease activity

    PubMed Central

    Imran, Muhammad Yaser; Saira Khan, Elaine Anwer; Ahmad, Nighat Mir; Farman Raja, Sumaira; Saeed, Muhammad Ahmed; Ijaz Haider, Imran

    2015-01-01

    Objectives: To determine the level of depression in Rheumatoid Arthritis and its relationship with severity of Rheumatoid Arthritis. Methods: This cross sectional analytical study was conducted from March 2014 to May 2014. Total 102 cases of Rheumatoid Arthritis (RA) diagnosed as per ACR (American College of Rheumatology) 1987 criteria were enrolled from Rheumatology Department, Fatima Memorial Hospital. Severity of Rheumatoid Arthritis was assessed by Health Assessment Questionnaire (HAQ) and disease activity score (DAS - 28) while severity of depression was measured by Beck Depression Inventory (BDI) scale II questionnaire. The relationship between depression and disease activity (severity) of Rheumatoid Arthritis was assessed by calculating correlation coefficient between depression, disease activity score (DAS 28) of Rheumatoid Arthritis and health assessment questionnaire (HAQ). Results: Out of 102 patients, 77(75.5%) were females and 25(24.5%) males. The mean age of patients was 43.5± 11.9 years and the mean duration of disease was 7.8 ± 5.5 years.71.5% of Rheumatoid Arthritis patients were found to have some degree of depression and this was directly related to the severity of disease. Moderate and severe depression were present in 23 (22.5%) and 19(18.6%) patients respectively. Conclusion: In this study, almost three-fourths of Rheumatoid Arthritis patients were found to have depression. There was a strong association between Rheumatoid Arthritis disease activity and the level of depression. So it is imperative for clinicians treating Rheumatoid Arthritis patients to screen them for co morbid depression and manage it accordingly. PMID:26101498

  15. TOWARDS AN "EARLY NEURAL CIRCUIT SIMULATOR": A FPGA IMPLEMENTATION OF PROCESSING IN THE RAT WHISKER SYSTEM

    E-print Network

    Hartmann, Mitra J. Z.

    .leung, panyan, cshroeder, f-memik, g-memik, m-hartmann] @northwestern.edu ABSTRACT We have constructed a FPGA-based. As an initial step towards this long-term goal, we have constructed a FPGA-based neural circuit simulator in this system is a massively parallel problem. Furthermore, a FPGA-based system can be easily reconfigured

  16. 3D Simulations of the Early Mars Climate with a General Circulation Model

    NASA Technical Reports Server (NTRS)

    Forget, F.; Haberle, R. M.; Montmessin, F.; Cha, S.; Marcq, E.; Schaeffer, J.; Wanherdrick, Y.

    2003-01-01

    The environmental conditions that existed on Mars during the Noachian period are subject to debate in the community. In any case, there are compelling evidence that these conditions were different than what they became later in the amazonian and possibly the Hesperian periods. Indeed, most of the old cratered terrains are disected by valley networks (thought to have been carved by flowing liquid water), whereas younger surface are almost devoid of such valleys. In addition, there are evidence that the erosion rate was much higher during the early noachian than later. Flowing water is surprising on early Mars because the solar luminosity was significantly lower than today. Even with the thick atmosphere (up to several bars).To improve our understanding of the early Mars Climate, we have developed a 3D general circulation model similar to the one used on current Earth or Mars to study the details of the climate today. Our first objective is to answer the following questions : how is the Martian climate modified if 1) the surface pressure is increased up to several bars (our baseline: 2 bars) and 2) if the sun luminosity is decreased by 25 account the heat possibly released by impacts during short periods, although it may have played a role .For this purpose, we have coupled the Martian General Circulation model developed at LMD with a sophisticated correlated k distribution model developped at NASA Ames Research Center. It is a narrow band model which computes the radiative transfer at both solar and thermal wavelengths (from 0.3 to 250 microns).

  17. Association between low density lipoprotein and rheumatoid arthritis genetic factors with low density lipoprotein levels in rheumatoid arthritis and non-rheumatoid arthritis controls

    E-print Network

    Liao, K. P.

    Objectives: While genetic determinants of low density lipoprotein (LDL) cholesterol levels are well characterised in the general population, they are understudied in rheumatoid arthritis (RA). Our objective was to determine ...

  18. Short stem total hip arthroplasty in patients with rheumatoid arthritis.

    PubMed

    Bause, Ludwig

    2015-03-01

    Total hip arthroplasty (THA) has proven successful in patients with rheumatoid arthritis (RA). Patients with RA often require multiple revisions, and bone conservation is mandatory. A variety of short stems is currently available with mid-term results for osteoarthritis. This retrospective study evaluated mid-term clinical results of short stem THA in a series of patients with RA. Between 2005 and 2009, a total of 105 cementless short stems were implanted in patients with RA. Average patient age at the time of the index THA was 44.2 years, and average length of follow-up was 5 years. Clinical evaluation included physical examination and documentation of potential adverse events during the postoperative period. No radiographic failures occurred. Femoral and cup components showed some minor radiolucencies with sclerotic lines, but none involved 100% of the bone-prosthesis interface. Complications included femoral component subsidence in 2 hips after initial full weight bearing; 1 case resolved after 3 months, and the other case was revised to a standard shaft. One intraoperative dorsolateral stem tip perforation occurred with revision to a conventional length stem. Migration in 1 cup led to revision without removal of the short stem implant. No infections or joint dislocations were observed. The transfer of the short stem concept to an additional treatment option for patients with RA proved successful in the early to mid-term postoperative period. Complications and revisions were limited to early migration and early loosening of the implants in line with the results reported in the literature of cementless conventional THA in patients with RA. PMID:25826632

  19. Antibiotics for the treatment of rheumatoid arthritis

    PubMed Central

    Ogrendik, Mesut

    2014-01-01

    Antibiotic treatment for rheumatoid arthritis (RA) commenced in the 1930s with the use of sulfasalazine. Later, tetracyclines were successfully used for the treatment of RA. In double-blind and randomized studies, levofloxacin and macrolide antibiotics (including clarithromycin and roxithromycin) were also shown to be effective in the treatment of RA. There have been several reports in the literature indicating that periodontal pathogens are a possible cause of RA. Oral bacteria are one possible cause of RA. In this review, we aimed to investigate the effects of different antibiotics in RA treatment. PMID:24403843

  20. Magnetohydrodynamic simulations of the collapsar model for early and late evolution of gamma-ray bursts.

    PubMed

    Proga, Daniel

    2007-05-15

    I present results from magnetohydrodynamic (MHD) simulations of a gaseous envelope collapsing onto a black hole (BH). These results support the notion that the collapsar model is one of the most promising scenarios to explain the huge release of energy in a matter of seconds associated with gamma-ray bursts (GRBs). Additionally, the MHD simulations show that at late times, when the mass supply rate is expected to decrease, the region in the vicinity of the BH can play an important role in determining the rate of accretion, its time behaviour and ultimately the energy output. In particular, the magnetic flux accumulated around the BH can repeatedly stop and then restart the energy release. As proposed by Proga & Zhang, the episode or episodes of reoccurrence of accretion processes can correspond to X-ray flares discovered recently in a number of GRBs. PMID:17293321

  1. The early phases of galaxy clusters formation in IR: coupling hydrodynamical simulations with GRASIL-3D

    NASA Astrophysics Data System (ADS)

    Granato, Gian Luigi; Ragone-Figueroa, Cinthia; Domínguez-Tenreiro, Rosa; Obreja, Aura; Borgani, Stefano; De Lucia, Gabriella; Murante, Giuseppe

    2015-06-01

    We compute and study the infrared and sub-mm properties of high-redshift (z ? 1) simulated clusters and protoclusters. The results of a large set of hydrodynamical zoom-in simulations including active galactic nuclei (AGN) feedback, have been treated with the recently developed radiative transfer code GRASIL-3D, which accounts for the effect of dust reprocessing in an arbitrary geometry. Here, we have slightly generalized the code to adapt it to the present purpose. Then we have post-processed boxes of physical size 2 Mpc encompassing each of the 24 most massive clusters identified at z = 0, at several redshifts between 0.5 and 3, producing IR and sub-mm mock images of these regions and spectral energy distributions (SEDs) of the radiation coming out from them. While this field is in its infancy from the observational point of view, rapid development is expected in the near future thanks to observations performed in the far-IR and sub-mm bands. Notably, we find that in this spectral regime our prediction are little affected by the assumption required by this post-processing, and the emission is mostly powered by star formation (SF) rather than accretion on to super massive black hole (SMBH). The comparison with the little observational information currently available, highlights that the simulated cluster regions never attain the impressive star formation rates suggested by these observations. This problem becomes more intriguing taking into account that the brightest cluster galaxies (BCGs) in the same simulations turn out to be too massive. It seems that the interplay between the feedback schemes and the star formation model should be revised, possibly incorporating a positive feedback mode.

  2. Simulating IC reliability with emphasis on process-flaw related early failures

    Microsoft Academic Search

    M. S. Moosa; K. F. Poole

    1995-01-01

    A Monte-Carlo reliability simulator for integrated circuits (IC) that incorporates the effects of process flaws, material properties, the mask layout, and use conditions is presented. The mask layout is decomposed into distinct objects, such as contiguous metal runs, vias, contacts, and gate-oxides, for which user-defined distributions are used for determining the failure probability. These distributions are represented by a mixture

  3. Risk Factors for Asymptomatic Ventricular Dysfunction in Rheumatoid Arthritis Patients

    PubMed Central

    Garza-García, Carlos; Rocío, Sánchez-Santillán; Orea-Tejeda, Arturo; Castillo-Martínez, Lilia; Eduardo, Canseco; López-Campos, José Luis; Keirns-Davis, Candace

    2013-01-01

    Objective. The aim of the study was to describe echocardiographic abnormalities in patients with rheumatoid arthritis, concurrent systemic comorbidities, rheumatologic clinical activity, serologic markers of rheumatoid arthritis, and inflammatory activity. Methods. In an observational, cross-sectional study, rheumatoid arthritis outpatients were included (n = 105). Conventional transthoracic echocardiographic variables were compared between patients with arthritis and non-RA controls (n = 41). For rheumatoid arthritis patients, articular activity and rheumatologic and inflammatory markers were obtained. Results. Ventricular dysfunction was found in 54.3% of the population: systolic (18.1%), diastolic (32.4%), and/or right (24.8%), with lower ejection fraction (P < 0.0001). Pulmonary hypertension was found in 46.9%. Other echocardiographic findings included increased left atrial diameter (P = 0.01), aortic diameter (P = 0.01), ventricular septum (P = 0.01), left ventricular posterior wall (P = 0.013), and right ventricular (P = 0.01) and atrial diameters compared to control subjects. Rheumatoid factor and anti-CCP antibodies levels were significantly elevated in cases with ventricular dysfunction. Angina and myocardial infarction, diabetes, and dyslipidemia were the main risk factors for ventricular dysfunction. Conclusions. Ventricular dysfunction is common in rheumatoid arthritis and associated with longer disease duration and increased serologic markers of rheumatoid arthritis. Screening for cardiac abnormalities should be considered in this kind of patients. PMID:24368945

  4. Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques

    PubMed Central

    2014-01-01

    Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor ?B and its ligand, chemokine receptors, vascular cell adhesion molecule-1, ?V?3 integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein. PMID:25099015

  5. [Occupational therapy in rheumatoid arthritis: what rheumatologists need to know?].

    PubMed

    de Almeida, Pedro Henrique Tavares Queiroz; Pontes, Tatiana Barcelos; Matheus, João Paulo Chieregato; Muniz, Luciana Feitosa; da Mota, Licia Maria Henrique

    2015-01-01

    Interventions focusing on education and self-management of rheumatoid arthritis (RA) by the patient improves adherence and effectiveness of early treatment. The combination of pharmacologic and rehabilitation treatment aims to maximize the possibilities of intervention, delaying the appearance of new symptoms, reducing disability and minimizing sequelae, decreasing the impact of symptoms on patient's functionality. Occupational therapy is a health profession that aims to improve the performance of daily activities by the patient, providing means for the prevention of functional limitations, adaptation to lifestyle changes and maintenance or improvement of psychosocial health. Due to the systemic nature of RA, multidisciplinary follow-up is necessary for the proper management of the impact of the disease on various aspects of life. As a member of the health team, occupational therapists objective to improve and maintaining functional capacity of the patient, preventing the progression of deformities, assisting the process of understanding and coping with the disease and providing means for carrying out the activities required for the engagement of the individual in meaningful occupations, favoring autonomy and independence in self-care activities, employment, educational, social and leisure. The objective of this review is to familiarize the rheumatologist with the tools used for assessment and intervention in occupational therapy, focusing on the application of these principles to the treatment of patients with RA. PMID:25440699

  6. The early stage of formation of self-organized nanocolumns in thin films: Monte Carlo simulations versus atomic-scale observations in Ge-Mn

    SciTech Connect

    Mouton, I.; Talbot, E., E-mail: etienne.talbot@univ-rouen.fr; Pareige, C.; Lardé, R.; Blavette, D. [Groupe de Physique des Matériaux (GPM) UMR 6634, Normandie Université, Université et INSA de Rouen - CNRS, Av. de l'Université, BP 12, 76801 Saint Etienne du Rouvray (France)

    2014-02-07

    Formation kinetics of self-organized nanocolumns during epitaxial growth of a thin film composed of immiscible elements (A,B) has been investigated using Kinetic Monte Carlo simulations. Simulated nanostructures show a good agreement with those observed in Ge-Mn using Atom Probe Tomography and Transmission Electron Microscopy. Self organisation is observed although the rigid lattice simulations used do not account for misfit elastic strain. Simulations reveal that the final nanostructure, in term of number density and diameter of nanocolumns, is controlled by the early stages of growth of the film. The influence of both growth temperature and solute concentration on the nanostructure features is discussed in details.

  7. Effects of simulated oilfield produced water on early seedling growth after treatment in a pilot-scale constructed wetland system.

    PubMed

    Pardue, Michael J; Castle, James W; Rodgers, John H; Huddleston, George M

    2015-01-01

    Seed germination and early seedling growth bioassays were used to evaluate phytotoxicity of simulated oilfield produced water (OPW) before and after treatment in a subsurface-flow, pilot-scale constructed wetland treatment system (CWTS). Responses to untreated and treated OPW were compared among seven plant species, including three monocotyledons: corn (Zea mays), millet (Panicum miliaceum), and sorghum (Sorghum bicolor); and four dicotyledons: lettuce (Lactuca sativa), okra (Abelmoschus esculents), watermelon (Citrullus lanatus), and soybean (Glycine max). Phytotoxicity was greater in untreated OPW than in treated OPW. Exposures to untreated and treated OPW enhanced growth in some plant species (sorghum, millet, okra, and corn) relative to a negative control and reduced growth in other plant species (lettuce, soybean, and watermelon). Early seedling growth parameters indicated that dicotyledons were more sensitive to test waters compared to monocotyledons, suggesting that morphological differences between plant species affected phytotoxicity. Results indicated the following sensitivity scale for plant species: lettuce > soybean > watermelon > corn> okra?millet >sorghum. Phytotoxicity of the treated OPW to lettuce and soybean, although concentrations of COCs were less than irrigation guideline concentrations, suggests that chemical characterization and comparison to guideline concentrations alone may not be sufficient to evaluate water for use in growing crops. PMID:25409245

  8. ACPA and bone loss in rheumatoid arthritis.

    PubMed

    Kocijan, Roland; Harre, Ulrike; Schett, Georg

    2013-10-01

    Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by bone loss. Degree of inflammation and autoantibody positivity have both been identified as important initiators of skeletal damage in RA. Whereas it is well appreciated that inflammation initiates bone loss via the action of cytokines, the effect of autoantibodies in initiating bone destruction has long been underestimated. It has, nonetheless, been known for years that antibodies against citrullinated proteins (ACPA) and rheumatoid factor are associated with a more destructive disease course. It was recently shown that ACPA bind osteoclast precursor cells and directly promote their differentiation into bone-resorbing osteoclasts. Other results have shown that in ACPA-positive individuals bone loss starts even before the onset of clinical disease; this is indicative of the independent effect of these antibodies in initiating skeletal damage. The observation that the mere presence of ACPA is associated with pathological changes suggests that these antibodies have functional properties and initiate the onset of disease long before patients consult the rheumatologist because of symptomatic joint disease. These findings also indicate that "RA" is a syndrome rather than a single disease, suggesting that autoantibody-positive patients are both genetically and clinically distinct phenotypes. PMID:23955066

  9. Acute ocular myositis occurring under etanercept for rheumatoid arthritis.

    PubMed

    Couderc, Marion; Mathieu, Sylvain; Tournadre, Anne; Dubost, Jean-Jacques; Soubrier, Martin

    2014-10-01

    Ocular myositis is a rare disorder characterized by inflammation of single or multiple extra-ocular eye muscles presenting with painful diplopia and/or ophthalmoplegia. The etiology remains obscure and it is rarely associated with rheumatoid arthritis. We here reported the case of a 61-year-old woman treated by TNF-? blockade, namely etanercept, for rheumatoid arthritis for ten years who developed an acute ocular myositis. The patient improved after etanercept was stopped and initiation of high doses of corticosteroids. To our knowledge, this is the second report of ocular myositis occurring under TNF-? blockade treatment for rheumatoid arthritis. PMID:24746476

  10. Beyond the joint: Subclinical atherosclerosis in rheumatoid arthritis

    PubMed Central

    Scarno, Antongiulio; Perrotta, Fabio Massimo; Cardini, Francesca; Carboni, Alessia; Annibali, Gianmarco; Lubrano, Ennio; Spadaro, Antonio

    2014-01-01

    Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with increased cardiovascular risk and higher mortality in respect to general population. Beyond joint disease, inflammation is the major determinant of accelerated atherosclerosis observed in rheumatoid arthritis. We review the relationship between inflammation, atherosclerosis and cardiovascular risk in rheumatoid arthritis, focusing on the assessment of subclinical atherosclerosis by functional and morphological methods. These tools include flow mediated dilatation, carotid intima-media thickness, ankle/brachial index, coronary calcium content, pulse wave analysis and serum biomarker of subclinical atherosclerosis. PMID:25035836

  11. Modelling the cost effectiveness of TNF  antagonists in the management of rheumatoid arthritis: results from the British Society for Rheumatology Biologics Registry

    Microsoft Academic Search

    A. Brennan; N. Bansback; R. Nixon; J. Madan; M. Harrison; K. Watson; D. Symmons

    2007-01-01

    Objective. To evaluate the cost effectiveness of TNF-? antagonist therapies for rheumatoid arthritis (RA) in the United Kingdom using data from the British Society for Rheumatology Biologics Registry (BSRBR). Methods. A simulation model is constructed to quantify the cost effectiveness of the TNF-? antagonist therapies (infliximab, etanercept and adalimumab) as a group versus traditional disease-modifying anti-rheumatic drugs, with a time

  12. Early stages of carbonate mineralization revealed from molecular simulations: Implications for biomineral formation

    NASA Astrophysics Data System (ADS)

    Wallace, A. F.; DeYoreo, J.; Banfield, J. F.

    2011-12-01

    The carbonate mineral constituents of many biomineralized products, formed both in and ex vivo, grow by a multi-stage crystallization process that involves the nucleation and structural reorganization of transient amorphous phases. The existence of transient phases and cluster species has significant implications for carbonate nucleation and growth in natural and engineered environments, both modern and ancient. The structure of these intermediate phases remains elusive, as does the nature of the disorder to order transition, however, these process details may strongly influence the interpretation of elemental and isotopic climate proxy data obtained from authigenic and biogenic carbonates. While molecular simulations have been applied to certain aspects of crystal growth, studies of metal carbonate nucleation are strongly inhibited by the presence of kinetic traps that prevent adequate sampling of the potential landscape upon which the growing clusters reside within timescales accessible by simulation. This research addresses this challenge by marrying the recent Kawska-Zahn (KZ) approach to simulation of crystal nucleation and growth from solution with replica-exchange molecular dynamics (REMD) techniques. REMD has been used previously to enhance sampling of protein conformations that occupy energy wells that are separated by sizable thermodynamic and kinetic barriers, and is used here to probe the initial formation and onset of order within hydrated calcium and iron carbonate cluster species during nucleation. Results to date suggest that growing clusters initiate as short linear ion chains that evolve into two- and three-dimensional structures with continued growth. The planar structures exhibit an obvious 2d lattice, while establishment of a 3d lattice is hindered by incomplete ion desolvation. The formation of a dehydrated core consisting of a single carbonate ion is observed when the clusters are ~0.75 nm. At the same size a distorted, but discernible calcite-type lattice is also apparent. Continued growth results in expansion of the dehydrated core, however, complete desolvation and incorporation of cations into the growing carbonate phase is not achieved until the cluster grows to ~1.2 nm. Exploration of the system free energy along the crystallization path reveals "special" cluster sizes that correlate with ion desolvation milestones. The formation of these species comprise critical bottlenecks on the energy landscape and for the establishment of order within the growing clusters.

  13. Simulation of early vision mechanisms and application to object shape recognition

    NASA Astrophysics Data System (ADS)

    Asif, Muhammad; Choi, Tae-Sun

    2004-11-01

    In early stages of vision, the images are processed to generate "maps" or point-by point distributions of values of various quantities including the edge elements, fields of local motion, depth maps and color constancy, etc. These features are then refined and processed in visual cortex. The next stage is recognition which also leads to simple control of behaviors such as steering and obstacle avoidance, etc. In this paper we present a system for object shape recognition that utilizes the features extracted by use of human vision model. The first block of the system performs processing analogous to that in retina for edge feature extraction. The second block represents the processing in visual cortex, where features are refined and combined to form a stimulus to be presented to the recognition model. We use the normalized distances of the edge pixels from the mean to form a feature vector. The next block that accomplishes the task of recognition consists of a counterpropagation neural network model. We use gray scale images of 3D objects to train and test the performance of the system. The experiments show that the system can recognize the objects with some variations in rotation, scaling and translation.

  14. Multiscale simulations of the early stages of the growth of graphene on copper

    NASA Astrophysics Data System (ADS)

    Gaillard, P.; Chanier, T.; Henrard, L.; Moskovkin, P.; Lucas, S.

    2015-07-01

    We have performed multiscale simulations of the growth of graphene on defect-free copper (111) in order to model the nucleation and growth of graphene flakes during chemical vapour deposition and potentially guide future experimental work. Basic activation energies for atomic surface diffusion were determined by ab initio calculations. Larger scale growth was obtained within a kinetic Monte Carlo approach (KMC) with parameters based on the ab initio results. The KMC approach counts the first and second neighbours to determine the probability of surface diffusion. We report qualitative results on the size and shape of the graphene islands as a function of deposition flux. The dominance of graphene zigzag edges for low deposition flux, also observed experimentally, is explained by its larger dynamical stability that the present model fully reproduced.

  15. Modeling the energy spectrum of precipitating electrons with early RBSP observations and test particle simulations

    NASA Astrophysics Data System (ADS)

    Kersten, K.; Cattell, C. A.; Wygant, J. R.; Breneman, A. W.; Bonnell, J. W.; Tao, J.; Blake, B.; Kletzing, C.; Kurth, W. S.; Roth, I.; Zhang, S.

    2012-12-01

    The Radiation Belt Storm Probe satellites (RBSP) allow for unprecedented simultaneous measurement of both high time resolution VLF wave fields and local energetic electron pitch angle and energy distributions. By coupling these measurements with relativistic test particle simulations, we attempt to assess the role of oblique whistler wave-particle interactions in the acceleration, transport, and loss of energetic radiation belt electrons. The relativistic test particle code is capable of tracking the individual trajectories of large populations of particles interacting with oblique whistler mode waves through bounce and gyromotion in a magnetic dipole guide field scaled to Earth's surface field, allowing for simple quantification of test particle scattering and loss. By weighting input energy and pitch angle distributions by those observed with RBSP, we attempt to model the expected energy spectrum of the precipitating electron population, e.g., what may be observed at BARREL due to wave-particle interactions in the radiation belts.

  16. Early treatment in early undifferentiated arthritis.

    PubMed

    Olivieri, Ignazio; Sarzi-Puttini, Piercarlo; Bugatti, Serena; Atzeni, Fabiola; d'Angelo, Salvatore; Caporali, Roberto

    2012-06-01

    The early diagnosis of new-onset rheumatoid arthritis (RA) has become a major objective for rheumatologists in order to identify a management strategy able to change the natural history of the disease and to prevent joint damage and functional impairment. Emergent evidence emphasizes the benefits of early aggressive therapy of RA. By the nineties, early arthritis cohorts have been collected throughout the world with the aim to increase the early referral of patients with early onset disease by the general practitioners and to collect data on the development of full-blown RA. The frequency of undifferentiated arthritis (UA) ranged from 23% to 81% in these early cohorts with most of them reporting a rate of 30%. The transition rate from UA to RA was between 13% and 54%. A percentage of 20-60% of patients with UA had a self-limiting disease. Our article deals with the controversy existing in the management of UA. Should every patient with UA be treated? Could patients with a favorable disease course be exposed to unnecessary risk with initiation of aggressive therapy with synthetic disease-modifying anti-rheumatic drugs (DMARDs) or biologic agents? The pros and cons of treating patients with UA are examined. PMID:22037115

  17. Challenges in the management of rheumatoid arthritis in developing countries.

    PubMed

    Mody, Girish M; Cardiel, Mario H

    2008-08-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease which is characterized by chronic inflammation of the joints. Patients experience chronic pain and suffering, and increasing disability; without treatment, life expectancy is reduced. It is imperative to identify patients early so that control of inflammation can prevent joint destruction and disability. Although great advances have been made in the developed nations, early diagnosis remains a great challenge for developing countries during the Bone and Joint Decade (2000-2010) and beyond. Developing countries face important and competitive social, economic, health- and poverty-related issues, and this frequently results in chronic diseases such as RA being forgotten in health priorities when urgent health needs are considered in an environment with poor education and scarce resources. Epidemiological studies in developing countries show a lower but still important prevalence in different regions when compared to that in Caucasians. It seems that the severity of RA varies among different ethnic groups, and probably starts at a younger age in developing countries. Practising rheumatologists in these regions need to take into account several important problems that include suboptimal undergraduate education, inadequate diagnosis, late referrals, lack of human and technical resources, poor access to rheumatologists, and some deficiencies in drug availability. Infections are very important in RA, and special care is needed in developing countries as some endemic infections include tuberculosis, human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. These infections should be carefully taken into account when medications are prescribed and monitored. This chapter presents published information covering the main challenges faced in these environments, and suggests strategies to overcome these important problems in RA management. PMID:18783741

  18. The Clinical Application of Anti-CCP in Rheumatoid Arthritis and Other Rheumatic Diseases

    PubMed Central

    Chou, CT; Liao, HT; Chen, CH; Chen, WS; Wang, HP; Su, KY

    2007-01-01

    Rheumatoid arthritis (RA) is a common rheumatic disease in Caucasians and in other ethnic groups. Diagnosis is mainly based on clinical features. Before 1998, the only serological laboratory test that could contribute to the diagnosis was that for rheumatoid factor (RF). The disease activity markers for the evaluation of clinical symptoms or treatment outcome were the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). As a matter of fact, the diagnosis of early RA is quite impossible, as the clinical criteria are insufficient at the beginning stage of the disease. In 1998, Schelleken reported that a high percentage of RA patients had a specific antibody that could interact with a synthetic peptide which contained the amino acid citrulline. The high specificity (98%) for RA of this new serological marker, anti-cyclic citrullinated antibody (anti-CCP antibody), can be detected early in RA, before the typical clinical features appear. The presence or absence of this antibody can easily distinguish other rheumatic diseases from RA. Additionally, the titer of anti-CCP can be used to predict the prognosis and treatment outcome after DMARDs or biological therapy. Therefore, with improvement of sensitivity, the anti-CCP antibody will be widely used as a routine laboratory test in the clinical practice for RA. PMID:19662201

  19. Postcollapse hydrodynamics of SN 1987A - Two-dimensional simulations of the early evolution

    NASA Technical Reports Server (NTRS)

    Herant, Marc; Benz, Willy; Colgate, Stirling

    1992-01-01

    The first few seconds of the explosion of SN 1987A are modeled here using a 2D cylindrical geometry smooth particle hydrodynamics code. The success of the explosion is determined to be sensitive to the duration of the infall, the timing of the bounce, and the subsequent neutrino heating. A semianalytical model for the initial structure of the collapsed object is used to present two simulations that differ by the mass that has been allowed to collapse into a neutron star prior to the bounce. In the case of a short initial infall, the explosion fails due to excessive cooling. For a longer initial infall, the cooling is less and the explosion is successful although relatively weak. It is shown that in this case, a successful explosion is brought about by the presence of an entropy gradient which, combined with the gravitational pull of the neutron star, leads to extremely strong instabilities. The critical importance of the global circulation for the success of the explosion is demonstrated.

  20. Postcollapse hydrodynamics of SN 1987A - Two-dimensional simulations of the early evolution

    SciTech Connect

    Herant, M.; Benz, W.; Colgate, S. (Harvard-Smithsonian Center for Astrophysics, Cambridge, MA (United States) Steward Observatory, Tucson, AZ (United States) Los Alamos National Laboratory, NM (United States))

    1992-08-01

    The first few seconds of the explosion of SN 1987A are modeled here using a 2D cylindrical geometry smooth particle hydrodynamics code. The success of the explosion is determined to be sensitive to the duration of the infall, the timing of the bounce, and the subsequent neutrino heating. A semianalytical model for the initial structure of the collapsed object is used to present two simulations that differ by the mass that has been allowed to collapse into a neutron star prior to the bounce. In the case of a short initial infall, the explosion fails due to excessive cooling. For a longer initial infall, the cooling is less and the explosion is successful although relatively weak. It is shown that in this case, a successful explosion is brought about by the presence of an entropy gradient which, combined with the gravitational pull of the neutron star, leads to extremely strong instabilities. The critical importance of the global circulation for the success of the explosion is demonstrated. 43 refs.

  1. SIMULATIONS OF EARLY BARYONIC STRUCTURE FORMATION WITH STREAM VELOCITY. II. THE GAS FRACTION

    SciTech Connect

    Naoz, Smadar [Institute for Theory and Computation, Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States)] [Institute for Theory and Computation, Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Yoshida, Naoki [Department of Physics, University of Tokyo, Tokyo 113-0033 (Japan)] [Department of Physics, University of Tokyo, Tokyo 113-0033 (Japan); Gnedin, Nickolay Y., E-mail: snaoz@cfa.harvard.edu [Particle Astrophysics Center, Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States)

    2013-01-20

    Understanding the gas content of high-redshift halos is crucial for studying the formation of the first generation of galaxies and reionization. Recently, Tseliakhovich and Hirata showed that the relative 'stream' velocity between the dark matter and baryons at the time of recombination-formally a second-order effect, but an unusually large one-can influence the later structure formation history of the universe. We quantify the effect of the stream velocity on the so-called characteristic mass-the minimum mass of a dark matter halo capable of retaining most of its baryons throughout its formation epoch-using three different high-resolution sets of cosmological simulations (with separate transfer functions for baryons and dark matter) that vary in box size, particle number, and the value of the relative velocity between the dark matter and baryons. In order to understand this effect theoretically, we generalize the linear theory filtering mass to properly account for the difference between the dark matter and baryonic density fluctuation evolution induced by the stream velocity. We show that the new filtering mass provides an accurate estimate for the characteristic mass, while other theoretical ansatzes for the characteristic mass are substantially less precise.

  2. Drug Therapy for Rheumatoid Arthritis in Adults: An Update

    MedlinePLUS

    ... Players, and Plug-ins EHC Component EPC Project Topic Title Drug Therapy for Rheumatoid Arthritis in Adults: ... Review Jun. 1, 2012 Related Products for this Topic Research Protocol Dec. 6, 2010 Executive Summary Apr. ...

  3. Common Therapy for Rheumatoid Arthritis Reduces Risk of Death

    MedlinePLUS

    ... for Rheumatoid Arthritis Reduces Risk of Death Taking methotrexate—a commonly prescribed anti-inflammatory medication—may reduce ... diseases. Previous studies have suggested that treatment with methotrexate is associated with a lower risk of death ...

  4. Drug for Rheumatoid Arthritis May Also Help Ease Vitiligo

    MedlinePLUS

    Drug for Rheumatoid Arthritis May Also Help Ease Vitiligo Case study showed tofacitinib cleared up skin pigmentation ... treatment for the discoloring skin condition known as vitiligo. Vitiligo is characterized by a disfiguring loss of ...

  5. Impact of Rheumatoid Arthritis Disease Activity Test on Clinical Practice

    PubMed Central

    Peabody, John W.; Strand, Vibeke; Shimkhada, Riti; Lee, Rachel; Chernoff, David

    2013-01-01

    Background Variability exists in the assessment of disease activity in rheumatoid arthritis (RA) patients that may affect quality of care. Objectives To measure the impact on quality of care of a Multi-Biomarker Disease Activity (MBDA) test that quantitatively assesses RA disease activity. Methods Board-certified rheumatologists without prior experience with the MBDA test (N?=?81) were randomized into an intervention or control group as part of a longitudinal randomized-control study. All physicians were asked to care for three simulated RA patients, using Clinical Performance and Value (CPV™) vignettes, in a before and after design. CPV™ vignettes have been validated to assess the quality of clinical practice and identify variation in care. The vignettes covered all domains of a regular patient visit; scores were determined as a percentage of explicit predefined criteria completed. Three vignettes, representing typical RA cases, were administered each round. In the first round, no physician received information about the MBDA test. In the second round, only physicians in the intervention group were given educational materials about the test and hypothetical test results for each of the simulated patients. The outcome measures were the overall quality of care, disease assessment and treatment. Results The overall quality scores in the intervention group improved by 3 percent (p?=?0.02) post-intervention compared with baseline, versus no change in the control group. The greatest benefit in the intervention group was to the quality of disease activity assessment and treatment decisions, which improved by 12 percent (p<0.01) compared with no significant change in the control group. The intervention was associated with more appropriate use of biologic and/or combination DMARDs in the co-morbidity case type (p<0.01). Conclusions Based on these results, use of the MBDA test improved the assessment and treatment decisions for simulated cases of RA and may prove useful for rheumatologists in clinical practice. PMID:23667587

  6. Rubens and the question of antiquity of rheumatoid arthritis.

    PubMed

    Appelboom, T; de Boelpaepe, C; Ehrlich, G E; Famaey, J P

    1981-02-01

    Analysis of the hands in paintings attributed to Peter Paul Rubens during the last 30 years of his life seems to show progressive rheumatoid arthritis. Not only does this suggest that rheumatoid arthritis was present at the time, 200 years before some modern authors are willing to date its appearance, but also that Rubens or a major and consistent collaborator suffered from the disease. PMID:7005475

  7. Breast lumps: a rare site for rheumatoid nodules.

    PubMed

    Iqbal, Fahad Mujtaba; Ali, Hiam; Vidya, Raghavan

    2015-01-01

    Granulomatous mastitis (GM) of the breast is a rare benign inflammatory disease and its presentation closely mimics breast cancer. Its diagnosis is mainly based on histology and there is no consensus agreement regarding its management. We report a case of a 60-year-old woman presenting with a right breast lump associated with a history of rheumatoid arthritis and raised rheumatoid factor. Following triple assessment (history and examination, imaging and biopsy), GM was diagnosed and she was treated conservatively. PMID:25903203

  8. Impact of rheumatoid arthritis on sexual function

    PubMed Central

    Tristano, Antonio G

    2014-01-01

    Sexuality is a complex aspect of the human being’s life and is more than just the sexual act. Normal sexual functioning consists of sexual activity with transition through the phases from arousal to relaxation with no problems, and with a feeling of pleasure, fulfillment and satisfaction. Rheumatic diseases may affect all aspects of life including sexual functioning. The reasons for disturbing sexual functioning are multifactorial and comprise disease-related factors as well as therapy. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by progressive joint destruction resulting from chronic synovial inflammation. It leads to various degrees of disability, and ultimately has a profound impact on the social, economic, psychological, and sexual aspects of the patient’s life. This is a systemic review about the impact of RA on sexual functioning. PMID:24829873

  9. Adipokines as Potential Biomarkers in Rheumatoid Arthritis

    PubMed Central

    Del Prete, Annalisa; Salvi, Valentina; Sozzani, Silvano

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease characterized by severe joint injury. Recently, research has been focusing on the possible identification of predictor markers of disease onset and/or progression, of joint damage, and of therapeutic response. Recent findings have uncovered the role of white adipose tissue as a pleiotropic organ not only specialized in endocrine functions but also able to control multiple physiopathological processes, including inflammation. Adipokines are a family of soluble mediators secreted by white adipose tissue endowed with a wide spectrum of actions. This review will focus on the recent advances on the role of the adipokine network in the pathogenesis of RA. A particular attention will be devoted to the action of these proteins on RA effector cells, and on the possibility to use circulating levels of adipokines as potential biomarkers of disease activity and therapeutic response. PMID:24799765

  10. Moving towards personalized medicine in rheumatoid arthritis.

    PubMed

    de Jong, Tamarah D; Vosslamber, Saskia; Verweij, Cornelis L

    2014-01-01

    To develop personalized medicine strategies for improvement of patient management in rheumatoid arthritis, the clinical and molecular properties of the individual patients need to be well characterized. A crucial step in this approach is to discover subgroups of patients that are characterized by a good or poor treatment outcome. Dennis and colleagues have identified distinct pretreatment gene expression profiles in affected synovial tissue specimens and a tissue type-related systemic protein pattern which are associated with a positive or negative clinical outcome to monotherapy with adalumimab (anti-TNF?) and tocilizumab (anti-IL-6 receptor). These observations assign biological pathways associated with response outcome and provide evidence for the existence of systemic,easy-to-measure predictive biomarkers for clinical benefit of these biologics. PMID:25166016

  11. Light scattering study of rheumatoid arthritis

    SciTech Connect

    Beuthan, J; Netz, U; Minet, O; Mueller, G [Institut fur Medizinische Physik/Laser-medizin, Freie Universitat Berlin, Universitaetsklinikum Benjamin Franklin, Berlin (Germany); Klose, Annerose D; Hielscher, A H [Columbia University, New York (United States); Scheel, A [Department of Medicine, Nephrology and Rheumatology, Georg-August-University, Goettingen (Germany); Henniger, J [Department of Physics, Technical University Dresden (Germany)

    2002-11-30

    The distribution of light scattered by finger joints is studied in the near-IR region. It is shown that variations in the optical parameters of the tissue (scattering coefficient {mu}{sub s}, absorption coefficient {mu}{sub a}, and anisotropy factor g) depend on the presence of the rheumatoid arthritis (RA). At the first stage, the distribution of scattered light was measured in diaphanoscopic experiments. The convolution of a Gaussian error function with the scattering phase function proved to be a good approximation of the data obtained. Then, a new method was developed for the reconstruction of distribution of optical parameters in the finger cross section. Model tests of the quality of this reconstruction method show good results. (laser biology and medicine)

  12. Anti-Citrullinated Peptide Antibody (ACPA) Assays and their Role in the Diagnosis of Rheumatoid Arthritis

    PubMed Central

    Aggarwal, Rohit; Liao, Katherine; Nair, Raj; Ringold, Sarah; Costenbader, Karen H.

    2010-01-01

    Increasingly, assays for the detection of anti-citrullinated peptide antibodies (ACPA) are used in RA diagnosis. This review summarizes the biologic basis and development of ACPA assays, available ACPA assays and their performance characteristics, and diagnostic properties of ACPA alone and compared to rheumatoid factor (RF) in early RA. We also review correlations, precision, costs and cost-effectiveness, availability, stability and reproducibility of the available assays. Taken together, data indicate that ACPA has a higher specificity than RF for early RA, good predictive validity, high sensitivity, apparent cost-effectiveness and good stability and reproducibility. Given its superior performance characteristics and increasing availability, ACPA is emerging as the most useful single assay for the diagnosis of RA. PMID:19877103

  13. Inflammatory lesions in the bone marrow of rheumatoid arthritis patients: a morphological perspective

    PubMed Central

    2012-01-01

    The synovial tissue stands at the epicenter of joint pathology in rheumatoid arthritis (RA). As a primary target of the disease, studies on the synovium have provided invaluable insights into the mechanisms involved in disease pathogenesis. Recent work has, however, revealed the importance of a previously unseen anatomic compartment in direct contact with the joint space, namely the subchondral bone marrow. Bone marrow edema (BME) visible on magnetic resonance imaging (MRI) is clinically meaningful in both early and late RA as it associates with future development of bone erosions and poor functional outcomes. Although the histopathologic correlates of MRI-based BME in early RA remain obscure, studies in advanced disease are consistent in describing lymphocytic inflammatory infiltrates within the subchondral marrow cavity of affected joints. In this review, we discuss the nature of bone marrow lesions in patients with RA, analyze their relationship with synovitis, and explore their potential contribution to the pathological processes of the disease. PMID:23270711

  14. Occurrence of a rheumatoid factor cross-reactive kappa light-chain idiotope in rheumatoid arthritis families

    Microsoft Academic Search

    R. E. Schrohenloher; G. S. Alarcón; W. J. Koopman

    1990-01-01

    The occurrence of IgM rheumatoid factor (RF) and RF-associated?-III light-chain idiotope identified by monoclonal antibody 6B6.6 in the serum from 22 patients with rheumatoid arthritis (RA) and 68 relatives without connective tissue diseases in 15 families was determined by solid-phase enzyme-linked immunosorbent assays. Serum IgM RF was present in 19 RA patients from 12 families and 12 arthritis-free relatives of

  15. Modeling and simulation of blast-induced, early-time intracranial wave physics leading to traumatic brain injury.

    SciTech Connect

    Ford, Corey C. (University of New Mexico, Albuquerque, NM); Taylor, Paul Allen

    2008-02-01

    The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution (1 mm{sup 3} voxels), 5 material model of the human head was created by segmentation of color cryosections from the Visible Human Female dataset. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH, and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior and lateral directions. Three dimensional plots of maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric (shear) stress within the first 2 milliseconds of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 msec time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.

