Sample records for simulating early rheumatoid

  1. Radiographic changes in early rheumatoid disease

    Microsoft Academic Search

    A Brook; M Corbett

    1977-01-01

    We have studied the radiological features in 94 patients with early rheumatoid disease followed prospectively for 5 years. The changes appeared very early and occurred in up to 71-3% of patients. Erosive changes occurred in the feet much more commonly than in the hands and considerably earlier. Erosive changes were present before there was joint-space loss. Frequent x-ray examination of

  2. Prospective study of early rheumatoid arthritis. I. Prognostic value of IgA rheumatoid factor.

    PubMed Central

    Teitsson, I; Withrington, R H; Seifert, M H; Valdimarsson, H

    1984-01-01

    Thirty-three patients with early arthritis, 28 of whom developed classical/definite rheumatoid arthritis (RA), were followed up for two to four years. Rheumatoid factor (RF) levels of the IgM, IgA, and IgG isotypes were measured in serum and synovial fluid by an ELISA technique developed in our laboratory. All seven patients who presented with raised IgA RF developed erosions of their hands and wrists. This was significantly different from the remaining 26. By contrast none of the five patients who presented with isolated elevation of IgM RF developed erosive disease. The patients with raised IgA RF needed significantly more treatment with 'specific' drugs than the remaining 26. It is suggested that the detection of IgA RF in early RA indicates poor prognosis, justifying a more aggressive treatment at an early stage. PMID:6497459

  3. 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

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

    PubMed

    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

  5. Left ventricular function in treatment-naive early rheumatoid arthritis

    PubMed Central

    Løgstrup, Brian B; Deibjerg, Lone K; Hedemann-Andersen, Agnete; Ellingsen, Torkell

    2014-01-01

    Background: The role of inflammation and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the pathogenesis of cardiovascular disease in early rheumatoid arthritis (RA) remains unclear. Previous studies have suggested that both disease activity and disease duration are associated with atherosclerosis and a higher mortality rate caused primarily by coronary artery disease. Objective: We investigated how disease activity, anti-CCP status and coronary calcium score in treatment-naive early RA impacts left ventricular (LV) systolic function. Methods: Fifty-tree patients (30 women) with mean age 58.3±1.3 years and steroid- and disease-modifying antirheumatic drug (DMARD)-naive early RA were included. Disease activity was scored by the use of the Danish national DANBIO registry (number of swollen joints (NSJ (28)), number of tender joints (NTJ (28)), C-reactive protein (CRP) and Health Assessment Questionnaire (HAQ)). Pain, fatigue, patient and physician global assessment and a composite disease activity score (DAS28-CRP) were assessed by visual analog scales (VAS) 0-100. IgM rheumafactor (IgM-RF) and anti-CCP titers were evaluated by standardized techniques. Coronary calcium score was estimated by computed tomography by calculating the Agaston score. One experienced senior rheumatologist and one experienced cardiologist performed all the clinical assessments as well as all the transthoracic echocardiography (TTE) and coronary CT analysis. Results: Disease activity scores before treatment at baseline were: NSJ (28) 7.1±2.7, NTJ (28) 8.5±3.5, CRP 11.7±12.9 mmol/l, HAQ 0.71±0.6, pain VAS 51.1±23.7, fatigue VAS 49.3±24.9, physician global assessment 54.2±15.0 and DAS28-CRP 4.8±0.7. Twenty-three (43%) patients were IgM-RF positive and 33 (62%) were anti-CCP positive. We found LV systolic function by conventional ejection fraction (EF) to be 54.1±9.2% and to be non-significant correlated to disease activity (CRP: r=0.07, p=0.64; baseline NSJ: r=-0.13, p=0.33; NTJ: r=-0.08, p=0.58; HAQ: r=0.23, p=0.1; pain VAS: r=-0.05, p=0.74; fatigue VAS: r=0.03, p=0,83; physician global assessment: r=-0.09, p=0.54 and DAS28: r=-0.03, p=0.84). However, using a more sensitive measurement of the LV function by global longitudinal systolic strain (GLS), we found a significant correlation: HAQ (r=0.29; p=0.037), patient global assessment by VAS (r=0.35; p=0.011), patient fatigue assessment by VAS (r=0.3; p=0.03) and DAS28-CRP (r=0.28; p=0.043); all corrected for relevant confounders (age, gender, pulse and blood pressure). Furthermore, anti-CCP was highly significantly correlated with GLS (r=-0.44; p=0.001) in univariate analysis. In multivariate analysis, it still remained significantly correlated (p=0.018), after correction for age, gender, pulse, and blood pressure. Using strain analysis of LV function, we found a significant difference in GLS in patients with high values of anti-CCP (titers ?340) compared to patients with anti-CCP (titers <340); (-19.9±2.1% vs. -16.4±2.8%; p=0.0001). For patients with high IgM-RF, results were non-significant. Conclusions: We observed a significant correlation between increased disease activity and cardiac function in treatment-naive early RA. PMID:25006535

  6. Identification of Patients With Early Rheumatoid Arthritis: Challenges and Future Directions

    PubMed Central

    Orozco, Catalina; Olsen, Nancy J.

    2006-01-01

    Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis that affects the adult population. Early diagnosis and treatment are the cornerstones to prevent joint damage and avoid long-term costs and disability. This article reviews the limitations of the currently available tools for the evaluation of patients with early arthritis, including clinical assessment, serologic markers and imaging modalities. It also discusses gene expression analysis, a newer and potentially promising approach to the early diagnosis of RA. PMID:17162371

  7. 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

  8. Implementation of a treat-to-target strategy in very early rheumatoid arthritis: results of the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study

    Microsoft Academic Search

    M. Vermeer; H. H. Kuper; M. Hoekstra; C. J. Haagsma; M. D. Posthumus; H. L. Brus; P. L. van Riel; M. A. van der Laar

    2011-01-01

    OBJECTIVE: Clinical remission is the ultimate therapeutic goal in rheumatoid arthritis (RA). Although clinical trials have proven this to be a realistic goal, the concept of targeting at remission has not yet been implemented. The objective of this study was to develop, implement, and evaluate a treat-to-target strategy aimed at achieving remission in very early RA in daily clinical practice.

  9. Management of the early and late presentations of rheumatoid arthritis: a survey of Ontario primary care physicians.

    PubMed Central

    Glazier, R H; Dalby, D M; Badley, E M; Hawker, G A; Bell, M J; Buchbinder, R; Lineker, S C

    1996-01-01

    OBJECTIVE: To examine primary care physicians' management of rheumatoid arthritis, ascertain the determinants of management and compare management with that recommended by a current practice panel. DESIGN: Mail survey (self-administered questionnaire). SETTING: Ontario. PARTICIPANTS: A stratified computer-generated random sample of 798 members of the College of Family Physicians of Canada. OUTCOME MEASURES: Proportions of respondents who chose various items in the management of two hypothetical patients, one with early rheumatoid arthritis and one with late rheumatoid arthritis. Scores for investigations, interventions and referrals for each scenario were generated by summing the recommended items chosen by respondents and then dividing by the total number of items recommended in that category. The scores were examined for their association with physician and practice characteristics and physician attitudes. RESULTS: The response rate was 68.3% (529/775 eligible physicians). Recommended investigations were chosen by more than two thirds of the respondents for both scenarios. Referrals to physiotherapy, occupational therapy and rheumatology, all recommended by the panel, were chosen by 206 (38.9%), 72 (13.6%) and 309 (58.4%) physicians respectively for early rheumatoid arthritis. These proportions were significantly higher for late rheumatoid arthritis (p < 0.01). In multiple regression analysis, for early rheumatoid arthritis, internship or residency training in rheumatology was associated with higher investigation and intervention scores, for late rheumatoid arthritis, older physicians had higher intervention scores and female physicians had higher referral scores. CONCLUSIONS: Primary care physicians' investigation of rheumatoid arthritis was in accord with panel recommendations. However, rates of referral to rheumatologists and other health care professionals were very low, especially for the early presentation of rheumatoid arthritis. More exposure to rheumatology and to the role of physiotherapy, occupational therapy and social work during primary care training is strongly recommended. PMID:8823213

  10. Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis

    Microsoft Academic Search

    M. M. Newkirk; R. Goldbach-Mansky; B. W. Senior; J. Klippel; H. R. Schumacher Jr; H. S. El-Gabalawy

    2005-01-01

    Objective. Antibodies to Proteus mirabilis were previously detected in patients with established rheumatoid arthritis (RA). We examined the prevalence of antibodies to P. mirabilis and their associations with RA in early synovitis patients. Methods. Two hundred and forty-six patients with inflammatory arthritis for less than 1 yr were prospectively evaluated for 1 yr. Of these patients, 30% had rheumatoid factor

  11. Immune complexes in early arthritis. L Detection of immune complexes before rheumatoid arthritis is definite.

    PubMed Central

    Jones, V E; Jacoby, R K; Wallington, T; Holt, P

    1981-01-01

    Fifty-three patients with early arthritis were studied longitudinally for up to 3 years. During this time, 24 developed sufficient features for definite rheumatoid arthritis (RA) to be diagnosed. The other (arthralgia patients) differed from the RA patients as, in the majority, C-reactive protein and ESR were normal and anti-nuclear antibodies or rheumatoid factors were rarely found. Moreover, in time their signs and symptoms improved or disappeared. Circulating immune complexes were detected in both groups of patients by the platelet aggregation test whereas complexes detected by abnormal Clq-binding activity were found mainly in the RA patients. Platelet-aggregating complexes were usually present in the first samples studied and disappeared in the arthralgia patients with recovery from their symptoms. In the RA patients, Clq-binding complexes appeared simultaneously or later than platelet-aggregating complexes but both tests were positive several months before RA could be diagnosed. These results suggest that immune complexes are one of the first immunological abnormalities to appear in patients with arthritis. Although the constituent antigen and antibody of complexes detected by either test are unknown, their possible nature is discussed. PMID:6976861

  12. Effect of age at menopause on disease presentation in early rheumatoid arthritis: Results from the Canadian Early Arthritis Cohort.

    PubMed

    Wong, Lauren E; Huang, Wei-Ti; Pope, Janet E; Haraoui, Boulos; Boire, Gilles; Thorne, J Carter; Hitchon, Carol A; Tin, Diane; Keystone, Edward C; Bykerk, Vivian P

    2014-10-01

    Objective. Studies suggest that hormonal states affect disease characteristics in women with rheumatoid arthritis (RA). This study investigated how age at menopause affects disease in women presenting with early RA. Methods. This was a cross-sectional study of post-menopausal women with early RA under age 65 at time of enrollment in the Canadian Early Arthritis Cohort. RA-related disease characteristics in women who had early age at menopause (EM, age at menopause < 45) were compared to those who had usual age at menopause (UM, age at menopause ? 45). The t-test was applied to continuous variables and Chi-square test to categorical variables. Multivariate logistic regression analysis was used to adjust for age at menopause, smoking, and use of exogenous hormones. Results. 534 women were included; 93 were in the EM group. The age at RA-onset was similar between groups. The EM group had higher mean patient global and pain scores and was more likely to be RF positive and meet 1987 ACR criteria for RA. Using multivariate logistic regression, the EM group was more likely to be RF positive (OR 2.2 [95% CI 1.3-3.8], P=0.005). Symptom duration, joint counts, DAS28, HAQ and inflammatory markers did not differ between groups. Conclusion. These data suggest that early age at menopause, compared to usual age at menopause, is associated with seropositivity in women with early RA. © 2014 American College of Rheumatology. PMID:25303739

  13. The usefulness of magnetic resonance imaging of the hand and wrist in very early rheumatoid arthritis

    PubMed Central

    2011-01-01

    Introduction Magnetic resonance imaging (MRI) was used to study the hand and wrist in very early rheumatoid arthritis (RA), and the results were compared with early and established disease. Methods Fifty-seven patients fulfilling the new American College of Rheumatology criteria for RA, 26 with very early RA (VERA), 18 with early RA (ERA), and 13 with established RA (ESTRA), (disease duration < 3 months, < 12 months, and > 12 months, respectively) were enrolled in the study. MRI of the dominant hand and wrist was performed by using fat-suppressed T2-weighted and plain and contrast-enhanced T1-weighted sequences. Evaluation of bone marrow edema, synovitis, and bone erosions was performed with the OMERACT RA MRI scoring system. Results Edema, erosions, and synovitis were present in VERA, and the prevalence was 100%, 96.15%, and 92.3%, respectively. Significant differences in edema and erosions were found between VERA and ESTRA (P < 0.05). No significant difference was found in synovitis. Conclusions Edema, erosions, and synovitis are findings of very early RA. MRI, by detecting these lesions, may play an important role in the management of these patients. PMID:21658223

  14. Matrix-mini-tablets of lornoxicam for targeting early morning peak symptoms of rheumatoid arthritis

    PubMed Central

    Mohd, Abdul Hadi; Raghavendra Rao, Nidagurthi Guggilla; Avanapu, Srinivasa Rao

    2014-01-01

    Objective(s): The aim of present research was to develop matrix-mini-tablets of lornoxicam filled in capsule for targeting early morning peak symptoms of rheumatoid arthritis. Materials and Methods: Matrix-mini-tablets of lornoxicam were prepared by direct compression method using microsomal enzyme dependent and pH-sensitive polymers which were further filled into an empty HPMC capsule. To assess the compatibility, FT-IR and DSC studies for pure drug, polymers and their physical mixture were performed. The formulated batches were subjected to physicochemical studies, estimation of drug content, in vitro drug release, drug release kinetics, and stability studies. Results: When FTIR and DSC studies were performed it was found that there was no interaction between lornoxicam and polymers which used. All the physicochemical properties of prepared matrix-mini-tablets were found to be in normal limits. The percentage of drug content was found to be 99.60±0.07%. Our optimized matrix mini-tablets-filled-capsule formulation F30 released lornoxicam after a lag time of 5.02±0.92 hr, 95.48±0.65 % at the end of 8 hr and 99.90±0.83 % at the end of 12 hr. Stability was also found for this formulation as per the guidelines of International Conference on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. Conclusion: A novel colon targeted delivery system of lornoxicam was successfully developed by filling matrix-mini-tablets into an empty HPMC capsule shell for targeting early morning peak symptoms of rheumatoid arthritis. PMID:24967065

  15. 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

  16. A randomised controlled trial of occupational therapy for people with early rheumatoid arthritis

    PubMed Central

    Hammond, A; Young, A; Kidao, R

    2004-01-01

    Background: Occupational therapy (OT) aims at improving performance of daily living tasks, facilitating successful adjustments in lifestyle, and preventing losses of function. Objective: To evaluate the effects of a pragmatic, comprehensive OT programme on self management and health status of people with early rheumatoid arthritis (RA) (<2.5 years). Methods: A randomised, controlled "assessor blinded" trial was conducted with assessments made at entry, 6, 12, and 24 months. Main outcomes were AIMS2: physical function (PF), pain visual analogue scale (VAS), and Arthritis Self-Efficacy Scale (ASES). Results: Groups had similar disease duration (9 months OT (n = 162) v 10 months control (n = 164)). The OT group received 7.57 (SD 3.04) hours of therapy. Self management significantly increased in the OT group. Otherwise, there were no significant differences in any outcome measures, or between groups, by ACR functional class: AIMS2: PF (F = 0.04; p = 0.96); pain VAS (F = 0.29; p = 0.74); total ASES score (F = 0.93; p = 0.39). Conclusions: OT improved self management but not health status in early RA. Functional ability remains reasonably good for many in the first five years, so preventive benefits of self management may not yet be apparent and longer follow up is needed. Although many considered the education and therapy useful, insufficient numbers in the OT group used self management sufficiently to make a difference. Behavioural approaches can improve adherence and, potentially, the long term benefits. Future research should evaluate OT as a complex intervention and develop programmes from a theoretical and evidence base. PMID:14672887

  17. HLA-DRB1*04 subtypes are associated with increased inflammatory activity in early rheumatoid arthritis

    Microsoft Academic Search

    C. SEIDL; U. KOCH; T. BUHLEIER; R. FRANK; B. MOLLER; E. MARKERT; G. KOLLER-WAGNER; E. SEIFRIED; J. P. KALTWASSER

    1997-01-01

    SUMMARY The sequence polymorphism of HLA-DRB1 molecules in 84 rheumatoid arthritis (RA) patients with early RA has been ana- lysed to evaluate whether particular HLA-DR alleles influence disease progression in the early stage of the disease. Clinical data were analysed by grouping the patients according to disease-associated haplotype combinations (DRB1*04,04\\/ DRB1*04,01\\/DRB1*04,X\\/DRB1*01,X) in comparison to patients who did not carry these

  18. Airways abnormalities and rheumatoid arthritis-related autoantibodies in subjects without arthritis: early injury or initiating site of autoimmunity?