  16. Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity

    PubMed Central

    Curtis, Jeffrey R; van der Helm-van Mil, Annette H; Knevel, Rachel; Huizinga, Tom W; Haney, Douglas J; Shen, Yijing; Ramanujan, Saroja; Cavet, Guy; Centola, Michael; Hesterberg, Lyndal K; Chernoff, David; Ford, Kerri; Shadick, Nancy A; Hamburger, Max; Fleischmann, Roy; Keystone, Edward; Weinblatt, Michael E

    2012-01-01

    Objective Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts. Methods Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6–12 weeks after initiation of anti–tumor necrosis factor or methotrexate treatment were evaluated by the AUROC. Results The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28-CRP (P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6–12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses (P = 0.03) and DAS28-CRP improvement (P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P = 0.02). Conclusion Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an objective measure of RA disease activity to aid in the management of RA in patients with this condition. PMID:22736476

  17. Leaders’ and followers’ individual experiences during the early phase of simulation-based team training: an exploratory study

    PubMed Central

    Meurling, Lisbet; Hedman, Leif; Felländer-Tsai, Li; Wallin, Carl-Johan

    2013-01-01

    Background A growing body of evidence shows that team training can develop essential team skills and contribute to better patient outcomes. Current simulation-based team training (SBTT) programmes most often include targets and feedback focused on the whole team and/or leader, ignoring the follower as a unique entity. By considering followers’ individual experiences, and tailoring behavioural targets for training and feedback, SBTT could be improved. Our aim was to explore the individual experiences and behaviours of leaders and followers during the early phase of SBTT, and we hypothesised that leaders and followers would show different responses. Methods Medical students (n=54) participated in half-day SBTT including three video-recorded scenarios. Self-efficacy was assessed pretraining and post-training. For each scenario (n=36), the individual teamwork behaviours, concentration, mental strain and the team's clinical performance were recorded. Data were analysed using a mixed model allowing for participants to be their own control in their roles as leader or follower. Results Self-efficacy improved. In the role of leader, participants communicated to a greater extent and experienced higher mental strain and concentration than they did in the role of follower. Discussion The increased self-efficacy enables a positive learning outcome after only three scenarios. Individual experiences and behaviours differed between the role of leader and that of follower. By shedding further light on leaders’ and followers’ individual experiences and behaviours, targets for training and feedback could be specified in order to improve SBTT. PMID:23293119

  18. Molecular dynamical simulation of the behavior of early precipitated stage in aging process in dilute Cu-Cr alloy

    SciTech Connect

    Feng, J.; Liu, L.; Chen, J.; Du, Y.; Zhou, R. [Key Laboratory of Advanced Materials of Precious-Nonferrous Metals, Education Ministry of China, and Key Lab of Advanced Materials of Yunnan Province, Kunming University of Science and Technology, Kunming 650093 (China); Xiao, B. [Department of Physics, School of Science and Engineering, Tulane University, New Orleans 70118 (United States)

    2010-06-15

    The aging behaviors of Cu-Cr alloys in the early stage at different temperatures are investigated by molecular dynamics simulations. First principles potentials are used for the interactions between Cu and Cr atoms. The initial behavior of precipitation is characterized by transmission electron microscope and electron energy disperse spectroscopy. The results showed that Cu-Cr supersaturated solid solution is thermodynamically unstable. The mean-square displacements of the atoms are used to describe the diffusivity. At room temperature, the atoms only show harmonic vibrations near the equilibrium positions. The mutual diffusion at 873 K is different from the unidirectional diffusion in low temperatures. The calculation shows that aging process is accelerated with increasing temperature, which is not only due to the lower diffusion activation energy of Cr at higher temperature, but also because Cu atoms are also participated in the aging process. When ''aging'' at 1073 K, the precipitation of Cr element is dissolved again into Cu matrix, which is an ''over-aging'' state of Cu-Cr alloy at high temperature.

  19. Rheumatoid Arthritis When Your Immune System Attacks Your Body | NIH MedlinePlus the Magazine

    MedlinePLUS

    ... Understanding Rheumatoid Arthritis (RA) Rheumatoid Arthritis When Your Immune System Attacks Your Body Past Issues / Summer 2014 Table ... disease, which means the arthritis results from your immune system attacking your body's own tissues. The course of ...

  20. Rheumatoid Arthritis When Your Immune System Attacks Your Body | NIH MedlinePlus the Magazine

    MedlinePLUS

    ... In an autoimmune disease like rheumatoid arthritis, the immune system turns against parts of the body it is ... In an autoimmune disease like rheumatoid arthritis, the immune system turns against parts of the body it is ...

  1. New Insights Found in Pain Processing and Sleep Disturbance Among Rheumatoid Arthritis Patients

    MedlinePLUS

    ... 2013 New Insights Found in Pain Processing and Sleep Disturbance Among Rheumatoid Arthritis Patients People with rheumatoid ... in the journal Arthritis and Rheumatism. In addition, sleep disruptions, which are common among people with RA, ...

  2. Citrullinated peptides in the diagnosis of rheumatoid arthritis.

    PubMed

    Gómara, María J; Haro, Isabel

    2013-01-01

    Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing rheumatoid arthritis (RA). ACPAs may be detected several years before symptoms of RA appear, and their presence at disease onset is a good predictor of the development of erosive joint lesions. RA patients can be classified into two major groups: those who have ACPAs and those who do not. The presence of ACPAs at early stages of RA predicts the development of earlier and more widespread joint erosions, and low remission rates.Synthetic peptides can replace cognate proteins in solid-phase assays for specific autoantibody recognition in RA patients. The use of synthetic peptides instead of proteins represents an advantage in terms of the reproducibility of such immunoassays. Proteins also contain non-citrullinated epitopes that are recognized by non-RA sera and this could reduce the specificity of the test. The use of synthetic citrullinated peptides gives absolute control over the exact epitopes presented. Furthermore, it is difficult to prepare sufficient amounts of high-quality antigenic proteins with a well-defined degree of citrullination. Synthetic citrullinated peptides, in contrast, are easily obtained in a pure form with a well-defined chemical structure and the epitopes can be precisely oriented in the plate by covalent binding of the peptides.Chimeric peptides bearing different citrullinated protein domains have recently been used in the design of RA diagnosis systems. The results of the application of those systems indicate that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported (fibrin, vimentin and filaggrin) helps to identify a particular subset of RA patients. PMID:23574523

  3. The role of RANK ligand/osteoprotegerin in rheumatoid arthritis

    PubMed Central

    2012-01-01

    In the complex system of bone remodeling, the receptor activator of nuclear factor ?B ligand (RANKL)/osteoprotegerin (OPG) pathway is the coupling factor between bone formation and bone resorption. RANKL binds to the RANK receptor of pre-osteoclasts and mature osteoclasts and stimulates their activation and differentiation. The production of RANKL/OPG by osteoblasts is influenced by hormones, growth factors and cytokines, which each have a different effect on the production of RANKL and OPG. Ultimately, the balance between RANKL and OPG determines the degree of proliferation and activity of the osteoclasts. In rheumatoid arthritis (RA), bone erosions are the result of osteoclastic bone resorption at the sites of synovitis, where RANKL expression is also found. Furthermore, magnetic resonance imaging (MRI) bone edema in RA indicates the presence of active inflammation within bone and the presence of osteitis, which is also associated with the expression of RANKL. Bone loss has been documented in the cortical and trabecular bone in the joints of the hand of RA patients. Both synovitis and periarticular bone involvement (osteitis and bone loss) are essential components of RA: they occur early in the disease and both are predictive for the occurrence and progression of bone damage. RANKL knockout mice and mice treated with OPG did not develop focal bone loss, in spite of persistent joint inflammation. Inhibition of osteoclasts by denosumab, a humanized antibody that selectively binds RANKL, has revealed in patients with RA that the occurrence of erosions and periarticular bone loss can be halted, however without affecting synovial inflammation. This disconnect between inflammation and bone destruction opens new ways to separately focus treatment on inflammation and osteoclastogenesis for preventing and/or minimizing the connection between joints and subchondral bone and bone marrow. PMID:22859921

  4. Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis.

    PubMed Central

    Gravallese, E. M.; Harada, Y.; Wang, J. T.; Gorn, A. H.; Thornhill, T. S.; Goldring, S. R.

    1998-01-01

    Focal resorption of bone at the bone-pannus interface is common in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and can result in significant morbidity. However, the specific cellular and hormonal mechanisms involved in this process are not well established. We examined tissue sections from areas of bone erosion in patients with RA and JRA. Multinucleated cells (MNCs) were present in resorption lacunae in areas of calcified cartilage and in subchondral bone immediately adjacent to calcified cartilage, as previously described. mRNA for the calcitonin receptor (CTR) was localized to these MNCs in bone resorption lacunae, a finding that definitively identifies these cells as osteoclasts. These MNCs were also positive for tartrate-resistant acid phosphatase (TRAP) mRNA and TRAP enzymatic activity. Occasional mononuclear cells on the bone surface were also CTR positive. Mononuclear cells and MNCs not on bone surfaces were CTR negative. The restriction of CTR-positive cells to the surface of mineralized tissues suggests that bone and/or calcified cartilage provide signals that are critical for the differentiation of hematopoietic osteoclast precursors to fully differentiated osteoclasts. Some MNCs and mononuclear cells off bone and within invading tissues were TRAP positive. These cells likely represent the precursors of the CTR-TRAP-positive cells on bone. Parathyroid hormone receptor mRNA was present in cells with the phenotypic appearance of osteoblasts, in close proximity to MNCs, and in occasional cells within pannus tissue, but not in the MNCs in bone resorption lacunae. These findings demonstrate that osteoclasts within the rheumatoid lesion do not express parathyroid hormone receptor. In conclusion, the resorbing cells in RA exhibit a definitive osteoclastic phenotype, suggesting that pharmacological agents that inhibit osteoclast recruitment or activity are rational targets for blocking focal bone erosion in patients with RA and JRA. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9546355

  5. Diffuse chronic leptomeningitis with seropositive rheumatoid arthritis: report of a case successfully treated as rheumatoid leptomeningitis.

    PubMed

    Shimada, Kota; Matsui, Toshihiro; Kawakami, Misato; Hayakawa, Hiromi; Futami, Hidekazu; Michishita, Kazuya; Takaoka, Hirokazu; Ikenaka, Tatsuoh; Komiya, Akiko; Nakayama, Hisanori; Hagiwara, Futoshi; Sugii, Shoji; Furukawa, Hiroshi; Ozawa, Yoshinori; Tohma, Shigeto

    2009-01-01

    A case of biopsy-confirmed chronic leptomeningitis complicating rheumatoid arthritis in a 53-year old female is reported. Her symptoms included weight loss, severe depression, and pyrexia. Magnetic resonance imaging was useful in diagnosis. Intravenous methylprednisolone was prescribed (1 g/day for 3 days), followed by prednisolone (initial dose of 30 mg daily), and this treatment was effective. Her IgG-index, serum levels of soluble interleukin-2 receptor and ferritin, and cerebrospinal level of interleukin-6 paralleled her clinical course. PMID:19521743

  6. Viruses and lymphocytes in rheumatoid arthritis. I. Studies on cultured rheumatoid lymphocytes.

    PubMed Central

    Norval, M; Hart, H; Marmion, B P

    1979-01-01

    Synovial fluid lymphocytes from patients with rheumatoid arthritis have been examined for evidence of a productive infection with retroviruses by electron microscopy, labelling with 3H-uredine, growth in soft agar, and culturing in conditioned medium. No such viruses were detected. In addition, the synovial lymphocytes were activated before fusion and cocultivation with several cell lines which have proved permissive for primate retroviruses. Monitoring these cultures subsequently by reverse transcriptase assay, labelling with 3H-uridine, and membrane immunofluorescence gave no indication that retroviruses were present. Images PMID:539843

  7. Autoantibodies against interleukin 1? in rheumatoid arthritis: association with long term radiographic outcome

    PubMed Central

    Graudal, N; Svenson, M; Tarp, U; Garred, P; Jurik, A; Bendtzen, K

    2002-01-01

    Objectives: To investigate the possible association of interleukin 1? autoantibodies (IL1? aAb) with the long term course of joint erosion in patients with rheumatoid arthritis (RA). Methods: Serum samples from 176 patients with RA included in a prospective study over 30 years were analysed for IL1? aAb by binding to human [125I]IL1?. Erosions of 19 diarthrodial joints were radiographically scored by the Larsen method. Results: The relative risk (RR) of early IL1? aAb positive patients developing at least 30% of maximum radiographic joint destruction was significantly lower than for IL1? aAb negative patients, RR=0.29 (p=0.04). In rheumatoid factor positive patients RR was only 0.18 (p=0.02). Patients who seroconverted more than two years after the onset of RA showed the most aggressive development of joint erosion, with a relative risk of at least 40% of maximum radiographic joint destruction of 2.56 (p=0.048) Conclusions: The progression of radiographic joint destruction in patients with RA is associated with, and perhaps modified by, circulating IL1? aAb, suggesting that IL1? or IL1? aAb, or both, have a role in the erosive processes. IL1? aAb appear to be of prognostic significance in RA. PMID:12079899

  8. Evaluation of human serum of severe rheumatoid arthritis by confocal Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Carvalho, C. S.; Raniero, L.; Santo, A. M. E.; Pinheiro, M. M.; Andrade, L. E. C.; Cardoso, M. A. G.; Junior, J. S.; Martin, A. A.

    2010-02-01

    Rheumatoid Arthritis is a systemic chronic inflammatory disease, recurrent and systemic, initiated by autoantibodies and maintained by inflammatory mechanisms cellular applicants. The evaluation of this disease to promote early diagnosis, need an associations of many tools, such as clinical, physical examination and thorough medical history. However, there is no satisfactory consensus due to its complexity. In the present work, confocal Raman spectroscopy was used to evaluate the biochemical composition of human serum of 40 volunteers, 24 patients with rheumatoid arthritis presenting clinical signs and symptoms, and 16 healthy donors. The technique of latex agglutination for the polystyrene covered with human immunoglobulin G and PCR (protein c-reactive) was performed for confirmation of possible false-negative results within the groups, facilitating the statistical interpretation and validation of the technique. This study aimed to verify the changes for the characteristics Raman peaks of biomolecules such as immunoglobulins amides and protein. The results were highly significant with a good separation between groups mentioned. The discriminant analysis was performed through the principal components and correctly identified 92% of the donors. Based on these results, we observed the behavior of arthritis autoimmune, evident in certain spectral regions that characterize the serological differences between the groups.

  9. Ultrasound versus conventional radiography in the assessment of bone erosions in rheumatoid arthritis.

    PubMed

    Salaffi, Fausto; Gutierrez, Marwin; Carotti, Marina

    2014-01-01

    Bone erosions are the hallmark of joint damage in rheumatoid arthritis and both their detection and increase in number and/or in size are indicative of a poor outcome. To date, conventional radiography is still the most common imaging tool adopted for detecting and scoring joint damage in daily clinical practice, in spite of its low sensitivity with respect computerised tomography, magnetic resonance imaging or ultrasound. Ultrasound is a rapidly evolving technique that is gaining an increasing success in the assessment of patients with rheumatoid arthritis. It permits an early detection and careful characterisation of bone erosions playing a key role in both diagnostic and therapeutic procedures. Ultrasound presents several advantages over other imaging techniques: it is patient-friendly, safe and non-invasive, free of ionising radiation, less expensive, and permit multiple target assessment in real time without the need for external referral. The aim of this review is to compare conventional radiography and ultrasound in the assessment of bone erosions in RA in daily rheumatology practice and to provide insights into which modality can provide the optimal information for a desired outcome in a given clinical trial or practice situation. PMID:24528649

  10. Value of anti-mutated citrullinated vimentin antibodies in diagnosing rheumatoid arthritis.

    PubMed

    Sghiri, Rim; Bouajina, Elyes; Bargaoui, Dhaker; Harzallah, Latifa; Fredj, Hosni Ben; Sammoud, Samar; Ghedira, Ibtissem

    2008-11-01

    We assessed the diagnostic value of anti-mutated citrullinated vimentin antibodies (anti-MCV) and compared it with those of anti-cyclic citrullinated peptide antibodies (anti-CCP), IgA (ARF), IgM (MRF) and IgG (GRF) rheumatoid factors for rheumatoid arthritis (RA). Serum samples of 170 RA patients, with early and established RA, and 309 controls were tested for anti-MCV, anti-CCP, ARF, MRF and GRF using commercially available ELISA kits. Cut off of different tests was determined with ROC curves. The sensitivity and the specificity of anti-MCV were 74.1 and 79%, respectively. Sixty-five of 309 (21%) controls were anti-MCV positive. Sensitivity and specificity of anti-CCP were 72.4 and 96.1%, respectively. Only 12 of 309 (3.9%) controls were anti-CCP positive. Sensitivity of ARF, MRF and GRF were 64.1, 65.9 and 68.2%, respectively. Their specificity was 79.6, 74.4 and 68.9%, respectively. No significant association was observed between the antibodies tested and extrarticular manifestations. Anti-MCV shows comparable sensitivity but lower specificity than that of anti-CCP. They do not appear to be very useful in the diagnosis of RA. PMID:18496693

  11. The use of citrullinated peptides and proteins for the diagnosis of rheumatoid arthritis.

    PubMed

    Pruijn, Ger Jm; Wiik, Allan; van Venrooij, Walther J

    2010-01-01

    The presence or absence of antibodies to citrullinated peptides/proteins (ACPA) is an important parameter that helps a clinician set a diagnosis of early rheumatoid arthritis and, hence, initiate treatment. There are several commercial tests available to measure ACPA levels, although it can be difficult to decide what the best test for a given clinical question is. We analyzed literature data in which the diagnostic and other properties of various ACPA tests are compared. The results show that for diagnostic purposes the CCP2 test has the highest specificity, the highest sensitivity in stratified studies and the highest positive predictive value. For the prediction of future joint destruction the CCP2, MCV, and CCP3 tests may be used. The ability to predict the likelihood of not achieving sustained disease-modifying antirheumatic drug-free remission was highest for the CCP2 test. Finally, the levels of anti-CCP2 and anti-CCP3 (and possibly anti-mutated citrullinated vimentin) in rheumatoid arthritis patients are not significantly influenced by TNFalpha blocking agents. PMID:20236483

  12. Increased risk of revision for infection in rheumatoid arthritis patients with total hip replacements.

    PubMed

    Schrama, Johannes Cornelis; Fenstad, Anne M; Dale, Håvard; Havelin, Leif; Hallan, Geir; Overgaard, Søren; Pedersen, Alma B; Kärrholm, Johan; Garellick, Göran; Pulkkinen, Pekka; Eskelinen, Antti; Mäkelä, Keijo; Engesæter, Lars B; Fevang, Bjørg-Tilde

    2015-08-01

    Background and purpose - Medical treatment of rheumatoid arthritis (RA) has changed dramatically over the last 15 years, including immune modulation. We investigated the risk of revision for infection after primary total hip replacement (THR) in patients with rheumatoid arthritis over a 16-year period, and compared it with that in THR patients with osteoarthritis (OA). Patients and methods - We identified 13,384 THRs in RA patients and 377,287 THRs in OA patients from 1995 through 2010 in a dataset from the Nordic Arthroplasty Register Association (NARA). Kaplan-Meier survival curves, with revision for infection as the endpoint, were constructed. Cox regression analyses were performed to calculate the relative risk (RR) of revision for infection adjusted for age, sex, fixation technique, and year of primary surgery. Results - RA patients had a 1.3 times (95% CI 1.0-1.6) higher risk of revision for infection. After 2001, this risk increased more for RA patients than for OA patients. During the first 3 months and from 8 years postoperatively, the risk of revision for infection was higher in RA patients with THRs fixated with antibiotic-loaded cement than in corresponding OA patients. Interpretation - We found a slightly higher overall risk of revision for infection in RA patients than in OA patients, but this difference was only present after 2001. In THRs with antibiotic-loaded cement, the risk of very early and late infections leading to revision was higher in RA patients than in OA patients. PMID:25782042

  13. Detection of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis patients undergoing total knee arthroplasty

    PubMed Central

    Guo, Chong-Jun; Lv, Jin-Han; Niu, Dong-Sheng; Ma, Tao; Sun, Shou-Xuan; Li, Li-Xin; Zhao, Xin; Wu, Long; Jin, Qun-Hua

    2015-01-01

    Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disorder and anti-cyclic citrullinated peptide antibody (anti-CCP Ab) is regarded as a serological marker for diagnosing early and late RA. In the present study, we aimed to determine the levels of anti-CCP Ab in serum, synovial tissue (ST) and synovial fluid (SF) in RA patients undergoing total knee arthroplasty (TKA). 23 patients were included. Rheumatoid factor (RF) and anti-CCP Ab in serum were detected prior to surgery and then at 1, 3, 6 and 12 months after TKA. Synovial samples were obtained by knee arthroscopy and used for anti-CCP detection. One month after TKA, anti-CCP levels were significantly reduced (P < 0.01) in RA patients. However, their levels were not significantly different between pre-surgery and 1 year post-surgery (P > 0.05). Furthermore, anti-CCP levels in ST were much higher than in serum. These findings suggest that RA patients should continue antirheumatic therapy after TKA. ST is the preferred place for the synthesis of anti-CCP Ab.

  14. Avian viral arthritis as a model for rheumatoid arthritis: a gross, histologic, and immunofluorescent study of experimentally induced viral arthritis in chickens 

    E-print Network

    Wilson, Susan Emmagene

    1976-01-01

    Model for Rheumatoid Arthritis-- A Gross, Histologic, and Immunofluorescent Study of Experimentally Induced Viral Arthritis in Chickens. (August 1976) Susan Emmagene Wilson, B. S. , Texas A&M University D. V. M. , Texas A&M University Chairman... arthritis. In the acute phase the gross changes included edema, hyperemia, and joint effusion. The synovial membrane became noticeably thickened early in the disease. In the chronic disease, fibrosis of tendons and other joint structures became apparent...

  15. Role for osteoprotegerin in rheumatoid inflammation.

    PubMed

    Saidenberg-Kermanac'h, Nathalie; Cohen-Solal, Martine; Bessis, Natacha; De Vernejoul, Marie-Christine; Boissier, Marie-Christophe

    2004-01-01

    Osteoprotegerin (OPG), a member of the TNF-receptor family expressed by osteoblasts, has documented effects on the regulation of bone metabolism. OPG inhibits bone resorption and binds with strong affinity to its ligand RANKL, thereby preventing RANKL from binding to its receptor RANK. This system is regulated by calcium-modifying hormones. OPG may also be pivotal in modulating the immune system. RANKL-deficient mice exhibit both severe immunological abnormalities and osteopetrosis, and activated T cells express RANKL mRNA. RANKL secretion by activated T cells may induce osteoclastogenesis via a mechanism enhanced by several cytokines (TNF-alpha, IL-1, and IL-17) that promote both inflammation and bone resorption. Conversely, this mechanism is inhibited by OPG, IL-4, and IL-10, which have antiinflammatory effects and inhibit osteoclast formation. Activated T cells in the rheumatoid synovium express RANKL. Synoviocytes can differentiate to osteoclast-like cells under specific conditions, particularly when they are cultured with M-CSF and RANKL. Thus, the bony erosions seen in RA may result from RANKL/RANK system activation by activated T cells. This raises the possibility that OPG therapy to block this mechanism might prove beneficial in patients with RA. PMID:14769514

  16. Genetics of neuroendocrine factors in rheumatoid arthritis.

    PubMed

    Mravcova, M; Chovanova, L; Paulikova, L; Vlcek, M; Rovensky, J; Killinger, Z; Wendl, J; Imrich, R

    2015-06-01

    Inadequate production of cortisol related to inflammation and decrease in adrenal androgen production are hallmarks of hypothalamic-pituitary-adrenal (HPA)-related endocrine findings in rheumatoid arthritis (RA). In particular, lower dehydroepiandrosterone sulfate (DHEAS) levels were consistently found in a subset of premenopausal RA females. Recently, several new gene variants have been identified in association with serum DHEAS concentrations, such as in SULT2A1 and HHEX genes. These DHEAS-related genes and other variants involved in HPA regulation may play a role in the adrenal androgen deficiency in RA. The aim of our study was to review involvement of genetic mechanisms of HPA regulation, with focus on adrenal androgens, in the context of RA pathophysiology. Although, effects of the DHEAS-related gene variants appear to be relatively small compared to other well-known factors such as age, complex interactions between DHEAS-associated genotypes and adrenal androgen hypofunction phenotype may exist in RA. Further studies analyzing specific neuroendocrine phenotype/genotype in RA are needed. PMID:25502945

  17. Mutated citrullinated vimentin antibodies in rheumatoid arthritis.

    PubMed

    Kuna, Andrea Tesija

    2012-01-18

    Rheumatoid arthritis (RA) is the most common inflammatory systemic autoimmune disease, primarily affecting the peripheral joints. The past decade has been marked with revolutionary changes both in the therapeutic and diagnostic perspectives of RA. The discovery of an RA-specific citrullination-driven immune reaction gave a substantial contribution in the diagnostic approach to RA. Efforts directed towards the identification of the antigenic target specifically recognized by these autoantibodies resulted in the identification of vimentin in citrullinated form as the potential native antigen, among other proteins. Furthermore, it was found that the mutation of vimentin represents an independent trigger of antigenic properties, in addition to citrullination. As a result of this discovery, a commercial ELISA using mutated citrullinated vimentin (MCV) was developed. Increasingly, data now support the use of anti-MCV in RA diagnosis and prognosis for errosion. This review summarizes the research to date on the use of anti-MCV in RA diagnosis and prognosis and its potential use as a therapeutic marker. The pathologic role of these antibodies in RA disease is also discussed. PMID:22037509

  18. Impaired polymorphonuclear leucocyte chemotaxis in rheumatoid arthritis.

    PubMed Central

    Goddard, D H; Kirk, A P; Kirwan, J R; Johnson, G D; Holborow, E J

    1984-01-01

    This study has investigated the chemotactic activity of polymorphonuclear cells (PMNs) isolated from the blood of patients with either articular rheumatoid arthritis (RA) or RA with extra-articular manifestations. A double fluorochrome immunofluorescent staining test has been employed to identify cell-associated immunoglobulins, probably immune complexes. The results suggest an inverse relationship between PMN chemotaxis and staining for cell-associated immunoglobulins, either surface bound or internalised. PMNs from RA patients showed reduced chemotaxis, and this was further reduced when RA PMNs were incubated for 30 minutes in autologous serum. A similar reduction in chemotaxis of normal PMNs occurred after incubation in RA sera. Preincubation of both RA and normal PMNs in RA serum (but not normal serum) resulted in an increase in the number of cells in which cell-associated immunoglobulins were demonstrable. This further reduction in RA PMN chemotaxis after exposure to autologous serum, together with an increase in immunoglobulin staining, may indicate selection of certain PMNs at the time of venepuncture due to cell margination. Such a selection process would call for a re-evaluation of previous studies of RA PMN function in relation to the disease process. PMID:6324704

  19. Rheumatoid arthritis, spondyloarthropathies, and relapsing polychondritis.

    PubMed

    Ostrowski, Rochella A; Takagishi, Troy; Robinson, John

    2014-01-01

    The neurologic complications of rheumatic disease are highly variable and their manifestations are linked to the pathogenesis and clinical phenotype of the specific rheumatologic syndrome. In active rheumatoid arthritis (RA), the peripheral nervous system is most commonly involved and mononeuritis multiplex, nerve entrapment and vascultitic sensorimotor neuropathy are not uncommon. Central nervous system complications such as pachymeningitis and cerebral vasculitis are rare. TNF blockade therapy of RA is rarely associated with demyelinating syndromes. In the spondyloarthropathies, especially ankylosing spondylitis (AS), neurologic complications are more frequent in long-standing, advanced disease and include atlantoaxial subluxation, cauda equina syndrome, spinal stenosis, and acute vertebral fractures. Peripheral nervous system involvement in any of the spondyloarthropaties is rare. Relapsing polychondritis (RP) is characterized by recurring bouts of inflammation, destruction of cartilaginous structures, and systemic and rarely central nervous system vasculitis. Visual-oculo and auditory complications are common. Definitive treatment of the neurologic complications and prevention of subsequent ones is dependent upon effective treatment of RA, AS or RP. PMID:24365312

  20. Cell-mediated immunity in rheumatoid arthritis.

    PubMed Central

    Andrianakos, A A; Sharp, J T; Person, D A; Lidsky, M D; Duffy, J

    1977-01-01

    Cell-mediated immunity in rheumatoid arthritis (RA) was assessed by skin testing with six antigens in 107 patients, 94 of whom were age, sex, and race-matched with healthy individuals or patients with diseases unrelated to immunological abnormalities. 20% of RA patients were anergic. Impaired cell-mediated immunity in the RA patients was manifested by a decrease in the magnitude of skin reactivity as well as a decrease in the incidence of positive reactions to multiple antigens. Depression in cell-mediated immunity was related to age but not to sex, duration of disease, or disease activity. A slight correlation was found between absolute peripheral lymphocyte counts and the number of positive skin tests, and was confirmed by finding an association between lymphocyte counts and the size of skin reactions. A correlation was also found between lymphocyte counts and disease activity. Four explanations of the observed depression in cell-mediated immunity in RA were considered: (1) a preoccupation of the immune mechanism of the host with cell-mediated immunity reactions related to the pathogenesis of the disease; (2) a depression of cell-mediated immune reactivity by a virus infection; (3) depression of cell-mediated immunity by therapy; and (4) immune complex suppression of cell-mediated immunity. No effect of gold therapy was found. The near universal use of salicylates or other anti-inflammatory drugs did not permit investigation of the effect of these drugs on cell-mediated immunity. PMID:843109

  1. Autoantibodies in rheumatoid arthritis and their clinical significance.

    PubMed

    Steiner, Günter; Smolen, Josef

    2002-01-01

    Autoantibodies are proven useful diagnostic tools for a variety of rheumatic and non-rheumatic autoimmune disorders. However, a highly specific marker autoantibody for rheumatoid arthritis (RA) has not yet been determined. The presence of rheumatoid factors is currently used as a marker for RA. However, rheumatoid factors have modest specificity (~70%) for the disease. In recent years, several newly characterized autoantibodies have become promising candidates as diagnostic indicators for RA. Antikeratin, anticitrullinated peptides, anti-RA33, anti-Sa, and anti-p68 autoantibodies have been shown to have >90% specificity for RA. These autoantibodies are reviewed and the potential role of the autoantibodies in the pathogenesis of RA is briefly discussed. PMID:12110150

  2. Certolizumab pegol: a new biologic targeting rheumatoid arthritis

    PubMed Central

    Patel, Aarat M; Moreland, Larry W

    2013-01-01

    The past decade has been an exciting period for clinical research and patient care in rheumatoid arthritis. This is mostly due to targeted biologic agents that have changed the outcome of this disease. Certolizumab pegol (Cimzia®, UCB Inc., GA, USA), which targets TNF-? with a different mechanism of action than widely used biologics, was initially investigated for Crohn's disease but has now been shown to be effective for rheumatoid arthritis. There have been three significant clinical trials demonstrating the efficacy of certolizumab pegol in active rheumatoid arthritis; two with combination methotrexate and one with monotherapy. This article will summarize the data from those trials and compare some of the characteristics of certolizumab pegol to conventional disease-modifying antirheumatic drugs and other biologic agents. Treatment recommendations are beyond the scope of this review; however, with many options available, there will be annotations on current trends in the care of this chronic disease. PMID:20979550

  3. Ascites and other incidental findings revealing undiagnosed systemic rheumatoid arthritis.

    PubMed

    Szeto, Matthew Chak Hin; Disney, Benjamin; Perkins, Philip; Wood, Gordon

    2015-01-01

    We describe a case of a 43-year-old man presenting to the gastroenterology outpatient department with exudative ascites. Mediastinal lymphadenopathy, pericardial effusion and pleural effusion were detected on further imaging. Further clinical examination revealed subcutaneous nodules on the left arm, which were confirmed to be rheumatoid nodules on histology. Inflammatory markers were elevated with positive serology for rheumatoid factor and anticyclic citrullinated protein antibody. Our investigations excluded tuberculosis, pancreatitis and malignancy in the patient. Following review by a rheumatologist, a diagnosis of systemic rheumatoid arthritis (RA) was made. Pleuritis and pericarditis are well recognised as extra-articular manifestation of RA. Ascites, however, is rarely recognised as a manifestation of RA. Our literature search revealed two other cases of ascites due to RA disease activity, and both patients had long-standing known RA. This case adds to the discussion on whether ascites and peritonitis should be classified as extra-articular manifestations of RA. PMID:26055583

  4. Cells of the synovium in rheumatoid arthritis. Macrophages

    PubMed Central

    Kinne, Raimund W; Stuhlmüller, Bruno; Burmester, Gerd-R

    2007-01-01

    The multitude and abundance of macrophage-derived mediators in rheumatoid arthritis and their paracrine/autocrine effects identify macrophages as local and systemic amplifiers of disease. Although uncovering the etiology of rheumatoid arthritis remains the ultimate means to silence the pathogenetic process, efforts in understanding how activated macrophages influence disease have led to optimization strategies to selectively target macrophages by agents tailored to specific features of macrophage activation. This approach has two advantages: (a) striking the cell population that mediates/amplifies most of the irreversible tissue destruction and (b) sparing other cells that have no (or only marginal) effects on joint damage. PMID:18177511

  5. In vivo imaging approaches in animal models of rheumatoid arthritis

    PubMed Central

    Dustin, Michael L

    2003-01-01

    The interaction of activated leukocytes with the rheumatoid synovial environment is a key process in arthritis. Understanding this process will play an important role in designing effective treatments. In vivo imaging approaches combined with molecular genetics in animal models provide important tools to address these issues. The present review will focus on approaches to in vivo imaging, with particular attention to approaches that are proving useful for, or have promise for, research on animal models of rheumatoid arthritis. These approaches will probably shed light on the specific local mechanisms involved in chronic inflammation and provide real time monitoring approaches to follow cellular and molecular events related to disease development. PMID:12823846

  6. Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

    SciTech Connect

    Kitahara, Kanako [Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541 (Japan); Department of Immunology, Toho University School of Medicine, Tokyo (Japan); Kusunoki, Natsuko [Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541 (Japan); Kakiuchi, Terutaka [Department of Immunology, Toho University School of Medicine, Tokyo (Japan); Suguro, Toru [Department of Orthopaedic Surgery, Toho University School of Medicine, Tokyo (Japan); Kawai, Shinichi [Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo 143-8541 (Japan)], E-mail: skawai@med.toho-u.ac.jp

    2009-01-09

    The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.

  7. Fatal Histoplasma capsulatum mitral endocarditis in a French patient treated for rheumatoid arthritis.

    PubMed

    Letranchant, Lorraine; Debourgogne, Anne; Doco-Lecompte, Thanh; Contet-Audonneau, Nelly; May, Thierry; Machouart, Marie

    2012-03-01

    Histoplasmosis is an infectious disease caused by the inhalation of Histoplasma capsulatum spores, a fungus encountered in many diverse areas around the world. Although this infection is often asymptomatic, it may become dramatic in immunocompromised patients. In November 2005, an endocarditis due to Histoplasma capsulatum was diagnosed in a French woman treated for rheumatoid arthritis and who had traveled to South America 2 years earlier. We confirmed the biological diagnosis by mycological, serological, and histological methods. In spite of receiving the appropriate treatment, the patient died 3 months later of cardiac insufficiency. We report here this additional case of Histoplasma endocarditis, by hoping to help rapid and accurate diagnosis of such infections in their early stages of development, in non-endemic areas. PMID:22042634

  8. [Quality management of treatment of rheumatoid arthritis in a rheumatological setting].

    PubMed

    Hülsemann, Jan L; Mattussek, Sigrid; Hennig, Heide; Stucki, Gerold

    2003-01-01

    Rheumatoid arthritis is a chronic inflammatory rheumatic disease affecting about 1% of the general population world-wide. It is characterised by severe pain and a reduction of functional capacity leading to a reduced quality of life. The initiation of an early, effective, continuous and long-term treatment is essential for preventing or delaying progression of disease as long as possible. The implementation of a comprehensive and structured quality management program including both general practitioners and specialists in rheumatology will help to support structural, procedural and outcome quality based on special indices that can be used for benchmarking. The Swiss Clinical Quality Management (SCQM) and the regional model project of the Regional Co-operative Rheumatology Centre in Hanover, Germany (Regionales Kooperatives Rheumazentrum Hannover e.V.) are two examples for total quality management (TQM) of inflammatory rheumatic diseases. PMID:14524053

  9. Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial

    PubMed Central

    Capell, H; Madhok, R; Hunter, J; Porter, D; Morrison, E; Larkin, J; Thomson, E; Hampson, R; Poon, F

    2004-01-01

    Background: Evidence for disease modifying activity of low dose corticosteroid treatment in rheumatoid arthritis is contradictory. Studies showing radiological benefit suggest that continued treatment is required to sustain the effect. Objective: To evaluate the effect of low dose oral prednisolone in early rheumatoid arthritis on disease activity over two years. Design: Double blind placebo controlled trial. Methods: Patients with rheumatoid arthritis, duration <3 years (n = 167), were started on a disease modifying antirheumatic drug (DMARD; sulphasalazine) and allocated by stratified randomisation to prednisolone 7 mg/day or placebo. Primary outcome measure was radiological damage, assessed by the modified Sharp method. Clinical benefit was a secondary outcome. A proactive approach to identifying and treating corticosteroid adverse events was adopted. Patients who discontinued sulphasalazine were offered an alternative DMARD. Results: 90 of 257 patients eligible for the study refused to participate (more women than men). Of those enrolled, 84% were seropositive for rheumatoid factor, median age 56 years, median disease duration 12 months, female to male ratio 1.8:1. Prednisolone was given to 84 patients; of these 73% continued prednisolone and 70% sulphasalazine at 2 years. Of the 83 patients on placebo, 80% continued placebo and 64% sulphasalazine at 2 years. There were no significant differences in radiological score or clinical and laboratory measures at 0 and 2 years. Conclusions: Low dose prednisolone conferred no radiological or clinical benefit on patients maintained on a DMARD over two years. Low dose corticosteroids have no role in the routine management of rheumatoid arthritis treated with conventional disease modifying drugs. PMID:15194574

  10. The Early Stage of Folding of Villin Headpiece Subdomain Observed in a 200Nanosecond Fully Solvated Molecular Dynamics Simulation

    Microsoft Academic Search

    Yong Duan; Lu Wang; Peter A. Kollman

    1998-01-01

    A new approach in implementing classical molecular dynamics simulation for parallel computers has enabled a simulation to be carried out on a protein with explicit representation of water an order of magnitude longer than previously reported and will soon enable such simulations to be carried into the microsecond time range. We have used this approach to study the folding of

  11. Interleukin 35 Synovial Fluid Levels Are Associated with Disease Activity of Rheumatoid Arthritis

    PubMed Central

    Šenolt, Ladislav; Šumová, Barbora; Jandová, Romana; Hulejová, Hana; Mann, He?man; Pavelka, Karel; Vencovský, Ji?í; Filková, Mária

    2015-01-01

    Objectives To study the association of systemic and local interleukin-35 (IL-35) levels in rheumatoid arthritis. Methods 37 patients with treatment naïve early RA, 49 with established RA and 29 control patients with osteoarthritis (OA) were studied. Serum and paired synovial fluid samples were analysed for IL-35. Disease activity of RA patients was assessed according to the 28-Joint Count Disease Activity Score (DAS28). Results The levels of serum IL-35 were significantly higher in patients with treatment naïve early RA compared to those with established disease and control OA subjects. In addition, serum levels of IL-35 significantly decreased 12 weeks after initiation of glucocorticoids and conventional synthetic disease modifying antirheumatic drugs in patients with treatment naïve early RA. Synovial fluid IL-35 levels were significantly higher in RA compared to OA patients, were significantly elevated compared to serum counterparts and correlated with synovial fluid leukocyte count (r=0.412; p<0.01), serum CRP levels (r=0.362; p<0.05) and DAS28 (r=0.430, p<0.01). Conclusion This is the first study showing elevated circulating levels of IL-35 in treatment naïve early RA, its significant decrease after treatment initiation and positive association between increased synovial fluid IL-35 and disease activity in patients with long-lasting RA. PMID:26204444

  12. Inflammation predicts accelerated brachial arterial wall changes in patients with recent-onset rheumatoid arthritis

    PubMed Central

    Hannawi, Suad; Marwick, Thomas H; Thomas, Ranjeny

    2009-01-01

    Introduction Patients with recent-onset rheumatoid arthritis (RA) have impaired brachial artery endothelial function compared with controls matched for age, sex and cardiovascular risk factors. The present study examined endothelium-dependent (flow-mediated dilatation (FMD)) and independent (glyceryl trinitrate (GTN)-mediated dilatation (GMD)) structural responses in early RA patients, and determined progress over one year. Methods Brachial artery FMD and GMD and carotid intima media thickness (cIMT) were studied using ultrasound in 20 patients diagnosed with early RA in whom symptoms had been present for less than 12 months, and in 20 control subjects matched for age, sex and established cardiovascular risk factors. FMD and GMD were re-assessed after 12 months in RA patients and the change in each parameter was calculated. Data were analysed by univariate regression. Results Mean FMD and GMD were significantly lower in early RA patients at baseline than in controls, but each parameter significantly improved in one year. FMD and GMD responses were positively associated with each other. Patients' age, C-reactive protein (CRP) level and cIMT at baseline and CRP level at one year, were negatively associated with change in brachial responses in one year. Conclusions Patients with recent-onset RA have altered brachial artery responses signifying both functional and structural abnormalities. However, early control of inflammation may reduce arterial dysfunction and thus the tendency for atherosclerotic progression. PMID:19344530

  13. Neutrophil function in pregnancy and rheumatoid arthritis

    PubMed Central

    Crocker, I; Baker, P; Fletcher, J

    2000-01-01

    BACKGROUND—Pregnancy exerts suppressive effects on rheumatoid arthritis (RA). An attenuation in neutrophil function in late pregnancy which may explain this amelioration has previously been reported.?OBJECTIVE—A longitudinal investigation of neutrophil activity in healthy pregnant women (n=9) and pregnant patients with RA (n=9), compared with age matched non-pregnant patients with RA (n=12) and healthy controls (n=22).?METHODS—Neutrophil activation was measured in response to the physiological receptor agonists, n-formyl-methionyl-leucyl-phenylalanine (fMLP) and zymosan activated serum (ZAS). Superoxide anion production (respiratory burst) was determined by lucigenin enhanced chemiluminescence (LUCL); secondary granule lactoferrin release by enzyme linked immunosorbent assay (ELISA); and CD11b, CD18, and CD62L expression by flow cytometric analysis.?RESULTS—Stimulated neutrophil LUCL was significantly reduced in both pregnant women with RA and healthy pregnant women in the second (fMLP 43% and 69%, ZAS 43% and 59%, respectively) and third trimesters (fMLP 24% and 44%, ZAS 32% and 38%, respectively). Responses returned to normal within eight weeks of delivery and unstimulated levels remained unchanged throughout pregnancy. Basal and stimulated CD11b, CD18, and CD62L expression showed no variations throughout gestation for both pregnancy groups. Likewise, stimulated lactoferrin release and plasma lactoferrin remained unchanged. Certain morphological differences in RA neutrophils were highlighted by the flow cytometric analysis. Moreover, resting neutrophils and stimulated cells from patients with RA, including pregnant subjects, showed a marked increase in LUCL, but a reduction in CD11b, CD18, and CD62L. Low dose prednisolone and methylprednisolone had no effect on neutrophil parameters over the period of treatment with non-steroidal anti-inflammatory drugs.?CONCLUSION—The attenuation to neutrophil respiratory burst in both healthy and RA pregnancies may offer an explanation for the pregnancy induced remission of this inflammatory disorder.?? PMID:10873967

  14. Development of macromolecular prodrug for rheumatoid arthritis.

    PubMed

    Yuan, Fang; Quan, Ling-dong; Cui, Liao; Goldring, Steven R; Wang, Dong

    2012-09-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that is considered to be one of the major public health problems worldwide. The development of therapies that target tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6) and co-stimulatory pathways that regulate the immune system have revolutionized the care of patients with RA. Despite these advances, many patients continue to experience symptomatic and functional impairment. To address this issue, more recent therapies that have been developed are designed to target intracellular signaling pathways involved in immunoregulation. Though this approach has been encouraging, there have been major challenges with respect to off-target organ side effects and systemic toxicities related to the widespread distribution of these signaling pathways in multiple cell types and tissues. These limitations have led to an increasing interest in the development of strategies for the macromolecularization of anti-rheumatic drugs, which could target them to the inflamed joints. This approach enhances the efficacy of the therapeutic agent with respect to synovial inflammation, while markedly reducing non-target organ adverse side effects. In this manuscript, we provide a comprehensive overview of the rational design and optimization of macromolecular prodrugs for treatment of RA. The superior and the sustained efficacy of the prodrug may be partially attributed to their Extravasation through Leaky Vasculature and subsequent Inflammatory cell-mediated Sequestration (ELVIS) in the arthritic joints. This biologic process provides a plausible mechanism, by which macromolecular prodrugs preferentially target arthritic joints and illustrates the potential benefits of applying this therapeutic strategy to the treatment of other inflammatory diseases. PMID:22433784

  15. Choline kinase inhibition in rheumatoid arthritis

    PubMed Central

    Guma, M; Sanchez-Lopez, E; Lodi, A; Garcia-Carbonell, R; Tiziani, S; Karin, M; Lacal, J C; Firestein, G S

    2014-01-01

    Objectives Little is known about targeting the metabolome in non-cancer conditions. Choline kinase (ChoK?), an essential enzyme for phosphatidylcholine biosynthesis, is required for cell proliferation and has been implicated in cancer invasiveness. Aggressive behaviour of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) led us to evaluate whether this metabolic pathway could play a role in RA FLS function and joint damage. Methods Choline metabolic profile of FLS cells was determined by 1H magnetic resonance spectroscopy (1HMRS) under conditions of ChoK? inhibition. FLS function was evaluated using the ChoK? inhibitor MN58b (IC50=4.2 ?M). For arthritis experiments, mice were injected with K/BxN sera. MN58b (3 mg/kg) was injected daily intraperitoneal beginning on day 0 or day 4 after serum administration. Results The enzyme is expressed in synovial tissue and in cultured RA FLS. Tumour necrosis factor (TNF) and platelet-derived growth factor (PDGF) stimulation increased ChoK? expression and levels of phosphocholine in FLS measured by Western Blot (WB) and metabolomic studies of choline-containing compounds in cultured RA FLS extracts respectively, suggesting activation of this pathway in RA synovial environment. A ChoK? inhibitor also suppressed the behaviour of cultured FLS, including cell migration and resistance to apoptosis, which might contribute to cartilage destruction in RA. In a passive K/BxN arthritis model, pharmacologic ChoK? inhibition significantly decreased arthritis in pretreatment protocols as well as in established disease. Conclusions These data suggest that ChoK? inhibition could be an effective strategy in inflammatory arthritis. It also suggests that targeting the metabolome can be a new treatment strategy in non-cancer conditions. PMID:25274633

  16. Chromosome 14 markers in rheumatoid arthritis.

    PubMed Central

    Ollier, W; Thomson, W; Welch, S; de Lange, G G; Silman, A

    1988-01-01

    Phenotype frequencies for variants of the chromosome 14 markers, alpha 1 antitrypsin (protease inhibitor--Pi), and immunoglobulin heavy chain gene allotypes (Gm and Am) were examined in affected and unaffected members of multicase rheumatoid arthritis (RA) families and compared with published population data. Significantly higher frequencies of phenotypes containing Pi*Z and Pi*S were observed in unrelated index RA cases compared with UK population data. There was also a higher frequency of Pi*Z in family members without RA than in population controls but no such difference for the frequency of Pi*S. No difference in the frequency of PiM1M2 heterozygotes was seen between patients with RA and population controls. An examination of clinical data failed to show any relation between any particular feature of RA and positivity for Pi*Z or Pi*S. No significant differences in frequency of Gm phenotypes were observed between patients with RA and controls. Significant association was found, however, between Pi*Z and Gm phenotypes containing Gm(zax;g). These associations are interpreted as indicating linkage disequilibria between these alleles. No interactions between DR4 and either G1m(z), (a), or (x) allotypes were apparent in patients with RA. A significant association was seen in the index RA cases between DR4 and Pi phenotypes carrying Z or S alleles. Observations from this study provide evidence for the existence of a genetic component for RA susceptibility encoded on chromosome 14. An interactive effect of these genes with DR4 towards susceptibility appears likely. PMID:3264137

  17. Chromosome 14 markers in rheumatoid arthritis.

    PubMed

    Ollier, W; Thomson, W; Welch, S; de Lange, G G; Silman, A

    1988-10-01

    Phenotype frequencies for variants of the chromosome 14 markers, alpha 1 antitrypsin (protease inhibitor--Pi), and immunoglobulin heavy chain gene allotypes (Gm and Am) were examined in affected and unaffected members of multicase rheumatoid arthritis (RA) families and compared with published population data. Significantly higher frequencies of phenotypes containing Pi*Z and Pi*S were observed in unrelated index RA cases compared with UK population data. There was also a higher frequency of Pi*Z in family members without RA than in population controls but no such difference for the frequency of Pi*S. No difference in the frequency of PiM1M2 heterozygotes was seen between patients with RA and population controls. An examination of clinical data failed to show any relation between any particular feature of RA and positivity for Pi*Z or Pi*S. No significant differences in frequency of Gm phenotypes were observed between patients with RA and controls. Significant association was found, however, between Pi*Z and Gm phenotypes containing Gm(zax;g). These associations are interpreted as indicating linkage disequilibria between these alleles. No interactions between DR4 and either G1m(z), (a), or (x) allotypes were apparent in patients with RA. A significant association was seen in the index RA cases between DR4 and Pi phenotypes carrying Z or S alleles. Observations from this study provide evidence for the existence of a genetic component for RA susceptibility encoded on chromosome 14. An interactive effect of these genes with DR4 towards susceptibility appears likely. PMID:3264137

  18. Rheumatoid factor as a potentiator of anti-citrullinated protein antibody mediated inflammation in rheumatoid arthritis

    PubMed Central

    Sokolove, Jeremy; Johnson, Dannette S.; Lahey, Lauren J.; Wagner, Catriona A.; Cheng, Danye; Thiele, Geoffrey M.; Michaud, Kaleb; Sayles, Harlan; Reimold, Andreas M.; Caplan, Liron; Cannon, Grant W.; Kerr, Gail; Mikuls, Ted R.; Robinson, William H.

    2014-01-01

    Objectives The co-occurrence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) is well described in rheumatoid arthritis (RA). However, the mechanisms underlying the potential interaction between these two distinct autoantibodies has not been well defined. We sought to evaluate the epidemiologic and molecular interaction of ACPA and RF with both disease activity as well as measures of RA-associated inflammation. Methods In a cohort of 1,488 Veterans with RA, measures of disease activity and levels of serum cytokines and multiplex ACPA were compared between the double-negative (aCCP-/RF-), ACPA-positive and RF-negative (aCCP+/RF-), ACPA-negative and RF-positive (aCCP-/RF+), or double-positive (aCCP+/RF+) subgroups. Studies were additionally performed using an in vitro immune complex (IC) stimulation assay in which macrophages were incubated with ACPA-ICs in the presence or absence of monoclonal IgM RF, and TNF? production measured as readout of macrophage activation. Results Compared with the double negative (as well each single positive) subgroup, the aCCP+/RF+ subgroup exhibited higher disease activity, serum CRP, and inflammatory cytokines (all P<0.001). In vitro stimulation of macrophages by ACPA-ICs induced increased cytokine production with the addition of monoclonal IgM RF as compared to ACPA-ICs alone (P=0.003) Conclusions The combined presence of ACPA and IgM RF mediates increased proinflammatory cytokine production in vitro, and is associated with increased systemic inflammation and disease activity in RA. Our data suggest that IgM RF enhances the capacity of ACPA-ICs to stimulate macrophage cytokine production, thereby providing a mechanistic link by which RF enhances the pathogenicity of ACPA-ICs in RA. PMID:24757134

  19. Classification of Rheumatoid Joint Inflammation Based on Laser Imaging

    E-print Network

    Tresp, Volker

    1 Classification of Rheumatoid Joint Inflammation Based on Laser Imaging Anton Schwaighofer, Volker effective therapeutic approaches are now widely available. Objective quantification of joint inflammation, the imaging technique with the automatic inflammation clas- sification can be combined to realize a novel

  20. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin

    Microsoft Academic Search

    Erik R Vossenaar; Normand Després; Elvy Lapointe; Annemarie van der Heijden; Maximillian Lora; Tatsuo Senshu; Walther J van Venrooij; Henri A Ménard

    2004-01-01

    Antibodies directed to the Sa antigen are highly specific for rheumatoid arthritis (RA) and can be detected in approximately 40% of RA sera. The antigen, a doublet of protein bands of about 50 kDa, is present in placenta and in RA synovial tissue. Although it has been stated that the Sa antigen is citrullinated vimentin, experimental proof for this claim

  1. Insights into rheumatoid arthritis derived from the Sa immune system

    Microsoft Academic Search

    Henri A Ménard; Elvy Lapointe; Moulay D Rochdi; Zhi J Zhou

    2000-01-01

    The Sa system is a recently described immune system that has a specificity and positive predictive value of nearly 100% for rheumatoid arthritis (RA) in Asia, Europe and the Americas. Its sensitivity of 30-40% suggests that it identifies a subset of RA patients. Anti-Sa antibodies are present from disease onset and are predictive of disease severity. The immune reactants are

  2. Inflammation, vascular injury and repair in rheumatoid arthritis

    Microsoft Academic Search

    A J van Zonneveld; H C de Boer; E P van der Veer; T J Rabelink

    2010-01-01

    The systemic pro-inflammatory state present in patients with rheumatoid arthritis (RA) accelerates the progression of atherosclerosis through chronic endothelial activation. Uncoupling of endothelial nitric oxide synthase plays a central role in the amplification of oxidative signalling pathways that chronically activate and, ultimately, injure the endothelium. Recent studies indicate that the resultant loss of endothelial integrity in patients with RA may

  3. Periodontitis, Porphyromonas, and the pathogenesis of rheumatoid arthritis

    Microsoft Academic Search

    D Farquharson; J P Butcher; S Culshaw

    2012-01-01

    Epidemiological data indicate a link between rheumatoid arthritis (RA) and periodontal disease (PD). In vitro and in vivo studies have sought to dissect potential mechanisms by which PD may contribute to initiation and progression of RA. However, these are both multifactorial, chronic diseases, and their complex etiologies and pathogenesis themselves remain incompletely understood. Could there really be an etiological link

  4. Posterior occipito-cervical fusion in rheumatoid arthritis

    Microsoft Academic Search

    D. Grob; J. Dvorak; N. Gschwend; M. Froehlich

    1990-01-01

    The instability of atlanto-axial subluxation remains a challenging problem in patients with rheumatoid arthritis. In order to preserve as much function of the cervical spine as possible, inclusion of the occiput into the fusion should exclusively be performed when there is a radiologically or clinically manifest pathological condition of the atlanto-occipital joint or marked upward migration of the dens axis.

  5. Digital artery thrombosis and vasculitis in juvenile rheumatoid arthritis

    PubMed Central

    Carson, R. Annan

    1973-01-01

    A case of juvenile rheumatoid arthritis with vasculitis is presented. Sixteen months after the onset of the disease the patient developed digital artery thrombosis with incipient gangrene. Both the latter and the skin lesions resolved during treatment with azathioprine. PMID:4742476

  6. Studies in healthy volunteers and patients with rheumatoid arthritis

    Microsoft Academic Search

    A. H. Gerards; S. de Lathouder; E. R. de Groot; B. A. C. Dijkmans; L. A. Aarden

    Objectives. To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. Methods. Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients. Cultures were stimulated with either bacterial products such as lipo-oligosaccharide (LOS) or Staphylococcus aureus Cowan I (SAC) to activate

  7. Unresolved issues in biologic therapy for rheumatoid arthritis

    Microsoft Academic Search

    Ronald F. van Vollenhoven

    2011-01-01

    The advent of biologic therapies for the treatment of rheumatoid arthritis (RA) has radically changed this therapeutic area. The currently available biologic agents have been studied extensively as part of their development and also during their subsequent years of use in clinical practice; as a result, the knowledge base regarding these therapeutics is very large. Nonetheless, a number of important

  8. Optimizing Long-Term Treatment of Rheumatoid Arthritis

    E-print Network

    Hammerton, James

    scoring algorithms (e.g. Disease Activity Score (DAS), Health Assessment Questionnaire (HAQ)), which, and with increasing incidence, between the ages of 40 and 60. To this day, the etiology of rheumatoid arthritis and proliferates, thereby gradually overgrowing and destroying the articular cartilage. Depending on the stage

  9. The epigenome of synovial fibroblasts: an underestimated therapeutic target in rheumatoid arthritis.

    PubMed

    Frank-Bertoncelj, Mojca; Gay, Steffen

    2014-01-01

    Perturbed epigenetic landscape and deregulated microRNA networks are central to the permanent activation and aggressiveness of synovial fibroblasts in rheumatoid arthritis. Current anti-cytokine therapies, although effectively halting synovitis, cannot reverse the stably activated destructive phenotype of rheumatoid arthritis synovial fibroblasts,offering rather limited protection against ongoing joint destruction in rheumatoid arthritis. Targeting the deregulated epigenome of rheumatoid arthritis synovial fibroblasts is key to developing joint-protective strategies in rheumatoid arthritis. To date, different pathogenic mechanisms have been identified that can profoundly impact the epigenetic derangements in rheumatoid arthritis synovial fibroblasts, including increased consumption of S-adenosylmethionine,a principal methyl donor in DNA methylation reactions, together with deregulation of crucial DNA- and histonemodifying enzymes. Re-establishing globally disturbed DNA methylation patterns in rheumatoid arthritis synovial fibroblasts by supplementing S-adenosylmethionine while preventing its leakage into polyamine cycles may bea promising therapeutic strategy in rheumatoid arthritis and the first epigenetic treatment to target rheumatoid arthritis synovial fibroblasts at the scene of the crime. Given the dynamic nature and reversibility of epigenetic modifications, their involvement in human diseases and recent perspectives on epigenetic therapies in cancer, epigenetic targeting of rheumatoid arthritis synovial fibroblasts should be within future reach. PMID:25165988

  10. Complement activating properties of monoreactive and polyreactive IgM rheumatoid factors.

    PubMed Central

    Sato, Y; Sato, R; Watanabe, H; Kogure, A; Watanabe, K; Nishimaki, T; Kasukawa, R; Kuraya, M; Fujita, T

    1993-01-01

    OBJECTIVES--To estimate the complement activating properties of monoclonal, monoreactive, and polyreactive IgM rheumatoid factors derived from Epstein-Barr virus transformed B cells isolated from peripheral blood and synovial tissue of patients with rheumatoid arthritis (RA). METHODS--An enzyme linked immunosorbent assay (ELISA) was used to measure the activation of the classical pathway of complement by monoclonal IgM rheumatoid factor. Monoclonal IgM rheumatoid factor was bound to IgG Fc adsorbed onto microtitre plates and then reacted with diluted normal human serum as a source of complement. The activation and binding of C4 were measured with F(ab')2 antibody to human C4. The complement activating property of IgM rheumatoid factor bound to IgG Fc was tentatively expressed as the ratio of the amount of bound C4 to the amount of bound IgM rheumatoid factor. RESULTS--The complement activating property of monoreactive IgM rheumatoid factor was shown to be about three times higher than that of polyreactive IgM rheumatoid factor. CONCLUSIONS--Monoreactive IgM rheumatoid factor with the higher complement activating property would result in a greater degree of complement dependent inflammation and might have a more important pathogenic role in RA than polyreactive IgM rheumatoid factor. Images PMID:8250611

  11. Subaxial subluxation after atlantoaxial transarticular screw fixation in rheumatoid patients

    PubMed Central

    Neo, Masashi; Sakamoto, Takeshi; Fujibayashi, Shunsuke; Yoshitomi, Hiroyuki; Nakamura, Takashi

    2009-01-01

    The most common cervical abnormality associated with rheumatoid arthritis (RA) is atlantoaxial subluxation, and atlantoaxial transarticular screw fixation has proved to be one of the most reliable, stable fixation techniques for treating atlantoaxial subluxation. Following C1–C2 fixation, however, subaxial subluxation reportedly can bring about neurological deterioration and require secondary operative interventions. Rheumatoid patients appear to have a higher risk, but there has been no systematic comparison between rheumatoid and non-rheumatoid patients. Contributing radiological factors to the subluxation have also not been evaluated. The objective of this study was to evaluate subaxial subluxation after atlantoaxial transarticular screw fixation in patients with and without RA and to find contributing factors. Forty-three patients who submitted to atlantoaxial transarticular screw fixation without any concomitant operation were followed up for more than 1 year. Subaxial subluxation and related radiological factors were evaluated by functional X-ray measurements. Statistical analyses showed that aggravations of subluxation of 2.5 mm or greater were more likely to occur in RA patients than in non-RA patients over an average of 4.2 years of follow-up, and postoperative subluxation occurred in the anterior direction in the upper cervical spine. X-ray evaluations revealed that such patients had a significantly smaller postoperative C2–C7 angle, and that the postoperative AA angle correlated negatively with this. Furthermore, anterior subluxation aggravation was significantly correlated with the perioperative atlantoaxial and C2–C7 angle changes, and these two changes were strongly correlated to each other. In conclusion, after atlantoaxial transarticular screw fixation, rheumatoid patients have a greater risk of developing subaxial subluxations. The increase of the atlantoaxial angel at the operation can lead to a decrease in the C2–C7 angle, followed by anterior subluxation of the upper cervical spine and possibly neurological deterioration. PMID:19337758

  12. The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on patients with rheumatoid arthritis (RA) does not interfere with the chance of clinical remission in a follow-up of 3 years.

    PubMed

    da Mota, Licia Maria Henrique; Dos Santos Neto, Leopoldo Luiz; de Carvalho, Jozélio Freire; Pereira, Ivânio Alves; Burlingame, Rufus; Ménard, Henri A; Laurindo, Ieda Maria Magalhães

    2012-12-01

    Autoantibodies in early rheumatoid arthritis (RA) have important diagnostic value. The association between the presence of autoantibodies against cyclic citrullinated peptide and the response to treatment is controversial. To prospectively evaluate a cohort of patients with early rheumatoid arthritis (<12 months of symptoms) in order to determine the association between serological markers (rheumatoid factor (RF), anti-citrullinated protein antibodies) such as anti-cyclic citrullinated peptide antibodies (anti-CCP) and citrullinated anti-vimentin (anti-Sa) with the occurrence of clinical remission, forty patients diagnosed with early RA at the time of diagnosis were evaluated and followed for 3 years, in use of standardized therapeutic treatment. Demographic and clinical data were recorded, disease activity score 28 (DAS 28), as well as serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1) and anti-Sa in the initial evaluation and at 3, 6, 12, 18, 24, and 36 months of follow-up. The outcome evaluated was the percentage of patients with clinical remission, which was defined by DAS 28 lower than 2.6. Comparisons were made through the Student t test, mixed-effects regression analysis, and analysis of variance (significance level of 5%). The mean age was 45 years, and a female predominance was observed (90%). At the time of diagnosis, RF was observed in 50% of cases (RF IgA-42%, RF IgG-30%, and RF IgM-50%), anti-CCP in 50% (no difference between CCP2, CCP3, and CCP3.1) and anti-Sa in 10%. After 3 years, no change in the RF prevalence and anti-CCP was observed, but the anti-Sa increased to 17.5% (P = 0.001). The percentage of patients in remission, low, moderate, and intense disease activity, according to the DAS 28, was of 0, 0, 7.5, and 92.5% (initial evaluation) and 22.5, 7.5, 32.5, and 37.5% (after 3 years). There were no associations of the presence of autoantibodies in baseline evaluation and in serial analysis with the percentage of clinical remission during follow-up of 3 years The presence of autoantibodies in early RA has no predictive value for clinical remission in early RA. PMID:22187055

  13. Efficacy of tocilizumab on MRI-determined bone oedema in rheumatoid arthritis.

    PubMed

    Bensaoud, Nada; Rostom, Samira; Bahiri, Rachid; Hajjaj-Hassouni, Najia

    2015-06-01

    The aim of this study was to assess the impact of tocilizumab on bone oedema in rheumatoid arthritis (RA) as shown by magnetic resonance imaging (MRI). In this longitudinal study, patients with rheumatoid arthritis according to the American College of Rheumatology (ACR) 2009 criteria with inadequate response or intolerance to disease-modifying anti-rheumatic drugs (DMARDs), treated with tocilizumab, were included. Sociodemographic characteristics and clinical and laboratory data for the disease were collected at baseline (M0) and 06 months (M6) of treatment. Disease activity was assessed using disease activity score in 28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI). MRI of the dominant hand was performed at baseline and M6 of treatment. The primary outcome measure was the assessment of bone oedema by rheumatoid arthritis MRI scoring system (RAMRIS) bone oedema. Secondary outcomes included RAMRIS synovitis, DAS28, C-reactive protein (CRP) and SDAI at baseline and M6. Twenty-two patients with RA were included, 19 females (86.4 %), with a mean of age 42?±?13.7. The mean disease duration was 8?±?5.2 years. The mean DAS28 was 5.78?±?0.87. The median CRP was 16 mg/l (6.7 to 36.3). The average SDAI was 90?±?34. Three patients were excluded from the study for serious side effects. At baseline, bone oedema was present in 41 % of patients (N?=?9), with a median bone oedema RAMRIS 0 (0 to 7.2). At M6, bone oedema decreased or disappeared in 32 % (N?=?7) with a significant improvement in the RAMRIS bone oedema score (p?=?0.04). Moreover, there is a significant improvement in RAMRIS synovitis (p?early structural effect could be discussed. Further studies are needed to confirm these results. PMID:25903819

  14. The role of side-chain interactions in the early steps of aggregation: Molecular dynamics simulations of an

    E-print Network

    Caflisch, Amedeo

    The role of side-chain interactions in the early steps of aggregation: Molecular dynamics- determining domain of the yeast protein Sup35, was studied by 20 molecular dynamics runs for a total a greater chance of assuming alternative native states as multimers. Molecular dynamics (MD) simula- tions

  15. Anticitrullinated protein/peptide antibodies and rheumatoid factors: two distinct autoantibody systems

    PubMed Central

    2009-01-01

    In a previous issue of Arthritis Research and Therapy, Ursum and colleagues report the relative stabilities of anticitrullinated protein/peptide antibodies (ACPAs) and IgM rheumatoid factors during the course of rheumatoid arthritis and their differential correlation with markers of the acute-phase response. These findings add to a growing body of evidence highlighting the distinct nature of these two autoantibody systems and the role of ACPAs as a disease-specific marker of rheumatoid arthritis. PMID:19796372

  16. Prospective study of the radiological changes in hands, feet, and cervical spine in adult rheumatoid disease

    Microsoft Academic Search

    J Winfield; A Young; P Williams; M Corbett

    1983-01-01

    Annual radiographs of hands, feet, and cervical spine were taken in 100 patients with rheumatoid arthritis from the first year of disease for a mean follow-up period of 9.5 years. Seventy-six patients developed peripheral erosive disease and 54 developed rheumatoid changes of the cervical spine, of whom 34 (63%) had subluxations. The severity of rheumatoid neck damage correlated strongly with

  17. Coronary arterial calcification in rheumatoid arthritis: comparison with the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Giles, Jon T; Szklo, Moyses; Post, Wendy; Petri, Michelle; Blumenthal, Roger S; Lam, Gordon; Gelber, Allan C; Detrano, Robert; Scott, William W; Kronmal, Richard A; Bathon, Joan M

    2009-01-01

    Introduction Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients. Methods Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis. Results The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category. Conclusions Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors. PMID:19284547

  18. A randomized controlled trial examining Iyengar yoga for young adults with rheumatoid arthritis: a study protocol

    Microsoft Academic Search

    Subhadra Evans; Laura Cousins; Jennie CI Tsao; Saskia Subramanian; Beth Sternlieb; Lonnie K Zeltzer

    2011-01-01

    BACKGROUND: Rheumatoid arthritis is a chronic, disabling disease that can compromise mobility, daily functioning, and health-related quality of life, especially in older adolescents and young adults. In this project, we will compare a standardized Iyengar yoga program for young people with rheumatoid arthritis to a standard care wait-list control condition. METHODS\\/DESIGN: Seventy rheumatoid arthritis patients aged 16-35 years will be

  19. Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset.

    PubMed

    Goldbach-Mansky, R; Lee, J; McCoy, A; Hoxworth, J; Yarboro, C; Smolen, J S; Steiner, G; Rosen, A; Zhang, C; Ménard, H A; Zhou, Z J; Palosuo, T; Van Venrooij, W J; Wilder, R L; Klippel, J H; Schumacher, H R; El-Gabalawy, H S

    2000-01-01

    STATEMENT OF FINDINGS: An inception cohort of 238 patients having peripheral joint synovitis of less than 12 months duration was evaluated clinically and followed prospectively for 1 year to determine the clinical significance of a number of rheumatoid arthritis (RA) associated autoantibodies. Serum samples collected at the time of the initial evaluation were tested for rheumatoid factor (RF) and antibodies to Sa (anti-Sa), RA-33, (pro)filaggrin [antifilaggrin antibody (AFA)], cyclic citrullinated peptide (anti-CCP), calpastatin, and keratin [antikeratin antibody (AKA)]. RF had a sensitivity of 66% and a specificity of 87% for RA. Anti-Sa, AFA, and anti-CCP all had a specificity of more than 90%, but a sensitivity of less than 50% for this diagnosis. Overall, there was a high degree of correlation between AFA, AKA, anti-Sa or anti-CCP, this being highest between anti-Sa and anti-CCP (odds ratio, 13.3; P < 0.001). Of the 101 patients who were positive for at least one of these four autoantibodies, 57% were positive for only one. Finally, anti-SA identified a subset of predominantly male RA patients with severe, erosive disease. Anti-SA, AFA and anti-CCP are all specific for early RA but, overall, have little additional diagnostic value over RF alone. Although these antibodies may preferentially recognize citrullinated antigens, the modest degree of concordance between them in individual patient sera suggests that it is unlikely a single antigen is involved in generating these responses. PMID:11056669

  20. Diagnostic value and clinical significance of anti-CCP in patients with advanced rheumatoid arthritis.

    PubMed Central

    Samanci, Nehir; Ozdem, Sebahat; Akbas, Halide; Mutlu, Derya; Gultekin, Meral; Arman, Mehmet; Donmez, Levent

    2005-01-01

    OBJECTIVES: To investigate the prevalence of anticyclic citrullinated peptide (anti-CCP) in patients with advanced rheumatoid arthritis (RA) and to compare it with those in control subjects. Further, to study the relation between the anti-CCP and the disease activity parameters in these patients. PATIENTS AND METHODS: Seventy-six RA patients who had a mean disease duration of 9.8 years were included. Eighty-three age-matched non-RA volunteers were enrolled as the control group. Disease duration, duration of morning stiffness, swollen and tender joint counts, hand deformity, patient's assessment of pain, anti-CCP, rheumatoid factor (RF) and acute phase proteins were evaluated. The functional disability was also assessed with the Modified Health Assessment Questionnaire (HAQ). RESULTS: Thirty-seven sera (48.7%) in the patient group and one serum (1.2%) in the control group were positive for anti-CCP. RF was positive in 45% of the RA cases and in 5% of controls. Sensitivity and specificity of anti-CCP reactivity for RA were 49.0% and 99.0%, respectively. HAQ score and duration of morning stiffness were found to be significantly associated with anti-CCP positivity. Disease duration, swollen joint count and anti-CCP positivity were the most important variables predicting hand deformity. CONCLUSION: The prevalence, sensitivity and specificity of anti-CCP in patients with advanced RA were found to be similar to those reported in patients with early disease. Anti-CCP was significantly associated with some parameters of both disease activity and severity. Anti-CCP might be a useful parameter in clinical evaluation of patients with advanced RA. PMID:16173327

  1. Porphyromonas gingivalis and Disease-Related Autoantibodies in Individuals at Increased Risk of Rheumatoid Arthritis

    PubMed Central

    Mikuls, Ted R.; Thiele, Geoffrey M.; Deane, Kevin D.; Payne, Jeffrey B.; O'Dell, James R.; Yu, Fang; Sayles, Harlan; Weisman, Michael H.; Gregersen, Peter K.; Buckner, Jane H.; Keating, Richard M.; Derber, Lezlie A.; Robinson, William H.; Holers, V. Michael; Norris, Jill M.

    2012-01-01

    Purpose To examine the relationship of Porphyromonas gingivalis (Pg) with the presence of autoantibodies in individuals at risk for rheumatoid arthritis (RA). Methods Participants included: 1) a cohort enriched with HLA-DR4 and 2) those at risk for RA by virtue of having a first-degree relative with RA. None satisfied 1987 ACR RA classification criteria. Autoantibodies measured included anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF; nephelometry, IgA, IgM, IgG). Individuals were considered autoantibody positive (n = 113) with ? 1 positive autoantibody with individuals further categorized as `high-risk' (n = 38; positive ACPA or ? 2 RF assays). Autoantibody negative individuals served as comparators (n = 171). Antibody to Pg, P. intermedia (Pi), and F. nucleatum (Fn) were measured. Associations of bacterial antibodies with group status were examined using logistic regression. Results Anti-Pg concentrations were higher in high-risk (p = 0.011) and autoantibody positive group (p = 0.010) than in the autoantibody negative group. There were no group differences in anti-Pi or anti-Fn concentrations. After multivariable adjustment, anti-Pg concentrations (but not anti-Pi or anti-Fn) were significantly associated with autoantibody positive and high-risk status (p < 0.05). Conclusion Immunity to Pg, but not Pi or Fn, is significantly associated with the presence of RA-related autoantibodies in individuals at risk for RA. These results support the hypothesis that infection with Pg may play a central role in the early loss of tolerance to self-antigens in RA pathogenesis. PMID:22736291

  2. A three-dimensional simulation of transition and early turbulence in a time-developing mixing layer

    NASA Technical Reports Server (NTRS)

    Cain, A. B.; Reynolds, W. C.; Ferziger, J. H.

    1981-01-01

    The physics of the transition and early turbulence regimes in the time developing mixing layer was investigated. The sensitivity of the mixing layer to the disturbance field of the initial condition is considered. The growth of the momentum thickness, the mean velocity profile, the turbulence kinetic energy, the Reynolds stresses, the anisotropy tensor, and particle track pictures of computations are all examined in an effort to better understand the physics of these regimes. The amplitude, spectrum shape, and random phases of the initial disturbance field were varied. A scheme of generating discrete orthogonal function expansions on some nonuniform grids was developed. All cases address the early or near field of the mixing layer. The most significant result shows that the secondary instability of the mixing layer is produced by spanwise variations in the straining field of the primary vortex structures.

  3. Bone resorption by cells isolated from rheumatoid synovium.

    PubMed Central

    Chang, J S; Quinn, J M; Demaziere, A; Bulstrode, C J; Francis, M J; Duthie, R B; Athanasou, N A

    1992-01-01

    Cellular mechanisms accounting for the osteolysis of rheumatoid erosions are poorly understood. Cells were isolated and characterised from the synovium of 16 patients with rheumatoid arthritis (RA) and four patients with osteoarthritis and their ability to resorb bone was assessed using a scanning electron microscope bone resorption assay. Macrophages were the major cell type isolated from the synovium of patients with RA. These produced extensive roughening of the bone surface without resorption pit formation. This low grade type of bone resorption was not affected by systemic (calcitonin, parathyroid hormone, 1,25-dihydroxyvitamin D3) or local (interleukin 1, prostaglandin E2) factors influencing bone resorption. Macrophage mediated bone resorption differs qualitatively and quantitatively from that of osteoclasts but is likely to play an important part in the development of marginal erosions in RA. Images PMID:1334644

  4. Impairment and disability: Renoir's adaptive coping strategies against rheumatoid arthritis.

    PubMed

    Kowalski, Evan; Chung, Kevin C

    2012-12-01

    Pierre-Auguste Renoir was one of the most influential painters in art history, but few people know that he suffered from debilitating rheumatoid arthritis. Despite his arthritis, he was able to maintain an incredible level of precision and efficiency with his painting. More importantly, he remained positive and did not let his condition affect his passion for painting or take away from the beauty that he saw in the world around him. Renoir applied a wide variety of coping mechanisms and used his ingenuity to come up with different ways to continue painting even as his arthritis weakened him. Renoir's long battle with rheumatoid arthritis serves as an inspiration to patients who experience the pain and limited mobility associated with this disease, encouraging them to persevere and to develop coping mechanisms that prevent the effects of their impairment from disabling them. PMID:24294153

  5. A population study on rheumatoid arthritis in Lesotho, southern Africa.

    PubMed Central

    Moolenburgh, J D; Valkenburg, H A; Fourie, P B

    1986-01-01

    Motivated by the results of a hospital study on rheumatoid arthritis (RA) in Lesotho (southern Africa) a survey of inflammatory polyarthritis (IP) and RA was undertaken in a sample of the rural population of that country. Contrary to expectations the prevalence of IP grades 2-4 (definite disease) was low (0.4%) and equal in both sexes, while probable and definite RA combined (American Rheumatism Association (ARA) criteria) occurred in 1.8% of both males and females. RA was slightly more severe than in other rural African Negro studies but less so when compared with the disease condition of the patients observed in the hospital study. Rheumatoid factor and particularly that directed against heterologous antigen occurred in 41% of the RA patients and in 16% of the controls. Two thirds of the definite cases and 29% of the combined probable and definite group showed radiological abnormalities. PMID:3740998

  6. B cell therapies for rheumatoid arthritis: beyond B cell depletion.

    PubMed

    Calero, Ismael; Nieto, Jose Antonio; Sanz, Iñaki

    2010-05-01

    Initially suggested by the presence of rheumatoid factor autoantibodies, multiple pathogenic roles for B cells (both antibody-mediated and antibody-independent) in rheumatoid arthritis (RA) now are supported by a growing body of experimental observations and human studies. The pathogenic significance of B cells in this disease also has been established conclusively by the proven benefit of Rituximab-induced B cell depletion in RA patients refractory to tumor necrosis factor (TNF) blockade. This article reviews the rationale for the use of B cell-targeting therapies in RA and discusses the caveats and limitations of indiscriminate B cell depletion as currently applied, ncluding incomplete depletion of pathogenic B cells and elimination of protective B cells. Finally, it presents alternative therapeutic strategies that exploit current knowledge of B cell activation, survival, and differentiation to provide more selective B cell and plasma cell targeting. PMID:20510237

  7. 25(OH) vitamin D serum values and rheumatoid arthritis disease activity (DA S28 ESR)

    PubMed Central

    Sahebari, Maryam; Mirfeizi, Zahra; Rezaieyazdi, Zahra; Rafatpanah, Houshang; Goshyeshi, Ladan

    2014-01-01

    Background: The role of vitamin D in the pathogenesis of rheumatoid arthritis is under investigation. This study was designed to evaluate the correlation between serum values of 25(OH) vitamin D [25(OH)D] and disease activity in rheumatoid arthritis (RA) patients according to Disease Activity Score 28 joints and ESR (DA S28 ESR). Methods: Ninety-nine patients according to ACR classification criteria for RA and 68 healthy controls were included in this study. The participants with known confounding risk factors affecting serum values of 25(OH)D were excluded. All patients were under treatment with supplementary calcium carbonate (1500mg), 25(OH)D (800U), and Hydroxychloroquine (6mg/kg). The control group was mostly recruited from patients’ relatives who lived with them to minimize the impact of diverse lifestyles on 25(OH)D status. Disease activity was assessed by DA S28 ESR. Serum concentrations of 25(OH)D were measured. Serum values of 25(OH)D less than 50 nmol/L were considered 25(OH)D deficiency. Results: The mean 25(OH)D serum values were 83.74±46.45 nmol/L in patients and 46.53±34.07 nmol/L in controls. After adjustment for age, sex and BMI, multivariate analysis showed no correlation between 25(OH)D serum levels and DAS in RA (P=0.29, rp=0.11). However, 25(OH)D serum values were significantly lower in patients with early diagnosed RA compared with the other patients (p=0.012). In the early diagnosed patients, 25(OH)D and anti-CCP serum values were negatively correlated (P=0.04, rs=-0.5). Conclusion: This study showed that there was no correlation between 25(OH)D serum values and DAS over a short duration of disease course. However, in early RA, 25(OH) D serum values were lower than the established RA. PMID:25202442

  8. Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

    PubMed Central

    Zhao, Xiaoyan; Okeke, Nwora Lance; Sharpe, Orr; Batliwalla, Franak M; Lee, Annette T; Ho, Peggy P; Tomooka, Beren H; Gregersen, Peter K; Robinson, William H

    2008-01-01

    Introduction There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised. Methods We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue. Results C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen. Conclusion Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients. PMID:18710572

  9. [A cardiorespiratory decompensation in the course of rheumatoid arthritis].