    PubMed Central

    Demoruelle, M. Kristen; Weisman, Michael H.; Simonian, Philip L.; Lynch, David A.; Sachs, Peter B.; Pedraza, Isabel F.; Harrington, Annie R.; Kolfenbach, Jason R.; Striebich, Christopher C.; Pham, Quyen N.; Strickland, Colin D.; Petersen, Brian D.; Parish, Mark C.; Derber, Lezlie A.; Norris, Jill M.; Holers, V. Michael; Deane, Kevin D.

    2011-01-01

    Objective To evaluate the presence of pulmonary abnormalities in subjects with rheumatoid arthritis (RA)-related autoantibody (Ab) positivity without inflammatory arthritis (IA). Methods 42 subjects without IA but with elevations of anti-cyclic citrullinated peptide antibodies and/or 2 or more rheumatoid factor isotypes (a profile that is 96% specific for RA), 15 Ab(?) controls and 12 patients with early established seropositive RA (<1 year duration) underwent spirometry and high-resolution computed tomographic (HRCT) lung imaging. Results The median age of Ab(+) subjects was 54 years-old, 52% were female and 38% were smokers (not significantly different than Ab(?) controls). No Ab(+) subject had IA on joint examination. On HRCT, 76% of Ab(+) subjects had airways abnormalities including bronchial wall thickening, bronchiectasis, centrilobular opacities and air trapping, compared to 33% of Ab(?) controls (p=0.005). The Ab(+) subjects had similar prevalence and type of lung abnormalities compared to patients with early RA. Two Ab(+) subjects with airways disease developed IA classifiable as articular RA ~13 months after lung evaluation. Conclusion Airways abnormalities that are consistent with inflammation are common in Ab(+) subjects without IA, and similar to airways abnormalities seen in early RA. These findings suggest that the lung may be an early site of autoimmune-related injury, and potentially a site of generation of RA-related autoimmunity. Further studies are needed to define the mechanistic role of lung inflammation in the development of RA. PMID:22183986

  19. Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels

    PubMed Central

    2014-01-01

    Introduction We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity. Methods Serum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman’s correlation analysis were utilized to determine relationships between variables. Results In both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort. Conclusion Using both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose disease is shaped by or responsive to RF production. PMID:24766912

  20. 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

  1. Expression of the Inherently Autoreactive Idiotope 9G4 on Autoantibodies to Citrullinated Peptides and on Rheumatoid Factors in Patients with Early and Established Rheumatoid Arthritis

    PubMed Central

    Cambridge, Geraldine; Moura, Rita A.; Santos, Tania; Khawaja, Akif A.; Polido-Pereira, Joaquim; Canhão, Helena; Leandro, Maria J.; Fonseca, João E.

    2014-01-01

    Background The pre-symptomatic stage of Rheumatoid arthritis (RA) is associated with pro-inflammatory cytokines and autoantibodies. High levels and epitope spread by Rheumatoid factors (RhF) and autoantibodies to citrullinated proteins signify progression towards disease expression. In established RA, the persistence of high autoantibody levels reflects production by both long-lived plasma cells and short-lived plasmablasts. Neither the relative contributions to pathogenesis by autoantibodies from either source, nor the factors responsible for deciding the fate of autoantigen specific ‘parent’ B-cells, is understood. Phenotypic markers identifying subsets of autoreactive B-cells are therefore of interest in understanding the origin and perpetuation of the autoimmune response in RA. One such phenotypic marker is the rat monoclonal antibody, 9G4, which recognises an idiotope on immunoglobuins derived from the inherently autoreactive VH-gene, VH4-34. We therefore investigated whether the 9G4 idiotope was expressed on autoantibodies in patients with RA. Methodology/Principal Findings Sera from 19 patients with established RA and those with <1year history of untreated polyarthritis either resolving into RA (n?=?42) or non-RA diagnosis (n?=?31) were included. Autoantibodies to cyclic citrullinated peptides (CCP), RhF and co-expression of the 9G4 idiotope were measured by ELISA. 9G4 recognised a population of anti-CCP antibodies in the majority of sera from patients with established disease and also in samples from patients with early disaese. 9G4+RhF levels were generally lower and not associated with positivity for, or levels of 9G4+CCP. Conclusions/Significance The persistence of 9G4+ immunoglobulins, of any isotype, in serum is rare. We describe here the novel finding of 9G4 expression on anti-CCP antibodies in patients from the earliest symptoms of RA through to established disease. Our results suggest that 9G4 expression on anti-CCP autoantibodies was not due to polyclonal expansion of VH4-34-encoded immunoglobulins. These studies may therefore provide a new focus for investigation into the evolution of the autoimmune response in RA patients. PMID:25222933

  2. 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

  3. Rheumatoid Arthritis Educational Video Series

    MedlinePLUS Videos and Cool Tools

    2015 Rheumatology Conference early bird registration ends March 23! Register Today! Appointments • Support Our Research Arthritis Information Disease Information Rheumatoid Arthritis Psoriatic Arthritis Ankylosing Spondylitis ...

  4. The relationship between psychological distress and traditional clinical variables: a 2 year prospective study of 216 patients with early rheumatoid arthritis

    Microsoft Academic Search

    L. M. SMEDSTAD; P. VAGLUM; T. MOUM; T. K. KVIEN

    1997-01-01

    SUMMARY In this longitudinal study (12 and 24 months follow-up) of 216 patients with early rheumatoid arthritis (RA) (E4 yr dura- tion), we assessed the strength and stability of the relationship between psychological distress and traditional clinical vari- ables, examined the ability of these clinical variables to predict changes in mental distress, and explored the directionality between mental distress and

  5. Dilemmas of participation in everyday life in early rheumatoid arthritis: a qualitative interview study (The Swedish TIRA Project).

    PubMed

    Sverker, Annette; Ostlund, Gunnel; Thyberg, Mikael; Thyberg, Ingrid; Valtersson, Eva; Björk, Mathilda

    2014-09-22

    Abstract Purpose: To explore the experiences of today's patients with early rheumatoid arthritis (RA) with respect to dilemmas of everyday life, especially regarding patterns of participation restrictions in valued life activities. Methods: A total of 48 patients, aged 20-63, three years post-RA diagnosis were interviewed using the Critical Incident Technique. Transcribed interviews were condensed into meaningful units describing actions/situations. These descriptions were linked to ICF participation codes according to the International Classification of Functioning, Disability and Health (ICF) linking rules. Results: Dilemmas in everyday life were experienced in domestic life, interpersonal interactions and relationships, community, social and civic life. Most dilemmas were experienced in domestic life, including participation restrictions in, e.g. gardening, repairing houses, shovelling snow, watering pot plants, sewing or walking the dog. Also many dilemmas were experienced related to recreation and leisure within the domain community, social and civic life. The different dilemmas were often related to each other. For instance, dilemmas related to community life were combined with dilemmas within mobility, such as lifting and carrying objects. Conclusions: Participation restrictions in today's RA patients are complex. Our results underline that the health care needs to be aware of the patients' own preferences and goals to support the early multi-professional interventions in clinical practice. Implications of Rehabilitation Today's rheumatoid arthritis (RA) patients experience participation restrictions in activities not included in International Classification of Functioning, Disability and Health (ICF) core set for RA or in traditionally questionnaires with predefined activities. The health care need to be aware of the patients' own preferences and goals to meet the individual needs and optimize the rehabilitation in early RA in clinical practice. PMID:25243767

  6. Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors

    PubMed Central

    Westhovens, R; Robles, M; Ximenes, A C; Nayiager, S; Wollenhaupt, J; Durez, P; Gomez-Reino, J; Grassi, W; Haraoui, B; Shergy, W; Park, S-H; Genant, H; Peterfy, C; Becker, J-C; Covucci, A; Helfrick, R; Bathon, J

    2009-01-01

    Objectives: To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. Methods: In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (?10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. Results: At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p<0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p?=?0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. Conclusions: In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile. PMID:19124524

  7. 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

  8. Periarticular Osteoporosis Is a Prominent Feature in Early Rheumatoid Arthritis: Estimation Using Shaft to Periarticular Bone Mineral Density Ratio

    PubMed Central

    Moon, Su-Jin; Ahn, Inhye E.; Kwok, Seung-Ki; Park, Kyung-Su; Min, Jun-Ki; Park, Sung-Hwan; Kim, Ho-Youn

    2013-01-01

    We aimed to quantify periarticular osteoporosis and investigate its significance in 45 patients with rheumatoid arthritis (RA) and 106 controls. Dual-energy X-ray absorptiometry (DXA) was used to determine the ratio of shaft to periarticular bone mineral density (BMD) as an index of periarticular demineralization. Periarticular osteoporosis was measured by conventional radiography. The BMDs of shaft and periarticular regions in eight designated areas on proximal phalanges were quantified. Clinical variables were examined to identify risk factors for periarticular osteoporosis. The assessment of periarticular osteoporosis on X-ray images reached a moderate degree of interobserver agreement among four physicians (? = 0.47). For BMD quantification, we designed three types of mathematical formulae: the ratio of shaft to periarticular BMD, the mean of the ratios, and the ratio of the sums. These ratios were significantly higher in the patients with early RA (disease duration ? 3 yr) than in controls (P < 0.01). The findings were not as distinctive in patients with established RA. Body mass index, cumulative dose of corticosteroid, and C-terminal telopeptide were correlated with BMD ratios. Conclusively, DXA-assisted localized quantification and BMD ratio calculations are feasible for assessing periarticular demineralization. Periarticular osteoporosis is a relatively distinctive feature of early RA. PMID:23399828

  9. Early lessons from the recent-onset rheumatoid arthritis cohort ESPOIR.

    PubMed

    Combe, Bernard; Rincheval, Nathalie

    2015-01-01

    ESPOIR is a French multicenter cohort of patients with undifferentiated arthritis enrolled within six months of symptom onset, naive to disease-modifying antirheumatic drugs and corticosteroid therapy, and either having rheumatoid arthritis (RA) or being at risk for progression to RA. The cohort is sponsored by the French Society for Rheumatology (Société française de rhumatologie [SFR]). Between December 2002 and March 2005, 813 patients were enrolled at 14 regional university hospitals, with the participation of a network of community-based rheumatologists. The objective was to establish a database on recent-onset inflammatory joint disease and, more specifically, on RA to serve for scientific research in the clinical, epidemiological, pathophysiological, and healthcare-cost fields. Ten years after enrolment were started, the cohort still has about 500 patients. The scientific committee has approved 104 clinical research projects, of which many are ongoing, and 54 original articles written by numerous French and international groups have been published. These projects cover a vast spectrum of topics including environmental factors, diagnosis, outcomes, prognosis, disease evaluation, imaging, genetics, biomarkers, costs, and RA management strategies. PMID:25238951

  10. The PTPN22 1858C\\/T polymorphism is associated with anti-cyclic citrullinated peptide antibody-positive early rheumatoid arthritis in northern Sweden

    Microsoft Academic Search

    Heidi Kokkonen; Martin Johansson; Lena Innala; Erik Jidell; Solbritt Rantapää-Dahlqvist

    2007-01-01

    The PTPN22 1858C\\/T polymorphism has been associated with several autoimmune diseases including rheumatoid arthritis (RA). We have shown that carriage of the T variant (CT or TT) of PTPN22 in combination with anti-cyclic citrullinated peptide (anti-CCP) antibodies highly increases the odds ratio for developing RA. In the present study we analysed the association between the PTPN22 1858C\\/T polymorphism and early

  11. [Popliteal aneurysm simulating a Baker's cyst in a patient with rheumatoid arthritis: a case presentation].

    PubMed

    Chalmeta Verdejo, Concepción; Alegre Sancho, Juan José; Román Ivorra, José Andrés; Ivorra Cortes, José

    2011-01-01

    Baker's cyst is the most common mass located in the back side of the knee, the popliteal fossa, in patients with degenerative and inflamatory disease of the knee. Popliteal mass may also be due to proliferation of adipose tissue, popliteal artery aneurysm, thrombotic vein, or tumor. These lesions are rarer and may easily be misinterpreted as cysts. We show a man with rheumatoid arthritis who is presenting a palpable mass in the popliteal fossa. Ultrasonography examination demostrated a popliteal artery aneurysms. PMID:21794798

  12. Improved radiological outcome of rheumatoid arthritis: the importance of early treatment with methotrexate in the era of biological drugs.

    PubMed

    Fiehn, Christoph; Belke-Voss, Elisabeth; Krause, Dietmar; Wassenberg, Siegfried; Rau, Rolf

    2013-12-01

    The objective of this study is to compare the radiological progression in patients with rheumatoid arthritis (RA) diagnosed in the 1980s with those of the late 1990s until 2005 and to evaluate prognostic factors. Ninety-two RA patients who were firstly seen in our clinic from 1997 to 2005 were identified. As a control group, 89 RA patients from 1986 to 1990 were matched for the criteria disease duration (mean, 22 ± 17 months), age, and number of x-ray controls. Radiological damage was measured by the Ratingen score (RS). The baseline RS of the 1997-2005 group was significantly lower (mean, 3.8 ± 8.7 vs 7.7 ± 13.0; p < 0.0001) and showed less radiological progression during follow-up than the 1986-1990 group (?RS/year of 0.95 ± 2.19 vs. 5.69 ± 8.43; p < 0.0001). In the later group, more patients (73 vs. 28%) had methotrexate (MTX). Twenty-one (23%) of the patients in the later group received biological drugs. However, the subgroup 1997-2000 (n = 29), before the approval of TNF-inhibitors, had already lower baseline RS in comparison to 1986-1990 (2.7 ± 4.9; p < 0.001). Multivariate analysis showed that early start of MTX (before or directly after first consultation) was a predictor of favorable outcome (p < 0.005), as were low erythrocyte sedimentation rate at baseline and belonging to the later group. In contrast, neither treatment with glucocorticoids or biological drugs nor the overall rate of MTX or other disease-modifying antirheumatic drug use was predictive. Radiological damage is markedly diminished in RA patients seen since mid of the 1990s. Early treatment with MTX seems to be the key factor for this improved prognosis. PMID:23925553

  13. Disease Progression and Treatment Responses in a Prospective DMARD-naïve Seropositive Early Rheumatoid Arthritis Cohort: Does Gender Matter?

    PubMed Central

    Jawaheer, Damini; Maranian, Paul; Park, Grace; Lahiff, Maureen; Amjadi, Sogol S.; Paulus, Harold E.