    PubMed

    Marilier, S; Martin-Pfitzenmeyer, I; Mazen, E; Da Silva, S; Pfitzenmeyer, P; Manckoundia, P

    2009-11-01

    Rheumatoid arthritis (RA) may include rare extra-articular manifestations, and particularly cardiopulmonary involvement. We report a 83-year-old woman, with RA, who presented with both pulmonary and heart failures that were related to the RA, resulting from the presence of mediastinal and axillary lymph nodes, and pleural and pericardial effusions. This was confirmed by the dramatic improvement after a specific treatment of RA. PMID:19303672

  10. Effect and mechanism of AR6 in experimental rheumatoid arthritis

    Microsoft Academic Search

    Shi-xue Sun; Yun-man Li; Wei-rong Fang; Peng Cheng; Lifang Liu; Fengwen Li

    2010-01-01

    The root of Clematis chinensis Osbeck has been used widely in rheumatoid arthritis in Chinese traditional medicine and AR-6 is a triterpene saponin isolated from\\u000a it. In this present study, we investigated in vivo effects of oral AR-6 in chronic rat adjuvant-induced arthritis (AA) and\\u000a in vitro effect in macrophage and synoviocytes cells. Arthritic scores and serum inflammatory mediators were

  11. Variables Related to Posttraumatic Growth in Turkish Rheumatoid Arthritis Patients

    Microsoft Academic Search

    Gulay Dirik; A. Nuray Karanci

    2008-01-01

    Rheumatoid arthritis (RA) is a chronic, deteriorative disease, which can cause great psychological distress. Although RA has\\u000a negative psychological consequences, it may also lead to positive changes, which has been given relatively little attention\\u000a in the research literature. The Posttraumatic Growth Inventory (PTGI) has been used to evaluate growth in survivor’s thinking,\\u000a feeling and\\/or behavior following the experiencing of traumatic

  12. TNF? and chemerin cross-talk in rheumatoid arthritis

    Microsoft Academic Search

    M Cristina Lebre; M Inês Ramos; Claudia L Hofstra; Hans van Eenennaam; Saïda Aarrass; Paul P Tak

    2011-01-01

    Background and objectivesRheumatoid arthritis (RA) synovium is characterised by a dense infiltrate, consisting of macrophages, T and B cells, plasma cells and dendritic cells (DC). Inflammatory chemokines present in RA synovium may contribute to the accumulation of these immune cells. The authors have recently shown that plasmacytoid DC (pDC) are enriched in RA synovial tissue (ST) compared to CD1c myeloid

  13. Genome-wide meta-analysis for rheumatoid arthritis

    Microsoft Academic Search

    Carol J. Etzel; Wei V. Chen; Neil Shepard; Damini Jawaheer; Francois Cornelis; Michael F. Seldin; Peter K. Gregersen; Christopher I. Amos

    2006-01-01

    Meta-analysis is being increasingly used as a tool for integrating data from different studies of complex phenotypes, because the power of any one study to identify causal loci is limited. We applied a novel meta-analytical approach (Loesgen et al. in Genet Epidemiol 21(Suppl 1):S142–S147, 2001) in compiling results from four studies of rheumatoid arthritis in Caucasians including two studies from NARAC

  14. Antigen-specific T cells in rheumatoid arthritis

    Microsoft Academic Search

    Sean R. Bennett; Michael T. Falta; Jerry Bill; Brian L. Kotzin

    2003-01-01

    There is considerable evidence of a key role for CD4+ T cells in the pathogenesis of rheumatoid arthritis. Several attractive candidate antigens, mostly joint-specific, have been\\u000a studied, but information regarding T cell responses to these antigens in patients is limited and occasionally contra-dictory.\\u000a Novel reagents (such as major histocompatibility complex and peptide tetramers) and sensitive techniques (such as intracellular\\u000a cytokine

  15. Aspects of TNF inhibitor therapy in rheumatoid arthritis

    Microsoft Academic Search

    Jackie Nam; Paul Emery

    2010-01-01

    Treatment outcomes in rheumatoid arthritis (RA) have improved considerably with the use of biological therapies. Since the\\u000a discovery of the role of tumor necrosis factor (TNF) alpha in the pathogenesis of the disease, three TNF inhibitors, infliximab,\\u000a etanercept and adalimumab, have become widely used for the treatment of RA. More recently, two newer TNF inhibitors—certolizumab\\u000a pegol and golimumab—have become available,

  16. The economic burden of rheumatoid arthritis: beyond health care costs

    Microsoft Academic Search

    Wei Zhang; Aslam H. Anis

    2011-01-01

    Rheumatoid arthritis (RA) not only causes significant morbidity, but also leads to substantial losses in terms of productivity\\u000a that have a negative impact on the individual and the society. In countries, such as Canada, the US, and the UK, it is known\\u000a that the costs to the economy in terms of sick leave and work-related disability run into billions of

  17. Oral phosphatidylcholine pretreatment alleviates the signs of experimental rheumatoid arthritis

    Microsoft Academic Search

    Gabor Er?s; Saleh Ibrahim; Nikolai Siebert; Mihály Boros; Brigitte Vollmar

    2009-01-01

    INTRODUCTION: Phosphatidylcholine and phosphatidylcholine-derived metabolites exhibit anti-inflammatory properties in various stress conditions. We hypothesized that dietary phosphatidylcholine may potentially function as an anti-inflammatory substance and may decrease inflammatory activation in a chronic murine model of rheumatoid arthritis (collagen-induced arthritis). METHODS: The experiments were performed on male DBA1\\/J mice. In groups 1 to 3 (n = 10 each), collagen-induced arthritis was

  18. Animal models of rheumatoid arthritis and related inflammation

    Microsoft Academic Search

    Bina Joe; Marie M. Griffiths; Elaine F. Remmers; Ronald L. Wilder

    1999-01-01

    The major, extensively studied, experimentally-induced rat and mouse models of arthritis with features resembling rheumatoid\\u000a arthritis are reviewed here. Etiopathogenetic studies that were recently published are emphasized. In summary, multiple triggering\\u000a stimuli can induce disease in genetically-prone strains of inbred rats and mice. Multiple genetic loci, including both MHC\\u000a and non-MHC, regulate disease expression in these animals. By comparison with

  19. [The psychological personality characteristics of patients with rheumatoid arthritis].

    PubMed

    Soroka, N F

    1991-01-01

    A psychological examination of 135 patients with rheumatoid arthritis (RA) (Bechterew Institute questionnaire) was made. Harmonious, neurasthenic, hypochondriac, paranoiac, apathetic and anxious attitudes to the disease were most frequent. Psychological features of personality in patients with RA do not depend on the sex, degree of activity, course, stage and the disease duration. The psychological characteristics of the patients allow one to make a differentiated approach to psychotherapy and prescription of psychotropic drugs. PMID:1812554

  20. Adult-Onset Acquired Partial Lipodystrophy Accompanied by Rheumatoid Arthritis

    PubMed Central

    Muto, Yusuke; Fujimura, Taku; Kakizaki, Aya; Tsuchiyama, Kenichiro; Kusakari, Yoshiyuki; Aiba, Setsuya

    2015-01-01

    Lipodystrophy is a group of metabolic disorders, possibly caused by autoimmune disease. In this report, we describe a case of adult-onset acquired partial lipodystrophy accompanied by rheumatoid arthritis without a family history. Interestingly, immunohistochemical staining revealed dense infiltration of IL-27-producing cells as well as MMP-7-and MMP-28-expressing cells, both of which have been reported to facilitate the development of autoimmune disease. Our present case might suggest possible mechanisms for acquired partial lipodystrophy. PMID:26034476

  1. Pathogenic role of antibodies to citrullinated proteins in rheumatoid arthritis.

    PubMed

    Kinloch, Andrew J; Lundberg, Karin E; Moyes, David; Venables, Patrick J

    2006-05-01

    In the last 10 years, the discovery that antibodies to citrullinated proteins are highly specific for rheumatoid arthritis has led to a model of pathogenesis that ties together the genetic and environmental risk factors for susceptibility and severity of disease. The authors propose that the chronic inflammation is driven by two phases of an immune response. The first phase is the priming of autoimmunity, which may occur many years before the onset of disease and is caused by environmental factors, such as smoking and infectious agents, in the context of disease susceptibility alleles. This may occur in sites outside the joint, such as the respiratory tract. The second phase is the induction of arthritis, which is associated with the generation of citrullinated proteins within the joint, which is then perpetuated as the erosive disease by a local chronic immune response. The identity of candidate synovial citrullinated antigen(s), whether fibrin, vimentin, alpha-enolase, collagen type II or others yet to be described, may be the key to the pathogenesis of the destructive disease characteristic of rheumatoid arthritis. There is emerging evidence that citrullination may already be modified by established therapy in rheumatoid arthritis, but more specific inhibitors of deimination may provide new agents for future treatments. PMID:20476908

  2. Angiogenesis in the human corpus luteum: simulated early pregnancy by HCG treatment is associated with both angiogenesis and vessel stabilization

    Microsoft Academic Search

    Christine Wulff; Sarah E. Dickson; W. Colin Duncan; Hamish M. Fraser

    BACKGROUND: This study examined changes in the luteal vasculature throughout the menstrual cycle and during simulated pregnancy with human chorionic gonadotrophin (HCG) in the human. METHODS: Endothelial cell and pericyte area were assessed by quantitative immunocytochemistry for CD34 and ?-smooth muscle actin respectively, taking into consideration the dynamics of lutein cell hypertrophy and atrophy throughout the cycle and after HCG

  3. Rheumatoid arthritis vaccine therapies: perspectives and lessons from therapeutic ligand epitope antigen presentation system vaccines for models of rheumatoid arthritis.

    PubMed

    Rosenthal, Kenneth S; Mikecz, Katalin; Steiner, Harold L; Glant, Tibor T; Finnegan, Alison; Carambula, Roy E; Zimmerman, Daniel H

    2015-06-01

    The current status of therapeutic vaccines for autoimmune diseases is reviewed with rheumatoid arthritis as the focus. Therapeutic vaccines for autoimmune diseases must regulate or subdue responses to common self-antigens. Ideally, such a vaccine would initiate an antigen-specific modulation of the T-cell immune response that drives the inflammatory disease. Appropriate animal models and types of T helper cells and signature cytokine responses that drive autoimmune disease are also discussed. Interpretation of these animal models must be done cautiously because the means of initiation, autoantigens, and even the signature cytokine and T helper cell (Th1 or Th17) responses that are involved in the disease may differ significantly from those in humans. We describe ligand epitope antigen presentation system vaccine modulation of T-cell autoimmune responses as a strategy for the design of therapeutic vaccines for rheumatoid arthritis, which may also be effective in other autoimmune conditions. PMID:25787143

  4. Biochemical markers of ongoing joint damage in rheumatoid arthritis - current and future applications, limitations and opportunities

    PubMed Central

    2011-01-01

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with potentially debilitating joint inflammation, as well as altered skeletal bone metabolism and co-morbid conditions. Early diagnosis and aggressive treatment to control disease activity offers the highest likelihood of preserving function and preventing disability. Joint inflammation is characterized by synovitis, osteitis, and/or peri-articular osteopenia, often accompanied by development of subchondral bone erosions, as well as progressive joint space narrowing. Biochemical markers of joint cartilage and bone degradation may enable timely detection and assessment of ongoing joint damage, and their use in facilitating treatment strategies is under investigation. Early detection of joint damage may be assisted by the characterization of biochemical markers that identify patients whose joint damage is progressing rapidly and who are thus most in need of aggressive treatment, and that, alone or in combination, identify those individuals who are likely to respond best to a potential treatment, both in terms of limiting joint damage and relieving symptoms. The aims of this review are to describe currently available biochemical markers of joint metabolism in relation to the pathobiology of joint damage and systemic bone loss in RA; to assess the limitations of, and need for additional, novel biochemical markers in RA and other rheumatic diseases, and the strategies used for assay development; and to examine the feasibility of advancement of personalized health care using biochemical markers to select therapeutic agents to which a patient is most likely to respond. PMID:21539724

  5. Smoking history and serum cotinine and thiocyanate concentrations as determinants of rheumatoid factor in non-rheumatoid subjects

    Microsoft Academic Search

    T. Korpilahde; M. Heliovaara; P. Knekt; J. Marniemi; A. Aromaa; K. Aho

    2004-01-01

    Objectives. Smoking is associated with false-positive rheumatoid factor (RF). We explored the dose-response relationship of this association, using smoking history and serum cotinine and thiocyanate concentrations as measures of tobacco exposure. Methods. A total of 6947 men and women aged 30 yr or over and free of clinical arthritis were included in the Mini-Finland Health Survey carried out between 1978

  6. The role of side-chain interactions in the early steps of aggregation: Molecular dynamics simulations of an amyloid-forming peptide from the yeast prion Sup35

    NASA Astrophysics Data System (ADS)

    Gsponer, Jörg; Haberthür, Urs; Caflisch, Amedeo

    2003-04-01

    Understanding the early steps of aggregation at atomic detail might be crucial for the rational design of therapeutics preventing diseases associated with amyloid deposits. In this paper, aggregation of the heptapeptide GNNQQNY, from the N-terminal prion-determining domain of the yeast protein Sup35, was studied by 20 molecular dynamics runs for a total simulation time of 20 ?s. The simulations generate in-register parallel packing of GNNQQNY -strands that is consistent with x-ray diffraction and Fourier transform infrared data. The statistically preferred aggregation pathway does not correspond to a purely downhill profile of the energy surface because of the presence of enthalpic barriers that originate from out-of-register interactions. The parallel -sheet arrangement is favored over the antiparallel because of side-chain contacts; in particular, stacking interactions of the tyrosine rings and hydrogen bonds between amide groups. No ordered aggregation was found in control simulations with the mutant sequence SQNGNQQRG in accord with experimental data and the strong sequence dependence of aggregation.

  7. Laboratory Drop Towers for the Experimental Simulation of Dust-aggregate Collisions in the Early Solar System

    PubMed Central

    Blum, Jürgen; Beitz, Eike; Bukhari, Mohtashim; Gundlach, Bastian; Hagemann, Jan-Hendrik; Heißelmann, Daniel; Kothe, Stefan; Schräpler, Rainer; von Borstel, Ingo; Weidling, René

    2014-01-01

    For the purpose of investigating the evolution of dust aggregates in the early Solar System, we developed two vacuum drop towers in which fragile dust aggregates with sizes up to ~10 cm and porosities up to 70% can be collided. One of the drop towers is primarily used for very low impact speeds down to below 0.01 m/sec and makes use of a double release mechanism. Collisions are recorded in stereo-view by two high-speed cameras, which fall along the glass vacuum tube in the center-of-mass frame of the two dust aggregates. The other free-fall tower makes use of an electromagnetic accelerator that is capable of gently accelerating dust aggregates to up to 5 m/sec. In combination with the release of another dust aggregate to free fall, collision speeds up to ~10 m/sec can be achieved. Here, two fixed high-speed cameras record the collision events. In both drop towers, the dust aggregates are in free fall during the collision so that they are weightless and match the conditions in the early Solar System. PMID:24962693

  8. Laboratory drop towers for the experimental simulation of dust-aggregate collisions in the early solar system.

    PubMed

    Blum, Jürgen; Beitz, Eike; Bukhari, Mohtashim; Gundlach, Bastian; Hagemann, Jan-Hendrik; Heißelmann, Daniel; Kothe, Stefan; Schräpler, Rainer; von Borstel, Ingo; Weidling, René

    2014-01-01

    For the purpose of investigating the evolution of dust aggregates in the early Solar System, we developed two vacuum drop towers in which fragile dust aggregates with sizes up to ~10 cm and porosities up to 70% can be collided. One of the drop towers is primarily used for very low impact speeds down to below 0.01 m/sec and makes use of a double release mechanism. Collisions are recorded in stereo-view by two high-speed cameras, which fall along the glass vacuum tube in the center-of-mass frame of the two dust aggregates. The other free-fall tower makes use of an electromagnetic accelerator that is capable of gently accelerating dust aggregates to up to 5 m/sec. In combination with the release of another dust aggregate to free fall, collision speeds up to ~10 m/sec can be achieved. Here, two fixed high-speed cameras record the collision events. In both drop towers, the dust aggregates are in free fall during the collision so that they are weightless and match the conditions in the early Solar System. PMID:24962693

  9. The impact of rheumatoid foot on disability in Colombian patients with rheumatoid arthritis

    PubMed Central

    Rojas-Villarraga, Adriana; Bayona, Javier; Zuluaga, Natalia; Mejia, Santiago; Hincapie, Maria-Eugenia; Anaya, Juan-Manuel

    2009-01-01

    Background Alterations in the feet of patients with rheumatoid arthritis (RA) are a cause of disability in this population. The purpose of this research was to evaluate the impact that foot impairment has on the patients' global quality of life (QOL) based on validated scales and its relationship to disease activity. Methods This was a cross-sectional study in which 95 patients with RA were enrolled. A complete physical examination, including a full foot assessment, was done. The Spanish versions of the Health Assessment Questionnaire (HAQ) Disability Index and of the Disease Activity Score (DAS 28) were administered. A logistic regression model was used to analyze data and obtain adjusted odds ratios (AORs). Results Foot deformities were observed in 78 (82%) of the patients; hallux valgus (65%), medial longitudinal arch flattening (42%), claw toe (lesser toes) (39%), dorsiflexion restriction (tibiotalar) (34%), cock-up toe (lesser toes) (25%), and transverse arch flattening (25%) were the most frequent. In the logistic regression analysis (adjusted for age, gender and duration of disease), forefoot movement pain, subtalar movement pain, tibiotalar movement pain and plantarflexion restriction (tibiotalar) were strongly associated with disease activity and disability. The positive squeeze test was significantly associated with disability risk (AOR = 6,3; 95% CI, 1.28–30.96; P = 0,02); hallux valgus, and dorsiflexion restriction (tibiotalar) were associated with disease activity. Conclusion Foot abnormalities are associated with active joint disease and disability in RA. Foot examinations provide complementary information related to the disability as an indirect measurement of quality of life and activity of disease in daily practice. PMID:19527518

  10. Fatigue in patients with rheumatoid arthritis: British and Dutch nurses' knowledge, attitudes and management

    Microsoft Academic Search

    J. W. J. Repping-Wuts; Sarah Hewlett; Theo van Achterberg

    2009-01-01

    AIM: This paper is a report of a study conducted to compare the knowledge, attitudes and current management of rheumatoid arthritis-related fatigue in British and Dutch rheumatology nurses. BACKGROUND: After pain, fatigue is the most important symptom for patients with rheumatoid arthritis, but little is known about the current management of this fatigue by healthcare professionals. METHODS: A questionnaire was

  11. A Genomewide Screen in Multiplex Rheumatoid Arthritis Families Suggests Genetic Overlap with Other Autoimmune Diseases

    Microsoft Academic Search

    Damini Jawaheer; Michael F. Seldin; Christopher I. Amos; Wei V. Chen; Russell Shigeta; Joanita Monteiro; Marlene Kern; Lindsey A. Criswell; Salvatore Albani; J. Lee Nelson; Daniel O. Clegg; Richard Pope; Harry W. Schroeder; S. Louis Bridges; David S. Pisetsky; Ryk Ward; Daniel L. Kastner; Ronald L. Wilder; Theodore Pincus; Leigh F. Callahan; Donald Flemming; Mark H. Wener; Peter K. Gregersen

    2001-01-01

    Rheumatoid arthritis (RA) is an autoimmune\\/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 families containing 301 affected sibling pairs with RA. A genome screen for allele sharing was performed, using

  12. The rheumatoid foot: a systematic literature review of patient-reported outcome measures

    Microsoft Academic Search

    Steven Walmsley; Anita E Williams; Mike Ravey; Andrea Graham

    2010-01-01

    BACKGROUND: The foot is often the first area of the body to be systematically affected by rheumatoid arthritis. The multidimensional consequences of foot problems for patients can be subjectively evaluated using patient-reported outcome measures (PROMs). However, there is currently no systematic review which has focused specifically upon the PROMs available for the foot with rheumatoid arthritis. The aim of this

  13. Pannus resolution after occipitocervical fusion in a non-rheumatoid atlanto-axial instability

    Microsoft Academic Search

    Alfonso Lagares; Iñaki Arrese; Beatriz Pascual; Pedro A. Gòmez; Ana Ramos; Ramiro D. Lobato

    2006-01-01

    Periodontoid pseudotumor or pannus is considered to be an inflammatory mass most frequently associated with rheumatoid arthritis. Transoral resection of the pannus has been the treatment of choice for patients with associated myelopathy, followed in many instances by posterior stabilization. However, some authors have reported resolution of pannus associated with rheumatoid arthritis and other forms of chronic atlanto-axial instability only

  14. Elimination of rheumatoid synovium in situ using a Fas ligand 'gene scalpel'

    Microsoft Academic Search

    Haidi Zhang; Guangping Gao; Gilda Clayburne; H Ralph Schumacher

    2005-01-01

    Surgical synovectomy to remove the inflammatory synovium can temporarily ameliorate rheumatoid inflammation and delay the progress of joint destruction. An efficient medically induced programmed cell death (apoptosis) in the rheumatoid synovium might play a role similar to synovectomy but without surgical tissue damage. Gene transfer of Fas ligand (FasL) has increased the frequency of apoptotic cells in mouse and rabbit

  15. Variability in synovial inflammation in rheumatoid arthritis investigated by microarray technology

    Microsoft Academic Search

    Johan Lindberg; Erik af Klint; Ann-Kristin Ulfgren; André Stark; Tove Andersson; Peter Nilsson; Lars Klareskog; Joakim Lundeberg

    2006-01-01

    In recent years microarray technology has been used increasingly to acquire knowledge about the pathogenic processes involved in rheumatoid arthritis. The present study investigated variations in gene expression in synovial tissues within and between patients with rheumatoid arthritis. This was done by applying microarray technology on multiple synovial biopsies obtained from the same knee joints. In this way the relative

  16. A single tumor necrosis factor haplotype influences response to adalimumab in rheumatoid arthritis

    E-print Network

    Paris-Sud XI, Université de

    1 A single tumor necrosis factor haplotype influences response to adalimumab in rheumatoid by the Club Rhumatismes et Inflammation with a grant from Abbott France. Key words: TNF, adalimumab are geneticpredictors of response to adalimumab (ADA) in rheumatoid arthritis (RA). Methods. This ancillary study

  17. Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis

    Microsoft Academic Search

    Pei Jin; Juan Zhang; Percy F Sumariwalla; Irene Ni; Brett Jorgensen; Damian Crawford; Suzanne Phillips; Marc Feldmann; H Michael Shepard; Ewa M Paleolog

    2008-01-01

    INTRODUCTION: Despite the advent of biological therapies for the treatment of rheumatoid arthritis, there is a compelling need to develop alternative therapeutic targets for nonresponders to existing treatments. Soluble receptors occur naturally in vivo, such as the splice variant of the cell surface receptor for vascular endothelial growth factor (VEGF) – a key regulator of angiogenesis in rheumatoid arthritis. Bioinformatics

  18. Multispectral near-IR reflectance imaging of simulated early occlusal lesions: Variation of lesion contrast with lesion depth and severity

    PubMed Central

    Simon, Jacob C.; Chan, Kenneth H.; Darling, Cynthia L.; Fried, Daniel

    2014-01-01

    Background and Objectives Early demineralization appears with high contrast at near-IR wavelengths due to a ten to twenty fold difference in the magnitude of light scattering between sound and demineralized enamel. Water absorption in the near-IR has a significant effect on the lesion contrast and the highest contrast has been measured in spectral regions with higher water absorption. The purpose of this study was to determine how the lesion contrast changes with lesion severity and depth for different spectral regions in the near-IR and compare that range of contrast with visible reflectance and fluorescence. Materials and Methods Forty-four human molars were used in this in vitro study. Teeth were painted with an acid-resistant varnish, leaving a 4×4 mm window on the occlusal surface of each tooth exposed for demineralization. Artificial lesions were produced in the unprotected windows after 12–48 hr exposure to a demineralizing solution at pH-4.5. Near-IR reflectance images were acquired over several near-IR spectral distributions, visible light reflectance, and fluorescence with 405-nm excitation and detection at wavelengths greater than 500-nm. Crossed polarizers were used for reflectance measurements to reduce interference from specular reflectance. Cross polarization optical coherence tomography (CP-OCT) was used to non-destructively assess the depth and severity of demineralization in each sample window. Matching two dimensional CP-OCT images of the lesion depth and integrated reflectivity were compared with the reflectance and fluorescence images to determine how accurately the variation in the lesion contrast represents the variation in the lesion severity. Results Artificial lesions appear more uniform on tooth surfaces exposed to an acid challenge at visible wavelengths than they do in the near-IR. Measurements of the lesion depth and severity using CP-OCT show that the lesion severity varies markedly across the sample windows and that the lesion contrast in the visible does not accurately reflect the large variation in the lesion severity. Reflectance measurements at certain near-IR wavelengths more accurately reflect variation in the depth and severity of the lesions. Conclusion The results of the study suggest that near-IR reflectance measurements at longer wavelengths coincident with higher water absorption are better suited for imaging early caries lesions. PMID:24375543

  19. Bio-imaging and Photodynamic Therapy with Tetra Sulphonatophenyl Porphyrin (TSPP)-TiO2 Nanowhiskers: New Approaches in Rheumatoid Arthritis Theranostics.

    PubMed

    Zhao, Chunqiu; Ur Rehman, Fawad; Yang, Yanlong; Li, Xiaoqi; Zhang, Dong; Jiang, Hui; Selke, Matthias; Wang, Xuemei; Liu, Chongyang

    2015-01-01

    Since Rheumatoid arthritis (RA) is one of the major human joint diseases with unknown etiology, the early diagnosis and treatment of RA remains a challenge. In this contribution we have explored the possibility to utilize novel nanocomposites of tetera suplhonatophenyl porphyrin (TSPP) with titanium dioxide (TiO2) nanowhiskers (TP) as effective bio-imaging and photodynamic therapeutic (PDT) agent for RA theranostics. Our observations demonstrate that TP solution PDT have an ameliorating effect on the RA by decreasing significantly the IL-17 and TNF-? level in blood serum and fluorescent imaging could enable us to diagnose the disease in subclinical stages and bio-mark the RA insulted joint. PMID:26153895

  20. Monitoring the Remineralization of Early Simulated Lesions using a pH Cycling Model with CP-OCT

    PubMed Central

    Kang, Hobin; Chan, Kenneth; Darling, Cynthia L.; Fried, Daniel

    2013-01-01

    If caries lesions are detected early enough they can be arrested by chemical intervention and dietary changes without the need for chemical intervention. Optical coherence tomography is ideally suited to monitor the changes that occur in caries lesions as a result of nonsurgical intervention, since OCT can nondestructively image the internal structure of the lesion. One of the most important changes that occurs in a lesion is preferential deposition of mineral in the outer surface zone. The deposition creates a highly mineralized and weakly scattering surface zone that is clearly visible in OCT images. Since this zone is near the highly reflective surface it is necessary to use cross-polarization OCT imaging to resolve this zone. Several CP-OCT studies have been conducted employing different remineralization models that produce lesions with varying mineral gradients. Previous studies have also demonstrated that automated algorithms can be used to assess the lesion depth and severity even with the presence of the weakly reflective surface zone. In this study we investigated the remineralization of lesions of varying severity using a pH cycling remineralization model and the change of the lesion was monitored using CP-OCT. Although the lesion depth and severity decreased after remineralization, there was still incomplete remineralization of the body of the lesion. PMID:24353383

  1. Simulation of the passage of fast electrons and the early stage of water radiolysis by the Monte Carlo method.

    PubMed

    Kaplan, I G; Sukhonosov VYa

    1991-07-01

    A numerical computer simulation of the processes of the interaction of electrons with liquid water and vapor was performed, beginning with the absorption of the energy of ionizing radiation and including the chemical changes in the medium. The specific features of the liquid phase compared with the gaseous phase were taken into account. Among them are the decrease of the ionization potential and collective excitations of the plasmon type. The mass stopping powers and ranges of electrons in liquid water and vapor were calculated. Within the frames of the stochastic model the kinetics of water radiolysis in the picosecond range of radiolysis was calculated by the Monte Carlo method. The mechanism of water radiolysis was found with the electron-ion recombination and the reactions of quasi-free and solvated electrons taken into account. PMID:2068265

  2. Mortality in patients with rheumatoid arthritis treated actively from the time of diagnosis

    PubMed Central

    Peltomaa, R; Paimela, L; Kautiainen, H; Leirisalo-Repo, M

    2002-01-01

    Objectives: To evaluate the mortality rates among patients with early rheumatoid arthritis (RA) treated actively according to the "sawtooth" strategy. Methods: The study included 150 early, disease modifying antirheumatic drug (DMARD) naive patients with RA from two patient cohorts. The first cohort was assembled between 1986 and 1989 (87 patients, aged 19–65 years at onset) and the second between 1991 and 1993 (63 patients, aged 27–83 years at onset). The mean duration of symptoms at the time of diagnosis was 7.1 months (range 2–24). The clinical data and the use of DMARDs were systematically recorded. The causes of death were obtained from death certificates and medical records, if available. The data were collected up to 1 November 2000. Results: During a follow up time of 7–14 years, 24 patients died. The standardised mortality ratio was not increased (0.93 in the first cohort and 1.62 in the second cohort). Age adjusted mortality rates did not differ statistically significantly between the two patient cohorts. The causes of death included malignancy (8 patients); cardiovascular diseases (10); respiratory disease (4), including two patients with pneumonia; sepsis (one); and RA (one). High inflammatory activity, disease activity, and poor functional ability at study entry, and the presence of extra-articular features during the follow up were more common among the patients who had died. Conclusions: No statistically significant increase in mortality rates was seen in these actively treated early RA cohorts during the follow up. High disease activity at the onset and the development of extra-articular features seem to be associated with mortality. PMID:12228159

  3. Optimal use of non-biologic therapy in the treatment of rheumatoid arthritis.

    PubMed

    Jacobs, Johannes W G

    2012-06-01

    With the evolution of therapies for RA, new treatment strategies and goals of therapy have evolved. Recent European League Against Rheumatism (EULAR) guidelines on the treatment of RA proposed three phases of therapy: phase I comprising first-line synthetic DMARD with or without glucocorticoid; phase II comprising second-line synthetic DMARD with or without glucocorticoid, or combination synthetic DMARD therapy, or (if prognostic factors are poor) first-line biologic DMARD; and phase III comprising alternative biologic DMARDs. In all phases, the key principle is tight control: striving to achieve a predefined goal of remission or low disease activity (treat to target) with frequent dose and medication adjustments tailored to the individual patient, preferably within the window of opportunity during early RA. In all phases, MTX is recognized as an anchor drug; it is characterized by proven efficacy in combination DMARD strategies, relatively low cost, relatively rapid onset of action, proven beneficial impact on radiological progression and mortality and a wide dose range that facilitates dose adjustments. Prednisone and its active metabolite, prednisolone, have similar characteristics, making them ideal anchor drugs too. The EULAR guidelines reserve a place for MTX and glucocorticoids in all phases of treatment. The second CAMERA (Computer Assisted Management in Early Rheumatoid Arthritis) study in early RA has demonstrated that including prednisone from the start in an MTX-based tight control strategy aimed at remission improves disease activity variables, time to remission, functional disability and radiological joint damage compared with the same strategy without prednisone. In conclusion, both MTX and prednisone play key roles in modern RA treatment strategies. PMID:22513146

  4. Anti-rheumatoid arthritic activity of flavonoids from Daphne genkwa.

    PubMed

    Jiang, Cui-Ping; He, Xin; Yang, Xiao-Lin; Zhang, Su-Li; Li, Hui; Song, Zi-Jing; Zhang, Chun-Feng; Yang, Zhong-Lin; Li, Ping; Wang, Chong-Zhi; Yuan, Chun-Su

    2014-05-15

    The aim of the study was to investigate the anti-rheumatoid arthritic activity of four flavonoids from Daphne genkwa (FFD) in vivo and in vitro. Flavonoids of D. genkwa were extracted by refluxing with ethanol and purified by polyamide resin. An in vivo carrageenan-induced paw edema model, tampon-granuloma model and Freund's complete adjuvant (FCA)-induced arthritis mouse model were used to evaluate the anti-rheumatoid arthritic activities of FFD. Moreover, nitric oxide (NO) release and neutral red uptake (NRU) in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were used to evaluate the anti-inflammatory effect in vitro. In addition, antioxidant effect of FFD was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A high dose of FFD significantly reduced the degree of acute inflammatory paw edema in mice as a response to carrageenan administration (p<0.01). FFD displayed a dose-dependent inhibition of granuloma formation in mice (p<0.05). FFD also inhibited chronic inflammation in adjuvant-induced arthritis rats when administered orally at the dose of 50mg/kg/day (p<0.001). In addition, FFD suppressed the production of NO and exhibited immunoregulatory function in LPS-activated RAW264.7 cells in a dose-related manner. Simultaneously, FFD revealed conspicuous antioxidant activity with IC50 values of 18.20?g/ml. FFD possesses significant anti-inflammatory and antioxidant activity, which could be a potential therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis. PMID:24561028

  5. Risk of cancer among rheumatoid arthritis patients in California

    Microsoft Academic Search

    Arti Parikh-Patel; Richard H. White; Mark Allen; Rosemary Cress

    2009-01-01

    Objective  The objective of this retrospective cohort study was to evaluate cancer risk among rheumatoid arthritis (RA) patients in California.\\u000a \\u000a \\u000a \\u000a Methods  The study cohort derived from statewide patient discharge records was followed via linkage with cancer registry data over\\u000a the period 1991–2002. Age and sex adjusted standardized incidence ratios (SIRs) and 95% confidence intervals were calculated\\u000a to compare observed to expected numbers

  6. Imaging in rheumatoid arthritis: results of group discussions.

    PubMed

    Molenaar, E T; Boers, M; van der Heijde, D M; Alarcón, G; Bresnihan, B; Cardiel, M; Edmonds, J; Felson, D; Furst, D E; Kirwan, J; Lassere, M; Paulus, H; Rau, R; van Riel, P L; Scott, D; Simon, L; Strand, V

    1999-03-01

    None of the current scoring methods for radiological damage in rheumatoid arthritis (RA) is ideal. The objective for RA imaging at OMERACT IV was to start discussion about the problems and applicability of the current scoring methods for radiological damage and to start discussion on the challenge of new imaging techniques. The RA imaging module comprised preconference reading material, plenary sessions, small group discussions, and a plenary report of the group sessions, combined with interactive voting. The OMERACT filter guided the discussions. Priorities for further research in imaging studies were: (1) pathologies versus features on radiographs; (2) relation with longterm outcome; and (3) definition of minimum clinically important difference. PMID:10090196

  7. Bone metabolism in rheumatoid arthritis compared with postmenopausal osteoporosis.

    PubMed Central

    van Soesbergen, R M; Lips, P; van den Ende, A; van der Korst, J K

    1986-01-01

    Calcium and bone metabolism in 29 rheumatoid arthritis (RA) patients were compared with those in 27 postmenopausal osteoporotic patients. Signs of vitamin D deficiency were found in 20 RA patients, including 12 who took recommended amounts of vitamin D in their diets and were exposed to sufficient sunlight, and in none of the osteoporotic patients. There were no signs of malabsorption. In six out of 15 patients we found increased liver enzyme activity, which may have a role in vitamin D metabolism. We propose the influence of non-steroidal anti-inflammatory drugs (NSAIDs) on vitamin D metabolism in the liver as a possible explanation. PMID:3947143

  8. A case of sclerosing mesenteritis with rheumatoid arthritis.

    PubMed

    Makdsi, Fadi; Brit, Michael

    2010-01-01

    Sclerosing mesenteritis (SM) is an uncommon disorder characterized by chronic nonspecific inflammation involving the adipose tissue of the mesentery. The etiology remains unclear. It has been reported in association with and as an initial presentation in some autoimmune diseases. Its clinical presentation and laboratory findings are typically nonspecific and definitive diagnosis usually requires biopsy or surgical excision. We report a patient with a history of rheumatoid arthritis who was found to have an intra-abdominal mass suspicious for malignancy. A biopsy revealed the diagnosis of SM. PMID:19996846

  9. Surgical footwear in rheumatoid arthritis--a patient acceptability study.

    PubMed

    Park, C; Craxford, A D

    1981-04-01

    One hundred patients wih rheumatoid arthritis were questioned about the acceptability of the surgical shoes that they had been prescribed for their foot problems. The approach was made from the records of a surgical supplies manufacturer. While 90 per cent experienced good alleviation of symptoms, 50 per cent had complaints regarding fit, comfort and styling. The implications of changes in the supply of shoes and the staffing of orthotic concerns are discussed, and suggestions are made for the direction of future research. PMID:7279612

  10. Production of nitrogen oxides by lightning and coronae discharges in simulated early Earth, Venus and Mars environments.

    PubMed

    Nna Mvondo, D; Navarro-Gonzalez, R; McKay, C P; Coll, P; Raulin, F

    2001-01-01

    We present measurements for the production of nitrogen oxides (NO and N2O) in CO2-N2 mixtures that simulate different stages of the evolution of the atmospheres of the Earth, Venus and Mars. The nitrogen fixation rates by two different types of electrical discharges, namely lightning and coronae, were studied over a wide range in CO2 and N2 mixing ratios. Nitric oxide (NO) is formed with a maximum energy yield estimated to be ~1.3 x 10(16) molecule J-1 at 80% CO2 and ~1.3 x 10(14) molecule J-1 at 50% CO2 for lightning and coronae discharges, respectively. Nitrous oxide (N2O) is only formed by coronae discharge with a maximum energy yield estimated to be ~1.2 x 10(13) molecule J-1 at 50% CO2. The pronounced difference in NO production in lightning and coronae discharges and the lack of formation of N2O in lightning indicate that the physics and chemistry involved in nitrogen fixation differs substantially in these two forms of electric energy. PMID:11605635

  11. Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in the CAMERA tight control study

    PubMed Central

    Bakker, Marije F; Cavet, Guy; Jacobs, Johannes WG; Bijlsma, Johannes W J; Haney, Douglas J; Shen, Yijing; Hesterberg, Lyndal K; Smith, Dustin R; Centola, Michael; van Roon, Joel A G; Lafeber, Floris P J G; Welsing, Paco M J

    2012-01-01

    Objectives To evaluate the performance of individual biomarkers and a multi-biomarker disease activity (MBDA) score in the early rheumatoid arthritis (RA) patient population from the computer assisted management in early rheumatoid arthritis (CAMERA) study. Methods Twenty biomarkers were measured in the CAMERA cohort, in which patients were treated with either intensive or conventional methotrexate-based treatment strategies. The MBDA score was calculated using the concentrations of 12 biomarkers (SAA, IL-6, TNF-RI, VEGF-A, MMP-1, YKL-40, MMP-3, EGF, VCAM-1, leptin, resistin and CRP) according to a previously trained algorithm. The performance of the scores was evaluated relative to clinical disease activity assessments. Change in MBDA score over time was assessed by paired Wilcoxon rank sum test. Logistic regression was used to evaluate the ability of disease activity measures to predict radiographic progression. Results The MBDA score had a significant correlation with the disease activity score based on 28 joints-C reactive protein (DAS28-CRP) (r=0.72; p<0.001) and an area under the receiver operating characteristic curve for distinguishing remission/low from moderate/high disease activity of 0.86 (p<0.001) using a DAS28-CRP cut-off of 2.7. In multivariate analysis the MBDA score, but not CRP, was an independent predictor of disease activity measures. Additionally, mean (SD) MBDA score decreased from 53 (18) at baseline to 39 (16) at 6 months in response to study therapy (p<0.0001). Neither MBDA score nor clinical variables were predictive of radiographic progression. Conclusions This multi-biomarker test performed well in the assessment of disease activity in RA patients in the CAMERA study. Upon further validation, this test could be used to complement currently available disease activity measures and improve patient care and outcomes. PMID:22596166

  12. [New autoanti-bodies in rheumatoid arthritis: anti-citrullinated protein or peptide autoanti-bodies and the others].

    PubMed

    Fabien, Nicole; Goetz, Joëlle; Sordet, Christelle; Humbel, René-Louis; Sibilia, Jean

    2008-12-01

    New treatment strategies require that rheumatoid arthritis (RA) be diagnosed as early as possible. New diagnostic markers were required, because rheumatoid factors (RF), until now criteria for classification of RA, are not sufficiently specific and sometimes appear late, thereby limiting their diagnostic usefulness. The objective of this review is to describe the current state of knowledge and more particularly to analyze the interest of new RA autoanti-bodies, called anti-peptide or anti-citrullinated protein anti-bodies (ACPA). Other autoanti-bodies have been described, including anti-Sa, anti-alpha enolase, and anti-calpastatin autoanti-bodies. Nonetheless, their diagnostic value remains limited compared to ACPA. Accordingly, in daily practice today, the only autoanti-bodies that must be tested for to diagnose RA are the ACPAs and RFs. The discovery of ACPA (initially called anti-keratin and anti-perinuclear anti-bodies) was a major step forward for the laboratory diagnosis of RA. The tests most often used routinely areenzyme-linked immunosorbent assays(ELISA) with cyclic citrullinated peptides, whence the name anti-CCP autoanti-bodies. Accordingly, the two terms ACPA and anti-CCP can both be used. The diagnostic value, in particular their specificity, is on the order of 95%, regardless of the method of identification. These markers are very useful and are often present earlier than RF. These ACPA also have prognostic value because they are associated with more aggressive forms of RA. On the other hand, their value over time, in particular, their fluctuation as a function of treatment, is more controversial. In practice, it is recommended to test for both RF and ACPA in a diagnostic work-up for early RA. During follow-up, the value of testing for these autoanti-bodies has not been demonstrated, but additional studies are still necessary with the anti-CCP autoanti-bodies and the new anti-citrullinated protein autoanti-bodies. PMID:18951757

  13. Anti-microtubule organizing center with microtubule by autoimmune target test is also useful serological marker in rheumatoid arthritis evaluation.

    PubMed

    Kim, Duck-An; Kim, Think-You

    2013-03-01

    Seropositivity of rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody (anti-CCP) is one domain of scoring system in new American College of Rheumatology/European League against Rheumatism classification criteria for rheumatoid arthritis (RA). We investigated usefulness of antiperinuclear factor (APF) and autoantibody to microtubule organizing center with microtubule (anti-MTOC-MT), which was detected by autoimmune target (AIT) test, as serological markers for the diagnosis of early RA. The test results of 3,503 patients from the outpatient clinic of The Hospital for Rheumatic Diseases who underwent test for RF, APF, anti-CCP and anti-MTOC-MT simultaneously for the work-up of RA were analyzed. Four kinds of tests showed same results only in 53.1% (1,861/3,503) of all subjects. The kappa coefficient between each test was distributed from -0.011 to 0.622. The agreement was best between RF and anti-CCP (kappa coefficient: 0.622), but the agreement was poor between anti-MTOC-MT and other 3 tests (kappa coefficient: 0.007 to -0.025). In both of RF- and anti-CCP-negative patients, the patients who showed positive result for APF were 4.6% (160/3,503) and for anti-MTOC-MT were 13.2% (464/3,503). RF and anti-CCP positivity could not include all of APF and anti-MTOC-MT positivity. Anti-MTOC-MT detected by AIT test was independent serological marker, and it might be also helpful for the diagnosis of early RA. Therefore, the combined detection of all four serologic markers can be useful for the evaluation of suspected RA patients. PMID:22101553

  14. [The clinical informativeness of detection of antibodies to citrullinated proteins under rheumatoid arthritis].

    PubMed

    Cherkasova, M V; Novikov, A A; Alexndrova, E N; Karateev, D E; Popkova, T V; Luchikhina, E L; Avdeeva, A S; Nasonov, E L

    2015-02-01

    The main diagnostic laboratory markers of rheumatoid arthritis are IgM rheumatoid factor and antibodies to citrullinated proteins. The IgM rheumatoid factor is a sensitive but insufficiently specific marker of rheumatoid arthritis. The antibodies to citrullinated proteins have a higher specificity for diagnostic of rheumatoid arthritis. The antibodies to cyclic citrullinated peptide and modified citrullinated vimentin are the main representatives of family of antibodies to citrullinated proteins applying in clinical diagnostic practice. The study was carried out to deternine the role of antibodies to citrullinated proteins and modified citrullinated vimentin in diagnostic, evaluation of activity and severity of destructive alterations under rheumatoid arthritis. The samplings of 993 patients with reliable diagnosis of rheumatoid arthritis. 179 patients with other rheumatoid diseases and 30 healthy donors were examined. The measurement of serum concentration of IgM rheumatoid factor and C-reactive protein was implemented by immune nephelometric analysis and antibodies to citrullinated proteins were analyzed by enzymoimmunoassay The erythrocyte sedimentation rate was established using the Westergreen technique. It was established that antibodies to modified citrullinated vimentin had the highest diagnostic specificity (83%), antibodies to cyclic citrullinated peptide had the highest diagnostic specificity (87%). The diagnostic specificity of joint detection of IgM rheumatoid factor, antibodies to citrullinated proteins and antibodies to modified citrullinated vimentin made up to 87%. In patients negative to rheumatoid factor the rate ofdetection of antibodies to citrullinated proteins made up to 34% and antibodies to modified citrullinated vimentin made up to 48%. The diagnostic effectiveness of detection of antibodies to citrullinitted proteins (ratio of likelihood of positive and negative results of test was correspondingly 5.5 and 0.3; area under ROC curve 0.8) and antibodies to modified citrullinated vimentin (ratio of likelihood of positive and negative results of test was correspondingly 4.4 and 0.2; area under ROC curve 0.9) surpassed the same in analysis of IgM rheumatoid factor (ratio of likelihood of positive results--3.2, ratio of likelihood of negative results--0.4, area under ROC curve--0.8). The weak positive correlation relationship was established between concentration of antibodies to cyclic citrillinatedpeptide/antibodies to modified citrullinated vimentin in blood serum and indicators of clinical laboratory activity of rheumatoid arthritis (ESR, CRP DAS 28, (r-0.2. p < 0.05). The high positive levels of antibodies to modified citrullinated vimentin associated with expressed destructive affection of joints (p < 0.02). The antibodies to cyclic citrullinated peptide are the most highly specific and clinically informative laboratory diagnostic marker of rheumatoid arthritis. The detection of antibodies to modified citrullinated vimentin is an important additional serological test to diagnose rheumatoid arthritis in IgM rheumatoid factor-negative and/or antibodies to cyclic citrullinated peptide-negative patients and to forecast severe destructive affection of joints under the given disease. The joint study of IgM rheumatoid factor, antibodies to cyclic citrullinated peptide and antibodies to modified citrullinated vimentin under rheumatoid arthritis has higher diagnostic sensitivity as compared with isolated antibodies to citrullinated proteins. PMID:26027260

  15. Spatial modelling of rheumatoid arthritis in Turkey by geographic information systems (GIS).

    PubMed

    ?nan?r, Ahmet; Dogan, Hakan Mete; Çeçen, Osman; Dogan, Cisem Nildem

    2013-11-01

    We described the recent spatial distribution of rheumatoid arthritis in Turkey and assessed the role of environmental variables in this distribution. We developed an observed rheumatoid arthritis (RA) incidence grid map by using georeferenced rheumatoid arthritis case data (2011) from the centres of 81 provinces and the kriging method with a spherical variogram model in geographic information systems (GIS). We also modelled rheumatoid arthritis incidence in GIS by using complementary spatial database including the grid map layers of 14 environmental variables of Turkey. We conducted principle component analysis and multiple regression to investigate the relationships among variables and develop a model, respectively. The produced model was run in GIS to obtain a predicted (model) RA map. We tested the reliability of the model map by residual statistics and found the model map dependable. Observed and model incidence maps revealed the geographic distribution of rheumatoid arthritis cases in Turkey. The mean temperature, minimum temperature, maximum temperature, water vapour pressure, elevation, potential evapotranspiration, latitude, distance to seas, sunshine fraction, precipitation, longitude and aspect variables were found to have significant impacts on rheumatoid arthritis. Consequently, the model incidence map established a good background to predict rheumatoid arthritis cases following environmental changes. PMID:23832293

  16. Acute polyarthritis immediately after kidney transplantation: a medication-induced rheumatoid arthritis flare?

    PubMed

    Brumby, Catherine; Huang, Louis; Lee, Darren; McMahon, Lawrence

    2014-04-01

    A patient with known steroid-dependent rheumatoid arthritis (RA) developed an acute symmetrical polyarthropathy of small and medium-sized joints associated with markedly elevated inflammatory markers suggestive of RA flare, on day 4 after deceased-donor renal transplantation. The patient received standard induction immunosuppression with methylprednisolone and basiliximab, and had commenced prednisolone, tacrolimus and mycophenolate mofetil. Serological investigations and joint aspirate to exclude infective causes and crystal arthropathy were unremarkable. High-dose prednisolone (50?mg daily) resulted in partial but unsustained symptomatic improvement. On suspicion of a medication-related adverse event, tacrolimus and mycophenolate mofetil were changed to cyclosporine A and azathioprine on day 16. This was followed by rapid improvement in symptoms and normalization of inflammatory markers. Unexpected sequelae in the early post-transplantation period create diagnostic and management challenges. Medication-related adverse events are not uncommon, and we speculate in this case on the potential for medication-induced immune system dysregulation stimulating disease activity in a chronic autoimmune condition after introduction of new immunosuppressants. PMID:24467783

  17. The Role of Power Doppler Ultrasonography as Disease Activity Marker in Rheumatoid Arthritis

    PubMed Central

    Bhasin, Shaloo; Cheung, Peter P.

    2015-01-01

    Structural damage in rheumatoid arthritis (RA) occurs early if inflammation is not treated promptly. Treatment targeted to reduce inflammation, in particular, that of synovial inflammation in the joints (synovitis), has been recommended as standard treat-to-target recommendations by rheumatologists. The goal is to achieve disease remission (i.e., no disease activity). Several accepted remission criteria have not always equated to the complete absence of true inflammation. Over the last decade, musculoskeletal ultrasonography has been demonstrated to detect subclinical synovitis not appreciated by routine clinical or laboratory assessments, with the Power Doppler modality allowing clinicians to more readily appreciate true inflammation. Thus, targeting therapy to Power Doppler activity may provide superior outcomes compared with treating to clinical targets alone, making it an attractive marker of disease activity in RA. However, more validation on its true benefits such as its benefits to patients in regard to patient related outcomes and issues with standardized training in acquisition and interpretation of power Doppler findings are required.

  18. Hybrid 18F-FDG PET-MRI of the hand in rheumatoid arthritis: initial results.

    PubMed

    Miese, Falk; Scherer, Axel; Ostendorf, Benedikt; Heinzel, Alexander; Lanzman, Rotem S; Kröpil, Patric; Blondin, Dirk; Hautzel, Hubertus; Wittsack, Hans-Jörg; Schneider, Matthias; Antoch, Gerald; Herzog, Hans; Shah, N Jon

    2011-09-01

    18F-fluorodeoxyglucose PET (18F-FDG PET) is highly sensitive to inflammatory changes within the synovial tissue in rheumatoid arthritis (RA). However, the highest spatial resolution for soft tissue can be achieved with MRI. Here, we report on the first true hybrid PET-MRI examination of the hand in early RA exploiting the advantages of both modalities. PET-MRI was performed with a prototype of an APD-based magneto-insensitive BrainPET detector (Siemens Healthcare, Erlangen, Germany) operated within a standard 3T MR scanner (MAGNETOM Trio, Siemens). PET images were normalized, random, attenuation and scatter-corrected, iteratively reconstructed and calibrated to yield standardized uptake values (SUV) of 18F-FDG uptake. T1-weighted TSE in coronal as well as sagittal orientation prior to and following Gadolinium administration were acquired. Increased 18F-FDG uptake was present in synovitis and tenovaginitis as identified on contrast-enhanced MRI. The tracer distribution was surrounding the metacarpophalangeal joints II and III. Maximum SUV of 3.1 was noted. In RA, true hybrid 18F-FDG PET-MRI of the hand is technically feasible and bears the potential to directly visualize inflammation. PMID:21590292

  19. Erosive rheumatoid arthritis is associated with antibodies that activate PAD4 by increasing calcium sensitivity.

    PubMed

    Darrah, Erika; Giles, Jon T; Ols, Michelle L; Bull, Herbert G; Andrade, Felipe; Rosen, Antony

    2013-05-22

    Peptidylarginine deiminases (PADs) play a critical role in generating autoantigens in rheumatoid arthritis (RA), but the mechanisms underlying their dysregulation in this disease remain unknown. Although PADs require supraphysiologic concentrations of calcium for activity in vitro, the enzymes are active in vivo (for example, in RA synovial fluid) where calcium concentrations are much lower. We have discovered a subset of anti-PAD4 autoantibodies (identified by their cross-reactivity with PAD3) that markedly increase the catalytic efficiency of PAD4 by decreasing the enzyme's requirement for calcium into the physiologic range. Patients with these PAD3/PAD4 cross-reactive autoantibodies had higher baseline radiographic damage scores and a higher likelihood of radiographic progression compared to individuals negative for these antibodies. The ability of autoantibodies to activate an enzyme that itself generates citrullinated autoantigens identifies an important feed-forward loop, which may drive the erosive outcome observed in RA patients with these autoantibodies. PAD3 autoantibodies may therefore identify RA patients who would benefit from early aggressive treatment or addition of PAD inhibitor therapy. PMID:23698378

  20. The use of chimeric vimentin citrullinated peptides for the diagnosis of rheumatoid arthritis.

    PubMed

    Malakoutikhah, Morteza; Gómara, María J; Gómez-Puerta, José A; Sanmartí, Raimon; Haro, Isabel

    2011-11-10

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and, in many cases, destruction of the joints. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. The present study addresses the search of new RA citrullinated antigens that could supplement or complement diagnostic/prognostic existing tests. With this aim, the epitope anticitrullinated vimentin antibody response was mapped using synthetic peptides. To improve the sensitivity/specificity balance, a vimentin peptide that was selected, and its cyclic analogue, were combined with fibrin- and filaggrin-related peptides to render chimeric peptides. Our findings highlight the putative application of these chimeric peptides for the design of RA diagnosis systems and imply that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported here (fibrin, vimentin, filaggrin) has a specific utility in the identification of a particular subset of RA patients. PMID:21981664

  1. The use of citrullinated peptides for the diagnosis and prognosis of rheumatoid arthritis.

    PubMed

    Haro, Isabel; Gómara, Maria J

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint inflammation and extra-articular manifestations. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing RA. ACPAs may be detected several years before symptoms appear, and their presence at disease onset is a good predictor of the development of erosive joint lesions. Synthetic peptides can replace cognate proteins in solid-phase assays for specific autoantibody recognition in RA patients. The use of synthetic peptides instead of proteins represents an advantage in terms of the reproducibility of such immunoassays. They give absolute control over the exact epitopes presented. Furthermore, it is difficult to prepare sufficient amounts of high-quality antigenic proteins with a well-defined degree of citrullination. Synthetic citrullinated peptides, in contrast, are easily obtained in a pure form with a well-defined chemical structure and the epitopes can be precisely oriented in the plate by covalent binding of the peptides. We have recently obtained and highlighted the application of chimeric peptides bearing different citrullinated protein domains for the design of RA diagnosis systems. Our results indicate that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported (fibrin, vimentin and filaggrin) helps to identify a particular subset of RA patients. PMID:25515746

  2. Dominant clonotypes in the repertoire of peripheral CD4+ T cells in rheumatoid arthritis.

    PubMed Central

    Goronzy, J J; Bartz-Bazzanella, P; Hu, W; Jendro, M C; Walser-Kuntz, D R; Weyand, C M

    1994-01-01

    Clonal expansion of T cell specificities in the synovial fluid of patients has been taken as evidence for a local stimulation of T cells. By studying the T cell receptor (TCR) repertoire of CD4+ T cells in the synovial and peripheral blood compartments of patients with early rheumatoid arthritis (RA), we have identified clonally expanded CD4+ populations. Expanded clonotypes were present in the peripheral blood and the synovial fluid but were not preferentially accumulated in the joint. Dominant single clonotypes could not be isolated from CD4+ cells of HLA-DRB1*04+ normal individuals. Clonal expansion involved several distinct clonotypes with a preference for V beta 3+, V beta 14+, and V beta 17+CD4+ T cells. A fraction of clonally related T cells expressed IL-2 receptors, indicating recent activation. The frequencies of clonally expanded V beta 17+CD4+ T cells fluctuated widely over a period of one year. Independent variations in the frequencies of two distinct clonotypes in the same patient indicated that different mechanisms, and not stimulation by a single arthritogenic antigen, were involved in clonal proliferation. These data support the concept that RA patients have a grossly imbalanced TCR repertoire. Clonal expansion may result from intrinsic defects in T cell generation and regulation. The dominance of expanded clonotypes in the periphery emphasizes the systemic nature of RA and suggests that T cell proliferation occurs outside of the joint. Images PMID:7962553

  3. Quality indicators in rheumatoid arthritis care: using measurement to promote quality improvement.

    PubMed

    Bombardier, Claire; Mian, Samra

    2013-04-01

    Quality of care improvement has become a priority for decision-makers. Important variations in the quality and cost of care are being documented often without evidence of improved outcomes. Therapeutic advances are not consistently applied to practice despite efforts from professional organisations to create guidelines. The quality movement emerged following increasing evidence that the creation and measurement of quality indicators can improve quality of care and health outcomes. Quality indicators can measure healthcare system performance across providers, system levels and regions. In rheumatology, early efforts to develop quality measures have focused on examining all aspects of care while more recent efforts have focused on disease course monitoring. The American College Rheumatology has recently endorsed seven quality indicators for rheumatoid arthritis (RA) that are evidence based and measurable for use in routine rheumatology practices. This review provides an overview on quality indicators in rheumatology with a focus on RA, and discusses the application of quality measures into routine rheumatology practices to improve quality of care for RA. PMID:23253925

  4. Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients

    PubMed Central

    2014-01-01

    Background Rheumatoid arthritis and osteoarthritis are two common musculoskeletal disorders that affect the joints. Despite high prevalence rates, etiological factors involved in these disorders remain largely unknown. Dissecting the molecular aspects of these disorders will significantly contribute to improving their diagnosis and clinical management. In order to identify proteins that are differentially expressed between these two conditions, a quantitative proteomic profiling of synovial fluid obtained from rheumatoid arthritis and osteoarthritis patients was carried out by using iTRAQ labeling followed by high resolution mass spectrometry analysis. Results We have identified 575 proteins out of which 135 proteins were found to be differentially expressed by ?3-fold in the synovial fluid of rheumatoid arthritis and osteoarthritis patients. Proteins not previously reported to be associated with rheumatoid arthritis including, coronin-1A (CORO1A), fibrinogen like-2 (FGL2), and macrophage capping protein (CAPG) were found to be upregulated in rheumatoid arthritis. Proteins such as CD5 molecule-like protein (CD5L), soluble scavenger receptor cysteine-rich domain-containing protein (SSC5D), and TTK protein kinase (TTK) were found to be upregulated in the synovial fluid of osteoarthritis patients. We confirmed the upregulation of CAPG in rheumatoid arthritis synovial fluid by multiple reaction monitoring assay as well as by Western blot. Pathway analysis of differentially expressed proteins revealed a significant enrichment of genes involved in glycolytic pathway in rheumatoid arthritis. Conclusions We report here the largest identification of proteins from the synovial fluid of rheumatoid arthritis and osteoarthritis patients using a quantitative proteomics approach. The novel proteins identified from our study needs to be explored further for their role in the disease pathogenesis of rheumatoid arthritis and osteoarthritis. Sartaj Ahmad and Raja Sekhar Nirujogi contributed equally to this article. PMID:24393543

  5. Acute-onset paralysis in a patient of rheumatoid arthritis.

    PubMed

    Varshney, Ankur Nandan; Prasad, Pratibha; Kumar, Nilesh; Singh, Nand Kumar

    2015-01-01

    Renal tubular acidosis (RTA) is a disorder of renal acidification characterized by inability to acidify urine to pH < 5.5 despite the presence of severe systemic metabolic acidosis and hypokalemia. Hypokalemia leads to acute-onset paralysis and may be a presenting manifestation of RTA. Its association with various autoimmune disease has been reported previously in published reports, but has not been much em.phasized. We, hereby, report a case of RTA that presented during the flare of rheumatoid arthritis (RA). A 42-year-old female, a known case of RA for 5 years, presented with persistent joint pain for 1 week and acute-onset quadriparesis for 3 days. Primary investigations revealed hypokalemia with metabolic acidosis. She was managed conservatively with potassium supplements and bicarbonate supplements along with steroids and disease-modifying anti-rheumatic drugs. Such a presentation of renal tubular acidosis in a patient during the flare of rheumatoid arthritis is distinctly rare and previously unreported in published studies. PMID:26142942

  6. Therapy gloves for patients with rheumatoid arthritis: a review

    PubMed Central

    Troynikov, Olga; Massy-Westropp, Nicola

    2014-01-01

    Rheumatoid arthritis is a chronic inflammatory disease that causes pain, joint stiffness and swelling leading to impaired hand function and difficulty with daily activities. Wearing therapy gloves has been recommended by occupational therapists as one of the alternative treatment methods for rheumatoid arthritis. This study aims to review the available literature on the effects of wearing therapy gloves on patients’ hand function and symptoms as well as to discuss the attributes of gloves that might influence the glove performance. An electronic databases search of MEDLINE, Physiotherapy Evidence Database, Occupational Therapy Systematic Evaluation of Evidence, Wiley Online Library, ScienceDirect and Cochrane Central Register of Controlled Trial was performed. Eight articles met the inclusion criteria, and covered seven clinical trials and one case study. Seven outcome measures were identified from the included studies and were then classified into two categories: hand function and hand symptoms. The hand symptoms such as pain, stiffness and swelling improve substantially when the therapy gloves are used. However, marginal or no improvement in hand function (with the exception of grip strength) linked to the use of therapy gloves is being reported. Further research is needed to quantify the effectiveness of therapy gloves, especially in improvement of hand function and in patients’ interest in wearing therapy gloves. Furthermore, future studies should include parameters which might influence therapy gloves’ performance, such as duration of trials, interface pressure generated by the gloves on the underlying skin and tissue, glove fit and construction, as well as thermophysiological comfort. PMID:25435925

  7. Citrullination and Carbamylation in the Pathophysiology of Rheumatoid Arthritis

    PubMed Central

    Pruijn, Ger J. M.

    2015-01-01

    The discovery that citrullination was crucial for the recognition of antigens by the most disease-specific class of autoantibodies in rheumatoid arthritis (RA) had a huge impact on studies aimed at understanding autoimmunity in this disease. In addition to the detailed characterization of anti-citrullinated protein antibodies, various studies have addressed the identity of citrullinated antigens. These investigations were facilitated by new methods to characterize these proteins, the analysis of protein citrullination by peptidylarginine deiminases, the generation of a catalog of citrullinated proteins present in the inflamed joints of patients and the finding that the formation of extracellular traps is dependent on the activity of peptidylarginine deiminase activity. Recently, it was found that in addition to citrullination also carbamylation, which results in chemically highly related modified proteins, yields antigens that are targeted by rheumatoid arthritis patient sera. Here, all of these aspects will be discussed, culminating in current ideas about the involvement of citrullination and carbamylation in pathophysiological processes in autoimmunity, especially RA. PMID:25964785

  8. The association between rheumatoid arthritis and periodontal disease

    PubMed Central

    2010-01-01

    Chronic, plaque-associated inflammation of the gingiva and the periodontium are among the most common oral diseases. Periodontitis (PD) is characterized by the inflammatory destruction of the periodontal attachment and alveolar bone, and its clinical appearance can be influenced by congenital as well as acquired factors. The existence of a rheumatic or other inflammatory systemic disease may promote PD in both its emergence and progress. However, there is evidence that PD maintains systemic diseases. Nevertheless, many mechanisms in the pathogenesis have not yet been examined sufficiently, so that a final explanatory model is still under discussion, and we hereby present arguments in favor of this. In this review, we also discuss in detail the fact that oral bacterial infections and inflammation seem to be linked directly to the etiopathogenesis of rheumatoid arthritis (RA). There are findings that support the hypothesis that oral infections play a role in RA pathogenesis. Of special importance are the impact of periodontal pathogens, such as Porphyromonas gingivalis on citrullination, and the association of PD in RA patients with seropositivity toward rheumatoid factor and the anti-cyclic citrullinated peptide antibody. PMID:21062513

  9. Deficient cytokine control modulates temporomandibular joint pain in rheumatoid arthritis.

    PubMed

    Ahmed, Neveen; Catrina, Anca I; Alyamani, Ahmed O; Mustafa, Hamid; Alstergren, Per

    2015-08-01

    The aim was to investigate how endogenous cytokine control of tumor necrosis factor (TNF) influences temporomandibular joint (TMJ) pain in relation to the role of anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA). Twenty-six consecutive patients with TMJ RA were included. Temporomandibular joint pain intensity was assessed at rest, on maximum mouth opening, on chewing, and on palpation. Mandibular movement capacity and degree of anterior open bite (a clinical sign of structural destruction of TMJ tissues) were also assessed. Systemic inflammatory activity was assessed using the Disease Activity Score in 28 joints (DAS28) for rheumatoid arthritis. Samples of TMJ synovial fluid and blood were obtained and analyzed for TNF, its soluble receptor, soluble TNF receptor II (TNFsRII), and ACPA. A high concentration of TNF in relation to the concentration of TNFsRII in TMJ synovial fluid was associated with TMJ pain on posterior palpation on maximum mouth opening. The ACPA concentration correlated significantly to the TNF concentration, but not to the TNFsRII concentration, indicating that increased inflammatory activity is mainly caused by an insufficient increase in anti-inflammatory mediators. This study indicates that TMJ pain on palpation in patients with RA is related to a deficiency in local cytokine control that contributes to increased inflammatory activity, including sensitization to mechanical stimuli over the TMJ. PMID:26010823

  10. Vascular Function and Handgrip Strength in Rheumatoid Arthritis Patients

    PubMed Central

    Alomari, Mahmoud A.; Keewan, Esraa F.; Shammaa, Rania A.; Alawneh, Khaldoon; Khatib, Said Y.; Welsch, Michael A.

    2012-01-01

    Objective. To examine the relationship of handgrip strength with forearm blood flow (BF) and vascular resistance (VR) in rheumatoid arthritis (RA) patients. Methods. Forearm BF at rest (RBF) and after upper arm occlusion (RHBF), and handgrip strength were examined in 78 individuals (RA = 42 and controls (CT) = 36). Subsequently, VR at rest (RVR) and after occlusion (RHVR) were calculated. Results. The patients' RBF (P = 0.02) and RHBF (P = 0.0001) were less, whereas RVR (P = 0.002) and RHVR (P = 0.0001) were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P = 0.0001). Finally, handgrip strength was directly associated with RBF (r = 0.43; P = 0.0001), and RHBF (r = 0.5; P = 0.0001), and inversely related to RVR (r = ?0.3; P = 0.009) and RHVR (r = ?0.3; P = 0.007). Conclusion. The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals. PMID:22606051

  11. Prohibitin as a novel autoantigen in rheumatoid arthritis

    PubMed Central

    Shi, Li-Li; Chen, Peng; Xun, Yi-Ping; Yang, Wei-Kang; Yang, Chun-He; Chen, Guang-Yu

    2015-01-01

    The aim of this study The aim of this study was to verify whether prohibitin is a novel autoantigen in rheumatoid arthritis. Material and methods First, recombinant human prohibitin (rhPHB) protein was cloned, expressed, and purified. Then the anti-prohibitin autoantibodies were detected by western blotting by using rhPHB protein to incubate sera from patients with rheumatoid arthritis (RA). Next, immunoprecipitation was employed to further illustrate whether anti-prohibitin antibodies exist in RA patients. And finally, autoantibodies against the rhPHB protein were investigated using a homemade ELISA kit through the assessment of 258 real clinical samples. Results It was revealed that anti-prohibitin antibodies existed in the sera of patients with RA. Reactivity of serum IgG against rhPHB was detected in 26 of 86 RA patients (30.3%), 7 of 86 systemic lupus erythematosus (SLE) patients (8.1%), and 1 of 86 apparently healthy donors (HC) (1.2%). Conclusions Prohibitin was proved to be a novel autoantigen and the corresponding anti-prohibitin autoantibodies were present in the RA patients' blood circulation.

  12. Rheumatoid arthritis, cytokines and hypoxia. What is the link?

    PubMed

    Al-Shukaili, Ahmed K; Al-Jabri, Ali A

    2006-11-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that affects approximately 1% of the population, in a female to male ratio of 3:1. The disease can occur at any age, but it is most common among those aged 40-70 years. Despite many years of study, the etiology of RA is still undefined. However, with increased understanding of the immune system the pathogenesis of RA has become clearer. A large bulk of data suggests that T lymphocytes and macrophages play a critical role in the initiation and perpetuation of synovial inflammation. Recently, the cytokine profile of T helper cells has been associated with the disease, the cytokine repertoire of inflamed synovia is categorized as that of T helper 1 response. Moreover, in RA elevated levels of pro-inflammatory or inflammatory cytokines such as Tumor Necrosis Factor - alpha (TNF-alpha) and Interleukin -1 beta (IL-1beta) have been detected. Hypoxia up-regulates TNF-alpha and IL-1beta; therefore, considerable research interest has been focused on the biological consequences of the hypoxic nature of the rheumatoid synovium. Hypoxia might underlie the functional polarization of the T cells and cytokine production, and thus may contribute to the progression and persistence of the disease. In this short review, we discuss our current knowledge of the link between cytokines and RA and the role of hypoxia in the pathogenesis of the disease. PMID:17106534

  13. Increased TTS expression in patients with rheumatoid arthritis.

    PubMed

    Chen, Jiaxi; Jun, Li; Shiyong, Chen; Li, Hou; Zhu, Ming; Shen, Bo

    2015-02-01

    Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The aim of this work was to study the imbalance expressions of indoleamine 2,3-dioxygenase (IDO) and tryptophanyl-tRNA synthetase (TTS) with RA patients. Forty-nine RA patients and 49 healthy controls were studied. The expressions of IDO and TTS were analyzed by real-time quantitative polymerase chain reaction and flow cytometry in peripheral blood mononuclear cells. The expression of TTS mRNA increased significantly in RA patients when compared with healthy controls and correlated with erythrocyte sedimentation rate (r = 0.424, P < 0.01). In addition, we found TTS increased significantly mainly in CD3(+) T cells in rheumatoid arthritis group. Increased TTS expressions from CD3(+) T cells might link to a pathogenic mechanism involved in increasing survival of autoreactive T cells in RA patients. Determination of expressions of TTS may provide a better understanding of progression of the disease. PMID:24515434

  14. NOAH-New York Online Access to Health: Arthritis and Rheumatoid Disorders

    NSDL National Science Digital Library

    From New York Online Access to Health (NOAH), this website offers links to numerous Internet resources for Arthritis and Rheumatoid Disorders. Care and Treatment resource categories include Diet; Medications; Total Hip Replacement; and Alternative Therapies-to name a few. Websites relating to diagnosis and symptoms, as well as specific concerns like arthritis in children, and rheumatoid diseases and pregnancy are available as well. In addition, the site links to websites for a wide range of Rheumatoid Disorders such as Avascular Necrosis, Gout, Osteoarthritis, Vasculitis, and more. Site visitors can also link to Internet resources for other health issues on the NOAH website including Heart Disease, Infections, Cancer, Asthma, and Dental Care.

  15. Complementary and Alternative Medicine Use in African Americans With Rheumatoid Arthritis

    PubMed Central

    TAMHANE, ASHUTOSH; McGWIN, GERALD; REDDEN, DAVID T.; HUGHES, LAURA B.; BROWN, ELIZABETH E.; WESTFALL, ANDREW O.; CONN, DOYT L.; JONAS, BETH L.; SMITH, EDWIN A.; BRASINGTON, RICHARD D.; MORELAND, LARRY W.; BRIDGES, S. LOUIS; CALLAHAN, LEIGH F.

    2014-01-01

    Objective. Racial/ethnic differences with regard to complementary and alternative medicine (CAM) use have been reported in the US. However, specific details of CAM use by African Americans with rheumatoid arthritis (RA) are lacking. Methods. Data were collected from African Americans with RA enrolled in a multicenter registry regarding the use of CAM, including food supplements, topical applications, activities, and alternative care providers. Factors associated with CAM use by sex and disease duration were assessed using t-test, Wilcoxon’s rank sum test, chi-square test, and logistic regression analyses. Results. Of the 855 participants, 85% were women and mean age at enrollment was 54 years. Overall, ever using any of the CAM treatments, activities, and providers was 95%, 98%, and 51%, respectively (median of 3 for number of treatments, median of 5 for activities, and median of 1 for providers). Those with longer disease duration (>2 years) were significantly more likely (odds ratio >2.0, P < 0.05) to use raisins soaked in vodka/gin, to take fish oils, or to drink alcoholic beverages for RA treatment than those with early disease. As compared to men, women were significantly (P < 0.05) more likely to pray/attend church, write in a journal, and use biofeedback, but were less likely to smoke tobacco or topically apply household oils for treatment of RA. Conclusion. CAM use was highly prevalent in this cohort, even in individuals with early disease. Health care providers need to be aware of CAM use as some treatments may potentially have interactions with conventional medicines. This could be important within this cohort of African Americans, where racial disparities are known to affect access to conventional care. PMID:23983105

  16. Rheumatoid arthritis and periodontitis – inflammatory and infectious connections. Review of the literature

    PubMed Central

    Rutger Persson, G.

    2012-01-01

    An association between oral disease/periodontitis and rheumatoid arthritis (RA) has been considered since the early 1820s. The early treatment was tooth eradication. Epidemiological studies suggest that the prevalence of RA and periodontitis may be similar and about 5% of the population are aged 50 years or older. RA is considered as an autoimmune disease whereas periodontitis has an infectious etiology with a complex inflammatory response. Both diseases are chronic and may present with bursts of disease activity. Association studies have suggested odds ratios of having RA and periodontitis varying from 1.8:1 (95% CI: 1.0–3.2, NS) to 8:1 (95% CI: 2.9–22.1, p<0.001). Genetic factors are driving the host responses in both RA and periodontitis. Tumor necrosis factor-?, a proinflammatory cytokine, regulates a cascade of inflammatory events in both RA and periodontitis. Porphyromonas gingivalis is a common pathogen in periodontal infection. P. gingivalis has also been identified in synovial fluid. The specific abilities of P. gingivalis to citrullinate host peptides by proteolytic cleavage at Arg-X peptide bonds by arginine gingipains can induce autoimmune responses in RA through development of anticyclic citrullinated peptide antibodies. In addition, P. gingivalis carries heat shock proteins (HSPs) that may also trigger autoimmune responses in subjects with RA. Data suggest that periodontal therapies combined with routine RA treatments further improve RA status. Conclusions Periodontal infection (P. gingivalis) carries a unique risk for development of autoimmune antibodies associated with RA. Patients with RA have either lost many teeth or usually have severe periodontitis. Additional research, both in regards to basic mechanisms as well as clinical studies, are necessary before it can be said that there are causative links between RA and periodontitis. Cross-disciplinary research in well-defined populations should be performed to further enhance knowledge and develop clinical strategies how to coordinate therapy and risk assessments of RA and periodontitis. PMID:22347541

  17. Symptom Complexes at the Earliest Phases of Rheumatoid Arthritis: A Synthesis of the Qualitative Literature

    PubMed Central

    Stack, Rebecca J; Sahni, Melanie; Mallen, Christian D; Raza, Karim

    2013-01-01

    Objective Understanding the features and patterns of symptoms that characterize the earliest stages of rheumatoid arthritis (RA) is of considerable importance if patients are to be identified and started on treatment early. However, little is known about the characteristics of symptoms at the onset of a disease that eventually progresses to RA. Methods A systematic review of qualitative peer-reviewed publications was conducted to identify the earliest symptoms associated with the onset of RA. A total of 1,736 abstracts were searched to identify relevant publications. Twenty-six publications were identified, assessed for quality, and subjected to analysis informed by thematic and grounded theory frameworks. Results Several interacting themes describing the early symptoms of RA were identified, including swelling, pain and tenderness, stiffness, fatigue and weakness, and the emotional impact of symptoms. For each symptom, different and evolving intensities were described; in some cases, patterns of symptom onset and symptom complexes at the onset of RA were highlighted. Importantly, this review has emphasized major deficiencies in the literature. None of the studies reviewed originally aimed to explore symptoms at RA onset (often discussions about symptom onset were secondary to the study's primary aim). Also, many of the articles identified sampled people diagnosed with RA many years previously, making their recollection of symptoms at onset less reliable. Conclusion In order for clinicians to fully understand the earliest phases of disease, the nature of symptoms at onset needs to be understood. The current work represents a useful starting point, but this area needs further qualitative investigation, followed by quantitative explorations of symptom clusters and their associated features. PMID:23926091

  18. Molecular Hydrogen: New Antioxidant and Anti-inflammatory Therapy for Rheumatoid Arthritis and Related Diseases

    PubMed Central

    Ishibashi, Toru

    2013-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease in which the progressive destruction of joint causes morbidity. It is also associated with an increased risk of atherosclerosis, which can result in cardiovascular disease and mortality. The therapeutic goal is to control the systemic inflammation to obtain not only the remission of symptoms, but also improve general state of health. Although recent biologic immunosuppressive therapies targeting pro-inflammatory cytokines have spawned a paradigm shift regarding the prognosis of RA, these therapies possess inherent side effects. Also, early diagnosis of the disease remains confounded by uncertainty. While the mechanisms responsible for the onset of RA remain unclear, reactive oxygen species (ROS) play a significant role in the pathogenesis of RA. ROS play a central role both upstream and downstream of NF-?B and TNF? pathways, which are located at the center of the inflammatory response. Among the ROS, the hydroxyl radical is the most harmful, and molecular hydrogen (H2) is a selective scavenger for this species. Recently, it has been shown that H2 is useful when administered along with the conventional therapy in RA as it acts to reduce oxidative stress in the patients. Especially in the early stage, H2 showed significant therapeutic potential, which also seemed to assist diagnosis and treatment decisions of RA. The possible expectations regarding the potential benefits of H2 by reducing the oxidative stress, resulting from inflammatory factors, are raised and discussed here. They include prevention of RA and related atherosclerosis, as well as therapeutic validity for RA PMID:23859555

  19. Anti-citrullinated protein/peptide autoantibodies in association with genetic and environmental factors as indicators of disease outcome in rheumatoid arthritis.

    PubMed

    Szodoray, Péter; Szabó, Zoltán; Kapitány, Anikó; Gyetvai, Agnes; Lakos, Gabriella; Szántó, Sándor; Szücs, Gabriella; Szekanecz, Zoltán

    2010-01-01

    Anti-citrullinated protein/peptide antibodies (ACPA) have recently emerged as sensitive and specific serological markers of rheumatoid arthritis (RA), providing superior alternative of the rheumatoid factor (RF) test in the laboratory diagnostics of RA. Citrullination is a post-translational modification of arginine by deimination, physiologically occurring during apoptosis, inflammation or keratinization. The presence of several citrullinated proteins has been demonstrated in the RA synovium. The identification of citrullinated epitopes as targets led to the development of the first and later second-generation anti-cyclic citrullinated peptide (anti-CCP) antibody assays. The anti-Sa antibody has been identified a decade ago; however, recent studies confirmed that anti-Sa is directed against citrullinated vimentin. The determination of ACPA may have important prognostic significance, since ACPA production can precede the onset of clinical RA symptoms by years. ACPA(+) individuals with early, undifferentiated arthritis may have higher risk to develop RA. ACPA has important prognostic role during the progression of RA and it has also been associated with pronounced radiographic progression. ACPA production has been associated with several genetic predisposing factors, including HLA-DRB1 and PTPN22 1858T alleles, as well as with environmental and lifestyle-related factors, primarily smoking and possibly, the use of oral contraceptives and excessive caffeine intake. Thus, the assessment of ACPA, in addition to clinical, radiographic and genetic outcome measures may be important to assess disease prognosis and aids to design effective, early therapeutic strategies. PMID:19427413

  20. The 29 September 2009 Samoa Islands Tsunami: Simulations Based on the First Focal Mechanism Solutions and Implications on Tsunami Early Warning Strategies

    NASA Astrophysics Data System (ADS)

    Tonini, Roberto; Armigliato, Alberto; Tinti, Stefano

    2011-06-01

    The tsunamigenic earthquake (Mw = 8.1) that occurred on 29 September 2009 at 17:48 UTC offshore of the Samoa archipelago east of the Tonga trench represents an example of the so-called "outer-rise" earthquakes. The areas most affected were the south coasts of Western and American Samoa, where almost 200 people were killed and run-up heights were measured in excess of 5 m at several locations along the coast. Moreover, tide gauge records showed a maximum peak-to-peak height of about 3.5 m near Pago Pago (American Samoa) and of 1.5 m offshore of Apia (Western Samoa). In this work, different fault models based on the focal mechanism solutions proposed by Global CMT and by USGS immediately after the 2009 Samoan earthquake are tested by comparing the near-field recorded signals (three offshore DART buoys and two coastal tide gauges) and the synthetic signals provided by the numerical simulations. The analysis points out that there are lights and shadows, in the sense that none of the computed tsunamis agrees satisfactorily with all the considered signals, although some of them reproduce some of the records quite well. This "partial agreement" and "partial disagreement" are analysed in the perspective of tsunami forecast and of Tsunami Early Warning System strategy.

  1. A study of the early-stage evolution of relativistic electron-ion shock using three-dimensional particle-in-cell simulations

    SciTech Connect

    Choi, E. J.; Min, K.; Choi, C. R. [Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Nishikawa, K.-I. [Department of Physics, ZP12, University of Alabama in Huntsville, Huntsville, Alabama 35899 (United States)

    2014-07-15

    We report the results of a 3D particle-in-cell simulation carried out to study the early-stage evolution of the shock formed when an unmagnetized relativistic jet interacts with an ambient electron-ion plasma. Full-shock structures associated with the interaction are observed in the ambient frame. When open boundaries are employed in the direction of the jet, the forward shock is seen as a hybrid structure consisting of an electrostatic shock combined with a double layer, while the reverse shock is seen as a double layer. The ambient ions show two distinct features across the forward shock: a population penetrating into the shocked region from the precursor region and an accelerated population escaping from the shocked region into the precursor region. This behavior is a signature of a combination of an electrostatic shock and a double layer. Jet electrons are seen to be electrostatically trapped between the forward and reverse shock structures showing a ring-like distribution in a phase-space plot, while ambient electrons are thermalized and become essentially isotropic in the shocked region. The magnetic energy density grows to a few percent of the jet kinetic energy density at both the forward and the reverse shock transition layers in a rather short time scale. We see little disturbance of the jet ions over this time scale.

  2. Cluster evolution during the early stages of heating explosives and its relationship to sensitivity: a comparative study of TATB, ?-HMX and PETN by molecular reactive force field simulations.

    PubMed

    Wen, Yushi; Zhang, Chaoyang; Xue, Xianggui; Long, Xinping

    2015-04-29

    Clustering is experimentally and theoretically verified during the complicated processes involved in heating high explosives, and has been thought to influence their detonation properties. However, a detailed description of the clustering that occurs has not been fully elucidated. We used molecular dynamic simulations with an improved reactive force field, ReaxFF_lg, to carry out a comparative study of cluster evolution during the early stages of heating for three representative explosives: 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), ?-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and pentaerythritol tetranitrate (PETN). These representatives vary greatly in their oxygen balance (OB), molecular structure, stability and experimental sensitivity. We found that when heated, TATB, HMX and PETN differ in the size, amount, proportion and lifetime of their clusters. We also found that the clustering tendency of explosives decreases as their OB becomes less negative. We propose that the relationship between OB and clustering can be attributed to the role of clustering in detonation. That is, clusters can form more readily in a high explosive with a more negative OB, which retard its energy release, secondary decomposition, further decomposition to final small molecule products and widen its detonation reaction zone. Moreover, we found that the carbon content of the clusters increases during clustering, in accordance with the observed soot, which is mainly composed of carbon as the final product of detonation or deflagration. PMID:25872486

  3. A bivariate Bayesian dose-finding procedure applied to a seamless phase I/II trial in rheumatoid arthritis.

    PubMed

    Thygesen, Helene; Dragalin, Vladimir; Whitehead, Anne; Whitehead, John

    2012-01-01

    We describe a dose escalation procedure for a combined phase I/II clinical trial. The procedure is based on a Bayesian model for the joint distribution of the occurrence of a dose limiting event and of some indicator of efficacy (both considered binary variables), making no assumptions other than monotonicity. Thus, the chances of each outcome are assumed to be non-decreasing in dose level. We applied the procedure to the design of a placebo-controlled, sequential trial in rheumatoid arthritis, in each stage of which patients were randomized between placebo and all dose levels that currently appeared safe and non-futile. On the basis of data from a pilot study, we constructed five different scenarios for the dose-response relationships under which we simulated the trial and assessed the performance of the procedure. The new design appears to have satisfactory operating characteristics and can be adapted to the requirements of a range of trial situations. PMID:23011957

  4. Economics of non-adherence to biologic therapies in rheumatoid arthritis.

    PubMed

    De Vera, Mary A; Mailman, Jonathan; Galo, Jessica S

    2014-11-01

    Adherence to biologic therapies among patients with rheumatoid arthritis is sub-optimal, with the proportion of adherent patients reported to be as low as 11 %. We found few studies evaluating economic outcomes, including health care costs, associated with non-adherence with biologic therapies. Findings suggest that while higher pharmacy costs drive total health care costs among adherent patients, non-adherent patients incur greater health care utilization including inpatient, outpatient, and laboratory services. Finally, economic factors are important determinants of adherence to biologics in patients with rheumatoid arthritis. Evidence to date has shown that higher out-of-pocket payments have a negative association with adherence to biologics. Furthermore, cost-related non-adherence is a highly prevalent problem in rheumatoid arthritis. Given the high costs of biologics and continued expansion of use in rheumatoid arthritis, there is need for more research to understand the economic implications of adherence to these therapies. PMID:25227187

  5. Interstitial Lung Disease of the UIP Variant as the Only Presenting Symptom of Rheumatoid Arthritis

    PubMed Central

    Agrawal, Abhinav; Thyagarajan, Braghadheeswar; Ceniza, Sidney; Hasan Yusuf, Syed

    2015-01-01

    Rheumatoid arthritis is a chronic inflammatory disease primarily manifesting with symptoms of joint pain. It also involves multiple organ systems in the body, including the lungs. Interstitial lung disease (ILD) is the most common form of pulmonary involvement in rheumatoid arthritis (RA). Without the typical symptoms such as chronic joint pain, establishing the diagnosis of RA could be quite challenging and a high index of suspicion is thereby required to diagnose ILD in patients with RA, thereby delaying treatment and increasing morbidity and mortality. We report a case of a 67-year-old Hispanic male with no previous history of rheumatoid arthritis or symptoms of typical joint pain who comes to the hospital only with the chief complaints of progressive worsening of shortness of breath for a duration of 6 months and was eventually diagnosed with ILD of the usual interstitial pneumonia variant with serologies positive for rheumatoid arthritis. PMID:26137341

  6. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5775 Rheumatoid factor immuno-logical test system. (a)...