    2010-01-01

    Objective To assess gender differences in disease characteristics and treatment responses over time in a DMARD-naïve seropositive early rheumatoid arthritis (RA) cohort. Methods DMARD-naïve, seropositive early RA (<14 months) patients with polyarticular disease were recruited by the Western Consortium of Practicing Rheumatologists. Each patient was examined at study entry, after 6 and 12 months, and yearly thereafter. Clinical and demographic data were collected. We investigated gender differences in baseline disease characteristics and treatment using Chi-square, Mann-Whitney and t tests. We used generalized estimating equations (GEE) models for repeated measures to examine whether the rate of change of specific disease outcomes during the first 2 years after DMARD initiation were significantly influenced by gender. Results At baseline, men (n=67) and women (n=225) had similar disease activity and radiographic damage; men, however, had significantly worse erosion, while women had worse joint space narrowing. Despite similar treatment, women had worse disease progression over the 2-year follow up, as assessed by trends in DAS28ESR4, physician global scores and tender joint counts. In the GEE model, gender was significantly associated with the rate of change of DAS28ESR4 scores (p=0.009), though not being independently associated with disease activity. Self-reported measures (HAQ-DI, patient global scores, fatigue, pain) were worse among women at baseline and throughout the study period. Men were more likely to achieve remission. Conclusion At baseline, men and women had similar disease activity and joint damage. Responses to treatment over time were, however, better among men in this pre-biologic era; women had worse progression despite similar treatment. PMID:20889597

  14. Early detection of bony alterations in rheumatoid and erosive arthritis of finger joints with high-resolution single photon emission computed tomography, and differentiation between them

    Microsoft Academic Search

    B. Ostendorf; K. Mattes-György; D. C. Reichelt; D. Blondin; A. Wirrwar; R. Lanzman; H. W. Müller; M. Schneider; U. Mödder; A. Scherer

    2010-01-01

    Objective  To evaluate high-resolution multi-pinhole single photon emission computed tomography (MPH-SPECT) for the detection of bony\\u000a alterations in early rheumatoid arthritis (ERA), early osteoarthritis (EOA) of the fingers and healthy controls.\\u000a \\u000a \\u000a \\u000a Methods  The clinically dominant hands of 27 patients (13 ERA, nine EOA, five healthy controls) were examined by MPH-SPECT and bone\\u000a scintigraphy. Additionally, magnetic resonance imaging (MRI) was performed in the

  15. Evolving concepts of rheumatoid arthritis

    Microsoft Academic Search

    Gary S. Firestein

    2003-01-01

    Rheumatoid arthritis is the most common inflammatory arthritis and is a major cause of disability. It existed in early Native American populations several thousand years ago but might not have appeared in Europe until the 17th century. Early theories on the pathogenesis of rheumatoid arthritis focused on autoantibodies and immune complexes. T-cell-mediated antigen-specific responses, T-cell-independent cytokine networks, and aggressive tumour-like

  16. Mannose-binding lectin deficiency is associated with early onset of polyarticular juvenile rheumatoid arthritis: a cohort study

    PubMed Central

    Dolman, Koert M; Brouwer, Nannette; Frakking, Florine NJ; Flatø, Berit; Tak, Paul P; Kuijpers, Taco W; Førre, Øystein; Smerdel-Ramoya, Anna

    2008-01-01

    Background Mannose-binding lectin (MBL) is an innate immune protein. The aim of our study was to determine whether genetically determined MBL deficiency is associated with susceptibility to juvenile rheumatoid arthritis (JRA) and whether MBL2 genotypes are associated with JRA severity. Methods In a retrospective cohort study of 218 patients with polyarthritis (n = 67) and oligoarthritis (n = 151), clinical and laboratory disease variables were obtained by clinical examination and chart reviews. Healthy Caucasian adults (n = 194) served as control individuals. MBL2 gene mutations were determined by Taqman analysis to identify genotypes with high, medium and low expression of MBL. Functional MBL plasma concentrations were measured using enzyme-linked immunosorbent assay. Associations between clinical and laboratory variables and MBL2 genotypes were determined by Kruskal-Wallis and ?2 tests. Results MBL2 genotype frequencies were similar in polyarthritis and oligoarthritis patients as compared with control individuals. MBL plasma concentrations were associated with the high, medium and low MBL genotype expression groups (P < 0.01). In polyarthritis patients, the presence of low-expressing (deficient) MBL2 genotypes was associated with early age at onset of disease (P = 0.03). In oligoarthritis patients, patients with low-expressing MBL2 genotypes were more often in remission (81%) than patients in the medium (54%) and high (56%) genotype groups (P = 0.02). The remaining clinical and laboratory variables, such as arthritis severity index, presence of radiographic erosions and antinuclear antibody positivity, were not associated with MBL2 genotypes. Conclusion Genetically determined MBL deficiency does not increase susceptibility to JRA, but MBL deficiency is associated with a younger age at onset of juvenile polyarthritis. On the other hand, MBL-deficient children with juvenile oligoarthritis are more often in remission. Therefore, MBL appears to play a dual role in JRA. PMID:18334024

  17. Immune response profiling in early rheumatoid arthritis: discovery of a novel interaction of treatment response with viral immunity

    PubMed Central

    2013-01-01

    Introduction It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA. Methods A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ?DAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ?1.2. Results A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-?) produced in response to CMV/EBV was found to correlate with the ?DAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P?=?0.029). The baseline CMV/EBV response was particularly driven by IFN-? (P?=?0.039) and IL-4 (P?=?0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P?=?0.002). Irrespective of the ?DAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P?=?0.32), suggesting this response was related to CMV exposure. Conclusions A profile of T-cell immunity associated with CMV exposure influences the clinical response to DMARD therapy in patients with early RA. Because CMV latency is associated with greater joint destruction, our findings suggest that changes in T-cell immunity mediated by viral persistence may affect treatment response and possibly long-term outcomes of RA. PMID:24267267

  18. Rheumatoid Factor

    MedlinePLUS

    ... Formal name: Rheumatoid Factor Related tests: Cyclic Citrullinated Peptide Antibody , ANA , ESR , C-Reactive Protein , Autoantibodies At ... is negative and symptoms persist. A cyclic citrullinated peptide (CCP) antibody test can help diagnose RA in ...

  19. Leflunomide increases the risk of early healing complications in patients with rheumatoid arthritis undergoing elective orthopedic surgery

    Microsoft Academic Search

    Martin Fuerst; Henrike Möhl; Kerstin Baumgärtel; Wolfgang Rüther

    2006-01-01

    The aim of this object is to study whether treatment with biological or leflunomide increases the risk of wound-healing complications after elective orthopedic surgery. Between March 2002 and September 2003, 201 patients participated in this study with the following inclusion criteria: (a) Rheumatoid arthritis (RA) or psoriatic arthritis (psA), (b) therapy with: MTX, leflunomide, etanercept, infliximab, adalimumab, anakinra, (c) undergoing

  20. Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment – a prospective, controlled study

    PubMed Central

    Georgiadis, Athanasios N; Papavasiliou, Eleni C; Lourida, Evangelia S; Alamanos, Yannis; Kostara, Christina; Tselepis, Alexandros D; Drosos, Alexandros A

    2006-01-01

    We investigated lipid profiles and lipoprotein modification after immuno-intervention in patients with early rheumatoid arthritis (ERA). Fifty-eight patients with ERA who met the American College of Rheumatology (ACR) criteria were included in the study. These patients had disease durations of less than one year and had not had prior treatment for it. Smokers or patients suffering from diabetes mellitus, hypothyroidism, liver or kidney disease, Cushing's syndrome, obesity, familiar dyslipidemia and those receiving medications affecting lipid metabolism were excluded from the study. Sixty-three healthy volunteers (controls) were also included. Patients were treated with methotrexate and prednisone. Lipid profiles, disease activity for the 28 joint indices score (DAS-28) as well as ACR 50% response criteria were determined for all patients. The mean DAS-28 at disease onset was 5.8 ± 0.9. After a year of therapy, 53 (91.3%) patients achieved the ACR 20% response criteria, while 45 (77.6%) attained the ACR 50% criteria. In addition, a significant decrease in the DAS-28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed. ERA patients exhibited higher serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides, whereas their serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower compared to controls. As a consequence, the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was significantly higher in ERA patients compared to controls. After treatment, a significant reduction of the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was observed, a phenomenon primarily due to the increase of serum HDL-C levels. These changes were inversely correlated with laboratory changes, especially CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves after therapy. Thus, early immuno-intervention to control disease activity may reduce the risk of the atherosclerotic process and cardiovascular events in ERA patients. PMID:16646989

  1. Apoptosis in rheumatoid arthritis

    Microsoft Academic Search

    Paul P. Tak; Gary S. Firestein

    \\u000a Rheumatoid arthritis (RA) — a chronic inflammatory disease affecting synovial tissue in multiple joints — is associated with\\u000a long-term morbidity and early mortality despite considerable advances in understanding its pathogenesis. Although the identity\\u000a and role of specific inciting agents is uncertain, immune-mediated mechanisms are likely of crucial importance. The evidence\\u000a to support a role of CD4+T cells in the immune

  2. Rheumatoid arthritis: evaluation and surgical management of the cervical spine

    Microsoft Academic Search

    Francis H. Shen; Dino Samartzis; Louis G. Jenis; Howard S. An

    2004-01-01

    Background contextRheumatoid arthritis is a debilitating polyarthropathic degenerative condition. Eighty-six percent of patients with rheumatoid arthritis have cervical spine involvement. Often these lesions are clinically asymptomatic or symptoms are erroneously attributed to peripheral manifestation of the patient's rheumatoid disease. Because these lesions are common and missed diagnosis can result in death, early recognition is vital.

  3. Presence and utility of IgA-class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis: the Swedish TIRA project

    PubMed Central

    Svärd, Anna; Kastbom, Alf; Reckner-Olsson, Åsa; Skogh, Thomas

    2008-01-01

    Introduction The present study was carried out to assess whether IgA-class antibodies against cyclic citrullinated peptides (IgA anti-CCP) in recent-onset rheumatoid arthritis add diagnostic and/or prognostic information to IgG anti-CCP analysis. Methods Serum samples were obtained from 228 patients with recent-onset (<12 months) rheumatoid arthritis at the time of inclusion in the Swedish TIRA cohort (Swedish Early Intervention in Rheumatoid Arthritis). Sera from 72 of these patients were also available at the 3-year follow-up. Disease activity and functional ability measures (erythrocyte sedimentation rate, serum C-reactive protein, 28-joint count Disease Activity Score, physician's assessment of disease activity, and the Swedish version of the Health Assessment Questionnaire) were registered at inclusion and at regular follow-ups during 3 years. An IgA anti-CCP assay was developed based on the commercially available IgG-specific enzyme immunoassay from EuroDiagnostica (Arnhem, the Netherlands), replacing the detection antibody by an anti-human-IgA antibody. A positive IgA anti-CCP test was defined by the 99th percentile among healthy blood donors. Results At baseline, a positive IgA anti-CCP test was observed in 29% of the patient sera, all of which also tested positive for IgG anti-CCP at a higher average level than sera containing IgG anti-CCP alone. The IgA anti-CCP-positive patients had significantly higher disease activity over time compared with the IgA anti-CCP-negative patients. After considering the IgG anti-CCP level, the disease activity also tended to be higher in the IgA anti-CCP-positive cases – although this difference did not reach statistical significance. The proportion of IgA anti-CCP-positive patients was significantly larger among smokers than among nonsmokers. Conclusion Anti-CCP antibodies of the IgA class were found in about one-third of patients with recent-onset rheumatoid arthritis, all of whom also had IgG anti-CCP. The occurrence of IgA-class antibodies was associated with smoking, and IgA anti-CCP-positive patients had a more severe disease course over 3 years compared with IgA anti-CCP-negative cases. Although IgA anti-CCP analysis does not seem to offer any diagnostic information in addition to IgG anti-CCP analysis, further efforts are justified to investigate the prognostic implications. PMID:18601717

  4. Are there more than cross-sectional relationships of social support and support networks with functional limitations and psychological distress in early rheumatoid arthritis? The European Research on Incapacitating Diseases and Social Support Longitudinal Study

    Microsoft Academic Search

    V. Demange; F. Guillemin; M. Baumann; T. P. B. M. Suurmeijer; T. Moum; D. Doeglas

    2004-01-01

    Objective. To investigate whether greater social support and support network are cross-sectionally associated with less functional limitations and psychological distress in patients with early rheumatoid arthritis (RA); whether this associ- ation is constant over time; and whether increases in social support or support network are associated with less functional limitations and psychological distress. Methods. Subjects were from the European Research

  5. 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

  6. 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

  7. Health Assessment Questionnaire disability progression in early rheumatoid arthritis: Systematic review and analysis of two inception cohorts

    PubMed Central

    Norton, Sam; Fu, Bo; Scott, David L.; Deighton, Chris; Symmons, Deborah P.M.; Wailoo, Allan J.; Tosh, Jonathan; Lunt, Mark; Davies, Rebecca; Young, Adam; Verstappen, Suzanne M.M

    2014-01-01

    Objective The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK. Methods Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership. Results The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression. Conclusion Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit. PMID:24925692

  8. 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.

  9. 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

    Rastogi, Anshul; 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/cm(2)/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

  10. Rheumatoid Arthritis

    NSDL National Science Digital Library

    Patient Education Institute

    This patient education program describes how rheumatoid arthritis develops, the causes, symptoms, diagnosis, and treatments. It also summarizes what patients can do to help manage their disease. This resource is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute. NOTE: This tutorial requires a special Flash plug-in, version 4 or above. If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial. You will also need an Acrobat Reader, available as a free download, in order to view the Reference Summary.

  11. Macrophages in rheumatoid arthritis

    PubMed Central

    Kinne, Raimund W; Bräuer, Rolf; Stuhlmüller, Bruno; Palombo-Kinne, Ernesta; Burmester, Gerd-R

    2000-01-01

    The abundance and activation of macrophages in the inflamed synovial membrane/pannus significantly correlates with the severity of rheumatoid arthritis (RA). Although unlikely to be the 'initiators' of RA (if not as antigen-presenting cells in early disease), macrophages possess widespread pro-inflammatory, destructive, and remodeling capabilities that can critically contribute to acute and chronic disease. Also, activation of the monocytic lineage is not locally restricted, but extends to systemic parts of the mononuclear phagocyte system. Thus, selective counteraction of macrophage activation remains an efficacious approach to diminish local and systemic inflammation, as well as to prevent irreversible joint damage. PMID:11094428

  12. Patient preferences for treatment: report from a randomised comparison of treatment strategies in early rheumatoid arthritis (BeSt trial)

    PubMed Central

    Goekoop?Ruiterman, Yvonne P M; de Vries?Bouwstra, Jeska K; Allaart, Cornelia F; Kerstens, Pit J S M; Grillet, Bernard A M; de Jager, Mike H; Han, K Huub; Speyer, Irene; van der Lubbe, Peter A H M; Seys, Patrick E H; Breedveld, Ferdinand C; Dijkmans, Ben A C

    2007-01-01

    Objective To determine treatment preferences among patients with recent onset rheumatoid arthritis participating in a randomised controlled trial comparing four therapeutic strategies. Methods A questionnaire was sent to all 508 participants of the BeSt trial, treated for an average of 2.2 years with either sequential monotherapy (group 1), step?up combination therapy (group 2), initial combination therapy with tapered high?dose prednisone (group 3), or initial combination therapy with infliximab (group 4). Treatment adjustments were made every 3?months to achieve low disease activity (DAS ?2.4). The questionnaire explored patients' preferences or dislikes for the initial therapy. Results In total, 440 patients (87%) completed the questionnaire. Despite virtually equal study outcomes at 2 years, more patients in group 4 reported much or very much improvement of general health: 50%, 56%, 46% and 74% in groups 1–4, respectively (overall, P<0.001). Almost half of the patients expressed no preference or aversion for a particular treatment group, 33% had hoped for assignment to group 4 and 38% had hoped against assignment to group 3. This negative perception was much less prominent in patients actually in group 3. Nevertheless, 50% of patients in group 3 disliked having to take prednisone, while only 8% in group 4 disliked going to the hospital for intravenous treatment. Conclusions Within the limitations of our retrospective study, patients clearly preferred initial combination therapy with infliximab and disliked taking prednisone. After actual exposure, this preference remained, but the perception of prednisone improved. Patient perceptions need to be addressed when administering treatment. PMID:17405834

  13. 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

  14. Patients with early rheumatoid arthritis exhibit elevated autoantibody titers against mildly oxidized low-density lipoprotein and exhibit decreased activity of the lipoprotein-associated phospholipase A2

    PubMed Central

    Lourida, Evangelia S; Georgiadis, Athanasios N; Papavasiliou, Eleni C; Papathanasiou, Athanasios I; Drosos, Alexandros A; Tselepis, Alexandros D