  7. Turmeric inhibits parathyroid hormone-related protein (PTHrP) secretion from human rheumatoid synoviocytes

    E-print Network

    Frye, J.; Timmermann, Barbara N.; Funk, J.

    2012-06-12

    Excessive production of parathyroid hormone-related protein (PTHrP) by tumor-like synoviocytes contributes to joint destruction in rheumatoid arthritis (RA). Having previously demonstrated that curcuminoid-only and essential oil-only fractions...

  8. Theory-based analysis of the anti-inflammatory effect of TNF inhibitors on rheumatoid arthritis.

    PubMed

    Kimura, Koji; Takayanagi, Risa; Yokoyama, Haruko; Yamada, Yasuhiko

    2014-01-01

    TNF inhibitors are used as therapeutic agents for rheumatoid arthritis (RA). Each has a different dosage regimen and it is thought that the differences among them have implications on efficacy. However, those differences have not been analyzed in a theoretical manner. In the present study, we tried to explain theoretically the differences. We theoretically analyzed the anti-inflammatory effect of infliximab (IFX), etanercept (ETN), and adalimumab (ADA) for RA by using a pharmacokinetic and pharmacodynamic model. Then, we simulated values for sequential changes of tender joint count (TJC) after repeated administrations of TNF inhibitors by using the model. The sequential changes of TJC obtained with our model were in good agreement with observed TJC ratio data, which was considered to show the validity of our analytical method. The following results were obtained: the onset of clinical response was fastest with IFX, the fluctuation of IFX was greater than that of the others, and the clinical response with ADA was as stable as that with ETN. The present model was useful to analyze theoretically the anti-rheumatic effect of TNF inhibitors. Our results showed that different dosage regimens have implications on the onset and fluctuation of clinical response. PMID:24418824

  9. Long-term results of simple hemiresection arthroplasty in the rheumatoid distal radio-ulnar joint.

    PubMed

    Lee, C H; Chung, U S; Lee, B G; Shim, J H; Lee, K H

    2013-09-01

    We retrospectively studied the radiological and clinical results of a simple hemiresection arthroplasty, a modification of previous oblique distal ulnar resections, in 62 patients with rheumatoid arthritis (68 wrists) over a mean follow-up of 103 (range 60-173) months. Fourteen wrists (20%) became fused at the radiocarpal joint and 28 wrists fused (41%) at the midcarpal joints during follow-up. Severe ulnar translocation of the carpus was observed in two wrists (3%), radio-ulnar convergence in five wrists (7%), as well as a significant decrease of carpal height ratio, without any radiological findings of stylocarpal impingement. Improvements in forearm pronation and supination, and reduction in pain were maintained at the last follow-up. Grip strength was not significantly improved. The Jebsen-Taylor hand function test showed improvements in writing, card turning, and simulated feeding. Fifty-two patients (58 wrists, 85%) were satisfied with the results at the last follow-up. Simple hemiresection arthroplasty showed good long-term results with few complications. PMID:23303834

  10. Development of rheumatoid arthritis following autologous peripheral blood stem cell transplantation

    Microsoft Academic Search

    R Imamura; H Inoue; K Kato; S Kobayashi; H Tsukamoto; K Nagafuji; K Shimoda; H Nakashima; T Otsuka; H Gondo; M Harada

    2002-01-01

    A 51-year-old man with non-Hodgkin's lymphoma (NHL) was treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). Although he had HLA-DRB1 0405 and a positive rheumatoid factor, he was unlikely to develop rheumatoid arthritis (RA) according to diagnostic criteria. However, the patient developed RA 40 days after transplantation. Our experience suggests that the systemic autoimmune disease,

  11. GCF Resistin As A Novel Marker in Patients with Chronic Periodontitis and Rheumatoid Arthritis

    PubMed Central

    Mittal, Manoj; Hassan, Basit; Desai, Khushboo; Kumar, Santosh; Reddy, Sharaschandra G.

    2015-01-01

    Background The associational studies between periodontitis and rheumatoid arthritis are less documented, although they are found to have similar inflammatory pathogenesis. Resistin, a novel adipokine is suggested to be a common link between periodontitis and rheumatoid arthritis. The aim of the present study was to reinforce the inter-relationship between periodontitis and rheumatoid arthritis by using resistin as a potent inflammatory marker. Materials and Methods Hundred patients (aged >30 y) of either sex were selected for this study and were divided equally into four groups of 25 patients each. Group A consisted of healthy individuals, Group B consisted of patients with chronic periodontitis, Group C of patients with rheumatoid arthritis and Group D had patients suffering from both arthritis and periodontitis. Periodontal parameters assessed were plaque index (PI), modified gingival index (GI) and probing depth (PD). Panoramic radiographs were taken to confirm the diagnosis of periodontitis. Rheumatoid arthritis was confirmed by the rheumatologists and seropositivity for rheumatoid factor (RF) was checked. Resistin levels were analysed in GCF collected from all the four groups and statistical analysis was done by using Pearson correlation coefficient. Results The GCF of all the patients showed presence of resistin. The level of resistin was highest in Group D patients and least in Group A patients. On analysing the samples together positive co-relation was found between GCF resistin and PD, PI, GI and RF. Conclusion Resistin levels are increased in both chronic periodontitis and rheumatoid arthritis. Therefore, the increased level of GCF resistin can be regarded as potential inflammatory marker for periodontitis and rheumatoid arthritis.

  12. Effects of hydrogen peroxide on the metabolism of human rheumatoid and osteoarthritic synovial fibroblasts in vitro

    Microsoft Academic Search

    N Hutadilok; M M Smith; P Ghosh

    1991-01-01

    The effects of hydrogen peroxide (H2O2) on the metabolism of cultured human synovial fibroblasts derived from joints of four patients with rheumatoid arthritis and three with osteoarthritis have been investigated. The exposure of rheumatoid cell cultures to this oxygen derived species at sublethal concentrations (1-100 mumol\\/l) induced a dose related inhibition of both hyaluronic acid (HA) and DNA synthesis. In

  13. STAT4 and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus

    Microsoft Academic Search

    Elaine F. Remmers; Robert M. Plenge; Annette T. Lee; Robert R. Graham; Geoffrey Hom; Timothy W. Behrens; Paul I. W. de Bakker; Julie M. Le; Hye-Soon Lee; Franak Batliwalla; Wentian Li; Seth L. Masters; Matthew G. Booty; John P. Carulli; Leonid Padyukov; Lars Alfredsson; Lars Klareskog; Wei V. Chen; Christopher I. Amos; Lindsey A. Criswell; Michael F. Seldin; Daniel L. Kastner; Peter K. Gregersen

    2007-01-01

    A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with es- tablished rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P = 2.81×10?7; odds ratio for having

  14. Polychondritis and rheumatoid arthritis. Case report and review of the literature

    Microsoft Academic Search

    M. J. A. M. Franssen; A. M. Th. Boerbooms; L. B. A. Putte

    1987-01-01

    Summary We present the case history of a 50-year-old man with seropositive erosive rheumatoid arthritis of 30-years standing who developed polychondritis simultaneously with several extra-articular rheumatoid manifestations, such as anaemia, subcutaneous nodules, pericarditis and episcleritis. The relevant literature is reviewed. Gradually, all symptoms and signs disappeared after start of treatment with 30 mg prednisone and 100 mg azathioprine daily. We

  15. Relationship Between Disease Activity and Serum Levels of Vitamin D Metabolites and PTH in Rheumatoid Arthritis

    Microsoft Academic Search

    P. Oelzner; A. Müller; F. Deschner; M. Hüller; K. Abendroth; G. Hein; G. Stein

    1998-01-01

    .   In several studies on patients with rheumatoid arthritis, an association of bone loss with a persistently high disease activity\\u000a has been found. The aim of our study was to investigate the relation between disease activity and serum levels of vitamin\\u000a D metabolites, parathyroid hormone (PTH), and parameters of bone turnover in patients with rheumatoid arthritis. A total of\\u000a 96

  16. The effect of corrective splinting on flexion contracture of rheumatoid fingers

    Microsoft Academic Search

    Cecilia W. P. Li-Tsang; Leung Kim Hung; Arthur F. T. Mak

    2002-01-01

    This paper reports a matched-pair experimental study to investigate the effect of corrective splinting on flexion contracture of rheumatoid fingers. Twenty-four patients with rheumatoid arthritis and finger flexion contracture participated in the study. After a 6-week baseline measurement of hand function—including measurement of grip strength and range of motion and administration of the Jebsen Hand Function Test—the patients were randomly

  17. A longitudinal study of in vitro tests for lymphocyte function in rheumatoid arthritis.

    PubMed

    Percy, J S; Davis, P; Russell, A S; Brisson, E

    1978-10-01

    In vitro tests of lymphocyte function have been performed in 61 patients with ;classical' or ;definite' rheumatoid arthritis. In vitro lymphocyte function was assessed by lymphocyte transformation responses to phytohaemagglutinin (PHA), Pokeweed mitogen (PWM), Candida antigen, and herpes simplex type I (HSV1). Follow up data were available after 6 months of treatment in 32 of these patients. Spontaneous lymphocyte transformation was assessed in all patients. Results obtained in patients with rheumatoid arthiritis were compared to those seen in a normal control population. Disease activity of patients with rheumatoid arthritis was assessed using standard clinical methods. Lymphocytes from patients with rheumatoid arthritis showed a similar degree of spontaneous transformation to that seen in normal subjects. In contrast, lymphocytes from patients with rheumatoid arthritis responded less well to PHA and Candida and HSV1 antigens when compared to normal patients. In patients with rheumatoid arthritis the response to PWM was markedly enhanced compared to normals. Clinical improvement was noted in 19 of the 32 patients seen at follow up, all of whom had received gold or penicillamine therapy. The abnormal responses of PHA and PWM seen before treatment became normal in those patients who improved clinically. The responses to Candida and HSV1 antigens not only returned to normal following treatment but were increased above those seen in normal controls. A statistically significant association was seen between clinical improvement and improvement of in vitro tests of lymphocyte function. PMID:214047

  18. A longitudinal study of in vitro tests for lymphocyte function in rheumatoid arthritis

    PubMed Central

    Percy, John S.; Davis, Paul; Russell, Anthony S.; Brisson, Estelle

    1978-01-01

    In vitro tests of lymphocyte function have been performed in 61 patients with `classical' or `definite' rheumatoid arthritis. In vitro lymphocyte function was assessed by lymphocyte transformation responses to phytohaemagglutinin (PHA), Pokeweed mitogen (PWM), Candida antigen, and herpes simplex type I (HSV1). Follow up data were available after 6 months of treatment in 32 of these patients. Spontaneous lymphocyte transformation was assessed in all patients. Results obtained in patients with rheumatoid arthiritis were compared to those seen in a normal control population. Disease activity of patients with rheumatoid arthritis was assessed using standard clinical methods. Lymphocytes from patients with rheumatoid arthritis showed a similar degree of spontaneous transformation to that seen in normal subjects. In contrast, lymphocytes from patients with rheumatoid arthritis responded less well to PHA and Candida and HSV1 antigens when compared to normal patients. In patients with rheumatoid arthritis the response to PWM was markedly enhanced compared to normals. Clinical improvement was noted in 19 of the 32 patients seen at follow up, all of whom had received gold or penicillamine therapy. The abnormal responses of PHA and PWM seen before treatment became normal in those patients who improved clinically. The responses to Candida and HSV1 antigens not only returned to normal following treatment but were increased above those seen in normal controls. A statistically significant association was seen between clinical improvement and improvement of in vitro tests of lymphocyte function. PMID:214047

  19. Fenoprofen in patients with rheumatoid arthritis receiving maintenance gold therapy.

    PubMed

    Duff, I F; Neukom, J E; Himes, J E

    1976-01-01

    Thirty patients with active definite or classic rheumatoid arthritis (RA), participated in a double-blind crossover study comparing fenoprofen calcium with placebo. All patients were receiving maintenance gold therapy. Fenoprofen was administered in doses ranging from 200 to 800 mg every six hours. The median daily dose was 1.8 gm. During this 16-week trial, most parameters of efficacy showed fenoprofen to be significantly more effective than placebo. Adverse reactions, which were minimal, suggest that fenoprofen will be useful in the management of patients with RA, particularly in those with gastrointestinal intolerance to the usually employed drugs. The longterm effectiveness in RA, and the side effects associated with chronic administration remain to be assessed. PMID:781228

  20. Pigmented villonodular synovitis developing in a patient with rheumatoid arthritis.

    PubMed

    Zhao, Xia; Ji, Wei; Qian, Xian; Lu, Yan

    2014-08-01

    A 56-year-old man developed pigmented villonodular synovitis (PVNS) 3 years after he was diagnosed with rheumatoid arthritis (RA). He had been successfully treated with methotrexate, leflunomide, sulfadiazine, and intra-articular knee injection of etanercept (tumor necrosis factor ? inhibitor) in 2010. He stopped all drugs for arthritis 1 year later for disease remission. He was readmitted for right knee pain and swelling in 2013, when the magnetic resonance imaging and arthroscopy of the right knee indicated PVNS. Following surgical resection, the patient was doing well after 1 year. This rare case is the first reported case in English-language literature of PVNS of the knee seen in RA patients and illustrates the importance of differential diagnosis of this condition with synovial cysts, which are commonly found in RA. PMID:25036563

  1. Clinical Biomarkers and Pathogenic-Related Cytokines in Rheumatoid Arthritis

    PubMed Central

    Niu, Xiaoyin; Chen, Guangjie

    2014-01-01

    Rheumatoid arthritis (RA) is a common autoimmune disease with unknown etiology and pathogenesis. Although major therapeutic advances have been made in recent years, there is no cure for the disease. Current medications mainly reduce inflammation in order to relieve pain and slow joint damage, but many have potentially serious side effects. Therefore, to find specific biomarkers will benefit both RA patients to find relief from the disease and physicians to monitor the disease development. A number of biomarkers have been discovered and used clinically, and others are still under investigation. The autoantibodies, which are widely used in diagnosis and prognosis, novel biomarkers, which reflect clinical disease activity, and newly found biomarkers and pathogenic-related cytokines are discussed in this review. PMID:25215307

  2. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens

    PubMed Central

    Ogrendik, Mesut

    2013-01-01

    A statistically significant association between periodontal disease (PD) and systemic diseases has been identified. Rheumatoid arthritis (RA), which is a chronic inflammatory joint disease, exhibits similar characteristics and pathogenesis to PD. The association between RA and PD has been investigated, and numerous publications on this subject exist. Approximately 20 bacterial species have been identified as periodontal pathogens, and these organisms are linked to various types of PD. The most analyzed species of periodontopathic bacteria are Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans. Antibodies and DNA from these oral pathogens have been isolated from the sera and synovial fluids of RA patients. This rapid communication describes the role of periodontal pathogens in the etiopathogenesis of RA. PMID:23737674

  3. LASER BIOLOGY AND MEDICINE: Light scattering study of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Beuthan, J.; Netz, U.; Minet, O.; Klose, Annerose D.; Hielscher, A. H.; Scheel, A.; Henniger, J.; Müller, G.

    2002-11-01

    The distribution of light scattered by finger joints is studied in the near-IR region. It is shown that variations in the optical parameters of the tissue (scattering coefficient ?s, absorption coefficient ?a, and anisotropy factor g) depend on the presence of the rheumatoid arthritis (RA). At the first stage, the distribution of scattered light was measured in diaphanoscopic experiments. The convolution of a Gaussian error function with the scattering phase function proved to be a good approximation of the data obtained. Then, a new method was developed for the reconstruction of distribution of optical parameters in the finger cross section. Model tests of the quality of this reconstruction method show good results.

  4. Positron emission tomography/computed tomography imaging and rheumatoid arthritis.

    PubMed

    Wang, Shi-Cun; Xie, Qiang; Lv, Wei-Fu

    2014-03-01

    Rheumatoid arthritis (RA) is a phenotypically heterogeneous, chronic, destructive inflammatory disease of the synovial joints. A number of imaging tools are currently available for evaluation of inflammatory conditions. By targeting the upgraded glucose uptake of infiltrating granulocytes and tissue macrophages, positron emission tomography/computed tomography with fluorine-18 fluorodeoxyglucose ((18) F-FDG PET/CT) is available to delineate inflammation with high sensitivity. Recently, several studies have indicated that FDG uptake in affected joints reflects the disease activity of RA. In addition, usage of FDG PET for the sensitive detection and monitoring of the response to treatment has been reported. Combined FDG PET/CT enables the detailed assessment of disease in large joints throughout the whole body. These unique capabilities of FDG PET/CT imaging are also able to detect RA-complicated diseases. Therefore, PET/CT has become an excellent ancillary tool to assess disease activity and prognosis in RA. PMID:24606324

  5. Rheumatoid arthritis and the alpha-chemokine IP-10.

    PubMed

    Di Domenicantonio, A

    2014-01-01

    Interferon(IFN)-gamma-induced protein 10 (IP-10) and its receptor, CXCR3, appear to contribute to the pathogenesis of rheumatoid arthritis (RA). IP-10 has been detected in sera, synovial fluid (SF), and synovial tissue in RA patients. IP-10 is mainly expressed by infiltrating macrophage-like cells and fibroblast-like synoviocytes in RA synovium. The elevated expression of CXCR3 on T cells from SF has been associated with high levels of IFN-gamma, which suggest a preferential Th1 phenotype. A human phase II clinical trial using an anti-IP-10 monoclonal antibody (MDX-1100) for RA patients who had an inadequate response to methotrexate treatment has shown that blocking IP-10 significantly increased response rate compared to the placebo group, suggesting a possible therapeutic use in humans. PMID:25524204

  6. The hand in systemic diseases other than rheumatoid arthritis.

    PubMed

    Fontaine, C; Staumont-Sallé, D; Hatron, P-Y; Cotten, A; Couturier, C

    2014-06-01

    This review outlines the skin, vascular and musculoskeletal symptoms affecting the hand during systemic inflammatory diseases other than rheumatoid arthritis. Skin lesions are diagnosed clinically and their symptomatology is documented through an extensive series of photographs. These conditions may require specific care before a surgical procedure can be performed. Vascular lesions are also diagnosed clinically and their symptomatology is described in detail. It is important to recognize that acrocyanosis is always benign. The surgeon should be able to distinguish between primary, but benign Raynaud's disease and secondary Raynaud's syndrome, which has a high risk of finger necrosis. Current preventative and curative treatments for finger necrosis are described. The clinical, radiological, progressive and therapeutic features of musculoskeletal lesions are reviewed, namely those associated with psoriatic arthritis, systemic sclerosis and lupus. PMID:24746866

  7. Gout Initially Mimicking Rheumatoid Arthritis and Later Cervical Spine Involvement

    PubMed Central

    Nunes, Eduardo Araújo Santana; Rosseti, Adroaldo Guimarães; Ribeiro, Daniel Sá; Santiago, Mittermayer

    2014-01-01

    Gout is clinically characterized by episodes of monoarthritis, but if not treated properly, it can lead to a chronic polyarthritis, which may eventually mimic rheumatoid arthritis (RA). We present the case of a 59-year-old man, with a history of symmetrical polyarthritis of the large and small joints with later development of subcutaneous nodules, which was initially misdiagnosed as RA, being treated with prednisone and methotrexate for a long period of time. He complained of occipital pain and paresthesia in his left upper limb, and computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of an expansive formation in the cervical spine with compression of the medulla. He was admitted for spinal decompressive surgery and the biopsy specimen demonstrated a gouty tophus. Chronic gout can mimic RA and rarely involves the axial skeleton, and thus its correct diagnosis and the implementation of adequate therapy can halt the development of such damaging complications. PMID:25574418

  8. Implications for managed care and specialty pharmacy in rheumatoid arthritis.

    PubMed

    Cardarelli, William J

    2012-12-01

    Treatment of rheumatoid arthritis (RA) can be very costly. Cost-effectiveness studies provide insight into the value of treatment from a number of perspectives (eg, societal, healthcare). In most cases, the indirect costs of RA can offset the direct costs in 2 ways. Prevention of disease progression can limit future costs, such as those related to surgery and hospitalization. When disease progression is minimized, patients feel better and can have improved work productivity. Disease control of RA has improved over time, and this is attributed primarily to the introduction of more effective therapies. Despite the effectiveness of new therapies, there are a number of barriers to optimal treatment. Barriers include lack of education for patients and practitioners about RA, poor patient-provider communication, uncertainty regarding which treatments to choose, cost, and lack of adherence. Specialty pharmacy and disease therapy management programs can assist patients by providing structure, education, and mechanisms to improve treatment adherence and persistence to optimize therapy. PMID:23327519

  9. [Social security system for patients with rheumatoid arthritis in Japan].

    PubMed

    Murasawa, Akira

    2013-07-01

    Support system for patients with rheumatoid arthritis (RA) is a wide variety, such as the health care, the medical economy, the environment, and mental activity. Among these measures, the laws called the social security system are defined. These systems consist of social insurance (medical insurance, long-term care insurance, pension insurance), social welfare (welfare for the disabled) and public health (measures for intractable diseases). As social support under total management of RA, patients can receive mitigation measures and subsidies (physically disabled person's certificate, high-cost medical care, etc.) for high medical expenses at use of biological products, hospitalization and surgery. Furthermore long-term care insurance and disability pension can be used as a further support of home care. PMID:23961682

  10. CD154: the atherosclerotic risk factor in rheumatoid arthritis?

    PubMed Central

    2013-01-01

    Atherosclerosis, now regarded as a chronic inflammatory disease of the arterial wall, and its clinical manifestations have increasingly been associated with rheumatoid arthritis (RA), supporting the notion that autoimmune diseases and vascular disorders share common etiological features. Indeed, evidence pertaining to this matter indicates that inflammation and its multiple components are the driving force behind the pathogenesis of these disorders. Interestingly, CD154 and its receptors have emerged as major players in the development of RA and atherosclerosis, which raises the possibility that this axis may represent an important biological link between both complications. Indeed, CD154 signaling elicits critical inflammatory responses that are common to the pathogenesis of both diseases. Here, we provide an overview of the traditional and disease-related interrelations between RA and vascular abnormalities, while focusing on CD154 as a potential mediator in the development of atherosclerotic events in RA patients. PMID:23433179

  11. Animal models of rheumatoid arthritis: How informative are they?

    PubMed

    McNamee, Kay; Williams, Richard; Seed, Michael

    2015-07-15

    Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. There is also increasing awareness of the ethical issues surrounding the use of animal models of disease and it is timely, therefore, to review the relevance and translatability of animal models of arthritis. In this paper we review the most commonly used animal models in terms of their pathological similarities to human rheumatoid arthritis as well as their response to drug therapy. In general, the ability of animal models to predict efficacy of biologics in man has been good. However, the predictive power of animal models for small molecules has been variable, probably because of differences in the levels of target knockdown achievable in vivo. PMID:25824900

  12. Mechanisms of Premature Atherosclerosis in Rheumatoid Arthritis and Lupus

    PubMed Central

    Kahlenberg, J. Michelle; Kaplan, Mariana J.

    2014-01-01

    Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), the two most common systemic autoimmune disorders, have both unique and overlapping manifestations. One feature they share is a significantly enhanced risk of atherosclerotic cardiovascular (CV) disease that significantly contributes to morbidity and mortality. The primary mechanisms that drive CV damage in these diseases remain to be fully characterized, but recent discoveries indicate that distinct inflammatory pathways and immune dysregulation characteristic of RA and SLE likely play prominent roles. This review focuses on analyzing the major mechanisms and pathways potentially implicated in the acceleration of atherothrombosis [**AU: Should this be atherosclerosis for consistency?**] and CV risk in SLE and RA, as well as in the identification of putative preventive strategies that may mitigate vascular complications in systemic autoimmunity. PMID:23020882

  13. Bee venom acupuncture for rheumatoid arthritis: a systematic review protocol

    PubMed Central

    Lee, Ju Ah; Son, Mi Ju; Choi, Jiae; Yun, Kyung-Jin; Jun, Ji Hee; Lee, Myeong Soo

    2014-01-01

    Introduction This systematic review aims to analyse the trial data on the effects of bee venom acupuncture (BVA) for rheumatoid arthritis (RA). Methods and analysis The following 14 databases will be searched from their inception to March 2014: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), AMED, CINAHL, six Korean medical databases (OASIS, Korean Traditional Knowledge Portal, Korean Studies Information Service System, KoreaMed, Korean Medical Database and DBPIA) and three Chinese databases including CNKI (China National Knowledge Infrastructure), Wanfang and VIP. The methodological quality will be assessed using the Cochrane risk of bias tool. Dissemination The systematic review will be published in a peer-reviewed journal. The review will also be disseminated electronically and in print. Trial registration number PROSPERO 2013: CRD42013005853 PMID:24760349

  14. Tumour necrosis factor-alpha, interleukin-2 soluble receptor and different inflammatory parameters in patients with rheumatoid arthritis.

    PubMed Central

    Fröde, Tânia Silvia; Tenconi, Patrícia; Debiasi, Marilei Reynaud; Medeiros, Yara Santos

    2002-01-01

    BACKGROUND AND AIMS: Although the participation of cytokines in the pathogenesis of rheumatoid arthritis (RA) seems to be unequivocal, their relationship with current serum markers of this disease is not clear. The present study analyses whether there is any correlation between the levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-2 soluble receptor (sIL-2R) and the concentrations of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and beta(2)-microglobulin in a group of 21 patients with RA, all rheumatoid factor positive. METHODS: The levels of TNF-alpha and sIL-2R were analysed in association with other parameters of inflammation (ESR, CRP and beta(2)-microglobulin). RESULTS: In comparison with the control group, RA patients presented high median levels of both cytokines, TNF-alpha (6.4 pg/ml) and sIL-2R (56 pmol/L), as well as of ESR (34 mm/h), CRP (0.9 mg/dl) and beta(2)-microglobulin (1.6 mg/dl) (p < 0.01). However, only ESR levels in the RA group significantly differ from the control group (p < 0.01). No correlation was found between the inflammatory parameters. CONCLUSIONS: These results suggested that TNF-alpha and slL-2R levels are up-regulated in RA patients but did not significantly differ from the control group. Due to the chronic course of this disease, other inflammatory markers must be identified in order to provide early therapeutic strategies to these patients. PMID:12581498

  15. Association of a Single-Nucleotide Polymorphism in CD40 With the Rate of Joint Destruction in Rheumatoid Arthritis

    PubMed Central

    Feitsma, Anouk L.; le Cessie, Saskia; Kern, Marlena; Olsson, Lina M.; Raychaudhuri, Soumya; Begovich, Ann B.; Chang, Monica; Catanese, Joseph J.; Kurreeman, Fina A. S.; van Nies, Jessica; van der Heijde, Désirée M.; Gregersen, Peter K.; Huizinga, Tom W. J.; Toes, René E. M.; van der Helm-van Mil, Annette H. M.

    2010-01-01

    Objective The severity of joint destruction in rheumatoid arthritis (RA) is highly variable from patient to patient and is influenced by genetic factors. Genome-wide association studies have enormously boosted the field of the genetics of RA susceptibility, but risk loci for RA severity remain poorly defined. A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA: CD40, KIF5A/PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14. The purpose of this study was to investigate whether these newly described genetic regions are associated with the rate of joint destruction. Methods RA patients enrolled in the Leiden Early Arthritis Clinic were studied (n = 563). Yearly radiographs were scored using the Sharp/van der Heijde method (median followup 5 years; maximum followup 9 years). The rate of joint destruction between genotype groups was compared using a linear mixed model, correcting for age, sex, and treatment strategies. A total of 393 anti–citrullinated protein antibody (ACPA)–positive RA patients from the North American Rheumatoid Arthritis Consortium (NARAC) who had radiographic data available were used for the replication study. Results The TT and CC/CG genotypes of 2 single-nucleotide polymorphisms, rs4810485 (CD40) and rs42041 (CDK6), respectively, were associated with a higher rate of joint destruction in ACPA-positive RA patients (P = 0.003 and P = 0.012, respectively), with rs4810485 being significant after Bonferroni correction for multiple testing. The association of the CD40 minor allele with the rate of radiographic progression was replicated in the NARAC cohort (P = 0.021). Conclusion A polymorphism in the CD40 locus is associated with the rate of joint destruction in patients with ACPA-positive RA. Our findings provide one of the first non–HLA-related genetic severity factors that has been replicated. PMID:19644859

  16. Dissociative depression among women with fibromyalgia or rheumatoid arthritis.

    PubMed

    Kilic, Ozge; Sar, Vedat; Taycan, Okan; Aksoy-Poyraz, Cana; Erol, Turgut C; Tecer, Ozlem; Emul, Murat H; Ozmen, Mine

    2014-01-01

    The aim of this study was to inquire about the possible relations of childhood trauma, anger, and dissociation to depression among women with fibromyalgia or rheumatoid arthritis. Fifty female patients diagnosed as having fibromyalgia (n = 30) or rheumatoid arthritis (n = 20) participated in the study. The Childhood Trauma Questionnaire, Somatoform Dissociation Questionnaire (SDQ), Dissociation Questionnaire (DIS-Q), Beck Depression Inventory (BDI), Spielberger State-Trait Anger Expression Inventory, and Dissociative Disorders Interview Schedule were administered to all participants. Women with a lifetime diagnosis of depressive disorder had higher scores for somatoform and psychoform dissociation than the nondepressive patients. However, childhood trauma scores did not differ between the 2 groups. In regression analysis, current severity of depression (BDI) was predicted by psychoform dissociation (DIS-Q) and lower education, and lifetime diagnosis of major depression was predicted by somatoform dissociation (SDQ). Whereas childhood emotional neglect predicted somatoform dissociation, psychoform dissociation was predicted by childhood sexual abuse. Mental processing of anger seems to be 1 of the dimensions of psychodynamics in trauma-related depressive conditions. In the context of the perceived threat of loss of control due to expressed anger and mental disintegration, somatoform dissociation seems to contribute to overmodulation of emotions in dissociative depression. Among patients suffering from physical illness with possible psychosomatic dimensions, assessment of somatoform dissociation in addition to psychoform dissociation may be helpful to understand diverse psychopathological trajectories emerging in the aftermath of childhood adversities. The recently proposed category of "dissociative depression" (Sar, 2011) seems to be a promising concept for future research on psychosomatic aspects of traumatic stress. PMID:24228798

  17. Analysis of immunoglobulins secreted by hybridomas derived from rheumatoid synovia.

    PubMed Central

    Brown, C M; Plater-Zyberk, C; Mageed, R A; Jefferis, R; Maini, R N

    1990-01-01

    Twenty-six IgG-secreting and eight IgM-secreting hybridomas were derived from the synovia of two patients with rheumatoid arthritis (RA). Hybridomas were obtained by fusing a heteromyeloma cell line, SPAZ-4 with synovial mononuclear cells that were not deliberately stimulated in vitro. Over 96% of the IgG-secreting hybridomas produced antibodies which belonged to the IgG1 subclass and showed lambda light chain predominance; the latter was not seen in IgM antibodies, where kappa light chains dominated by 3:1. All IgG antibodies were cationic. Synovial B cells were not exposed to extrinsic stimuli prior to fusion, therefore these results reflect the state of B cell activation and differentiation in vivo. Our results indicate that IgG-secreting B cells in the RA joint are under a selective influence which is, as yet, unidentified. One out of eight IgM-secreting and two out of 26 IgG-secreting hybridomas produced rheumatoid factors (RF). The IgM-RF specificity for IgG heavy chain subclasses was determined and showed that the monoclonal bound to IgG1, IgG2 and IgG4 but not IgG3 with exception of IgG3 Goe of the G3m (st) allotype, a profile typical of specificity for the Ga epitope. This monoclonal also distinguished a determinant in the Fc region of human IgG which was not present in rabbit IgG. The overall frequency of RF-secreting hybridomas we observed indicates that B cells committed to RF production in the synovium of a seropositive and a seronegative RA patient is below 10%. Images Fig. 1 PMID:2115418

  18. Resurfacing shoulder arthroplasty for the treatment of severe rheumatoid arthritis

    PubMed Central

    Voorde, Pia C ten; Rasmussen, Jeppe V; Olsen, Bo S; Brorson, Stig

    2015-01-01

    Background and purpose There is no consensus on which type of shoulder prosthesis should be used in patients with rheumatoid arthritis (RA). We describe patients with RA who were treated with shoulder replacement, regarding patient-reported outcome, prosthesis survival, and causes of revision, and we compare outcome after resurfacing hemi-arthroplasty (RHA) and stemmed hemi-arthroplasty (SHA). Patients and methods We used data from the national Danish Shoulder Arthroplasty Registry and included patients with RA who underwent shoulder arthroplasty in Denmark between 2006 and 2010. Patient-reported outcome was obtained 1-year postoperatively using the Western Ontario Osteoarthritis of the Shoulder index (WOOS), and rates of revision were calculated by checking revisions reported until December 2011. The patient-reported outcome of RHA was compared to that of SHA using regression analysis with adjustment for age, sex, and previous surgery. Results During the study period, 167 patients underwent shoulder arthroplasty because of rheumatoid arthritis, 80 (48%) of whom received RHA and 34 (26%) of whom received SHA. 16 patients were treated with total stemmed shoulder arthroplasty (TSA), and 24 were treated with reverse shoulder arthroplasty (rTSA). 130 patients returned a completed questionnaire, and the total mean WOOS score was 63. The cumulative 5-year revision rate was 7%. Most revisions occurred after RHA, with a revision rate of 14%. Mean WOOS score was similar for RHA and for SHA. Interpretation This study shows that shoulder arthroplasty, regardless of design, is a good option in terms of reducing pain and improving function in RA patients. The high revision rate in the RHA group suggests that other designs may offer better implant survival. However, this should be confirmed in larger studies. PMID:25673155

  19. Comparison of therapeutic effects between drainage blood reinfusion and temporary clamping drainage after total knee arthroplasty in patients with rheumatoid arthritis

    PubMed Central

    Li, Bin; Liu, Zhong-tang; Shen, Peng; Zhou, Bing-zheng; Bai, Lun-hao

    2015-01-01

    OBJECTIVE: To compare the therapeutic effects between drainage blood reinfusion and temporary clamping drainage after total knee arthroplasty in patients with rheumatoid arthritis to provide a basis for clinical practice. METHODS: Data from 83 patients with rheumatoid arthritis undergoing total knee arthroplasty were retrospectively analyzed. The 83 patients were divided into a drainage blood reinfusion group (DR group, n = 45) and a temporary clamping drainage group (CD group, n = 38). In the DR group, postoperative drainage blood was used for autotransfusion. In the CD group, closed drainage was adopted, and the drainage tube was clamped for 2 h postoperatively followed by patency. The postoperative drainage amount, hemoglobin level, rate and average volume of allogeneic blood transfusion, swelling and ecchymosis of the affected knee joint, time to straight-leg raising and range of active knee flexion were compared between the two groups. RESULTS: The total drainage volume was higher in the DR group than in the CD group (P = 0.000). The average volume of postoperative allogeneic blood transfusion (P = 0.000) and the decrease in the hemoglobin level 24 h after total knee arthroplasty (P = 0.012) were lower in the DR group than in the CD group. Swelling and ecchymosis of the affected knee joint, time to straight-leg raising and the range of active knee flexion were improved in the DR group compared with the CD group (all P<0.05). CONCLUSION: Compared with temporary clamping drainage, drainage blood reinfusion after total knee arthroplasty can reduce the allogeneic blood transfusion volume and is conducive to early rehabilitation in patients with rheumatoid arthritis. PMID:26017652

  20. The 29th September Samoa Islands tsunami: preliminary simulations based on the first focal mechanisms hypotheses and implications of uncertainties in tsunami early warning strategies

    NASA Astrophysics Data System (ADS)

    Tonini, R.; Pagnoni, G.; Armigliato, A.; Tinti, S.

    2009-12-01

    At 6:48 AM local time (17:48 UTC time) a strong earthquake of magnitude Mw=8.0 occurred less than 200 km south of the Samoa Islands (Western Samoa and American Samoa), triggering a tsunami that was detected by several tide gauges located all around the source area. The areas most affected were the south coasts of Western and American Samoa, where almost 200 persons were killed and run-up heights were measured in excess of 5 meters on several locations along the coast and and the tide gauges reached a maximum peak-to-peak height of about 3 meters near Pago-Pago (American Samoa) and 1.5 meters in front of Apia (Western Samoa) The existence of many tide gauge records is important to support the investigation of the source mechanism. The epicenter of this earthquake is located very close to the point where the Tonga trench turns its direction from northward to westward. Here the Pacific plate moves westward beneath the Australia plate, determining a subduction zone along the north-oriented segment of the trench and a transform zone along the west-oriented segment. The epicenter location in this complex tectonic context makes identifying the fault mechanism responsible for the tsunami generation a non-trivial task. The goal of this preliminary work is testing different fault models based on the focal mechanism solution proposed by USGS, CMT and EMSC for this earthquake, through the comparison between the tide gauge records and the synthetic signals provided by the numerical simulations, and possibly suggesting new source solutions trying to reproduce as better as possible the tsunami recordings. The numerical simulations are computed by means of the UBO-TSUFD code, developed and maintained by the Tsunami Research Team of the University of Bologna, Italy. The code solves the linear and non-linear shallow water equations and can compute inundation inland. Furthermore the computational domain can be split in grids of different space resolution in order to have more detailed results in specific areas. The objective difficulties in the identification of the tsunami source, due to the quite complex tectonic setting of the Tonga region in the epicentral area introduce uncertainties in the fault determination that maybe relevant a posteriori, and are a fortiori much more relevant in the real-time data processing practice. This reflects in uncertainties in the possibility of accurately forecasting tsunami propagation and arrival, which poses problems concerning the best strategy to adopt for tsunami early warning.

  1. Population Pharmacokinetics and Monte Carlo Dosing Simulations of Meropenem during the Early Phase of Severe Sepsis and Septic Shock in Critically Ill Patients in Intensive Care Units.

    PubMed

    Jaruratanasirikul, Sutep; Thengyai, Suriyan; Wongpoowarak, Wibul; Wattanavijitkul, Thitima; Tangkitwanitjaroen, Kanyawisa; Sukarnjanaset, Waroonrat; Jullangkoon, Monchana; Samaeng, Maseetoh

    2015-06-01

    Pathophysiological changes during the early phase of severe sepsis and septic shock in critically ill patients, resulting in altered pharmacokinetic (PK) patterns for antibiotics, are important factors influencing therapeutic success. The aims of this study were (i) to reveal the population PK parameters and (ii) to assess the probability of target attainment (PTA) for meropenem. The PK studies were carried out following administration of 1 g of meropenem every 8 h during the first 24 h of severe sepsis and septic shock in nine patients, and a Monte Carlo simulation was performed to determine the PTA of achieving 40% exposure time during which the free plasma drug concentration remains above the MIC (fT>MIC) and 80% fT>MIC. The volume of distribution (V) and total clearance (CL) of meropenem in these patients were 23.7 liters and 7.82 liters/h, respectively. For pathogens with MICs of 4 ?g/ml, the PTAs of 40% fT>MIC following administration of meropenem as a 1-h infusion of 1 g every 8 h and a 4-h infusion of 0.5 g every 8 h were 92.52% and 90.29%, respectively. For pathogens with MICs of 2 ?g/ml in immunocompromised hosts, the PTAs of 80% fT>MIC following administration of 1-h and 4-h infusions of 2 g of meropenem every 8 h were 84.32% and 94.72%, respectively. These findings indicated that the V of meropenem was greater and the CL of meropenem was lower than the values obtained in a previous study with healthy subjects. The maximum recommended dose, i.e., 2 g of meropenem every 8 h, may be required for treatment of life-threatening infections in this patient population. PMID:25753628

  2. The photometric latex test for rheumatoid factors in patients with rheumatoid arthritis. I. correlation with other serologic tests.

    PubMed

    Dezeli?, N; Zergollern, V; Dezeli?, G; Dürrigl, T; Jurak, H; Vitaus, M; Androi?, S

    1978-01-01

    The photometric latex test (PLT) for the detection of rheumatoid factors (RF) has been correlated with the sensitized sheep cell test (SSC) and the latex slide test (LST). A total of 377 sera from patients with rheumatoid arthritis (RA) and 120 sera from control subjects were examined. When the PLT was carried out on the native sera at a lower buffer ionic strength (0.05 M), agglutination was noted in over 99% of cases, indicating interaction of complement with human immunoglobulin bound to the latex particle surface. Although thermal inactivation eliminated most of the complement agglutination, an increase in ionic strength (0.5 M) was found to be essential for measuring only RF agglutination. The serologic data were analysed statistically by computer. A highly significant correlation was found between all serologic tests and RA sera, but there was no such correlation with the control sera. The specificity of all tests was generally over 90% and did not vary significantly, but the sensitivity varied from 52.0% to 71.1%, confirming that about one-third of all RA patients are seronegative. The tests were analysed for their total diagnostic capability. The PLT with native sera at higher ionic strenght proved to be the most sensitive, but with thermally inactivated sera it had a better diagnostic capacity. The SSC test appeared to be less sensitive and of lower diagnostic validity. Rapid LST tests were clearly inferior to PLT tests. The PLT can be used as a reliable and straightforward serologic method of diagnosis in RA, especially when carried out at a higher ionic strength and with thermally inactivated sera. It should be given preference over other serologic tests for RF and could well become standard practice in rheumatologic serology as a substitute for the SSC test. PMID:636670

  3. Multi-omic landscape of rheumatoid arthritis: re-evaluation of drug adverse effects

    PubMed Central

    Tieri, Paolo; Zhou, XiaoYuan; Zhu, Lisha; Nardini, Christine

    2014-01-01

    Objective: To provide a frame to estimate the systemic impact (side/adverse events) of (novel) therapeutic targets by taking into consideration drugs potential on the numerous districts involved in rheumatoid arthritis (RA) from the inflammatory and immune response to the gut-intestinal (GI) microbiome. Methods: We curated the collection of molecules from high-throughput screens of diverse (multi-omic) biochemical origin, experimentally associated to RA. Starting from such collection we generated RA-related protein-protein interaction (PPI) networks (interactomes) based on experimental PPI data. Pharmacological treatment simulation, topological and functional analyses were further run to gain insight into the proteins most affected by therapy and by multi-omic modeling. Results: Simulation on the administration of MTX results in the activation of expected (apoptosis) and adverse (nitrogenous metabolism alteration) effects. Growth factor receptor-bound protein 2 (GRB2) and Interleukin-1 Receptor Associated Kinase-4 (IRAK4, already an RA target) emerge as relevant nodes. The former controls the activation of inflammatory, proliferative and degenerative pathways in host and pathogens. The latter controls immune alterations and blocks innate response to pathogens. Conclusions: This multi-omic map properly recollects in a single analytical picture known, yet complex, information like the adverse/side effects of MTX, and provides a reliable platform for in silico hypothesis testing or recommendation on novel therapies. These results can support the development of RA translational research in the design of validation experiments and clinical trials, as such we identify GRB2 as a robust potential new target for RA for its ability to control both synovial degeneracy and dysbiosis, and, conversely, warn on the usage of IRAK4-inhibitors recently promoted, as this involves potential adverse effects in the form of impaired innate response to pathogens. PMID:25414848

  4. 14-3-3? is a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage

    PubMed Central

    2014-01-01

    Introduction The aim of this study was to investigate whether 14-3-3?, a specific isoform of a family of proteins regulating processes such as cellular signalling, activates cell-signalling pathways and induces factors known to contribute to the pathophysiology of rheumatoid arthritis (RA). We also investigated whether 14-3-3? is associated with more severe disease in both early and established RA. Methods We investigated the effect of 14-3-3? on the activation of RA-relevant signalling cascades and induction of proinflammatory mediators that contribute to the joint damage process. 14-3-3? titres from 33 patients with early RA (mean RA duration?=?1.8 months) and from 40 patients with established RA were measured in serum drawn at the 3-year time point of the Behandel Strategieën study. The relationship between 14-3-3? titres and standard clinical variables was investigated by correlation analysis. The association with radiographic damage and radiographic progression over at least a 2-year period was investigated using univariate and multivariate regression analyses. Results 14-3-3? activated selected members of the mitogen-activated protein kinase (MAPK) family, mainly extracellular regulated kinase 1/2 and c-Jun kinase, but not p38MAPK. Activation by 14-3-3?, using levels spanning the concentration range found in RA patient serum, resulted in the induction of inflammatory transcripts such as interleukin 1 (IL-1) and IL-6 and factors linked to the joint damage process, such as receptor activator of nuclear factor ?B ligand and matrix metalloproteinase 1. Serum 14-3-3? correlated significantly with rheumatoid factor (RF) (r?=?0.43) and anticitrullinated protein antibodies (ACPAs) (r?=?0.31) in the early RA cohort, but not with C-reactive protein (CRP) or the Disease Activity Score in 28 joints in either cohort. Serum 14-3-3? concentrations were significantly higher in patients with radiographically assessed joint damage and in those who had radiographic progression. By multivariate analysis, we show that 14-3-3? complemented markers such as CRP, RF and ACPA in informing RA radiographic status and/or progression. Conclusions Extracellular 14-3-3? activates key signalling cascades and induces factors associated with the pathogenesis of RA at concentrations found in patients with RA, and its expression is higher in patients with radiographic damage and RA progression. PMID:24751211

  5. Low dose prednisolone therapy (LDPT) retards radiographically detectable destruction in early rheumatoid arthritis -

    Microsoft Academic Search

    R. Rau; S. Wassenberg; H. Zeidler

    2000-01-01

    Zusammenfassung Ziel der Studie: Zu untersuchen, ob eine kontinuierliche, niedrig dosierte Prednisolon-Behandlung die im Röntgenbild erkennbare Gelenkdestruktion bei früher chronischer Polyarthritis verzögert. Methoden: In einer multizentrischen randomisierten Doppelblindstudie wurden Patienten mit einer frühen aktiven c. P. (Krankheitsdauer Ergebnisse: 196 Patienten wurden eingeschlossen. Die hier berichteten Ergebnisse betreffen 76 Kranke, die die Studie protokollgemäß beendeten. 34 Patienten wurden mit Prednisolon, 42

  6. TRAF1-C5 as a Risk Locus for Rheumatoid Arthritis — A Genomewide Study

    PubMed Central

    Plenge, Robert M.; Seielstad, Mark; Padyukov, Leonid; Lee, Annette T.; Remmers, Elaine F.; Ding, Bo; Liew, Anthony; Khalili, Houman; Chandrasekaran, Alamelu; Davies, Leela R.L.; Li, Wentian; Tan, Adrian K.S.; Bonnard, Carine; Ong, Rick T.H.; Thalamuthu, Anbupalam; Pettersson, Sven; Liu, Chunyu; Tian, Chao; Chen, Wei V.; Carulli, John P.; Beckman, Evan M.; Altshuler, David; Alfredsson, Lars; Criswell, Lindsey A.; Amos, Christopher I.; Seldin, Michael F.; Kastner, Daniel L.; Klareskog, Lars; Gregersen, Peter K.

    2009-01-01

    BACKGROUND Rheumatoid arthritis has a complex mode of inheritance. Although HLA-DRB1 and PTPN22 are well-established susceptibility loci, other genes that confer a modest level of risk have been identified recently. We carried out a genomewide association analysis to identify additional genetic loci associated with an increased risk of rheumatoid arthritis. METHODS We genotyped 317,503 single-nucleotide polymorphisms (SNPs) in a combined case-control study of 1522 case subjects with rheumatoid arthritis and 1850 matched control subjects. The patients were seropositive for autoantibodies against cyclic citrullinated peptide (CCP). We obtained samples from two data sets, the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Results from NARAC and EIRA for 297,086 SNPs that passed quality-control filters were combined with the use of Cochran-Mantel-Haenszel stratified analysis. SNPs showing a significant association with disease (P<1×10-8) were genotyped in an independent set of case subjects with anti-CCP-positive rheumatoid arthritis (485 from NARAC and 512 from EIRA) and in control subjects (1282 from NARAC and 495 from EIRA). RESULTS We observed associations between disease and variants in the major-histocompatibility-complex locus, in PTPN22, and in a SNP (rs3761847) on chromosome 9 for all samples tested, the latter with an odds ratio of 1.32 (95% confidence interval, 1.23 to 1.42; P = 4×10-14). The SNP is in linkage disequilibrium with two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5). CONCLUSIONS A common genetic variant at the TRAF1-C5 locus on chromosome 9 is associated with an increased risk of anti-CCP-positive rheumatoid arthritis. PMID:17804836

  7. The role of KIR2DL3/HLA-C*0802 in Brazilian patients with rheumatoid vasculitis

    PubMed Central

    Nishimura, Wester Eidi; Sachetto, Zoraida; Costallat, Lilian Teresa Lavras; Yazbek, Michel Alexandre; Londe, Ana Carolina Santos; Guariento, Edilaine Gildo; Marques, Silvia Barbosa Dutra; Bertolo, Manoel Barros

    2015-01-01

    OBJECTIVES: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis. METHODS: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers). RESULTS: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found. CONCLUSION: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions. PMID:26106958

  8. Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis

    PubMed Central

    Chalan, Paulina; Bijzet, Johan; Huitema, Minke G.; Kroesen, Bart-Jan; Brouwer, Elisabeth; Boots, Annemieke M. H.

    2015-01-01

    Objectives Precursor Th17 lineage cells expressing CD161 are implicated in Rheumatoid Arthritis (RA) pathogenesis. CD4+CD161+ T-cells accumulate in RA joints and may acquire a non classical Th1 phenotype. The endogenous ligand for CD161 is lectin-like transcript 1 (LLT1). CD161/LLT1 ligation may co-stimulate T-cell IFN-? production. We investigated the presence and identity of LLT1-expressing cells in RA synovial fluid (SF) and synovial tissue (ST). We also assessed levels of soluble LLT1 (sLLT1) in different phases of RA development. Methods Paired samples of peripheral blood mononuclear cells (MC) and SFMC (n = 14), digested ST cells (n = 4) and ST paraffin sections (n = 6) from late-stage RA were analyzed for LLT1 expression by flow cytometry and immunohistochemistry. sLLT1 was measured using a sandwich ELISA. Sera and SF from late-stage RA (n = 26), recently diagnosed RA patients (n = 39), seropositive arthralgia patients (SAP, n = 31), spondyloarthropathy patients (SpA, n = 26) and healthy controls (HC, n = 31) were assayed. Results In RA SF, LLT1 was expressed by a small proportion of monocytes. In RA ST, LLT1-expressing cells were detected in the lining, sublining layer and in areas with infiltrates. The LLT1 staining pattern overlapped with the CD68 staining pattern. FACS analysis of digested ST confirmed LLT1 expression by CD68+ cells. Elevated systemic sLLT1 was found in all patient groups. Conclusions In RA joints, LLT1 is expressed by cells of the monocyte/macrophage lineage. Serum levels of sLLT1 were increased in all patient groups (patients with early- and late-stage RA, seropositive arthralgia and spondyloarthropathy) when compared to healthy subjects. PMID:26147876

  9. Subclinical atherosclerosis in patients with rheumatoid arthritis. A meta-analysis of literature studies.

    PubMed

    Ambrosino, P; Lupoli, R; Di Minno, A; Tasso, M; Peluso, R; Di Minno, M N D

    2015-04-29

    We performed a systematic review with meta-analysis and meta-regression of literature studies evaluating the impact of rheumatoid arthritis (RA) on common carotid artery intima-media thickness (CCA-IMT) and on the prevalence of carotid plaques. Studies evaluating the relationship between RA and markers of cardiovascular (CV) risk (CCA-IMT and prevalence of carotid plaques) were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. A total of 59 studies (4,317 RA patients and 3,606 controls) were included in the final analysis, 51 studies with data on CCA-IMT (52 data-sets on 3,600 RA patients and 3,020 controls) and 35 studies reporting on the prevalence of carotid plaques (2,859 RA patients and 2,303 controls). As compared to controls, RA patients showed a higher CCA-IMT (mean difference [MD]: 0.10 mm; 95?% confidence interval [CI]: 0.07, 0.12; p early RA, the difference in CCA-IMT among RA patients and controls was even higher (MD: 0.21 mm; 95?%CI: 0.06, 0.35; p=0.006), and difference in the prevalence of carotid plaques was entirely confirmed (OR: 3.57; 95?%CI: 1.69, 7.51; p=0.0008). Meta-regression models showed that male gender and a more severe inflammatory status [as expressed by disease activity score in 28 joints (DAS28), C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR)] significantly impacted on CCA-IMT. In conclusion, RA appears significantly associated with subclinical atherosclerosis and CV risk. These findings can be useful to plan adequate prevention strategies and therapeutic approaches. PMID:25716931

  10. Inflammation, adiposity, and atherogenic dyslipidemia in rheumatoid arthritis: is there a paradoxical relationship?

    PubMed

    Bag-Ozbek, Ayse; Giles, Jon T

    2015-02-01

    Dyslipidemia is highly prevalent in rheumatoid arthritis (RA) and appears to be present very early in the RA disease process, in some studies even before a diagnosis of clinical RA has been made. The association between lipid measures and the risk of cardiovascular disease (CVD) in RA appears to be paradoxical, whereby lower levels of total cholesterol (TC), low-density lipoprotein (LDL-C), and atherogenic ratios are associated with higher CVD risk. This may be due to the lipid-lowering effects of RA-related systemic inflammation. Therefore, standard CVD risk calculators have been shown to underperform in RA. Data also suggest that lipoprotein particle sizes and the apolipoprotein cargo of lipoproteins skew toward atherogenic dyslipidemia in RA and may contribute to the initiation and progression of atherosclerosis. Inflammatory burden in RA may also alter the anti-inflammatory and atheroprotective roles associated with high-density lipoprotein cholesterol (HDL-C). Adipose tissue is quantitatively increased in RA patients compared with matched non-RA controls and may be more inflamed and metabolically dysfunctional compared with an otherwise similar non-RA patient. In vitro, animal, and a handful of non-RA human, studies suggest that inflamed, metabolically dysfunctional adipose tissue contributes directly to lower HDL-C levels. In turn, lower HDL-C that has been altered functionally by inflammation may lead to expanded adipose mass and further adipose dysfunction and inflammation. In the last part of this review, we speculate how the RA disease state may recapitulate these processes. PMID:25504261

  11. Long-term observation study of Austrian patients with rheumatoid arthritis.

    PubMed

    Skoumal, M; Wottawa, A

    2002-01-01

    We examined retrospectively in a long-term observation study the outcome of patients with RA in Austria. Eighty-one inpatients with definite rheumatoid arthritis (RA) completed a standardized clinical and laboratory examination 3-8 times between 1978 and 1999. The course of the disease was assessed by determining the disease activity score (DAS), 28-joint count (28 JC), 30 swollen joint count (30 SJC), proximal interphalangeal joint score (PIP), Ritchie index, Stoke index, Steinbrocker stage, and Larsen score. In a mean duration of follow-up of 10 years, we observed a statistically significant improvement in PIP, Ritchie index, Stoke index, and DAS. Steinbrocker stage and Larsen score increased significantly. A high percentage of the patients did not receive any disease-modifying antirheumatic drug (DMARD) within the first 2 years of disease. Of all drugs used, methotrexate (MTX) was continued longer than other DMARDs. The most frequent extra-articular manifestation was sicca syndrome. In our long-term follow-up, a change in treatment from the onset of the disease in the 1980s to a more aggressive treatment within the last decade could be observed. However, with respect to the significant increase in Steinbrocker stage and Larsen score as well, an early aggressive therapy is required. With respect to the association of ANA and extra-articular manifestations, elevated ANA should give rise to an exact organ screening. For the development of predictive factors for the outcome in patients with RA, it would be helpful to refer patients at risk to specialist care as soon as possible. PMID:12050946

  12. Limited effect of anti-rheumatic treatment on 15-prostaglandin dehydrogenase in rheumatoid arthritis synovial tissue

    PubMed Central

    2012-01-01

    Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disease in which prostaglandin E2 (PGE2) displays an important pathogenic role. The enzymes involved in its synthesis are highly expressed in the inflamed synovium, while little is known about 15- prostaglandin dehydrogenase (15-PGDH) that metabolizes PGE2. Here we aimed to evaluate the localization of 15-PGDH in the synovial tissue of healthy individuals or patients with inflammatory arthritis and determine the influence of common RA therapy on its expression. Methods Synovial tissue specimens from healthy individuals, psoriatic arthritis, ostheoarthritis and RA patients were immunohistochemically stained to describe the expression pattern of 15-PGDH. In addition, the degree of enzyme staining was evaluated by computer analysis on stained synovial biopsies from two groups of RA patients, before and after RA specific treatment with either intra-articular glucocorticoids or oral methotrexate therapy. Prostaglandins derived from the cyclooxygenase (COX) pathway were determined by liquid-chromatography mass spectrometry in supernatants from interleukin (IL) 1?-activated fibroblast-like synoviocytes (FLS) treated with methotrexate. Results 15-PGDH was present in healthy and inflamed synovial tissue, mainly in lining macrophages, fibroblasts and vessels. Intra-articular glucocorticoids showed a trend towards reduced 15-PGDH expression in RA synovium (p = 0.08) while methotrexate treatment left the PGE2 pathway unaltered both in biopsies ex vivo and in cultured FLS. Conclusions Early methotrexate therapy has little influence on the expression of 15-PGDH and on any of the PGE2 synthesizing enzymes or COX-derived metabolites. Thus therapeutic strategies involving blocking induced PGE2 synthesis may find a rationale in additionally reducing local inflammatory mediators. PMID:22616846

  13. Articular Joint Lubricants during Osteoarthritis and Rheumatoid Arthritis Display Altered Levels and Molecular Species

    PubMed Central

    Liebisch, Gerhard; Zhang, Ruiyan; Siebert, Hans-Christian; Wilhelm, Jochen; Kaesser, Ulrich; Dettmeyer, Reinhard B.; Klein, Heiko; Ishaque, Bernd; Rickert, Markus; Schmitz, Gerd; Schmidt, Tannin A.; Steinmeyer, Juergen

    2015-01-01

    Background Hyaluronic acid (HA), lubricin, and phospholipid species (PLs) contribute independently or together to the boundary lubrication of articular joints that is provided by synovial fluid (SF). Our study is the first reporting quantitative data about the molecular weight (MW) forms of HA, lubricin, and PLs in SF from cohorts of healthy donors, patients with early (eOA)- or late (lOA)-stage osteoarthritis (OA), and patients with active rheumatoid arthritis (RA). Methods We used human SF from unaffected controls, eOA, lOA, and RA. HA and lubricin levels were measured by enzyme-linked immunosorbent assay. PLs was quantified by electrospray ionization tandem mass spectrometry. Fatty acids (FAs) were analyzed by gas chromatography, coupled with mass spectrometry. The MW distribution of HA was determined by agarose gel electrophoresis. Results Compared with control SF, the concentrations of HA and lubricin were lower in OA and RA SF, whereas those of PLs were higher in OA and RA SF. Moreover, the MW distribution of HA shifted toward the lower ranges in OA and RA SF. We noted distinct alterations between cohorts in the relative distribution of PLs and the degree of FA saturation and chain lengths of FAs. Conclusions The levels, composition, and MW distribution of all currently known lubricants in SF—HA, lubricin, PLs—vary with joint disease and stage of OA. Our study is the first delivering a comprehensive view about all joint lubricants during health and widespread joint diseases. Thus, we provide the framework to develop new optimal compounded lubricants to reduce joint destruction. PMID:25933137

  14. Early maturation processes in coal. Part 2: Reactive dynamics simulations using the ReaxFF reactive force field on Morwell Brown coal structures

    Microsoft Academic Search

    Elodie Salmon; Adri C. T. van Duin; François Lorant; Paul-Marie Marquaire; William A. Goddard III

    2009-01-01

    This paper reports reactive dynamics (RD) simulations of a macro-model of Morwell Brown coal using the ReaxFF reactive force field. We find that these reactive MD simulations successfully reproduce thermal decomposition processes of defunctionalization, depolymerization and rearrangement of the residual structure observed in various experimental studies. For example, our simulations indicate that the decarboxylation and dehydroxylation of the lignin side

  15. Immunisation of guinea-pigs with circulating immune complexes from patients with rheumatoid arthritis.

    PubMed Central

    Hack, C E; Lim, H G; Aalberse, R C

    1984-01-01

    Sixteen guinea-pigs were immunised with immune complexes isolated from serum of nine patients with rheumatoid arthritis. The resulting antisera were analysed by radioimmunoassays. All guinea-pig sera were extensively absorbed with normal human serum. After this absorption eight guinea-pig sera contained antibodies specific for immune complexes isolated from the sera of three patients. One of these antisera reacted not only with immune complexes (and serum) from the corresponding patient but also with immune complexes (and sera) from other patients with rheumatoid arthritis. The antigen(s) to which the guinea-pig antibodies were directed sedimented as IgM, and they bound to IgG Sepharose. Therefore the guinea-pig sera were absorbed with IgM-rheumatoid factors isolated from the serum of the corresponding patient. After this absorption, the guinea-pig sera had lost their reactivity with immune complexes. We conclude that these antisera did not detect an exogenous antigen in immune complexes from patients with rheumatoid arthritis. The positive reactions found were due to antibodies specific for (idiotypic?) antigenic determinants on IgM-rheumatoid factors. PMID:6208856

  16. Back diffusion of hydrogen ions across gastric mucosa of patients with gastric ulcer and rheumatoid arthritis.

    PubMed

    Ivey, K J; Clifton, J A

    1974-01-01

    Ionic permeability of the gastric mucosa was measured in six patients with an acute exacerbation of severe generalized rheumatoid arthritis receiving either aspirin and prednisone or aspirin and indomethacin as therapy. The results were compared with those in four patients with benign gastric ulcer and nine normal subjects. Compared with controls H(+) concentration was decreased and Na(+) concentration increased while corrected H(+) flux out of the lumen and Na(+) flux into the lumen were significantly increased in the patient groups, indicating increased mucosal permeability. Abnormality of the gastric mucosal barrier persisted in two patients despite healing of their ulcers. Mucosal permeability of patients with rheumatoid arthritis and gastric ulcer did not differ significantly from one another. One rheumatoid patient with a gastric ulcer showed no difference in mucosal permeability to that of the other rheumatoid patients. These studies suggest that increased H(+) ion loss contributes to the apparent hyposecretion of acid in patients gastric ulcer; persistence of an abnormal gastric mucosal barrier to H(+) ions may explain the high recurrence rate of gastric ulcers; and an abnormal gastric mucosal barrier may be a precursor to gastric ulceration in rheumatoid arthritis. PMID:4808814

  17. [Immune function of rheumatoid arthritis treated by medicated-bath therapy in Tibetan medicine].

    PubMed

    Zhao, S L; Geng, P L; Sang, J

    1993-08-01

    The changes of the immune function of rheumatoid arthritis before and after the Tibetan medicated-bath was observed. It showed a higher level of the rheumatoid factor (RF) titre, immunoglobulin (Ig) G, M, A and CD4 cells, but the CD8 cells was obviously lower before the treatment. Clinical data indicated that the medicated-bath had significant effective rate. In order to elucidate the mechanism of the medicated-bath upon rheumatoid arthritis the RF titre, Ig level, complement C3, 3H-TdR incorporated with lymphocytes transformation and CD3, CD4, CD8 cell level were assayed. Results showed that RF titre decreased after the bath and the negative transforming rate reached 70.6%, Ig level obviously dropped as well as the number of CD4 cells while CD8 cell level increased. The transforming stimulation index of lymphocyte cells obviously decreased. All of the above mentioned showed that there was a higher concentration of the enhancing factor of interleukin-2 (IL2-EF) involved in lymphocyte culture of rheumatoid arthritis patients. They suggested that the Tibetan medicated-bath had an immunomodulating effect on rheumatoid arthritis patients through increasing the level of CD8 cells and reducing CD4 cells. PMID:8111198

  18. Ages of onset suggestive of genetic anticipation in rheumatoid arthritis multicase sibships can be explained by observational bias

    Microsoft Academic Search

    C. Deighton; L. A. Criswell; R. F. Lum; A. Silman

    2007-01-01

    Objectives. Previous work has suggested that features of genetic anticipation might be present in familial rheumatoid arthritis (RA), but bias is difficult to exclude when looking at disease in two consecutive generations. We used data from the North American Rheumatoid Arthritis Consortium (NARAC) and the Arthritis Research Campaign National repository for RA multicase pedigrees to determine whether differences in age

  19. Immune features of seronegative and seropositive arthritis in early synovitis studies.

    PubMed

    Hitchon, Carol A; El-Gabalawy, Hani S

    2002-07-01

    Synovitis of recent onset is a challenging problem, both from a diagnostic and a mechanistic point of view. The role of the immune system in mediating the systemic and synovial inflammatory response remains an area of active investigation. Studies in early synovitis cohorts have confirmed the relatively specific association of rheumatoid factor positive polyarthritis with a number of autoantibodies, particularly anticyclical citrullinated peptide (CCP) antibodies, antifilaggarin antibodies (AFA), and anti-Sa antibodies. Immunopathologic studies of synovial tissue samples from patients with early synovitis have generally suggested quantitative rather than qualitative differences between various forms of synovitis. In particular, Th1 cytokines appear to predominate in rheumatoid arthritis and psoriatic synovitis, while Th2 cytokines are more often detectable in the synovium of reactive arthritis patients. This latter observation is consistent with an immune response profile that favors persistence of intracellular organisms. PMID:12118166

  20. Antibodies to Mutated Citrullinated Vimentin in Rheumatoid Arthritis: Diagnostic Value, Association with Radiological Damage and Axial Skeleton Affection

    PubMed Central

    Mansour, Howaida E.; Metwaly, Khaled M.; Hassan, Iman A.; Elshamy, Hebat-Allah A.; Elbeblawy, Moataz M.S.

    2010-01-01

    Background: Early definitive diagnosis and effective treatment are mandatory in rheumatoid arthritis (RA) as it can halt the disease progression and subsequent joints destruction. Objective: To investigate the diagnostic and prognostic value of anti-mutated citrullinated vimentin (anti-MCV) and its correlation with disease activity, peripheral and axial skeleton affection in RA patients. Patients and methods: A total of 123 patients with different rheumatic diseases were enrolled in a prospective-two year study at Ain Shams University hospital: 64 patients with RA and 59 patients with other rheumatic diseases as controls. RA patients were fulfilling the traditional and the new ACR/EULAR diagnostic criteria for RA. They have been followed up for two years. At baseline, all RA patients were subjected to: Clinical assessment of disease activity by taking full histories, general and local examination, measurement of 28 joint count of tender and swollen joints with calculation of disease activity score (DAS-28) for each patient. Complete blood count, erythrocytes sedimentation rate, C-reactive protein and rheumatoid factor titers were performed. Anti-MCV IgG immunoglobulins’ assay was performed at the study endpoint by ELISA. RA patients were then classified into; anti-MCV positive and anti-MCV negative groups for statistical comparison. Plain X-ray was performed on the peripheral joints and scored by the Simple Erosion Narrowing score (SEN-score). Magnetic Resonance Imaging (MRI) scans were carried out to 22 RA patients on cervical and lumbosacral regions. Results: Anti-MCV antibodies were found to be of high sensitivity (79.6%) and specificity (96.6%) in diagnosing RA. The area under the curve was 0.893 at 95% confidence interval (CI), confers an odds ratio of 23.5. Anti-MCV positive RA patients had significantly higher DAS-28 and SEN-scores than anti-MCV negative patients; who were found to have more benign disease with lower incidence of erosions (P < 0.05). MRI scans revealed that; 17/22 (77%) had cervical joints involvement while, 8 (36%) had lumbo-sacral joint lesions (P < 0.05), both were correlated significantly with aggressive peripheral joint disease. Conclusion: Anti-MCV antibodies are promising diagnostic and prognostic marker in RA, with high sensitivity and specificity. They may identify a subset of RA patients with aggressive early erosive disease. The axial skeleton—especially the cervical spine—could be affected in RA and this was correlated with aggressive peripheral joints’ disease. MRI scanning is a sensitive method for detecting axial skeleton involvement in RA, in attempt for better disease control and outcomes. PMID:21124694

  1. Autoimmune Thyroid Disease in Rheumatoid Arthritis: A Global Perspective

    PubMed Central

    Cárdenas Roldán, Jorge; Amaya-Amaya, Jenny; Castellanos-de la Hoz, Juan; Giraldo-Villamil, Juliana; Montoya-Ortiz, Gladys; Cruz-Tapias, Paola; Rojas-Villarraga, Adriana; Mantilla, Rubén D.; Anaya, Juan-Manuel

    2012-01-01

    Objective. To determine the prevalence and impact of autoimmune thyroid disease (AITD) in patients with rheumatoid arthritis (RA). Methods. Eight-hundred patients were included. The association between AITD and RA was analyzed was analyzed by bivariate and multivariate analysis. In addition, a literature review was done focusing on geographical variations. Results. In our cohort the prevalence of AITD was 9.8% while the presence of antibodies was 37.8% for antithyroperoxidase enzyme (TPOAb) and 20.8% for antithyroglobulin protein (TgAb). The presence of type 2 diabetes, thrombosis, abnormal body mass index, and a high educational level was positively associated with AITD. The literature review disclosed a geographical variation of AITD in RA ranging from 0.5% to 27%. Autoantibody prevalence ranges from 6% to 31% for TgAb, 5% to 37% for TPOAb, and from 11.4% to 32% for the presence of either of the two. Conclusion. AITD is not uncommon in RA and should be systematically assessed since it is a risk factor for developing diabetes and cardiovascular disease. These results may help to further study the common mechanisms of autoimmune diseases, to improve patients' outcome, and to define public health policies. An international consensus to accurately diagnose AITD is warranted. PMID:23209899

  2. Insights into rheumatoid arthritis derived from the Sa immune system.

    PubMed

    Ménard, H A; Lapointe, E; Rochdi, M D; Zhou, Z J

    2000-01-01

    The Sa system is a recently described immune system that has a specificity and positive predictive value of nearly 100% for rheumatoid arthritis (RA) in Asia, Europe and the Americas. Its sensitivity of 30-40% suggests that it identifies a subset of RA patients. Anti-Sa antibodies are present from disease onset and are predictive of disease severity. The immune reactants are plentiful in the target tissue: antigen is present in the synovium, IgG antibody in the fluid. Immunologically, Sa is a hapten-carrier antigen in which vimentin is the carrier and citrulline is the hapten. The citrullination of vimentin is closely related to apoptosis, and citrullinated vimentin is extremely sensitive to digestion by the ubiquitous calpains. Nevertheless, Sa is found in only a few cell lines. Calpastatin, the natural specific inhibitor of calpains, is also a RA-associated, albeit non-specific, autoimmune system. Is it possible that calpain-related apoptotic pathways could be prominent in cells containing Sa? The task is to reconcile the specificity of Sa/citrullinated proteins in a multifactorial and polygenic disease such as RA. PMID:11094453

  3. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin.

    PubMed

    Vossenaar, Erik R; Després, Normand; Lapointe, Elvy; van der Heijden, Annemarie; Lora, Maximillian; Senshu, Tatsuo; van Venrooij, Walther J; Ménard, Henri A

    2004-01-01

    Antibodies directed to the Sa antigen are highly specific for rheumatoid arthritis (RA) and can be detected in approximately 40% of RA sera. The antigen, a doublet of protein bands of about 50 kDa, is present in placenta and in RA synovial tissue. Although it has been stated that the Sa antigen is citrullinated vimentin, experimental proof for this claim has never been published. In this study, we investigated the precise nature of the antigen. Peptide sequences that were obtained from highly purified Sa antigen were unique to vimentin. Recombinant vimentin, however, was not recognized by anti-Sa reference sera. In vivo, vimentin is subjected to various post-translational modifications, including citrullination. Since antibodies to citrullinated proteins are known to be highly specific for RA, we investigated whether Sa is citrullinated and found that Sa indeed is citrullinated vimentin. Anti-Sa antibodies thus belong to the family of anticitrullinated protein/peptide antibodies. The presence of the Sa antigen in RA synovial tissue, and the recent observation that vimentin is citrullinated in dying human macrophages, make citrullinated vimentin an interesting candidate autoantigen in RA and may provide new insights into the potential role of citrullinated synovial antigens and the antibodies directed to them in the pathophysiology of RA. PMID:15059278

  4. Developments in the scientific understanding of rheumatoid arthritis

    PubMed Central

    2009-01-01

    Rheumatoid arthritis (RA) is recognized to be an autoimmune disease that causes preclinical systemic abnormalities and eventually leads to synovial inflammation and destruction of the joint architecture. Recently identified genetic risk factors and novel insights from animal models of spontaneous arthritis have lent support to the concept that thymic selection of an autoreactive T-cell repertoire is an important risk factor for this disease. With advancing age, defects in the homeostatic control of the T-cell pool and in the setting of signaling thresholds lead to the accumulation of pro-inflammatory T-effector cell populations and loss of tolerance to neo-antigens, such as citrullinated peptides. As the breakdown of tolerance to modified self-antigens can precede synovitis by decades, repair of homeostatic defects may open a unique window of opportunity for preventive interventions in RA. The end result of RA, destruction of cartilage and bone, appears to be driven by cytokine- and cell contact-induced activation of synoviocytes and monocytic cells, some of which differentiate into tissue-destructive osteoclasts. Targeting mediators involved in this process has greatly improved the management of this chronic inflammatory syndrome. PMID:19835638

  5. Hyperlipidemia in rheumatoid arthritis patients in Saudi Arabia

    PubMed Central

    Attar, Suzan M.

    2015-01-01

    Objectives: To determine the prevalence of hyperlipidemia in patients from Saudi Arabia with rheumatoid arthritis (RA), and to investigate its relationship with C-reactive protein level and disease activity. Methods: A cross-sectional 3-year study was conducted on RA patients at King Abdulaziz University Hospital, Saudi Arabia between January 2011 and December 2013. Lipid profiles were determined following 12-hour overnight fasting, and the association of lipid profiles with C-reactive protein (CRP) levels and disease activity was determined. Results: This study involved a total of 180 RA patients (mean age: 40.49±12.19 years). These subjects displayed a high prevalence of elevated total cholesterol (55.1%), and low-density lipoprotein cholesterol (51.2%). Notably, we detected a significant association between increased total cholesterol and high CRP levels (p=0.002). Moreover, we observed a positive correlation between total cholesterol and disease activity, as measured using the 28-Joint Disease Activity Score index (r=0.23, p=0.036). Conclusions: Hyperlipidemia is common among RA patients and is significantly associated with CRP levels and disease activity. Our findings emphasize the need to raise awareness among healthcare professionals regarding the development of hyperlipidemia when RA is active. PMID:25987110

  6. The endocannabinoid system and its therapeutic implications in rheumatoid arthritis.

    PubMed

    Gui, Huan; Tong, Qiang; Qu, Wenchun; Mao, Chen-Mei; Dai, Sheng-Ming

    2015-05-01

    Since the discovery of the endogenous receptor for ?(9)-tetrahydrocannabinol, a main constituent of marijuana, the endocannabinoid system (comprising cannabinoid receptors and their endogenous ligands, as well as the enzymes involved in their metabolic processes) has been implicated as having multiple regulatory functions in many central and peripheral conditions, including rheumatoid arthritis (RA). RA is an immune-mediated inflammatory disease that is associated with the involvement of many kinds of cells (such as fibroblastlike synoviocytes [FLSs], osteoclasts, T cells, B cells, and macrophages) and molecules (such as interleukin-1?, tumor necrosis factor-?, interleukin-6, matrix metalloproteinases [MMPs], and chemokines). Increasing evidence suggests that the endocannabinoid system, especially cannabinoid receptor 2 (CB2), has an important role in the pathophysiology of RA. Many members of the endocannabinoid system are reported to inhibit synovial inflammation, hyperplasia, and cartilage destruction in RA. In particular, specific activation of CB2 may relieve RA by inhibiting not only the production of autoantibodies, proinflammatory cytokines, and MMPs, but also bone erosion, immune response mediated by T cells, and the proliferation of FLSs. In this review, we will discuss the possible functions of the endocannabinoid system in the modulation of RA, which may be a potential target for treatment. PMID:25791728

  7. Inhibition of rheumatoid arthritis by blocking connective tissue growth factor

    PubMed Central

    Nozawa, Kazuhisa; Fujishiro, Maki; Takasaki, Yoshinari; Sekigawa, Iwao

    2014-01-01

    The pathogenesis of rheumatoid arthritis (RA) remains to be completely elucidated so far; however, it is known that proinflammatory cytokines play a pivotal role in the induction of RA. Tumor necrosis factor (TNF-?), in particular, is considered to play a central role in bone destruction by mediating the abnormal activation of osteoclasts or the production of proteolytic enzymes through direct or indirect mechanisms. The use of TNF-? blocking agents has a significant impact on RA therapy. Anti-TNF-? blocking agents such as infliximab are very effective for treatment of RA, especially for the prevention of articular destruction. We have previously shown that several proteins exhibited extensive changes in their expression after amelioration of RA with infliximab treatment. Among the proteins, connective tissue growth factor (CTGF) has a significant role for the development of RA. Herein, we review the function of CTGF in the pathogenesis of RA and discuss the possibility of a novel treatment for RA. We propose that CTGF is a potentially novel effector molecule in the pathogenesis of RA. Blocking the CTGF pathways by biological agents may have great beneficial effect in patients with RA. PMID:25405094

  8. Genetics of rheumatoid arthritis contributes to biology and drug discovery

    PubMed Central

    Okada, Yukinori; Wu, Di; Trynka, Gosia; Raj, Towfique; Terao, Chikashi; Ikari, Katsunori; Kochi, Yuta; Ohmura, Koichiro; Suzuki, Akari; Yoshida, Shinji; Graham, Robert R.; Manoharan, Arun; Ortmann, Ward; Bhangale, Tushar; Denny, Joshua C.; Carroll, Robert J.; Eyler, Anne E.; Greenberg, Jeffrey D.; Kremer, Joel M.; Pappas, Dimitrios A.; Jiang, Lei; Yin, Jian; Ye, Lingying; Su, Ding-Feng; Yang, Jian; Xie, Gang; Keystone, Ed; Westra, Harm-Jan; Esko, Tõnu; Metspalu, Andres; Zhou, Xuezhong; Gupta, Namrata; Mirel, Daniel; Stahl, Eli A.; Diogo, Dorothée; Cui, Jing; Liao, Katherine; Guo, Michael H.; Myouzen, Keiko; Kawaguchi, Takahisa; Coenen, Marieke J.H.; van Riel, Piet L.C.M.; van de Laar, Mart A.F.J.; Guchelaar, Henk-Jan; Huizinga, Tom W.J.; Dieudé, Philippe; Mariette, Xavier; Bridges, S. Louis; Zhernakova, Alexandra; Toes, Rene E.M.; Tak, Paul P.; Miceli-Richard, Corinne; Bang, So-Young; Lee, Hye-Soon; Martin, Javier; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Rantapää-Dahlqvist, Solbritt; Ärlestig, Lisbeth; Choi, Hyon K.; Kamatani, Yoichiro; Galan, Pilar; Lathrop, Mark; Eyre, Steve; Bowes, John; Barton, Anne; de Vries, Niek; Moreland, Larry W.; Criswell, Lindsey A.; Karlson, Elizabeth W.; Taniguchi, Atsuo; Yamada, Ryo; Kubo, Michiaki; Liu, Jun S.; Bae, Sang-Cheol; Worthington, Jane; Padyukov, Leonid; Klareskog, Lars; Gregersen, Peter K.; Raychaudhuri, Soumya; Stranger, Barbara E.; De Jager, Philip L.; Franke, Lude; Visscher, Peter M.; Brown, Matthew A.; Yamanaka, Hisashi; Mimori, Tsuneyo; Takahashi, Atsushi; Xu, Huji; Behrens, Timothy W.; Siminovitch, Katherine A.; Momohara, Shigeki; Matsuda, Fumihiko; Yamamoto, Kazuhiko; Plenge, Robert M.

    2013-01-01

    A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery. PMID:24390342

  9. Rheumatoid arthritis and the role of oral bacteria

    PubMed Central

    Loyola-Rodriguez, Juan Pablo; Martinez-Martinez, Rita Elizabeth; Abud-Mendoza, Carlos; Patiño-Marin, Nuria; Seymour, Gregory J.