    2007-01-01

    Rheumatoid arthritis is a chronic inflammatory disease, associated with an excess of cardiovascular morbidity and mortality due to accelerated atherosclerosis. Oxidized low-density lipoprotein (oxLDL), the antibodies against oxLDL and the lipoprotein-associated phospholipase A2 (Lp-PLA2) may play important roles in inflammation and atherosclerosis. We investigated the plasma levels of oxLDL and Lp-PLA2 activity as well as the autoantibody titers against mildly oxLDL in patients with early rheumatoid arthritis (ERA). The long-term effects of immunointervention on these parameters in patients with active disease were also determined. Fifty-eight ERA patients who met the American College of Rheumatology criteria were included in the study. Patients were treated with methotrexate and prednisone. Sixty-three apparently healthy volunteers also participated in the study and served as controls. Three different types of mildly oxLDL were prepared at the end of the lag, propagation and decomposition phases of oxidation. The serum autoantibody titers of the IgG type against all types of oxLDL were determined by an ELISA method. The plasma levels of oxLDL and the Lp-PLA2 activity were determined by an ELISA method and by the trichloroacetic acid precipitation procedure, respectively. At baseline, ERA patients exhibited elevated autoantibody titers against all types of mildly oxLDL as well as low activity of the total plasma Lp-PLA2 and the Lp-PLA2 associated with the high-density lipoprotein, compared with controls. Multivariate regression analysis showed that the elevated autoantibody titers towards oxLDL at the end of the decomposition phase of oxidation and the low plasma Lp-PLA2 activity are independently associated with ERA. After immunointervention autoantibody titers against all types of oxLDL were decreased in parallel to the increase in high-density lipoprotein-cholesterol and high-density lipoprotein-Lp-PLA2 activity. We conclude that elevated autoantibody titers against oxLDL at the end of the decomposition phase of oxidation and low plasma Lp-PLA2 activity are feature characteristics of patients with ERA, suggesting an important role of these parameters in the pathophysiology of ERA as well as in the accelerated atherosclerosis observed in these patients. PMID:17326817

  15. 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

  16. Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability

    PubMed Central

    Pascual-Ramos, Virginia; Contreras-Yáñez, Irazú; Villa, Antonio R; Cabiedes, Javier; Rull-Gabayet, Marina

    2009-01-01

    Introduction Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators. Methods Charts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used. Results The proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P ? 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (? 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 ± 4.6 versus 13.6 ± 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P ? 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age at baseline was associated with therapy discontinuation (odds ratio = 1.1, 95% confidence interval = 1.007 to 1.103, P = 0.02). Conclusions Discontinuation of DMARDs was frequent and progressive in an early RA cohort. Patients with persistence on therapy were younger, had lower disease activity and disability during follow-up, and reached sustained remission more frequently and earlier than patients without it. MP should intentionally be evaluated during follow-up of early RA patients, as it seems to play a major role in outcome. PMID:19228421

  17. VALIDATING AND ASSESSING THE SENSITIVITY OF THE HEALTH ASSESSEMENT QUESTIONNAIRE-DISABLITY INDEX DERIVED SF-6D IN PATIENTS WITH EARLY AGGRESSIVE RHEUMATOID ARTHRITIS

    PubMed Central

    Amjadi, Sogol; Maranian, Paul; Paulus, Harold E.; Kaplan, Robert M.; Ranganath, Veena; Furst, Daniel; Khanna, Puja; Khanna, Dinesh

    2010-01-01

    Objective New methodologies allow the scores for the Health Assessment Questionnaire-Disability Index (HAQ-DI) to be translated into preferences/ utility scores. We evaluated the construct validity of the HAQ-DI derived SF-6D score and assessed its responsiveness to change over 6- and 12-month follow-up periods in patients with early aggressive rheumatoid arthritis (RA). Methods Patients (N=277) participating in an RA observational study completed self-reported measures of symptoms and the HAQ-DI at baseline, 6 and 12 months. Total Sharp scores, C-reactive protein and erythrocyte sedimentation rate were assessed using clinical data. Construct validity was assessed by examining the association between SF-6D score and patient-reported and clinical measures using Spearman correlation coefficients. The responsiveness of SF-6D to change was assessed using patient and physician assessments of the disease as clinical anchors. The magnitude of responsiveness was calculated using SF-6D effect size (ES). Result Mean SF-6D scores were 0.690, 0.720, and 0.723 at baseline, 6, and 12-month follow-up visits, respectively. Baseline patient-reported measures had moderate-to-high correlations with baseline SF-6D (r: 0.43 to 0.52); whereas clinical measures had negligible-to-low correlations with SF-6D (r: 0.001 to 0.32). ES was moderate for the groups that were deemed to have improved (ES: 0.63–0.75) but negligible-to-small for those who did not (ES: 0.13–0.46). Conclusion Our data supports the validity and responsiveness of the HAQ-DI derived SF-6D score in an early RA cohort. These results support the use of HAQ-DI derived SF-6D in RA cohorts and clinical trials lacking preference-based measures. PMID:19369459

  18. From Synovial Tissue to Peripheral Blood: Myeloid Related Protein 8/14 Is a Sensitive Biomarker for Effective Treatment in Early Drug Development in Patients with Rheumatoid Arthritis

    PubMed Central

    Choi, Ivy Y.; Gerlag, Danielle M.; Holzinger, Dirk; Roth, Johannes; Tak, Paul P.

    2014-01-01

    Objective The change in number of CD68-positive sublining macrophages in serial synovial biopsies has been successfully used to discriminate on the group level between effective and ineffective treatment during early drug development in rheumatoid arthritis (RA) patients. Measurement of a soluble biomarker would clearly have practical advantages. Therefore, we investigated the sensitivity to change of myeloid related protein (MRP)8/14 in serum. Methods 139 RA patients who received known effective biologics (infliximab, adalimumab and rituximab) and 28 RA patients who received placebo/ineffective therapies were included. MRP8/14 levels were analyzed in baseline and follow-up serum samples and the standardized response mean (SRM) was calculated to determine the sensitivity to change of MRP8/14 in comparison to C-reactive protein (CRP) levels and the disease activity score evaluated in 28 joints (DAS28). Results In patients treated with effective treatment, the SRM for MRP8/14 was moderate (0.56), but in patients treated with placebo/ineffective treatment the SRM was 0.06, suggesting that this biomarker is perhaps not susceptible to placebo effects in proof-of-concept studies of relatively short duration. In contrast, the SRM for DAS28 was high for effective treatment (1.07), but also moderate for ineffective treatment (0.58), representing the placebo effect. The SRM for CRP was low in the effective (0.33) and ineffective (0.23) treatment groups. Conclusion These data support the notion that quantification of changes in MRP8/14 serum levels could be used to predict potential efficacy of novel antirheumatic drugs in an early stage of drug development. A positive result would support the rationale for larger, conventional clinical trials to determine whether the effects are clinically relevant. PMID:25166859

  19. 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

  20. 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.

  1. Comparing Five Year Out-Come in Two Cohorts of Patients with Early Rheumatoid Arthritis – A BARFOT Study

    PubMed Central

    Andersson, Maria L.E; Forslind, Kristina; Hafström, Ingiäld

    2015-01-01

    The objective of the study was to compare disease characteristics over the first 5 years of disease in patients with RA, with disease onset in 1990s and 2000s, respectively. Methods : All 2235 patients with early RA (disease duration ?12 months) were recruited from the BARFOT prospective observational study. These patients were divided into group 1 included 1992 to 1999 (N=1084, 66% women) and group 2 included 2000 to 2006 (N=1151, 69% women). Disease Activity Score (DAS28), VAS pain and Health Assessment Questionnaire (HAQ) were assessed during 5 years. Remission was defined as DAS28 <2.6. Results : At inclusion, both women and men in group 2 had higher mean DAS28 (SD) than group 1, 5.42 (1.22) vs 5.26 (1.19), p=0.004 and 5.28 (1.22) vs 5.00 (1.27), p=0.004, respectively, mainly dependant on pain and not on inflammatory related measures. Over time DAS28 decreased and was in both genders, from 6 months to the 5-year follow-up, significantly lower in group 2. At 5-year, both women and men in group 2 had higher rate of remission than women and men in group 1. However, despite reduction of VAS pain and HAQ there were no differences in pain and HAQ between groups at any time point. Conclusion : Patients included in the 2000s achieved higher frequency of remission at the 5 year follow-up compared with those included in the 1990s, suggested to reflect the more active medical treatment. Interestingly, however, improvement in pain and HAQ did not differ between the two patient cohorts. PMID:25674182

  2. Optical imaging of rheumatoid arthritis

    PubMed Central

    Golovko, Daniel; Meier, Reinhard; Rummeny, Ernst; Daldrup-Link, Heike

    2011-01-01

    Optical Imaging (OI) for rheumatoid arthritis is a novel imaging modality. 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 article we describe the current techniques of OI and discuss potential future applications of this promising technology. Overall, we demonstrate that OI is a fast, inexpensive, noninvasive, nonionizing and accurate imaging modality. Furthermore, OI is a clinically applicable tool allowing for the early detection of inflammation and potentially facilitating the monitoring of therapy. PMID:21826190

  3. 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

  4. Rheumatoid arthritis affecting temporomandibular joint

    PubMed Central

    Sodhi, Amandeep; Naik, Shobha; Pai, Anuradha; Anuradha, Ardra

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune inflammatory disorder that is characterized by joint inflammation, erosive properties and symmetric multiple joint involvement. Temporomandibular joint (TMJ) is very rare to be affected in the early phase of the disease, thus posing diagnostic challenges for the dentist. Conventional radiographs fail to show the early lesions due to its limitations. More recently cone-beam computed tomography (CBCT) has been found to diagnose the early degenerative changes of TMJ and hence aid in the diagnosis of the lesions more accurately. Our case highlights the involvement of TMJ in RA and the role of advanced imaging (CBCT) in diagnosing the bony changes in the early phase of the disease. PMID:25684928

  5. The Rheumatoid Hand and Preventive Surgery

    PubMed Central

    Cook, William A.

    1983-01-01

    Preventive surgery in rheumatoid arthritis of the hand is aimed at avoiding or at least delaying deformity and disability and at alleviating symptoms, especially pain. This can be successfully accomplished only in the disease's early phases. The family physician is in a position to assess his rheumatoid patients and to develop a good sense of the disease's progression. He can therefore make timely referrals to a hand surgeon, before major deformity and disability are present and the optimum time for preventive surgery has passed. The common surgical procedures—including excision of rheumatoid nodules; release of nerve entrapments; tenosynovectomy; synovectomy, and resection and reconstruction of the ulnar head—are discussed, as are their indications. ImagesFig. 1Fig. 2Fig. 3Fig. 4 PMID:21283473

  6. Epigenetics in Rheumatoid Arthritis

    Microsoft Academic Search

    Michelle Trenkmann; Matthias Brock; Caroline Ospelt; Steffen Gay

    2010-01-01

    Epigenetics is a steadily growing research area. In many human diseases, especially in cancers, but also in autoimmune diseases,\\u000a epigenetic aberrations have been found. Rheumatoid arthritis is an autoimmune disease characterized by chronic inflammation\\u000a and destruction of synovial joints. Even though the etiology is not yet fully understood, rheumatoid arthritis is generally\\u000a considered to be caused by a combination of

  7. Autoantibodies, HLA and PTPN22: susceptibility markers for rheumatoid arthritis

    Microsoft Academic Search

    G. Orozco; D. Pascual-Salcedo; M. A. Lopez-Nevot; T. Cobo; A. Cabezon; E. Martin-Mola; A. Balsa; J. Martin

    2007-01-01

    Objective. To analyse the relationship between the presence of auto-antibodies (rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP)), HLA-DRB1 alleles and PTPN22 1858 C\\/T polymorphism and test the value of their combination as susceptibility markers for rheumatoid arthritis (RA). Methods. Patients with early arthritis were included. At entry in the cohort or during follow-up, 191 patients fulfilled the criteria for

  8. Filaggrin peptides with ?-hairpin structure bind rheumatoid arthritis antibodies.

    PubMed

    Fischer, Sabrina; Geyer, Armin

    2014-04-01

    In the early detection of rheumatoid arthritis (RA) synthetic filaggrin peptides serve as antigens for rheumatoid-specific autoantibodies (anti-citrullinated peptide antibody, ACPA) in ELISA tests. In this work we present a peptide that exhibits the binding epitope of ACPA in the form of a stable folding ?-hairpin. The homogeneity of the peptide folding was confirmed by NMR spectroscopy and might lead to the first proposed structure of the antibody-bound conformation of the epitope. PMID:24599792

  9. Genetics Home Reference: Rheumatoid arthritis

    MedlinePLUS

    ... rheumatoid arthritis affecting other parts of the body. Variations in dozens of genes have been studied as ... significant genetic risk factors for rheumatoid arthritis are variations in human leukocyte antigen (HLA) genes, especially the ...

  10. Occupational therapy for rheumatoid arthritis

    Microsoft Academic Search

    E. M. J. Steultjens; J. Dekker; L. M. Bouter; D. J. van Schaardenburg; M. A. H. van Kuyk; C. H. M. van den Ende

    2004-01-01

    Background: For persons with rheumatoid arthritis (RA) the physical, personal, familial, social and vocational consequences are extensive. Occupational therapy (OT), with the aim to facilitate task performance and to decrease the consequences of rheumatoid arthritis for daily life activities, is considered to be a cornerstone in the management of rheumatoid arthritis. Till now the efficacy of occupational therapy for patients

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

    E-print Network

    Petersen, Lutz

    2007-01-01

    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.

  12. 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.

  13. Rheumatoid arthritis in Saudi Arabia

    PubMed Central

    Almoallim, Hani M.; Alharbi, Laila A.

    2014-01-01

    The status of rheumatoid arthritis (RA) in Saudi Arabia (SA) was examined from various perspectives based on a systematic literature review and the authors’ personal experiences. In this regard, database and journal search were conducted to identify studies on RA in SA, yielding a total of 43 articles. Although efforts have been made to promote RA research in SA, current studies mostly represent only a few centers and may not accurately portray the national status of RA care. Notably, biological therapies were introduced early for almost all practicing rheumatologists in SA (government and private). However, no national guidelines regarding the management of RA have been developed based on local needs and regulations. Also, while efforts were made to establish RA data registries, they have not been successful. Taken together, this analysis can contribute to the planning of future guidelines and directives for RA care in SA. PMID:25491208

  14. Comparison between penicillamine and sulphasalazine in rheumatoid arthritis: Leeds-Birmingham trial

    Microsoft Academic Search

    V C Neumann; K A Grindulis; S Hubball; B McConkey; V Wright

    1983-01-01

    Sulphasalazine was first formulated by Svartz in the early 1940s, specifically for use as a remission inducing drug in rheumatoid arthritis. After the publication of an unfavourable trial, however, the drug was restricted to patients with ulcerative colitis. In the late 1970s sulphasalazine was re-examined in rheumatoid arthritis and favourable results reported in \\

  15. Early Eocene's climate and ocean circulation from coupled model simulations

    NASA Astrophysics Data System (ADS)

    Weber, Tobias; Thomas, Maik

    2014-05-01

    While proxy data provide a snapshot of climate conditions at a specific location, coupled atmosphere-ocean models are able to expand this knowledge over the globe. Therefore, they are indispensable tools for understanding past climate conditions. We model the dynamical state of atmosphere and ocean during the Early Eocene and pre-industrial times, using the coupled atmosphere-ocean model ECHAM5/MPIOM with realistic reconstructions of vegetation and CO2. The resulting simulated climate variables are compared to terrestrial and oceanic proxies. The Early Eocene climate is in the global mean warmer (~13°C) and wetter (~1 mm/d) than in pre-industrial times. Especially temperatures in the Southern Ocean, the Greenland Sea and Arctic Ocean raise by up to 25K, being in accordance with surface temperature estimates from terrestrial and marine proxy data. The oceans are hereby rendered ice-free, leading to a decrease of polar albedo and thereby facilitating polar warming. This leads to a by 5K diminished equator-to-pole temperature gradient. Warmer temperatures as well as changed bathymetry have an effect on ocean dynamics in the Early Eocene. Although deep-water formation can be found in the Greenland Sea, Weddell Sea, and Tethys Sea, it is weaker than in the pre-industrial run and the resulting circulation is shallower. This is not only visible in water transport through sea gates but also in the Atlantic Meridional Overturning Circulation (AMOC), adopting its maximum at 700m depths in the Early Eocene, while maximum transport is reached in the pre-industrial control run at 1200m. Albeit a shallow and weak thermohaline circulation, a global ocean conveyor belt is being triggered, causing a transport from the areas of subduction through the Atlantic and Southern Oceans into the Indian and Pacific Oceans.

  16. What Is Rheumatoid Arthritis?

    MedlinePLUS

    ... publication. To order Rheumatoid Arthritis Handout on Health full-text version, please contact NIAMS using the contact information ... mailed to you? Visit our online order form. Full NIAMS Site NIH… Turning Discovery Into Health ® ... Comments Moderation Policy Site Map | Viewers and Players

  17. Genetics in rheumatoid arthritis

    Microsoft Academic Search

    Tom W. J. Huizinga

    2002-01-01

    The data from the human genome project were published in 2001. Although this achievement will boost research in the genetics\\u000a of rheumatoid arthritis (RA), most of the work is in progress. Three of the four consortia that are performing linkage studies\\u000a to identify loci that are transmitted more often to patients than controls have published data on genome-wide searches in

  18. Rheumatoid pneumoconiosis (Caplan's syndrome)

    Microsoft Academic Search

    J. Schreiber; D. Koschel; J. Kekow; N. Waldburg; A. Goette; R. Merget

    2010-01-01

    In 1953, Caplan described a characteristic radiographic pattern in coal miners with rheumatoid arthritis (RA) that was distinct from the typical progressive massive fibrosis pattern of coalworkers' pneumoconiosis. It consists of multiple well-defined rounded nodules on chest X-ray, from about 0.5 to about several centimetres in diameter, distributed throughout the lungs but predominantly at the lung periphery. Lesions appear often

  19. The MIT Design Advisor : simple and rapid energy simulation of early-stage building designs

    E-print Network

    Urban, Bryan J. (Bryan James)

    2007-01-01

    Simulation tools, when applied early in the design process, can considerably reduce the energy demand of newly constructed buildings. For a simulation tool to assist with design, it must be easy to use, provide feedback ...

  20. Lower limb joint replacement in rheumatoid arthritis

    PubMed Central

    2012-01-01

    Introduction There is limited literature regarding the peri-operative and surgical management of patients with rheumatoid disease undergoing lower limb arthroplasty. This review article summarises factors involved in the peri-operative management of major lower limb arthroplasty surgery for patients with rheumatoid arthritis. Methods We performed a search of the medical literature, using the PubMed search engine (http://www.pubmed.gov). We used the following terms: ‘rheumatoid’ ‘replacement’ ‘arthroplasty’ and ‘outcome’. Findings The patient should be optimised pre-operatively using a multidisciplinary approach. The continued use of methotrexate does not increase infection risk, and aids recovery. Biologic agents should be stopped pre-operatively due the increased infection rate. Patients should be made aware of the increased risk of infection and periprosthetic fracture rates associated with their disease. The surgical sequence is commonly hip, knee and then ankle. Cemented total hip replacement (THR) and total knee replacement (TKR) have superior survival rates over uncemented components. The evidence is not clear regarding a cruciate sacrificing versus retaining in TKR, but a cruciate sacrificing component limits the risk early instability and potential revision. Patella resurfacing as part of a TKR is associated with improved outcomes. The results of total ankle replacement remain inferior to THR and TKR. RA patients achieve equivalent pain relief, but their rehabilitation is slower and their functional outcome is not as good. However, the key to managing these complicated patients is to work as part of a multidisciplinary team to optimise their outcome. PMID:22697352

  1. The Relationship between Personality, Supportive Transactions and Support Satisfaction, and Mental Health of Patients with Early Rheumatoid Arthritis. Results from the Dutch Part of the Euridiss Study

    ERIC Educational Resources Information Center

    Suurmeijer, Th. P. B. M.; Van Sonderen, F. L. P.; Krol, B.; Doeglas, D. M.; Van Den Heuvel, W. J. A.; Sanderman, R.

    2005-01-01

    The relationships between two personality characteristics (neuroticism, extraversion), three types of supportive transactions (emotional support, social companionship, instrumental support) and satisfaction with these transactions, and two aspects of mental health (feelings of anxiety and depressive mood) were studied among 280 patients with early

  2. Investigation of Turbulence in the Early Stages of a High Resolution Supernova Simulation

    E-print Network

    Bell, John B.

    Investigation of Turbulence in the Early Stages of a High Resolution Supernova Simulation Robert curves of Type Ia supernovae (SN Ia) as tools for surveying vast distances. Previous simulations have. In this video, we show the turbulence within the early "bubble" of a supernova via renderings of the magnitude

  3. Temporomandibular joint bone tissue resorption in patients with early rheumatoid arthritis can be predicted by joint crepitus and plasma glutamate level.

    PubMed

    Hajati, Anna-Kari; Näsström, Karin; Alstergren, Per; Bratt, Johan; Kopp, Sigvard

    2010-01-01

    The aim was to investigate whether bone tissue resorption in early RA is related to crepitus of the temporomandibular joint (TMJ) and systemic levels of inflammatory mediators and markers and sex steroid hormones. Twentynine women and 18 men with recently diagnosed RA were examined for TMJ bone erosions with computerized tomography and TMJ crepitus was assessed. Blood samples were analyzed for glutamate, 5-HT, TNF, IL-1beta, IL-6, VEGF, inflammatory markers, and estradiol, progesterone and testosterone. The TMJ erosion score was positively correlated to glutamate, and TMJ crepitus where crepitus, glutamate and ESR explained 40% of the variation in the bone erosion score. In the patients without crepitus, bone erosion score was positively correlated to glutamate, which was not the case in the patients with crepitus. In conclusion, the results of this study show that TMJ bone tissue resorption can be predicted by TMJ crepitus and glutamate in early RA. PMID:20671920

  4. Distinct trajectories of disease activity over the first year in early rheumatoid arthritis patients following a treat-to-target strategy.

    PubMed

    Siemons, Liseth; Ten Klooster, Peter M; Vonkeman, Harald E; W Glas, Cees A; van de Laar, Mart A F J

    2013-09-19

    Objective: Although treat-to-target (T2T) strategies are effective in early RA patients, important individual variations exist in the course towards remission. Growth mixture modeling (GMM) provides more insight into this heterogeneity by identifying subgroups of patients with similar response patterns. This study aimed to identify distinct trajectories of disease activity in early RA patients following a T2T strategy, during their first year. Methods: Data on various clinical and patient-reported measures were collected from the DREAM remission induction cohort. GMM was applied to examine the impact of T2T on subgroups characterized by different types of growth trajectories, as measured with the Disease Activity Score for 28 joints. Results: Three distinct trajectories of disease activity were found. The normative trajectory contained most patients (82.6%), showing a quickly decreasing disease activity, stabilizing at remission after 9 months. This group performed best on clinical and patient-reported measures over time and were more likely to be men. A smaller group (14.1%) also approached remission, but demonstrated a slower response to treatment. Finally, a minority (3.3%) showed no improvement after 1 year, despite an initial quick decrease in disease activity during the first months of treatment. Conclusion: Disease activity in early RA patients during the first year of a T2T strategy does not follow a linear pattern, nor is a single developmental trajectory applicable to all patients. Future studies should attempt to identify more specific risk factors for poor outcome to enable early identification of patients in need of alternative therapeutic approaches. © 2013 American College of Rheumatology. PMID:24106173

  5. Early growth response factor-1 mediates prostaglandin E2-dependent transcriptional suppression of cytokine-induced tumor necrosis factor-alpha gene expression in human macrophages and rheumatoid arthritis-affected synovial fibroblasts.

    PubMed

    Faour, Wissam H; Alaaeddine, Nada; Mancini, Arturo; He, Qing Wen; Jovanovic, Dragan; Di Battista, John A

    2005-03-11

    Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic proinflammatory cytokine that modulates a broad range of inflammatory and immunological processes. We have investigated the potential immunomodulatory properties of prostaglandin E2 (PGE2) by examining the molecular mechanism by which the eicosanoid suppresses T-cell-derived interleukin-17 (IL-17)-induced TNF-alpha mRNA expression and protein synthesis in human macrophages and rheumatoid arthritis-affected synovial fibroblasts. Initial studies confirmed that PGE2 induces egr-1 mRNA expression and protein synthesis by restricted SAPK2/p38 MAPK-dependent activating transcription factor-2 (ATF-2) dimer transactivation of the egr-1 promoter as judged by studies using wild-type (WT) and deletion mutant egr-1 promoter constructs, Northern and Western blotting, and standard and supershift electrophoretic mobility shift analyses. Using human leukemic monocytic THP-1 cells stably transfected with WT and dominant-negative mutant expression constructs of Egr-1, cotransfected or not with a WT pTNF-615SVOCAT construct, we observed that PGE2 inhibition of IL-17-stimulated TNF-alpha mRNA expression and promoter activity was dependent on Egr-1 expression, as mutants of Egr-1, alone or in combination, markedly abrogated any inhibitory effect of PGE2. Standard and supershift electrophoretic mobility shift analysis, signaling "decoy" overexpression studies, and pTNF-615SVOCAT promoter assays using WT and mutant promoter constructs revealed that IL-17-up-regulated promoter activity was largely dependent on ATF-2/c-Jun transactivation. PGE2 suppression of IL-17-induced ATF-2/c-Jun transactivation and DNA binding was dependent on Egr-1-mediated inhibition of induced c-Jun expression. We suggest that egr-1 is an immediate-early PGE2 target gene that may be a key regulatory factor in mediating eicosanoid control of genes involved in the immune and inflammatory responses. PMID:15640148

  6. Interferon-gamma microsatellite and rheumatoid arthritis.

    PubMed

    Pokorny, V; McLean, L; McQueen, F; Abu-Maree, M; Yeoman, S

    2001-07-14

    Several non-HLA genes contribute to the susceptibility to rheumatoid arthritis (RA). A recent report noted an allele (126 bp [CA(13)]) of the interferon-gamma intron A microsatellite repeat strongly associated with both the occurrence and the severity of RA. We assessed this locus in an independent set of 128 controls and 93 prospectively recruited patients with early RA. The reported association could not be confirmed. This discrepancy might be due to technical problems, which could be avoided by the use of reference samples. PMID:11463416

  7. [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

  8. Evolution of Direct Costs in the First Years of Rheumatoid Arthritis: Impact of Early versus Late Biologic Initiation - An Economic Analysis Based on the ESPOIR Cohort

    PubMed Central

    Chevreul, Karine; Haour, Georges; Lucier, Sandy; Harvard, Stephanie; Laroche, Marie-Laure; Mariette, Xavier; Saraux, Alain; Durand-Zaleski, Isabelle; Guillemin, Francis; Fautrel, Bruno

    2014-01-01

    Objectives To estimate annual direct costs of early RA by resource component in an inception cohort, with reference to four distinct treatment strategies: no disease modifying antirheumatic drugs (DMARDs), synthetic DMARDs only, biologic DMARDs in the first year (‘first-year biologic’, FYB), and biologic DMARDs from the second year after inclusion (‘later-year biologic’, LYB); to determine predictors of total and non-DMARD related costs. Methods The ESPOIR cohort is a French multicentric, prospective study of 813 patients with early arthritis. Data assessing RA-related resource utilisation and disease characteristics were collected at baseline, biannually during the first two years and annually thereafter. Costs predictors were determined by generalised linear mixed analyses. Results Over the 4-year follow-up, mean annual direct total costs per treatment strategy group were €3,612 for all patients and €998, €1,922, €14,791, €8,477 respectively for no DMARDs, synthetic DMARDs only, FYB and LYB users. The main predictors of higher costs were biologic use and higher Health Assessment Questionnaire (HAQ) scores at baseline. Being a biologic user led to a higher total cost (FYB Rate Ratio (RR) 7.22, [95% CI 5.59–9.31]; LYB RR 4.39, [95% CI 3.58–5.39]) compared to non-biologic users. Only LYB increased non-DMARD related costs compared to all other patients by 60%. Conclusions FYB users incurred the highest levels of total costs, while their non-DMARD related costs remained similar to non-biologic users, possibly reflecting better RA control. PMID:24811196

  9. Ns Simulator Tests for Random Early Detection (RED) Queue Sally Floyd and Kevin Fall \\Lambda

    E-print Network

    Floyd, Sally

    be run in our new simulator ns with the command ``test­all­red'', and the input files are availableNs Simulator Tests for Random Early Detection (RED) Queue Management Sally Floyd and Kevin Fall The input files in this document are in the format used by our old simulator, tcpsim. All of these tests can

  10. [Rheumatoid arthritis: milestones in classification and treatment].

    PubMed

    Fiehn, C

    2011-02-01

    New classification criteria of rheumatoid arthritis (RA) by the American College of Rheumatology and the European League Against Rheumatism (EULAR) allow the early assignment of arthritides as RA and thus early start of therapy. This is an important step towards early diagnosis and treatment. The EULAR recommendations for the treatment of RA for the first time define the value of biologicals by means of therapeutic algorithms based on extensive scientific evidence and taking into account cost-effectiveness. As a result biologicals can be used after the first failure of disease-modifying anti-rheumatic drugs (DMARDs), if there are unfavourable prognostic factors. Methotrexate is, as a DMARD, at the centre of treatment. PMID:21271482

  11. 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

  12. Handout on Health: Rheumatoid Arthritis

    MedlinePLUS

    ... osteoporosis with their doctors as part of their long-term, ongoing care. Osteoporosis is a condition in which bones become weakened and fragile. Having rheumatoid arthritis increases the risk of developing osteoporosis for both men and women, ...

  13. Certolizumab for rheumatoid arthritis.

    PubMed

    Markatseli, T E; Papagoras, C; Nikoli, A; Voulgari, P V; Drosos, A A

    2014-01-01

    This is a review of the pharmacology of certolizumab pegol and its efficacy and safety in the treatment of patients with rheumatoid arthritis refractory to synthetic disease-modifying anti-rheumatic drugs (DMARDs). Certolizumab is a new anti-TNF-? biologic agent injected subcutaneously with an innovative molecular structure and unique pharmacodynamic and pharmacokinetic properties. Data from controlled clinical trials indicate that the drug is effective in reducing disease activity and disability. It also inhibits radiographic progression. Certolizumab administration has an acceptable safety profile. The clinical data available suggest that the nature of adverse events is generally comparable to that of other TNF-? blockers. Given its rapid onset of action certolizumab presents an attractive alternative therapeutic option for patients with moderate to severe RA refractory to DMARDs. PMID:24447441

  14. [Atrioventricular blocks and rheumatoid arthritis].

    PubMed

    David-Chaussé, J; Blanchot, P; Warin, J; Dehais, J; Bullier, R; Texier, J M

    1976-03-01

    Among 379 hospitalized cases of rheumatoid polyarthritis, 12 auriculo-ventricular blocks were detected between 1965 and 1975. The formation of a complete AV block is usually preceded by a branch block or a first degree block. During the installation of a pacemaker, hypoexcitability was usually noted. Four of the patients died. In the other 8 the evolution has been satisfactory over periods from 6 months to 4 years. Conduction disturbances were found in cases of polyarthritis of 10 years duration on the average. The articular lesions were normally diffuse with considerable lesions detectable radiologically. In many cases the frequency of extra-articular lesions indicated the severity of the rheumatic disease. From the anatomical point of view, histological lesions of rheumatoid polyarthritis were found : granuloma and arteritis in the myocardium. Only 8 authors have previously reported lesions of the donducting vessels at autopsies carried out on rheumatoid polyarthritis cases who had presented AV blocks. Except for Thery's case related to amylosis of the nodal tissue, rheumatoid granulomas occupied the whole or part of the nodal tissue. In elderly subjects suffering from rheumatoid arthritis, it was difficult to establish a strictly rheumatoid origin for the AV blocks observed, unless specific granulomas were discovered anatomically in the nodal tissue. PMID:1265414

  15. [Understanding rheumatoid arthritis].