    2010-01-01

    Rheumatoid arthritis (RA) and periodontal disease (PD) have shown similar physiopathologic mechanisms such as chronic inflammation with adjacent bone resorption in an immunogenetically susceptible host; however, PD has a well-recognized bacterial etiology while the cause of RA is unclear. Some reports have indicated that an infectious agent in a susceptible host could be one possible trigger factor for RA, and it has been suggested that oral microorganisms, specialty periodontal bacteria could be the infectious agent (mainly Porphyromonas gingivalis). It has been reported that PD is more frequent and more severe in patients with RA, suggesting a positive association between both diseases. There have been reports regarding the detection of antibodies against periodontal bacteria while other studies have identified periodontal bacterial DNA in serum and synovial fluid of RA patients and have explored the possible pathways of transport of periodontal bacterial DNA. In conclusion, there is no question that RA and PD have pathologic features in common and there is strong evidence of an association between both diseases, but further studies, including experimental models, are needed to demonstrate the arthritogenicity of oral microorganisms. PMID:21523217

  10. Therapeutic effects of hybrid liposomes without drugs for rheumatoid arthritis.

    PubMed

    Matsumoto, Yoko; Ichihara, Hideaki; Hino, Motoki; Umebayashi, Masayo; Ueoka, Ryuichi

    2013-12-18

    Abstract Hybrid liposomes (HLs) can be prepared by simply sonicating a mixture of vesicular and micellar molecules in buffer solutions. This study aims to demonstrate inhibitory effects of HLs on the growth of fibroblast-like synoviocytes along with apoptosis and therapeutic effects of HLs in a mouse model with rheumatoid arthritis (RA). HLs composed of 95?mol% l-?-dimyristoylphosphatidylcholine (DMPC) and 5?mol% polyoxyethylene(23)dodecyl ether (C12(EO)23) were prepared by the sonication method. The inhibitory effects of HLs on the growth of human fibroblast-like synoviocytes-RA (HFLS-RA) cells in vitro and their inhibitory mechanism were examined. High inhibitory effects of HLs on the growth of HFLS-RA cells were observed. The induction of apoptosis by HLs was revealed on the basis of flow cytometric analysis. Furthermore, therapeutic effects of HLs in the mouse model with RA were examined in vivo. Our results demonstrate that HLs showed inhibitory effects on the growth of HFLS-RA cells in vitro along with apoptosis and therapeutic effects in mouse models of RA in vivo. PMID:24344811

  11. Antinuclear antibody and rheumatoid factor in silica-exposed workers.

    PubMed

    Aminian, Omid; Sharifian, Seyed Akbar; Mehrdad, Ramin; Haghighi, Khosro Sadeghniyat; Mazaheri, Maria

    2009-06-01

    A lot of workers in industries such as foundry, stonecutting, and sandblasting are exposed to higher than permissible levels of crystalline silica. Various alterations in humoral immune function have been reported in silicosis patients and workers exposed to silica dust. The aim of this study was to measure antinuclear antibody (ANA) and rheumatoid factor (RF) levels in foundry workers exposed to silica and to compare them with a control group without such exposure. ANA and RF were measured in 78 exposed and 73 non-exposed workers, and standard statistical methods were used to compare them. The two groups did not significantly differ in age and smoking. Mean work duration of the exposed and non-exposed workers was (14.9+/-4.72) years and (12.41+/-6.3) years, respectively. Ten exposed workers had silicosis. ANA was negative in all workers in either group. Its mean titer did not differ significantly between the exposed and control workers [(0.39+/-0.15) IU mL(-1) vs. (0.36+/-0.17) IU mL(-1), respectively]. RF was positive in two workers of each group. Other studies have reported an increase in ANA and RF associated with exposure to silica dust and silicosis.In contrast, our study suggests that exposure to silica dust does not increase the level of ANA and RF in exposed workers. PMID:19581212

  12. Atlanto-odontoid osteoarthritis in rheumatoid arthritis: dynamic CT findings.

    PubMed

    Baysal, Ozlem; Baysal, Tamer; Sigirci, Ahmet; Ersoy, Yuksel; Altay, Zuhal

    2004-10-01

    We analyzed the CT appearances of degenerative change in the atlanto-odontoid joint (AOJ) in patients with rheumatoid arthritis (RA) and evaluated the effect of these changes on atlanto-axial joint (AAJ) rotation by dynamic CT. This revealed that 9 patients (24%) treated with methotrexate had degenerative features in the AOJ. The ratio of AAJ rotation to the total rotation of the cervical spine was significantly higher in normal subjects (54 +/- 3%) than in patients (38 +/- 12%). The degree of AAJ rotation was significantly lower in the patient group with degenerative features in the AOJ (20.9 +/- 8.4 degrees ) than in patients without degenerative features (28.5 +/- 7.4 degrees ). RA patients with a history of longstanding disease and treatment with antirheumatic drugs may develop AO OA. Although secondary OA was described as healing phenomena in the joints of RA patients, it can limit rotation in the AAJ and cause suboccipital neck pain. A regular check-up of the AAJ and AOJ by means of dynamic CT in all RA patients is proposed to avoid possible antirheumatic drug complications. PMID:15459811

  13. When and Where Does Inflammation Begin in Rheumatoid Arthritis?

    PubMed Central

    Demoruelle, M. Kristen; Deane, Kevin D.; Holers, V. Michael

    2014-01-01

    Purpose of review The etiology of rheumatoid arthritis (RA), as well as the timing and anatomic site at which RA-related autoimmunity is initiated, is currently unknown. An improved understanding of the initial steps in the development of RA would provide insights into disease pathogenesis that could ultimately lead to more effective treatments and/or novel preventive strategies in RA. Recent findings Systemic inflammation and autoimmunity in RA begin long before the onset of detectable joint inflammation. Emerging data suggest that RA-related autoimmunity may be initiated at a mucosal site years before the onset of joint symptoms. The candidate sites of origin include the oral, lung and gastrointestinal mucosa, as data consistent with this hypothesis have been generated for each location. Individual patients may undergo initiation events at unique sites, but still converge on similar joint findings as the disease process evolves. Summary Further investigations are needed to determine when and where RA begins, including comprehensive prospective studies of individuals in the preclinical period of RA that can provide insight into the relationship between mucosal inflammation, RA-related autoantibody generation and subsequent joint inflammation in RA. PMID:24247116

  14. Feelings of guilt and shame in patients with rheumatoid arthritis.

    PubMed

    Ten Klooster, Peter M; Christenhusz, Lieke C A; Taal, Erik; Eggelmeijer, Frank; van Woerkom, Jan-Maarten; Rasker, Johannes J

    2014-07-01

    This study aims to determine whether patients with rheumatoid arthritis (RA) experience more general feelings of guilt and shame than their peers without RA and to examine possible correlates of guilt and shame in RA. In a cross-sectional survey study, 85 out-patients with RA (77 % female; median disease duration, 11 years) and 59 peer controls completed the Experience of Shame Scale (ESS) and the Test of Self-Conscious Affect (TOSCA). Patients additionally completed measures of health status, self-efficacy, cognitive emotion regulation, and numerical rating scales for life satisfaction and happiness. Patients and peer controls were well matched for sociodemographic characteristics. No significant differences between patients and controls were found for guilt or different types of shame as measured with the TOSCA or ESS. In multivariate analyses, female patients reported more feelings of bodily shame and higher guilt proneness, while younger patients reported more character and bodily shame. Worse social functioning and more self-blaming coping strategies were the strongest independent correlates of shame. Shame proneness was only independently associated with more self-blame, whereas guilt proneness was only associated with female sex. None of the physical aspects of the disease, including pain and physical functioning, correlated with feelings of guilt and shame. Patients with longstanding RA do not experience more general feelings of shame or guilt than their peers without RA. Shame and guilt in RA is primarily associated with demographic and psychosocial characteristics and not with physical severity of the disease. PMID:24510063

  15. Anaemia in rheumatoid arthritis: pathogenesis, diagnosis and treatment.

    PubMed

    Vreugdenhil, G; Swaak, A J

    1990-01-01

    The pathogenesis, diagnosis and treatment of the anaemia of chronic disorders (ACD) in rheumatoid arthritis (RA) were reviewed. Causes of anaemia other than ACD frequently present in RA. Decreased iron absorption was shown to be the result of active RA rather than a cause of ACD or iron deficiency. It has been hypothesized that bone marrow iron availability decreases due to decreased iron release by the mononuclear phagocyte system or that the anaemia in ACD is due to ineffective erythropoiesis; these remain controversial theories. Studies considering a decreased erythropoietin responsiveness have not produced consistent results. Erythroid colony growth is suppressed in vitro by interleukins and tumour necrosis factor but their role in vivo in ACD is unknown. The diagnosis of ACD is made by exclusion. Iron deficiency is detected by transferrin, ferritin, and cellular indices after adaptation of their normal values. Treatment of the anaemia consists merely of antirheumatic treatment. Iron administration is counterproductive since iron chelators or exogenous erythropoietin administration might increase erythropoiesis. PMID:2180049

  16. Association between Serum 25-Hydroxyvitamin D Level and Rheumatoid Arthritis

    PubMed Central

    Cen, Xiaomin; Liu, Yuan; Yin, Geng; Xie, Qibing

    2015-01-01

    The objective of this study is to examine and evaluate whether serum 25(OH)D is associated with disease activity in patients with rheumatoid arthritis (RA). Our results suggested that serum 25(OH)D in RA groups has significant lower level (35.99 ± 12.59?nmol/L) than that in the normal groups (54.35 ± 8.20?nmol/L, P < 0.05). Based on the DAS28, patients with RA were divided into four subgroups, and no differences were found in the four groups (P > 0.05). The 25(OH)D levels in complete remission, low disease activity, middle disease activity, and high disease activity group were 32.86 ± 12.26, 33.97 ± 13.28, 38.41 ± 10.64, and 38.94 ± 13.35?nmol/L, respectively. Based on the serum 25(OH)D levels, patients with RA were divided into inadequate group and normal group, and there were no significant differences in baseline characteristics and disease activity in the two groups. Our results showed that serum 25(OH)D levels in the inadequate group are significantly lower than those in the normal group. However, no correlations were found between 25(OH)D levels and disease activity among 116 patients with RA. The present findings will help to understand the association between 25(OH)D and disease activity of RA.

  17. How microchimerism can impart HLA susceptibility to rheumatoid arthritis

    PubMed Central

    Azzouz, Doua F; Rak, Justyna M; Balandraud, Nathalie; Auger, Isabelle; Martin, Marielle; Roudier, Jean

    2010-01-01

    Rheumatoid arthritis, a chronic inflammatory joint disease, is strongly associated with HLA-DRB1*01 and *04 alleles that have in common similar 5-amino acid motifs in the third hypervariable region of DR?1 (QKRAA, QRRAA, RRRAA), the so called shared epitope (SE). Most patients with RA carry 1 or 2 doses of the SE, with particular genetic combinations at higher risk. In recent work we provided evidence that patients who lack HLA-DRB1*01 and/or *04 alleles can acquire RA susceptibility through fetal, maternal or iatrogenic microchimerism. We also discuss how Mc carrying HLA-DRB1*04 alleles is more likely to be present in the peripheral blood of RA patients compared to Mc carrying HLA-DRB1*01 alleles. We further analyze our results in light of the hierarchy for RA risk with different combinations of the SE. How Mc could contribute to RA susceptibility and whether it also contributes to the hierarchy of risk observed with particular combinations of SE-containing alleles is certainly the beginning of an intriguing story and may offer hope for future therapeutic and/or preventative interventions. PMID:21327148

  18. How microchimerism can impart HLA susceptibility to rheumatoid arthritis.

    PubMed

    Azzouz, Doua F; Rak, Justyna M; Balandraud, Nathalie; Auger, Isabelle; Martin, Marielle; Roudier, Jean; Lambert, Nathalie C

    2010-07-01

    Rheumatoid arthritis, a chronic inflammatory joint disease, is strongly associated with HLA-DRB1*01 and *04 alleles that have in common similar 5-amino acid motifs in the third hypervariable region of DR?1 (QKRAA, QRRAA, RRRAA), the so called shared epitope (SE). Most patients with RA carry 1 or 2 doses of the SE, with particular genetic combinations at higher risk. In recent work we provided evidence that patients who lack HLA-DRB1*01 and/or *04 alleles can acquire RA susceptibility through fetal, maternal or iatrogenic microchimerism. We also discuss how Mc carrying HLA-DRB1*04 alleles is more likely to be present in the peripheral blood of RA patients compared to Mc carrying HLA-DRB1*01 alleles. We further analyze our results in light of the hierarchy for RA risk with different combinations of the SE. How Mc could contribute to RA susceptibility and whether it also contributes to the hierarchy of risk observed with particular combinations of SE-containing alleles is certainly the beginning of an intriguing story and may offer hope for future therapeutic and/or preventative interventions. PMID:21327148

  19. Pericardial mass in a patient with rheumatoid arthritis.

    PubMed

    Al-Ani, Mohammad; Weber, Michelle; Winchester, David; Kosboth, Matthew

    2015-01-01

    A 65-year-old man presented with long-standing rheumatoid arthritis (RA), severe fatigue and mild arthritis of metacarpophalaneal joints. Physical examination revealed S3, II/IV decrescendo diastolic murmur and 2+ LL oedema. Anticyclic citrullinated peptide antibodies were >250?units. Echocardiogram showed an 8?cm pericardial mass with no atrial or ventricular collapse and mild to moderate aortic regurgitation. Cardiac MRI defined the mass as a heterogeneous entity attached to the right, anterior and inferior heart borders, with compression on right cardiac structures and the left ventricle. CT-guided biopsy demonstrated fibrinous material without granulomas or infection. Fatigue did not improve on immunosuppression with low-dose prednisone and leflunamide. Cardiac tamponade was confirmed by heart catheterisation and the mass was surgically excised with partial pericardiectomy. The patient had a dramatic improvement and, 4?years later, he remains asymptomatic cardiac wise. This case highlights the clinical significance of pericardial disease in RA and its response to therapy. PMID:26055762

  20. The Development of Novel Therapies for Rheumatoid Arthritis

    PubMed Central

    Quan, Ling-dong; Thiele, Geoffrey M.; Tian, Jun; Wang, Dong

    2008-01-01

    Background Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease that affects approximately 0.5 to 1 percent of the adults worldwide and commonly results in joint destruction and significant impairment in the quality of life. RA is considered as an autoimmune disease with unknown etiology. Many pathogenic pathways of RA have been revealed recently, which led to development of various novel therapies. Objective The current treatments of RA include 4 categories: non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, non-biologic disease-modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs. In this review, we will discuss some of the most recent development in antirheumatic therapies. Methods Using SciFinder Scholar and PubMed as main searching tools, we evaluated various newly developed therapies for RA. Under each drug category, emphases are placed on the mode of action, limitation of the drugs and new drug candidates from the patents search. Those well-established therapies will only be reviewed briefly. Conclusion During the past 20 years, most of the development of new therapies is in DMARDs, especially biological DMARDs. With the discovery of new pathways and the application of drug delivery strategies, more growth is anticipated in this research field. PMID:19578469

  1. Co-occurrence of rheumatoid arthritis and sarcoidosis.

    PubMed

    Kobak, ?enol; Karaarslan, Ahmet Adnan; Yilmaz, Hatice; Sever, Fidan

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by erosive arthritis. Sarcoidosis is a chronic disease characterised by formation of non-calcified granulomas. Our case, a 35-year-old woman, presented with metacarpophalangeal, proximal interphalangeal (P?P) joints and arthritis of both ankles, of 6-month duration. She had morning stiffness lasting 1?h, restriction of range of motion and erythaema nodosum. Laboratory tests showed elevated acute phase responses and serum ACE levels, and anti-cyclic citrullinated peptide antibody positivity. There was periarticular osteoporosis on her hand and wrist on direct X-rays and hilar lymphadenopathy on her thorax CT. The pathological result of endobronchial ultrasound biopsy showed non-calcified granuloma congruent with sarcoidosis. According to clinical, laboratory and histopathological evaluation, the patient was diagnosed with RA and sarcoidosis. Corticosteroids and methotrexate were started, and on her sixth month of follow-up, her clinical and laboratory findings and lymphadenopathies on CT had regressed. The clinical follow-up continues; the patient appears to be in clinical remission. PMID:26150618

  2. Managing Macrophages in Rheumatoid Arthritis by Reform or Removal

    PubMed Central

    Li, Jun; Hsu, Hui-Chen

    2013-01-01

    Macrophages play a central role in the pathogenesis of rheumatoid arthritis (RA). There is an imbalance of inflammatory and antiinflammatory macrophages in RA synovium. Although the polarization and heterogeneity of macrophages in RA have not been fully uncovered, the identity of macrophages in RA can potentially be defined by their products, including the co-stimulatory molecules, scavenger receptors, different cytokines/chemokines and receptors, and transcription factors. In the last decade, efforts to understand the polarization, apoptosis regulation, and novel signaling pathways in macrophages, as well as how distinct activated macrophages influence disease progression, have led to strategies that target macrophages with varied specificity and selectivity. Major targets that are related to macrophage development and apoptosis include TNF-?, IL-1, IL-6, GM-CSF, M-CSF, death receptor 5 (DR5), Fas, and others, as listed in Table 1. Combined data from clinical, preclinical, and animal studies of inhibitors of these targets have provided valuable insights into their roles in the disease progression and, subsequently, have led to the evolving therapeutic paradigms in RA. In this review, we propose that reestablishment of macrophage equilibrium by inhibiting the development of, and/or eliminating, the proinflammatory macrophages will be an effective therapeutic approach for RA and other autoimmune diseases. PMID:22855296

  3. A case of REM sleep behavior disorder, narcolepsy-cataplexy, parkinsonism, and rheumatoid arthritis.

    PubMed

    Cosentino, Filomena I I; Distefano, Angela; Plazzi, Giuseppe; Schenck, Carlos H; Ferri, Raffaele

    2014-01-01

    A patient is reported in whom signs and symptoms of REM sleep behavior disorder (RBD) and narcolepsy have been associated for almost two decades with a late development of parkinsonism and rheumatoid arthritis. A 78-year-old male patient in whom RBD was first diagnosed was followed-up by clinical examination, video-polysomnography, multiple sleep latency test, cerebral magnetic resonance imaging, and dopamine transporter imaging by single-photon emission computerized tomography. The patient was found to present for almost two decades, in addition to RBD, also narcolepsy. Moreover, a late development of parkinsonism and the occurrence of rheumatoid arthritis were detected and clinically and instrumentally characterized. Patients predisposed to RBD and later parkinsonism might be susceptible to a variety of triggers that, in our patient, might have been represented by a possible latent autoimmune process leading to the development of narcolepsy with cataplexy and rheumatoid arthritis, later. PMID:24825961

  4. Rheumatoid arthritis and genetic markers in Syrian and French populations: different effect of the shared epitope

    PubMed Central

    Kazkaz, Leyla; Marotte, Hubert; Hamwi, Mayssa; Cazalis, Marie Angélique; Roy, Pascal; Mougin, Bruno; Miossec, Pierre

    2007-01-01

    Objective To investigate whether ethnic differences exist in the effect of the shared epitope and selected cytokine gene polymorphisms on the susceptibility and severity of rheumatoid arthritis in Syria (Damascus) and France (Rhône?Alpes area). Methods 156 patients with rheumatoid arthritis and 120 healthy controls from Syria were compared with 512 patients with rheumatoid arthritis and 471 healthy controls from France. Shared epitope status, cytokine gene polymorphisms interleukin (IL)?1B +3954, IL?1RN +2018 and tumour necrosis factor ? promoter (?238 and ?308) were analysed by enzyme?linked oligosorbent assay. Joint destruction was defined by a right wrist Larsen score ?2. Odds ratios (ORs) were calculated. Results In both countries, a dose effect was observed between the shared epitope copy number and rheumatoid arthritis (Syria: OR 1 v 0 copies?=?1.6, p?=?NS; OR 2 v 0?=?15.3, p<0.01; and France: OR 1 v 0?=?2.3, p<0.001; OR 2 v 0?=?7.2, p<0.001). A dose effect was also observed between the shared epitope copy number and joint destruction in Syria (OR 1 v 0?=?2.2, p?=?NS; OR 2 v 0?=?9.9, p<0.01) and France (OR 1 v 0?=?1.8, p<0.01; OR 2 v 0?=?4.8, p?=?0.001). The dose effect of the shared epitope was greater in Syria than in France. Only the ?238 tumour necrosis factor ? polymorphism was associated with joint destruction in the Syrian population (p<0.05). However, after adjustment for age, sex, disease duration and rheumatoid factor for severity, this association disappeared. Conclusion The frequency of the shared epitope was increased in the French population with rheumatoid arthritis and in controls, but the association between the shared epitope and joint destruction was more pronounced in the Syrian population, with an OR of almost 10 for the homozygotes. PMID:17068065

  5. IgG glycosylation in association with tropical infections and rheumatoid arthritis in the tropics.

    PubMed

    Adebajo, A O; Hazelman, B L

    1995-01-01

    Studies conducted in Europe suggest an association between IgG glycosylation abnormalities and rheumatoid arthritis (RA). Glycosylation abnormalities have been shown in other inflammatory diseases such as tuberculosis, systemic lupus erythematosus (SLE) and Crohn's disease. These observations led us to study glycosylation abnormalities among patients with RA and healthy controls in the tropics (sub-Saharan Africa). Using a lectin binding assay, we found that glycosylation differences were present in both groups when compared with British rheumatoid and healthy controls. This suggests that IgG glycosylation abnormalities may occur in association with chronic infections in the tropics. PMID:8835247

  6. [The indices of thrombocyte coagulating and fibrinolytic activity in rheumatoid arthritis patients].

    PubMed

    Amosova, E N; Poroshenko, M A

    1992-03-01

    Blood coagulation values (thrombocyte count, adhesive-aggregation thrombocytic activity, coagulographic data) were analysed in 90 patients with rheumatoid arthritis (RA). Increase of plasma coagulation activity was observed in all coagulation activity grades. The anticoagulation activity was most pronounced in grade III RA activity. Thrombocytes of RA patients possessed procoagulant properties and lost significantly their fibrinolytic activity most expressed in grade II RA. This increased the thrombophilic tendency of the plasma potential creating favourable conditions for intravascular coagulation and microthrombus formation, resulting in deterioration of the rheological properties of the blood and the course of the rheumatoid synovitis. PMID:1413678

  7. [The immunologic predictors of effect of anti-B-cell therapy under rheumatoid arthritis].

    PubMed

    Avdeeva, A S; Aleksandrova, E N; Novikov, A A; Cherkasova, M V; Nasonov, E L

    2014-03-01

    The article deals with results of study targeted to reveal laboratory biomarkers which can be useful in prognosis of effectiveness of rituximab therapy under rheumatoid arthritis. The sampling consisted of 34 patients with rheumatoid arthritis (31 women, average age 49 years, 42-64 years, mean duration of disease 66, 36-132 months). All patients were examined and received two infusions of rituximab intravenously with interval in 2 weeks against the background of standard therapy. The serum concentration of C-reactive protein, IgM rheumatoid factor IgG, IgM, IgA were measured using immune nephelometric method. The level of cyclic citrullinated peptide antibodies, modified citrullinated vimentin antibodies and IgA rheumatoid factor was measured using method of immune enzyme analysis. The panel of 27 cytokines was measured using multiplex technology xMAP. Before rituximab therapy indices DAS28 (6,12; 5. 52-6, 81), SDA1 (34.3; 23, 8-45, 9) and CDAI (31.3; 21, 8-38.5) corresponded to high activity of rheumatoid arthritis. Up to 24th week of therapy good response on criteria EULAR was registered in 15 patients, moderate response in 18 patients and was absent in 1 patient. The remission on DAS achieved more rarely in patients with initially negative/ low positive values of IgM rheumatoid factor, basal level of IgM less than 2.4 g/l and duration of disease more than 40 months. In the group of patients who attained remission on CDAI up to 24th week of therapy higher basal level of IL-IRA, IL-2, IL-8, IL-15, Eotaxin, GM-CSF, IFN-gamma, MIP-1alpha and TNF-alpha was registered In patients who attained remission on DAS 28 higher level of IL-1beta. IL-2, IL-6, G-CSF, IFN-gamma, MIP-1alpha and TNF-alpha was registered in comparison with patients with disease in active mode. The detection of basal level of IgM rheumatoid factor, IgM and also certain cytokines (IL-1beta, IL-IRA, IL-2, IL-8, IL-15, GM-CSF, IFN-gamma, MIP-1alpha, Eotaxin, TNF-alpha) can be useful in prognosis of effectiveness of rituximab therapy under rheumatoid arthritis. PMID:25080789

  8. Alterations in appendicular skeletal mass in patients with rheumatoid, psoriatic, and osteoarthropathy.

    PubMed Central

    Cooper, C; Poll, V; McLaren, M; Daunt, S O; Cawley, M I

    1988-01-01

    Appendicular bone mass was measured in a series of 50 patients with non-steroid treated rheumatoid arthritis, 20 with polyarticular seronegative psoriatic arthritis, and 30 with osteoarthrosis, and compared with that of 40 controls of similar age and sex. Distal forearm bone mineral content was reduced in patients with rheumatoid and psoriatic arthritis and increased in those with osteoarthrosis. The increase in bone mass in patients with osteoarthrosis was confined to those with isolated large joint disease and was not found in those with primary generalised osteoarthrosis. PMID:3382268

  9. NGF, a useful tool in the treatment of chronic vasculitic ulcers in rheumatoid arthritis.

    PubMed

    Tuveri, M; Generini, S; Matucci-Cerinic, M; Aloe, L

    2000-11-18

    Vasculitic necrosis and ulceration of the skin are frequent complications of connective tissue diseases and are very difficult to heal. We treated chronic vasculitic leg ulcers in rheumatoid arthritis and systemic sclerosis by topical application of nerve growth factor (NGF). In all patients with rheumatoid arthritis, NGF led to rapid healing, whereas less striking results were obtained in patients with systemic sclerosis. The efficacy of NGF could be due to its promoting activity on keratinocytes proliferation and vascular neoangiogenesis. We suggest that topical application of NGF could represent a powerful pharmacological tool for the treatment of vasculitic ulcers. PMID:11095266

  10. Periodontal disease, Porphyromonas gingivalis, and rheumatoid arthritis: what triggers autoimmunity and clinical disease?

    PubMed Central

    2013-01-01

    Rheumatoid arthritis, currently regarded as a complex multifactorial disease, was initially characterized as such at the turn of the 19th century. Ever since, multiple lines of investigation have attempted to elucidate the etiological factor(s) involved in disease incidence. Genes – including those risk alleles within HLA-DR4 – have been implicated but are insufficient to explain the vast majority of cases. Several environmental factors, therefore, are being studied. Among them, the role of periodontal disease and Porphyromonas gingivalis in the pathogenesis of rheumatoid arthritis has attracted both clinical and bench interest given supportive epidemiologic and mechanistic data. PMID:24229458

  11. Epigenetic contributions in the development of rheumatoid arthritis

    PubMed Central

    2012-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease, characterized by chronic inflammation of the joints with severe pain and swelling, joint damage and disability, which leads to joint destruction and loss of function. Despite extensive research efforts, the underlying cause for RA is still unknown and current therapies are more or less effective in controlling symptoms but still fail to cure the disease. In recent years, epigenetic modifications were found to strongly contribute to the development of RA by affecting diverse aspects of the disease and modifying gene expression levels and behavior of several cell types, first and foremost joint resident synovial fibroblasts (SF). RASF are the most common cell type at the site of invasion. Owing to their aggressive, intrinsically activated phenotype, RASF are active contributors in joint damage. RASF are characterized by their ability to secrete cytokines, chemokines and joint-damaging enzymes. Furthermore, these cells are resistant to apoptosis, leading to hyperplasia of the synovium. In addition, RASF have invasive and migratory properties that could lead to spreading of the disease to unaffected joints. Epigenetic modifications, including DNA methylation and post-translational histone modifications, such as histone (de)acetylation, histone methylation and histone sumoylation were identified as regulatory mechanisms in controlling aggressive cell activation in vitro and in disease outcome in animal models in vivo. In the last 5 years, the field of epigenetics in RA has impressively increased. In this review we consider the role of diverse epigenetic modifications in the development of RA, with a special focus on epigenetic modifications in RASF. PMID:23164162

  12. Periodontitis and Porphyromonas gingivalis in Patients with Rheumatoid Arthritis

    PubMed Central

    Mikuls, Ted R.; Payne, Jeffrey B.; Yu, Fang; Thiele, Geoffrey M.; Reynolds, Richard J.; Cannon, Grant W.; Markt, Jeffrey; McGowan, David; Kerr, Gail S.; Redman, Robert S.; Reimold, Andreas; Griffiths, Garth; Beatty, Mark; Gonzalez, Shawneen; Bergman, Debra A.; Hamilton, Bartlett C.; Erickson, Alan R.; Sokolove, Jeremy; Robinson, William; Walker, Clay; Chandad, Fatiha; O’Dell, James R.

    2014-01-01

    Purpose To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) with rheumatoid arthritis (RA) and to examine associations of PD and Porphyomonas gingivalis (Pg) with disease features. Methods RA cases (N=287) and controls (N=330) underwent a standardized periodontal examination. HLA-DRB1 status was imputed using SNPs from the extended MHC. Circulating anti-Pg antibody was measured using ELISA and subgingival plaque was assessed for the presence of Pg using PCR. Associations of PD with RA were examined using multivariable regression. Results PD was more common in RA (35%, p = 0.022) and aCCP positive RA (n=240; 37%; p = 0.006) vs. controls (26%). There were no RA-control differences in anti-Pg or the frequency of Pg positivity by PCR. Anti-Pg antibody showed weak but statistically significant associations with both anti-CCP (r=0.14, p=0.022) and RF (r=0.19, p=0.001). PD was associated with increased swollen joint counts (p=0.004), DAS-28-CRP (p=0.045), total Sharp scores (p=0.015), aCCP (p=0.011), and RF (p<0.001). Select anti-citrullinated peptide antibody (ACPA; including antibody to citrullinated filaggrin) were higher in patients with subgingival Pg and higher anti-Pg antibody levels irrespective of smoking. Associations of PD with established seropositive RA were independent of all covariates examined including evidence of Pg infection. Conclusions Both PD and Pg appear to shape RA-related autoreactivity in RA. In addition, PD demonstrates an independent relationship with established seropositive RA. PMID:24782175

  13. Purpose in life in patients with rheumatoid arthritis

    PubMed Central

    Verduin, Pieter J. M.; de Bock, Geertruida H.; Peeters, Andreas J.; Verhoef, John; Otten, Wilma

    2008-01-01

    To evaluate the role of purpose in life among people with rheumatoid arthritis (RA), a questionnaire comprising the Purpose in Life test (PIL) and the purpose in life dimension of the Psychological Well-Being test (PWB-pil) was sent to a random sample of 300 patients with RA. Additional questions comprised sociodemographic and disease characteristics, physical, mental and social functioning, coping (Coping with rheumatic stressors questionnaire), and quality of life (RAND-36). Associations between sociodemographic and disease characteristics, physical, mental and social functioning, and coping on the one side and the two measures of purpose in life on the other side and associations between the two purpose of life measures and physical and mental dimensions of quality of life were assessed by means of univariate and multivariate regression analyses. The response rate was 156 of 300 (52%). The median PIL and PWB-pil scores were 103 (range 63–131) and 82 (41–110), respectively. A lower age, a better mental health status, and an optimistic coping style were significantly associated with both higher PIL and PWB-pil scores, whereas more participation in leisure and/or social activities was associated with a higher PIL score. It was found that the PIL and PWB-pil contributed independently and significantly to the mental component summary scale of the RAND-36. In RA patients, lower age, a better mental health status, an optimistic coping style, and participation in leisure and/or social activities were significantly associated with more sense of purpose in life. Purpose in life pays a significant and independent contribution to the mental component of quality of life. These findings highlight the significance of the concept of purpose in life in patients with RA. PMID:18214572

  14. Receipt of Glucocorticoid Monotherapy Among Medicare Beneficiaries With Rheumatoid Arthritis

    PubMed Central

    YAZDANY, JINOOS; TONNER, CHRIS; SCHMAJUK, GABRIELA; LIN, GRACE A.; TRIVEDI, AMAL N.

    2015-01-01

    Objective Using disease-modifying antirheumatic drugs (DMARDs) improves outcomes in rheumatoid arthritis (RA) and is a nationally endorsed quality measure. We investigated the prevalence and predictors of receiving glucocorticoids alone for the treatment of RA in a nationwide sample of Medicare beneficiaries. Methods Among individuals ages ?65 years with RA enrolled in the Part D prescription drug benefit in 2009, we compared those with ?1 DMARD claim to those receiving glucocorticoid monotherapy, defined as no DMARD claim and an annual glucocorticoid supply of ?180 days or an annual dose of ?900 mg of prednisone or equivalent. We fit multivariable models to determine the sociodemographic and clinical factors associated with glucocorticoid monotherapy. Results Of 8,125 beneficiaries treated for RA, 10.2% (n = 825) received glucocorticoids alone. Beneficiaries with low incomes were more likely to receive glucocorticoids alone (12.3%; 95% confidence interval [95% CI] 10.9–13.8% versus 9.4%; 95% CI 8.6–10.1%), as were those living in certain US regions. More physician office visits and hospitalizations were associated with glucocorticoid monotherapy. Individuals who had no contact with a rheumatologist were significantly more likely to receive glucocorticoids alone (17.5%; 95% CI 16.0–19.0% versus 8.5%; 95% CI 7.4–9.5% for those with no rheumatology visits versus 1–4 visits). Conclusion Approximately 1 in 10 Medicare beneficiaries treated for RA received glucocorticoids without DMARDs in 2009. Compared to DMARD users, glucocorticoid users were older, had lower incomes, were more likely to live in certain US regions, and were less likely to have seen a rheumatologist, suggesting persistent gaps in quality of care despite expanded drug coverage under Part D. PMID:25244314

  15. A Comprehensive Molecular Interaction Map for Rheumatoid Arthritis

    PubMed Central

    Nardini, Christine

    2010-01-01

    Background Computational biology contributes to a variety of areas related to life sciences and, due to the growing impact of translational medicine - the scientific approach to medicine in tight relation with basic science -, it is becoming an important player in clinical-related areas. In this study, we use computation methods in order to improve our understanding of the complex interactions that occur between molecules related to Rheumatoid Arthritis (RA). Methodology Due to the complexity of the disease and the numerous molecular players involved, we devised a method to construct a systemic network of interactions of the processes ongoing in patients affected by RA. The network is based on high-throughput data, refined semi-automatically with carefully curated literature-based information. This global network has then been topologically analysed, as a whole and tissue-specifically, in order to translate the experimental molecular connections into topological motifs meaningful in the identification of tissue-specific markers and targets in the diagnosis, and possibly in the therapy, of RA. Significance We find that some nodes in the network that prove to be topologically important, in particular AKT2, IL6, MAPK1 and TP53, are also known to be associated with drugs used for the treatment of RA. Importantly, based on topological consideration, we are also able to suggest CRKL as a novel potentially relevant molecule for the diagnosis or treatment of RA. This type of finding proves the potential of in silico analyses able to produce highly refined hypotheses, based on vast experimental data, to be tested further and more efficiently. As research on RA is ongoing, the present map is in fieri, despite being -at the moment- a reflection of the state of the art. For this reason we make the network freely available in the standardised and easily exportable .xml CellDesigner format at ‘www.picb.ac.cn/ClinicalGenomicNTW/temp.html’ and ‘www.celldesigner.org’. PMID:20419126

  16. Association of antithyroid peroxidase antibody with fibromyalgia in rheumatoid arthritis.

    PubMed

    Ahmad, Jowairiyya; Blumen, Helena; Tagoe, Clement E

    2015-08-01

    To investigate how autoimmune thyroiditis (ATD) affects the clinical presentation of established rheumatoid arthritis (RA) with particular reference to fibromyalgia and chronic widespread pain (CWP). A cohort of 204 patients with RA for whom the presence or absence of autoimmune thyroid antibodies was documented was examined for the relationships between thyroid autoantibodies and fibromyalgia or CWP. We identified 29 % who tested positive for antithyroid peroxidase antibodies (TPOAb). The anti-thyroglobulin antibody (TgAb) was found in 24 %. Among the thyroid autoantibody-positive patients, 40 % had a diagnosis of fibromyalgia or CWP versus 17 % for antibody negative patients. Logistic regression analyses (adjusted by age, sex, diabetes and BMI) indicated that TPOAb-positive patients were more likely to have fibromyalgia or CWP, with an odds ratio (OR) of 4.641, 95 % confidence interval (CI) (2.110-10.207) P < .001. Adjusting for spinal degenerative disc disease did not change the association with fibromyalgia, OR 4.458, 95 % CI (1.950-10.191), P < .001. The OR between TgAb and fibromyalgia was not significant (P > .05). Additional logistic regression analyses (adjusted by age, sex and BMI) indicated a significant relationship between TPOAb and fibromyalgia or CWP in patients without diabetes and those without hypothyroidism (OR of 4.873, 95 % CI (1.877-12.653), P = .001 and OR of 4.615 95 % CI (1.810-11.770), P = .001, respectively). There may be a positive association between the ATD antibody TPOAb, and fibromyalgia syndrome and CWP in patients with established RA. PMID:25976307

  17. Stretch reflexes and joint dynamics in rheumatoid arthritis.

    PubMed

    Rajagopalan, Aparna; Burne, John A

    2010-02-01

    In clinically diagnosed rheumatoid arthritis (RA), studies were conducted to investigate the reflex and passive tissue contribution to measured increases in joint stiffness in the resting upper limb and during constant contractions of an attached muscle. The tonic stretch reflex was induced by a servo-controlled sinusoidal stretch perturbation of the metacarpophalangeal joint of RA patients, and age- and sex-matched controls. The resulting reflexes and mechanical changes in the RA affected joint were explored. Surface electromyographic (EMG) measurements were obtained from first dorsal interosseus muscle. Reflex gain (EMG/joint angle amplitude ratio), phase difference (reflex delay after stretch), coherence square (proportion of EMG variance accounted for by joint angle changes), joint mechanical gain (torque-joint angle amplitude ratio) and mechanical phase difference (torque response delay after stretch) were determined. RA patients showed decreased reflex gain that was partly due to coexistent severe muscle weakness, as determined from maximum voluntary contraction and grip pressure estimates. The decreased reflex gain was most evident at high stretch frequency suggesting a disproportionate loss of the large diameter afferent response and also increased reflex delay in the patients. These changes ensemble suggest significant loss of neural drive to the motor unit population. Patients also showed increased joint stiffness (measured as torque gain) in the contracting muscle, but there was no evidence of reflex activity or increased stiffness at rest. This suggests that the increased joint stiffness in RA was due to changes in the mechanical properties of the active muscle-joint system rather than changes in reflex properties. PMID:19771418

  18. Activation of the STAT1 pathway in rheumatoid arthritis

    PubMed Central

    Kasperkovitz, P; Verbeet, N; Smeets, T; van Rietschoten, J G I; Kraan, M; van der Pouw, Kraa... T C T M; Tak, P; Verweij, C

    2004-01-01

    Background: Expression of signal transducer and activator of transcription 1 (STAT1), the mediator of interferon (IFN) signalling, is raised in synovial tissue (ST) from patients with rheumatoid arthritis (RA). Objectives: To determine the extent to which this pathway is activated by phosphorylation in RA synovium. Additionally, to investigate the cellular basis of STAT1 activation in RA ST. Methods: ST specimens from 12 patients with RA and 14 disease controls (patients with osteoarthritis and reactive arthritis) were analysed by immunohistochemistry, using antibodies to STAT1, tyrosine phosphorylated STAT1, and serine phosphorylated STAT1. Lysates of cultured fibroblast-like synoviocytes stimulated with IFNß were analysed by western blotting. Phenotypic characterisation of cells expressing STAT1 in RA ST was performed by double immunolabelling for STAT1 and CD3, CD22, CD55, or CD68. Results: Raised levels of total STAT1 protein and both its activated tyrosine and serine phosphorylated forms were seen in RA synovium as compared with controls. STAT1 was predominantly abundant in T and B lymphocytes in focal inflammatory infiltrates and in fibroblast-like synoviocytes in the intimal lining layer. Raised levels of STAT1 are sustained in cultured RA compared with OA fibroblast-like synoviocytes, and STAT1 serine and tyrosine phosphorylation is rapidly induced upon stimulation with IFNß. Conclusion: These results demonstrate activation of the STAT1 pathway in RA synovium by raised STAT1 protein expression and concomitantly increased tyrosine (701) and serine (727) phosphorylation. High expression of STAT1 is intrinsic to RA fibroblast-like synoviocytes in the intimal lining layer, whereas activation of the pathway by phosphorylation is an active process. PMID:14962955

  19. PADI2 Is Significantly Associated with Rheumatoid Arthritis

    PubMed Central

    Chang, Xiaotian; Xia, Yifang; Pan, Jihong; Meng, Qingsong; Zhao, Yan; Yan, Xinfeng

    2013-01-01

    Citrullination, a posttranslational modification of peptidyl arginine to citrulline, plays an essential role in rheumatoid arthritis (RA). Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding PADI4 is a factor in susceptibility to RA. Some studies have detected PADI2 expression in RA synovial tissues, suggesting that PADI2 also plays an important role in the disease. This study evaluated the possible association between the PADI2-encoding gene and RA. Seventeen tag SNPs across the PAD locus were genotyped using a custom-designed Illumina 96-SNP VeraCode microarray. Peripheral blood samples were collected from patients with RA (n?=?267), ankylosing spondylitis (AS, n?=?51) and healthy controls (n?=?160). The results of genotyping were verified using Sequenom MassARRAY in an independent cohort of 307 patients with RA, 324 patients with AS and 509 healthy controls. A western blot analysis was performed using synovial tissue from patients with RA (n?=?7), osteoarthritis (OA, n?=?7) and AS (n?=?5) to determine the levels of expression of PADI2. A microarray analysis revealed a significant association between three selected PADI2 SNPs (rs2235926, rs2057094, rs2076616) and the presence of RA. The increased susceptibility to RA associated with rs2235926 (OR?=?1.706733, 95% CI?=?[1.576366–1.866587], p?=?0.000839) and rs2057094 (OR?=?1.360432, 95% CI?=?[1.065483–1.869482], p?=?0.003291) was further confirmed by the Sequenom MassARRAY. No tag SNPs in the PADI2 locus showed a significant association with AS. Increased expression of PADI2 was detected in RA synovial tissues compared with samples from patients with OA and AS. PADI2 is significantly associated with RA and may be involved in the pathogenesis of the disease. PMID:24339914

  20. The lp13.3 genomic region -rs599839- is associated with endothelial dysfunction in patients with rheumatoid arthritis

    PubMed Central

    2012-01-01

    Introduction Rheumatoid arthritis (RA) is an inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular (CV) disease. Since genome-wide association studies demonstrated association between rs599839 polymorphism and coronary artery disease, in the present study we assessed the potential association of this polymorphism with endothelial dysfunction, an early step in atherogenesis. Methods A total of 128 RA patients without history of CV events were genotyped for rs599839 A/G polymorphism. The presence of endothelial dysfunction was assessed by brachial ultrasonography (brachial flow-mediated endothelium-dependent (FMD)). Results Patients carrying the allele G exhibited more severe endothelial dysfunction (FMD%: 4.61 ± 3.94%) than those carrying the wild allele A (FMD%: 6.01 ± 5.15%) (P = 0.08). Adjustment for gender, age at the time of study, follow-up time and classic CV risk factors disclosed a significant association between the rs599839 polymorphism and FMD (G vs. A: P = 0.0062). Conclusions Our results confirm an association of the rs599839 polymorphism with endothelial dysfunction in RA. PMID:22380622