    PubMed

    Sibilia, Jean; Sordet, Christelle; Mrabet, Dalila; Wachsmann, Dominique

    2005-12-15

    Rheumatoid arthritis is a common and severe inflammatory rheumatic disease, for which the immune mechanisms are being decoded little by little. The pathogenic ncludes significant cellular actors of innate immunity (fibroblastic synoviocytes, macrophages, mastocytes...) and adaptive immunity (T and B lymphocytes). These actors interact through the production of and response to specific (cytokines, chemokines and auto-antibodies) and non-specific (prostaglandins, nitrous oxide [NO], complement, proteases) mediators. The chronology of this rheumatoid synovitis is becoming progressively clearer. Its initiation could be the consequence of a precocious activation of the innate immunity, induced by bacterial agents or debris (PAMP). The activation of the synoviocytes and the macrophages via specific receptors (PPR) unleashes an intense inflammatory reaction that triggers a cascade of events. The ongoing nature of this synovitis leads to the intra-articular recruitment of different cells of immunity. This cellular afflux amplifies the macrophagic and synoviocytic activation and proliferation. All of these interactive phenomena end in the production of large quantities of pro-inflammatory cytokines (TNFa, IL1, IL6, IL15, IL17, IL18) but also other pathogenic mediators (auto-antibodies, complement, prostaglandins, nitrous oxide...). This synovitis persists, as it is no longer regulated by a sufficient production of physiological regulators (soluble receptors and inhibitors of cytokines). The consequence of this intense inflammation and synovial proliferation leads to osteo-articular destruction by the production of proteases and the activation of osteoclasts by the RANK/RANK-ligand pathway under the effect of cytokines (TNFa, IL5, IL1, IL6, IL17) and other mediators (prostaglandins) liberated by synoviocytes, macrophages and lymphocytes. The decryption of this puzzle has already created new therapeutic orientations. The identification of new targets is one of the major consequences of this progress in immuno-rheumatology. PMID:16544924

  16. Cray XT4: an early evaluation for petascale scientific simulation

    Microsoft Academic Search

    Sadaf R. Alam; Jeffery A. Kuehn; Richard F. Barrett; Jeff M. Larkin; Mark R. Fahey; Ramanan Sankaran; Patrick H. Worley

    2007-01-01

    The scientific simulation capabilities of next generation high-end computing technology will depend on striking a balance among memory, processor, I\\/O, and local and global network performance across the breadth of the scientific simulation space. The Cray XT4 combines commodity AMD dual core Opteron processor technology with the second generation of Cray's custom communication accelerator in a system design whose balance

  17. Tropical Virus Symptoms Can Mimic Rheumatoid Arthritis

    MedlinePLUS

    ... features on this page, please enable JavaScript. Tropical Virus Symptoms Can Mimic Rheumatoid Arthritis: Study Similarities may ... 20, 2015 (HealthDay News) -- The mosquito-borne chikungunya virus causes joint pain and swelling similar to rheumatoid ...

  18. Cray XT4: An Early Evaluation for Petascale Scientific Simulation

    SciTech Connect

    Alam, Sadaf R [ORNL; Barrett, Richard F [ORNL; Fahey, Mark R [ORNL; Kuehn, Jeffery A [ORNL; Sankaran, Ramanan [ORNL; Worley, Patrick H [ORNL; Larkin, Jeffrey M [ORNL

    2007-01-01

    The scientific simulation capabilities of next generation high-end computing technology will depend on striking a balance among memory, processor, I/O, and local and global network performance across the breadth of the scientific simulation space. The Cray XT4 combines commodity AMD dual core Opteron processor technology with the second generation of Cray's custom communication accelerator in a system design whose balance is claimed to be driven by the demands of scientific simulation. This paper presents an evaluation of the Cray XT4 using microbenchmarks to develop a controlled understanding of individual system components, providing the context for analyzing and comprehending the performance of several petascale-ready applications. Results gathered from several strategic application domains are compared with observations on the previous generation Cray XT3 and other high-end computing systems, demonstrating performance improvements across a wide variety of application benchmark problems.

  19. Just Running Around: Some Reminiscences of Early Simulation/Gaming in the United Kingdom

    ERIC Educational Resources Information Center

    van Ments, Morry

    2011-01-01

    The article begins with an abbreviated CV of the author and then recounts the formation of Society for the Advancement of Games and Simulation in Education and Training (SAGSET) and the early days of simulation and gaming in the United Kingdom. Four strands of elements of development are described together with the key events of the 1970s and…

  20. 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

  1. 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

  2. A Simulated Universe of Dwarf Galaxies: The Early Days

    NASA Astrophysics Data System (ADS)

    Reed, D. S.; Brooks, A.; Governato, F.

    2011-07-01

    We use cosmological hydrodynamic simulations to model galaxy formation at redshift 5 and higher. We explore how galaxies populate dark matter halos, focusing on the implications for the clustering properties of galaxies in the context of current and future deep surveys. We find a significant trend for galaxies with high gas fractions to lie in denser environments than gas poor galaxies of the same halo mass, as reflected by their different clustering strengths.

  3. Advanced Simulation Capability for Environmental Management (ASCEM): Early Site Demonstration

    SciTech Connect

    Meza, Juan; Hubbard, Susan; Freshley, Mark D.; Gorton, Ian; Moulton, David; Denham, Miles E.

    2011-03-07

    The U.S. Department of Energy Office of Environmental Management, Technology Innovation and Development (EM-32), is supporting development of the Advanced Simulation Capability for Environmental Management (ASCEM). ASCEM is a state-of-the-art scientific tool and approach for understanding and predicting contaminant fate and transport in natural and engineered systems. The modular and open source high performance computing tool will facilitate integrated approaches to modeling and site characterization that enable robust and standardized assessments of performance and risk for EM cleanup and closure activities. As part of the initial development process, a series of demonstrations were defined to test ASCEM components and provide feedback to developers, engage end users in applications, and lead to an outcome that would benefit the sites. The demonstration was implemented for a sub-region of the Savannah River Site General Separations Area that includes the F-Area Seepage Basins. The physical domain included the unsaturated and saturated zones in the vicinity of the seepage basins and Fourmile Branch, using an unstructured mesh fit to the hydrostratigraphy and topography of the site. The calculations modeled variably saturated flow and the resulting flow field was used in simulations of the advection of non-reactive species and the reactive-transport of uranium. As part of the demonstrations, a new set of data management, visualization, and uncertainty quantification tools were developed to analyze simulation results and existing site data. These new tools can be used to provide summary statistics, including information on which simulation parameters were most important in the prediction of uncertainty and to visualize the relationships between model input and output.

  4. Rheumatoid arthritis, periodontal disease and coronary artery disease

    Microsoft Academic Search

    S. Abou-Raya; A. Abou-Raya; A. Naim; H. Abuelkheir

    2008-01-01

    Rheumatoid arthritis (RA), periodontal disease (PD), and coronary artery disease (CAD) are common chronic inflammatory diseases.\\u000a RA is associated with accelerated vascular risk resulting in an increased prevalence of CAD with attendant early mortality\\u000a and excess morbidity. RA and PD have a common pathobiology. Accordingly, the aim of this study was to evaluate the association\\u000a between RA, PD, and CAD

  5. Cancer morbidity in rheumatoid arthritis.

    PubMed Central

    Prior, P; Symmons, D P; Hawkins, C F; Scott, D L; Brown, R

    1984-01-01

    A consecutive series of 489 patients with rheumatoid arthritis seen at the centre was studied to determine their cancer morbidity. Overall the 36 cancers diagnosed in the series between 1964 and 1981 were not significantly in excess of the expected number, but there was a highly significant excess of tumours of the reticuloendothelial system. The excess was mainly due to 6 observed cases of lymphoma. We conclude that there is a highly significant association between rheumatoid arthritis and the subsequent development of lymphoproliferative malignancy in this series. PMID:6712287

  6. [Diagnosis and treatment of rheumatoid arthritis].

    PubMed

    Krüger, K

    2014-09-01

    Rheumatoid arthritis today is still not curable but satisfactory treatable. Treatment targets include clinical remission (or at least low disease activity), lack of radiological destructions and functional disability as well as acceptable life quality and unimpaired working ability. Diagnosing and adequately treating the disease as early as possible is essential for a favourable long-term outcome. Treatment to target with validation and if necessary modification at least every three months until target is achieved ensures good results. Predominantly treatment starts with a combination of methotrexate and glucocorticoids followed by a conventional DMARD combination and then addition of a biologic DMARD in case of failing target. Presence of adverse risk factors and/or high disease activity a cDMARD/bDMARD combination might be used already after starting treatment failure. Additional treatment options such as physiotherapy should be added. Altogether with current treatment possibilities burden of disease declined dramatically in recent years. PMID:25180998

  7. 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

  8. Detection of rheumatoid arthritis using infrared imaging

    NASA Astrophysics Data System (ADS)

    Frize, Monique; Adéa, Cynthia; Payeur, Pierre; Di Primio, Gina; Karsh, Jacob; Ogungbemile, Abiola

    2011-03-01

    Rheumatoid arthritis (RA) is an inflammatory disease causing pain, swelling, stiffness, and loss of function in joints; it is difficult to diagnose in early stages. An early diagnosis and treatment can delay the onset of severe disability. Infrared (IR) imaging offers a potential approach to detect changes in degree of inflammation. In 18 normal subjects and 13 patients diagnosed with Rheumatoid Arthritis (RA), thermal images were collected from joints of hands, wrists, palms, and knees. Regions of interest (ROIs) were manually selected from all subjects and all parts imaged. For each subject, values were calculated from the temperature measurements: Mode/Max, Median/Max, Min/Max, Variance, Max-Min, (Mode-Mean), and Mean/Min. The data sets did not have a normal distribution, therefore non parametric tests (Kruskal-Wallis and Ranksum) were applied to assess if the data from the control group and the patient group were significantly different. Results indicate that: (i) thermal images can be detected on patients with the disease; (ii) the best joints to image are the metacarpophalangeal joints of the 2nd and 3rd fingers and the knees; the difference between the two groups was significant at the 0.05 level; (iii) the best calculations to differentiate between normal subjects and patients with RA are the Mode/Max, Variance, and Max-Min. We concluded that it is possible to reliably detect RA in patients using IR imaging. Future work will include a prospective study of normal subjects and patients that will compare IR results with Magnetic Resonance (MR) analysis.

  9. Bronchocentric granulomatosis and rheumatoid arthritis.

    PubMed

    Bonafede, R P; Benatar, S R

    1987-04-01

    We report a 42-year-old patient with an 11-year history of rheumatoid arthritis (RA) who presented 8 years later with haemoptysis and was found to have multiple pulmonary opacities with histological features of bronchocentric granulomatosis (BCG). The association between BCG and RA is discussed and the literature is reviewed. PMID:3651314

  10. Conjunctival nodule in rheumatoid arthritis.

    PubMed

    Kheirkhah, Ahmad; Amoli, Fahimeh Asadi; Azari, Amir A; Molaei, Saber; Roozbahani, Mehdi

    2012-02-01

    Conjunctival nodule is very rarely seen in patients with rheumatoid arthritis. Previously reported cases were associated with the use of methotrexate. Here, we report a conjunctival rheumatoid nodule without such prior treatment. A 49-year-old woman with seropositive rheumatoid arthritis, who was being treated only with oral steroids and hydroxychloroquine, developed diffuse anterior scleritis in the right eye. In addition, examination showed a focal raised yellow/tan conjunctival nodule. The nodule was within the bulbar conjunctiva with no attachments to the underlying tissue, which is different from nodular scleritis. The nodule was not tender on palpation. The patient underwent excisional biopsy of the nodule. Intraoperatively, the lesion was noted to be a firm nodule within substantia propria of the conjunctiva. Hematoxylin-eosin staining of the specimen revealed a central area of necrosis surrounded by palisades of histiocytes. Increased dosage of oral steroid after the biopsy resulted in resolution of the ocular symptoms and signs. In conclusion, rheumatoid nodules may be seen in the conjunctiva even without prior treatment with methotrexate. These nodules may show the severity of the underlying disease and the need for more aggressive treatment. PMID:22271069

  11. Interest of modelling in rheumatoid arthritis.

    PubMed

    Beresniak, Ariel; Dupont, Danielle M; Becker, Jean-Claude; Merkesdal, Sonja

    2012-01-01

    Such as prospective studies can provide evidence-based information for clinicians and regulatory agencies, modelling studies provide useful information when experimental studies are to complex, too long, or too expensive to carry out. If modelling has been widely used in pharmacokinetics, it is in the field of pharmacoeconomics that numerous models have been published in recent years, including models relevant to the management of rheumatoid arthritis (RA). The most common modelling techniques published in RA are decision trees and Markov models which are used to perform cost-effectiveness and cost-utility analyses using real or simulated populations. This paper reviews the main types of modelling techniques used in pharmacoeconomic studies with the aim of clarifying their interest and limitations for the clinicians. Generating such evidence is highly relevant to assisting clinical recommendations and reimbursement decisions towards enabling the optimal management of RA and reducing its overall clinical and economic burden, for the benefits of patients and health systems. PMID:23078913

  12. Atypical Rheumatoid Nodules: A Possible Precursor to a Rheumatoid Variant in a Rheumatoid-Factor-Negative Patient. Case Report

    PubMed Central

    Kim, Sharon; Parker, Wendy L.

    2008-01-01

    Subcutaneous nodules occur in approximately 20–25% of rheumatoid factor (RF)-positive rheumatoid patients. In this paper, we present a unique case of a 47-year-old healthy RF-negative woman with a 3-year history of necrobiotic nodules over the dorsum of her hands, extensor forearms, and lower extremities. This may represent an atypical presentation or a new rheumatoid variant. PMID:19048351

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

    E-print Network

    Hartmann, Mitra J. Z.

    TOWARDS AN "EARLY NEURAL CIRCUIT SIMULATOR": A FPGA IMPLEMENTATION OF PROCESSING IN THE RAT WHISKER.leung, panyan, cshroeder, f-memik, g-memik, m-hartmann] @northwestern.edu ABSTRACT We have constructed a FPGA of the rat. The use of a FPGA is highly suitable for such an application, because the computation involved

  14. Pulmonary Cryptococcosis That Mimicked Rheumatoid Nodule in Rheumatoid Arthritis Lesion

    PubMed Central

    Jang, Dong Won; Kim, Seon Jae; Kim, Seok Won; Park, Soo Yeon; Kwon, Yong Hwan; Jeong, Yeon Oh; Lee, Ji Yeon; Kim, Bo Sung; Kim, Woo-Shik; Joh, Joon-Sung

    2014-01-01

    Recently, the incidence of pulmonary cryptococcosis is gradually increasing in rheumatoid arthritis (RA) patients. Pulmonary rheumatoid nodules (PRN) are rare manifestations of RA. Eighteen months ago, a 65-year old woman was admitted to hospital due to multiple nodules (2.5×2.1×2 cm) with cavitations in the right lower lobe. She was diagnosed with RA three year ago. She had been taking methotrexate, leflunomide, and triamcinolone. A video-assisted thoracoscopic surgery biopsy was performed and PRN was diagnosed. However, a newly growing huge opacity with cavitation was detected in the same site. Pulmonary cryptococcal infection was diagnosed through a transthoracic computed tomograpy guided needle biopsy. Cryptococcus antigen was detected in serum but not in cerebrospinal fluid. The patient was treated with oral fluconazole which resulted clinical improvement and regression of the nodule on a series of radiography. Herein, we report the case of pulmonary cryptococcosis occurring in the same location as that of the PRN. PMID:25580144

  15. Robust regression and posterior predictive simulation increase power to detect early bursts of trait evolution.

    PubMed

    Slater, Graham J; Pennell, Matthew W

    2014-05-01

    A central prediction of much theory on adaptive radiations is that traits should evolve rapidly during the early stages of a clade's history and subsequently slowdown in rate as niches become saturated--a so-called "Early Burst." Although a common pattern in the fossil record, evidence for early bursts of trait evolution in phylogenetic comparative data has been equivocal at best. We show here that this may not necessarily be due to the absence of this pattern in nature. Rather, commonly used methods to infer its presence perform poorly when when the strength of the burst--the rate at which phenotypic evolution declines--is small, and when some morphological convergence is present within the clade. We present two modifications to existing comparative methods that allow greater power to detect early bursts in simulated datasets. First, we develop posterior predictive simulation approaches and show that they outperform maximum likelihood approaches at identifying early bursts at moderate strength. Second, we use a robust regression procedure that allows for the identification and down-weighting of convergent taxa, leading to moderate increases in method performance. We demonstrate the utility and power of these approach by investigating the evolution of body size in cetaceans. Model fitting using maximum likelihood is equivocal with regards the mode of cetacean body size evolution. However, posterior predictive simulation combined with a robust node height test return low support for Brownian motion or rate shift models, but not the early burst model. While the jury is still out on whether early bursts are actually common in nature, our approach will hopefully facilitate more robust testing of this hypothesis. We advocate the adoption of similar posterior predictive approaches to improve the fit and to assess the adequacy of macroevolutionary models in general. PMID:24149077

  16. Peripheral corneal ulceration associated with rheumatoid arthritis

    PubMed Central

    Karampatakis, Vasileios; Konidaris, Vasileios; Michailidou, Maria; Gerofotis, Antonios; Daniilidis, Michail

    2013-01-01

    Patient: Female, 60 Final Diagnosis: Corneal ulceration Symptoms: Blurred vision Medication: Abatacept Clinical Procedure: — Specialty: Ophthalmology Objective: Management of emergency care Background: To report a case of a patient with rheumatoid arthritis (RA) and associated peripheral corneal ulceration. Case Report: A 60-year-old woman with RA diagnosed 15 years ago, under immunosuppressive therapy (IV abatacept 250 mg/month), demonstrated blurring of vision in her RE (right eye). Visual acuity was 6/10 in the RE and 10/10 in the LE. Slit lamp examination revealed a paracentral superior corneal melt in the RE. Anterior chamber reaction was 2+. Laboratory investigations revealed positive anti-Ro and anti-La, anti-Extractable Nuclear Antigens (anti-ENA, ELISA), while anti-Sm, anti-Rnp, anti-Jo1 and anti-Scl70 were found negative. IgG and IgA serum immunoglobulins were found elevated, but IgE and IgM were within normal levels. Further evaluation for the underlying disease revealed highly elevated rheumatoid factor and C-reactive protein. The patient, who had been receiving anti-TNF during the last 6 months, underwent treatment with topical tobramycin and lubricants and oral prednisone 60 mg/day with tapering doses, to which methotrexate p.os. 15 mg/week was added. The condition improved within a few days after the initiation of prednisone treatment. Re-epithelization occurred 1 week after the onset of the immunosuppressive treatment. Only punctate fluorescein dye uptake was detected in the margins of the lesion. Conclusions: The effective control of the underlying disease and early diagnosis of the dry eye syndrome in RA patients may prevent serious corneal complications such as corneal ulceration. The initiation of treatment with steroids and immunosuppresants was found to halt the progression of keratolysis, and assisted re-epithelization. PMID:23986797

  17. Tyrosine kinases in rheumatoid arthritis

    PubMed Central

    2011-01-01

    Rheumatoid arthritis (RA) is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor ?-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA. PMID:21861931

  18. Ayurvedic medicine for rheumatoid arthritis.

    PubMed

    Basnyat, Shristi; Kolasinski, Sharon L

    2014-08-01

    Ayurvedic medicine is the traditional medicine of India, which originated over 5,000 years ago. Parts of this alternative medical system have become increasingly popular worldwide as patients seek approaches to medical care that they perceive as more holistic and less toxic than those offered by conventional Western medicine. Despite the advent of highly effective pharmacologic therapy, most individuals with rheumatoid arthritis (RA) continue to use alternative therapy at some point in the treatment of their disease. This report discusses some of the in-vitro data that suggest potential mechanisms through which Ayurvedic herbal medicines might have beneficial actions in rheumatoid arthritis, and the available clinical data evaluating the use of Ayurvedic medicine for RA. PMID:24938440

  19. Osteoarticular tuberculosis mimicking rheumatoid arthritis.

    PubMed

    Seung, Ong Ping; Sulaiman, Wahinuddin

    2012-11-01

    Tuberculosis (TB) remains a global burden despite extensive efforts to control it. TB arthritis commonly manifest as monoarthritis of weight-bearing joints. We report a rare presentation of osteoarticular TB involving multiple small joints of the hands, which mimicked rheumatoid arthritis (RA). Magnetic resonance imaging showed tenosynovitis. The patient was initially treated for seronegative RA but failed to respond. Subsequently, synovial biopsy led to the diagnosis. Antituberculosis treatment was given for 1 year. PMID:22399018

  20. Cell death in rheumatoid arthritis

    Microsoft Academic Search

    Adelheid Korb; Hermann Pavenstädt; Thomas Pap

    2009-01-01

    Apoptosis plays a pivotal role in tissue homoeostasis both under physiological and pathological conditions and several studies\\u000a have shown that some characteristic changes in the composition and structure of the inflamed synovial membrane in rheumatoid\\u000a arthritis (RA) are linked to an altered apoptotic response of synovial cells. As a result, a hyperplastic synovial tissue\\u000a is generated that mediates the progressive

  1. Methotrexate in refractory rheumatoid arthritis

    Microsoft Academic Search

    A. M. Th. Boerbooms; M. E. C. Jeurissen; A. A. A. Westgeest; H. Theunisse; L. B. A. Putte

    1988-01-01

    Summary Fourteen patients with severe rheumatoid arthritis refractory to hydroxychloroquine, gold-thioglucose, D-penicillamine and azathioprine completed a 6-month open study with oral methotrexate (2.5 to 5 mg every 12 hours, three doses weekly). Twelve of them were followed up for 12 months. Compared with pretreatment values, there was a significant reduction in duration of morning stiffness (p<0.01), in the number of

  2. 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.

  3. Osteoporosis in rheumatoid arthritis

    Microsoft Academic Search

    Y. Suzuki; Y. Mizushima

    1997-01-01

    Summary  Periarticular osteopenia of appendicular bones occurs early in the course of RA.Loss of the balance between bone resorption\\u000a and formation contributes to the development of perarticular osteopenia and might be mediated through increased production\\u000a of cytokines and prostaglandins by the synovium and bone marrow. Generalized osteopenia isalso common and leads to an increased\\u000a risk of fracture. Although the pathogenesis of

  4. Low Incidence of Rheumatoid Factor and Autoantibodies in Nigerian Patients with Rheumatoid Arthritis

    PubMed Central

    Greenwood, B. M.; Herrick, E. M.

    1970-01-01

    Sera from 53 Nigerian patients satisfying the American Rheumatism Association criteria for a diagnosis of definite or probable rheumatoid arthritis and sera from sick and healthy Nigerian controls were tested for rheumatoid factor, autoantibodies, and immunoglobulin levels. Rheumatoid factor and autoantibodies were found no more frequently in patients with rheumatoid arthritis than in controls. These findings confirm the clinical impression that Nigerian patients with polyarthritis satisfying the criteria for a diagnosis of rheumatoid arthritis differ from Caucasian patients with the disease in a number of important respects. They suggest that either these patients do not have rheumatoid arthritis but a distinct clinical syndrome or that in Nigeria the course of rheumatoid arthritis is modified by genetic or environmental factors. PMID:5411447

  5. Regional precipitation simulations for the mid-1970s shift and early-2000s hiatus

    NASA Astrophysics Data System (ADS)

    Meehl, Gerald A.; Teng, Haiyan

    2014-11-01

    It has been demonstrated that climate models initialized with observations produce better simulations of Pacific sea surface temperature (SST) patterns than uninitialized simulations for the two major climate regime changes of the last 40 years, the mid-1970s climate shift and early-2000s hiatus. A fundamental feature of these hindcasts is the simulation of the SST anomalies associated with the phase of the Interdecadal Pacific Oscillation (IPO). Since regional precipitation patterns over selected land areas in south Asia, Australia, and North America are known to be affected by SST patterns over the Pacific, it is shown that the initialized climate model simulations produce qualitatively better agreement with observations for regional precipitation anomalies in those regions compared to uninitialized climate models. Though the signals are small, the anomalies are consistent with our physical process-based understanding of precipitation responses over certain land areas during different IPO phases.

  6. 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

  7. Rheumatoid Arthritis and Complementary and Alternative Medicine

    MedlinePLUS

    ... botanicals in osteoarthritis and rheumatoid arthritis: a review. Evidence-Based Complementary and Alternative Medicine: e-CAM . 2005;2( ... Medicine Zhang C, Jiang M, Lü A-P. Evidence-based Chinese medicine for rheumatoid arthritis. Journal of Traditional ...

  8. 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

  9. Treatment of Rheumatoid Arthritis with Traditional Chinese Medicine

    PubMed Central

    Lee, Wen-Yuan; Chen, Hsin-Yi

    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

  10. Tumour necrosis factor ? independent disease mechanisms in rheumatoid arthritis: a histopathological study on the effect of infliximab on rheumatoid nodules

    Microsoft Academic Search

    D Baeten; F De Keyser; E M Veys; Y Theate; F A Houssiau; P Durez

    2004-01-01

    Background: It has been suggested that the immunopathology of rheumatoid nodules parallels that of inflamed synovium in rheumatoid arthritis (RA).Objective: To analyse the effect of infliximab on the immunopathology of rheumatoid nodules in order to provide new insights into the relationship between synovial inflammation and rheumatoid nodules.Materials and methods: Nodules were present at baseline in six patients with RA and

  11. 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.

  12. [Renal involvement in patients with rheumatoid arthritis].

    PubMed

    Galesi?, Kresimir; Prkacin, Ingrid; Tisljar, Miroslav; Vergles, Jadranka Morovi?

    2009-01-01

    In rheumatoid arthritis (RA) kidney is commonly affected organ with clinical presentation characterised by proteinuria (often nephrotic range) and microhematuria followed by chronic renal failure. This condition is well recognized as a rheumatoid nephropathy (rheumatoid glomerulonephritis), which is mediated by an immunological inflammation and by nephrotoxic effects of numerous drugs usually used in rheumatoid arthiritis treatment, such as NSAID, DMARD. In the patohistological examination various kinds of associated renal lesions could be seen. The most often are amyloidosis, glomerulonephritis, interstitial nephritis. In this study, we presented 15 patients, 10 women and 5 men, mean age of 60.2 with average rheumatoid arthritis duration of 19.4 years and signs of rheumatoid nephropathy. In all patients renal biopsy was performed with frequency of histopathological findings as follows: amyloidosis in 5 patients, IgA nephropathy in 3 patients, FSGS in 3 patients, mesangial proliferative glomerulonephritis in 3 patients, minimal change disease, pauci-immune glomerulonephritis and thin membrane disease in 1 patient. In all patients (except patient with thin membrane nephropathy) we started immunossuppresive therapy with glucocorticoids in combination with cyclophosphamide or cyclosporin or azatioprine. In conclusion, in all patients with rheumatoid arthritis, parameters of renal function should be monitored and in the case of patologic results, renal biopsy should be be performed. In the treatment of RA patients with related renal disorder, suspected causal drug should be removed from the treatment and specific immunosuppressive therapy initiated. PMID:20954306

  13. Total Knee Arthroplasty in Rheumatoid Arthritis

    PubMed Central

    Lee, Jin Kyu

    2012-01-01

    The course of rheumatoid arthritis varies from mild disease to severe joint destructive variant that progresses rapidly, eventually leading to unremitting pain and joint deformity. In advanced disease, total knee arthroplasty has proven to be the most successful intervention that reduces knee pain and improves physical function in rheumatoid arthritis patients. However, as rheumatoid arthritis patients carry additional potential for late complications, many important considerations regarding preoperative evaluation and surgical technique must be taken into account in order to improve the results of total knee arthroplasty in this subgroup of patients. PMID:22570845

  14. Biomechanical analysis of rheumatoid arthritis of the wrist joint.

    PubMed

    Bajuri, M N; Kadir, Mohammed Rafiq Abdul; Amin, Iskandar M; Ochsner, Andreas

    2012-07-01

    The wrist is the most complex joint for virtual three-dimensional simulations, and the complexity is even more pronounced when dealing with skeletal disorders of the joint such, as rheumatoid arthritis (RA). In order to analyse the biomechanical difference between healthy and diseased joints, three-dimensional models of these two wrist conditions were developed from computed tomography images. These images consist of eight carpal bones, five metacarpal bones, the distal radius and ulna. The cartilages were developed based on the shape of the available articulations and ligaments were simulated via mechanical links. The RA model was developed accurately by simulating all ten common criteria of the disease related to the wrist. Results from the finite element (FE) analyses showed that the RA model produced three times higher contact pressure at the articulations compared to the healthy model. Normal physiological load transfer also changed from predominantly through the radial side to an increased load transfer approximately 5% towards the ulnar. Based on an extensive literature search, this is the first ever reported work that simulates the pathological conditions of the rheumatoid arthritis of the wrist joint. PMID:22913098

  15. Adalimumab in the treatment of rheumatoid arthritis.

    PubMed

    Voulgari, Paraskevi V; Drosos, Alexandros A

    2014-03-01

    Introduction: Rheumatoid arthritis (RA) is a systemic inflammatory disease that causes increased morbidity and mortality. The treatment of the disease has considerably advanced with the addition of biological agents targeting pro-inflammatory cytokines such as tumor necrosis factor (TNF). Adalimumab (ADA) is one of the currently available five TNF inhibitors for clinical use in RA. It is a fully humanized monoclonal antibody which may be prescribed as monotherapy or in combination with methotrexate or other disease-modifying antirheumatic drugs. Areas covered: This review summarizes the recent available data on efficacy and safety of ADA in patients with early and established RA as well as improvement of quality of life and finally we provide data on biologic drug comparison. Expert opinion: ADA has been evaluated in various randomized placebo-controlled trials in RA, prospective observational studies as well as open-label extensions of the original double-blind trials providing experience and data about the long-term efficacy and safety of the drug. Effectiveness of the drug is sustained, while in most cases RA patients treated with ADA experienced a slower radiographic progression and consequently less disability and improved health-related quality of life outcomes. Clinical trials demonstrated no new safety signals and a safety profile consistent with that of the anti-TNF class. PMID:24588123

  16. The influence of early aging on eye movements during motor simulation.

    PubMed

    McCormick, Sheree A; Causer, Joe; Holmes, Paul S

    2014-01-01

    Movement based interventions such as imagery and action observation are used increasingly to support physical rehabilitation of adults during early aging. The efficacy of these more covert approaches is based on an intuitively appealing assumption that movement execution, imagery and observation share neural substrate; alteration of one influences directly the function of the other two. Using eye movement metrics this paper reports findings that question the congruency of the three conditions. The data reveal that simulating movement through imagery and action observation may offer older adults movement practice conditions that are not constrained by the age-related decline observed in physical conditions. In addition, the findings provide support for action observation as a more effective technique for movement reproduction in comparison to imagery. This concern for imagery was also seen in the less congruent temporal relationship in movement time between imagery and movement execution suggesting imagery inaccuracy in early aging. PMID:25005270

  17. Early cardiovascular adaptation to zero gravity simulated by head-down tilt

    NASA Technical Reports Server (NTRS)

    Blomqvist, C. G.; Nixon, J. V.; Johnson, R. L., Jr.; Mitchell, J. H.

    1979-01-01

    The early cardiovascular adaptation to zero gravity, simulated by head-down tilt at 5 deg, was studied in a series of 10 normal young men. The validity of the model was confirmed by comparing the results with data from Apollo and Skylab flights. Tilt produced a significant central fluid shift with a transient increase in central venous pressure, later followed by an increase in left ventricular size without changes in cardiac output, arterial pressure, or contractile state. The hemodynamic changes were transient with a nearly complete return to the control state within 6 h. The adaptation included a diuresis and a decrease in blood volume, associated with ADH, renin, and aldosterone inhibition.

  18. 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

  19. Simulation of multiple ion channel block provides improved early prediction of compounds’ clinical torsadogenic risk

    PubMed Central

    Mirams, Gary R.; Cui, Yi; Sher, Anna; Fink, Martin; Cooper, Jonathan; Heath, Bronagh M.; McMahon, Nick C.; Gavaghan, David J.; Noble, Denis

    2011-01-01

    Aims The level of inhibition of the human Ether-à-go-go-related gene (hERG) channel is one of the earliest preclinical markers used to predict the risk of a compound causing Torsade-de-Pointes (TdP) arrhythmias. While avoiding the use of drugs with maximum therapeutic concentrations within 30-fold of their hERG inhibitory concentration 50% (IC50) values has been suggested, there are drugs that are exceptions to this rule: hERG inhibitors that do not cause TdP, and drugs that can cause TdP but are not strong hERG inhibitors. In this study, we investigate whether a simulated evaluation of multi-channel effects could be used to improve this early prediction of TdP risk. Methods and results We collected multiple ion channel data (hERG, Na, l-type Ca) on 31 drugs associated with varied risks of TdP. To integrate the information on multi-channel block, we have performed simulations with a variety of mathematical models of cardiac cells (for rabbit, dog, and human ventricular myocyte models). Drug action is modelled using IC50 values, and therapeutic drug concentrations to calculate the proportion of blocked channels and the channel conductances are modified accordingly. Various pacing protocols are simulated, and classification analysis is performed to evaluate the predictive power of the models for TdP risk. We find that simulation of action potential duration prolongation, at therapeutic concentrations, provides improved prediction of the TdP risk associated with a compound, above that provided by existing markers. Conclusion The suggested calculations improve the reliability of early cardiac safety assessments, beyond those based solely on a hERG block effect. PMID:21300721

  20. Rheumatoid lymphadenopathy: a morphological and immunohistochemical study.

    PubMed Central

    Kondratowicz, G M; Symmons, D P; Bacon, P A; Mageed, R A; Jones, E L

    1990-01-01

    Sixteen lymph nodes from 14 patients with rheumatoid arthritis were examined immunohistochemically and morphometrically and compared with 10 control nodes showing follicular hyperplasia from patients without rheumatoid disease. Frozen material was available from nine patients and all controls. The nodes from patients with rheumatoid arthritis seemed to share characteristic features. The most striking of these was follicular hyperplasia in which the germinal centres, in spite of being quite large, showed relatively sparse proliferative activity. The nodes often showed infiltration of germinal centres by CD8 positive T lymphocytes and contained fewer IL2R positive cells in the paracortex than controls. These and other features may have some correlation with disease activity. Lymphadenopathy in rheumatoid arthritis may not just be a manifestation of joint inflammation but an active component of this multisystem disease and may reflect a widespread immunological abnormality. Images PMID:2318986

  1. The molecular basis of rheumatoid arthritis

    Microsoft Academic Search

    CORNELIA M. WEYAND; Jörg J. Goronzy

    1997-01-01

    Rheumatoid arthritis (RA) is an inflammatory disease targeting the synovial membrane and extra-articular tissues. The most\\u000a feared consequences are significant levels of pain, functional disability, and rheumatoid organ involvement. Molecular investigations\\u000a of RA have markedly changed the understanding of the pathogenesis although the etiology remains unresolved. Despite the failure\\u000a of intense efforts to confirm the presence of an infectious micro-organism

  2. New understanding and approaches to treatment in rheumatoid arthritis.

    PubMed

    Tayar, Jean H; Suarez-Almazor, Maria E

    2010-01-01

    Rheumatoid arthritis (RA) is the most common autoimmune inflammatory polyarthritis. Significant advances in the understanding of its pathogenesis have led in the past two decades to major advancement in its therapy. We used data from articles in Cochrane Database of Systematic Reviews on 'rheumatoid arthritis', meta-analyses and randomized controlled trials on adult RA (age >19 years) published in English within the past 5 years and identified in PubMed, and other key papers on management of RA. Appropriate, early and aggressive therapy is required for confirmed active cases of RA. The choice of disease-modifying drugs and different combinations, especially the newer biologic agents in regards of their early and long-term usage remains debated because of high costs and long-term safety concerns. Development of newer biologic agents working on different pathways of inflammation is underway in different stages. It remains to be determined how and when each of these agents will fit in the overall management of RA. Furthermore, post-marketing surveillance of the safety and response sustainability of these drugs is warranted. PMID:20200013

  3. Simulating ultra-wideband imaging for the early detection of tissue injury

    NASA Astrophysics Data System (ADS)

    Niu, Weihong; Hlavaty, Kelan; Tanska, Daria; Tseng, Nancy; Li, Jia; Penprase, Barbara

    2009-02-01

    Various medical imaging techniques exist to detect the early development of tissue damage. However, a widely commercialized device that can be easily used and is cost effective is still needed. Through a literature review, we examined ultrasound, microwave tomography, and ultra-wideband (UWB) technology. Out of these techniques, UWB is the most promising since it has the capability to detect small adjustments in dielectric properties, which can change with minor alterations in perfusion and internal pressure. These minor alterations are vital in detecting the onset of ischemia, which precedes many serious conditions affecting tissue health. In addition to its ability in detection, UWB also has the potential to become a widely accessible technology to hospitals. Using software called XFdtd, we simulated ultrawideband pulses propagating through planes designed to resemble tissue in its dielectric properties. After testing several sizes of the horn antenna and configurations for the wire and port, the antenna's near field was finally able to reach the distance necessary to penetrate the tissue model. The resulting graph of voltage versus time was generated from the received antenna signal and it will be compared to the graphs that result after the dielectric properties of the model have been changed to simulate tissue injury. Through this manipulation of the tissue model, the sensitivity and selectivity of UWB in measuring small fluctuations in perfusion can be determined. In this future work with XFdtd, we want to show that UWB is a novel and viable technique in detecting early tissue injury.

  4. 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

  5. The Rheumatoid Arthritic At Home

    PubMed Central

    Hunt, T. E.

    1977-01-01

    Most management of rheumatoid arthritis must take place in the patient's own home with only intermittent professional help. With good planning and instruction it is possible to create in the home a milieu appropriate not only for possible inducement of remission, but also for continuing care during even protracted disability. The mainstay of treatment in all stages of this disease is the achievement of a right balance between rest and activity. In the initial stages, proper rest and support, including splinting of the joints with other simple measures, will greatly relieve pain and help control the inflammatory process. A variety of therapeutic exercises can reduce the likelihood of secondary immobility and promote restoration of strength and function. For the patient in whom the disease has become chronic and disabling a wide variety of self-help devices can be prescribed, together with appropriate home modifications. ImagesFig. 1Fig. 2Fig. 3Figs. 4 & 5Fig. 6Fig. 7 PMID:21307997

  6. Pharmacotherapy Options in Rheumatoid Arthritis

    PubMed Central

    Kumar, Pradeep; Banik, Snehashish

    2013-01-01

    Drugs form the mainstay of therapy in rheumatoid arthritis (RA). Five main classes of drugs are currently used: analgesics, non-steroidal anti-inflammatories (NSAIDs), glucocorticoids, nonbiologic and biologic disease-modifying antirheumatic drugs. Current clinical practice guidelines recommend that clinicians start biologic agents if patients have suboptimal response or intolerant to one or two traditional disease modifying agents (DMARDs). Methotrexate, sulfasalazine, leflunomide and hydroxychloroquine are the commonly used DMARDs. Currently, anti-TNF is the commonly used first line biologic worldwide followed by abatacept and it is usually combined with MTX. There is some evidence that tocilizumab is the most effective biologic as a monotherapy agent. Rituximab is generally not used as a first line biologic therapy due to safety issues but still as effective as anti-TNF. The long term data for the newer oral small molecule biologics such as tofacitinib is not available and hence used only as a last resort. PMID:23997576

  7. Albedo and heat transport in 3-D model simulations of the early Archean climate

    NASA Astrophysics Data System (ADS)

    Kienert, H.; Feulner, G.; Petoukhov, V.

    2013-08-01

    At the beginning of the Archean eon (ca. 3.8 billion years ago), the Earth's climate state was significantly different from today due to the lower solar luminosity, smaller continental fraction, higher rotation rate and, presumably, significantly larger greenhouse gas concentrations. All these aspects play a role in solutions to the "faint young Sun paradox" which must explain why the ocean surface was not fully frozen at that time. Here, we present 3-D model simulations of climate states that are consistent with early Archean boundary conditions and have different CO2 concentrations, aiming at an understanding of the fundamental characteristics of the early Archean climate system. In order to do so, we have appropriately modified an intermediate complexity climate model that couples a statistical-dynamical atmosphere model (involving parameterizations of the dynamics) to an ocean general circulation model and a thermodynamic-dynamic sea-ice model. We focus on three states: one of them is ice-free, one has the same mean surface air temperature of 288 K as today's Earth and the third one is the coldest stable state in which there is still an area with liquid surface water (i.e. the critical state at the transition to a "snowball Earth"). We find a reduction in meridional heat transport compared to today, which leads to a steeper latitudinal temperature profile and has atmospheric as well as oceanic contributions. Ocean surface velocities are largely zonal, and the strength of the atmospheric meridional circulation is significantly reduced in all three states. These aspects contribute to the observed relation between global mean temperature and albedo, which we suggest as a parameterization of the ice-albedo feedback for 1-D model simulations of the early Archean and thus the faint young Sun problem.

  8. 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.

    2014-11-01

    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 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 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 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 conditions.

  9. Comparing Stochastic Differential Equations and Agent-Based Modelling and Simulation for Early-Stage Cancer

    PubMed Central

    Figueredo, Grazziela P.; Siebers, Peer-Olaf; Owen, Markus R.; Reps, Jenna; Aickelin, Uwe

    2014-01-01

    There is great potential to be explored regarding the use of agent-based modelling and simulation as an alternative paradigm to investigate early-stage cancer interactions with the immune system. It does not suffer from some limitations of ordinary differential equation models, such as the lack of stochasticity, representation of individual behaviours rather than aggregates and individual memory. In this paper we investigate the potential contribution of agent-based modelling and simulation when contrasted with stochastic versions of ODE models using early-stage cancer examples. We seek answers to the following questions: (1) Does this new stochastic formulation produce similar results to the agent-based version? (2) Can these methods be used interchangeably? (3) Do agent-based models outcomes reveal any benefit when compared to the Gillespie results? To answer these research questions we investigate three well-established mathematical models describing interactions between tumour cells and immune elements. These case studies were re-conceptualised under an agent-based perspective and also converted to the Gillespie algorithm formulation. Our interest in this work, therefore, is to establish a methodological discussion regarding the usability of different simulation approaches, rather than provide further biological insights into the investigated case studies. Our results show that it is possible to obtain equivalent models that implement the same mechanisms; however, the incapacity of the Gillespie algorithm to retain individual memory of past events affects the similarity of some results. Furthermore, the emergent behaviour of ABMS produces extra patters of behaviour in the system, which was not obtained by the Gillespie algorithm. PMID:24752131

  10. 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

  11. The Argo Simulation: II. The Early Build-up of the Hubble Sequence

    E-print Network

    Feldmann, Robert

    2014-01-01

    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 ($z\\geq3$) 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 ($\\sim10^4$ M$_\\odot$, $\\sim100$ pc) and sub-grid physical model that was used in the Eris simulation but probes a sub-volume almost ten 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 ($\\log M_{\\star}/{\\rm M}_{\\odot}\\sim8-11$ at $z\\simeq3$), while resolving properly their structural properties. We recover a diversity of morphologies, including late-type/irregular disc galaxies with flat rotation curves, s...

  12. FORMING EARLY-TYPE GALAXIES IN {Lambda}CDM SIMULATIONS. I. ASSEMBLY HISTORIES

    SciTech Connect

    Johansson, Peter H. [Department of Physics, University of Helsinki, Gustaf Haellstroemin katu 2a, FI-00014 Helsinki (Finland); Naab, Thorsten [Max-Planck-Insitut fuer Astrophysik, Karl-Schwarzschild-Str. 1, D-85741 Garching bei Muenchen (Germany); Ostriker, Jeremiah P., E-mail: Peter.Johansson@helsinki.fi [Department of Astrophysics, Peyton Hall, Princeton, NJ 08544 (United States)

    2012-08-01

    We present a sample of nine high-resolution cosmological simulations in the mass range of M{sub vir} = 7 Multiplication-Sign 10{sup 11}-4 Multiplication-Sign 10{sup 12} M{sub Sun} starting from {Lambda}CDM initial conditions. Our simulations include primordial radiative cooling, photoionization, star formation, supernova II feedback, but exclude supernova-driven winds and active galactic nucleus feedback. The simulated galaxies assemble in two phases, with the initial growth dominated by compact (r < r{sub eff}) in situ star formation fueled by cold, low-entropy gas streams resulting in a very similar mean assembly redshift of z{sub f,ins} {approx} 2.5 for the in situ stellar component in all galaxies. The late growth is dominated by accretion of old stars formed in subunits outside the main galaxy (r > r{sub eff}) resulting in an assembly redshift of z{sub f,acc} {approx} 0.5-1.5 with much larger scatter. We find a positive correlation between the fraction of accreted stars and the final mass of our galaxies. We show that gravitational feedback strongly suppresses late star formation in massive galaxies contributing to the observed galaxy color bimodality. The accretion of stellar material is also responsible for the observed size growth of early-type galaxies. In addition, we find that the dark matter fractions within the stellar half-mass radii continuously increase toward lower redshift from about f{sub DM} {approx} 0.05 at z {approx} 3 to f{sub DM} {approx} 0.1-0.3 at z = 0. Furthermore, the logarithmic slope of the total density profile is nearly isothermal at the present day ({gamma}' {approx} 1.9-2.2). Finally, the input of gravitational heating lowers the central dark matter densities in the galaxies, with the effect being smaller compared to simulations without supernova feedback.

  13. Simulating multiple merger pathways to the central kinematics of early-type galaxies

    NASA Astrophysics Data System (ADS)

    Moody, Christopher E.; Romanowsky, Aaron J.; Cox, Thomas J.; Novak, G. S.; Primack, Joel R.

    2014-10-01

    Two-dimensional integral field surveys such as ATLAS3D are producing rich observational data sets yielding insights into galaxy formation. These new kinematic observations have highlighted the need to understand the evolutionary mechanisms leading to a spectrum of fast rotators and slow rotators in early-type galaxies. We address the formation of slow and fast rotators through a series of controlled, comprehensive hydrodynamical simulations, sampling idealized galaxy merger scenarios constructed from model spiral galaxies. Idealized and controlled simulations of this sort complement the more `realistic' cosmological simulations by isolating and analysing the effects of specific parameters, as we do in this paper. We recreate minor and major binary mergers, binary merger trees with multiple progenitors, and multiple sequential mergers. Within each of these categories of formation history, we correlate progenitor gas fraction, mass ratio, orbital pericentre, orbital ellipticity, and spin with remnant kinematic properties. We create kinematic profiles of these 95 simulations comparable to ATLAS3D data. By constructing remnant profiles of the projected specific angular momentum (? _R= < R|V|rangle / < R ?{V^2+? ^2}rangle), triaxiality, and measuring the incidences of kinematic twists and kinematically decoupled cores, we distinguish between varying formation scenarios. We find that binary mergers nearly always form fast rotators. Slow rotators can be formed from zero initial angular momentum configurations and gas-poor mergers, but are not as round as the ATLAS3D galaxies. Remnants of binary merger trees are triaxial slow rotators. Sequential mergers form round slow rotators that most resemble the ATLAS3D rotators.

  14. Simulating Earthquake Early Warning Systems in the Classroom as a New Approach to Teaching Earthquakes

    NASA Astrophysics Data System (ADS)

    D'Alessio, M. A.

    2010-12-01

    A discussion of P- and S-waves seems an ubiquitous part of studying earthquakes in the classroom. Textbooks from middle school through university level typically define the differences between the waves and illustrate the sense of motion. While many students successfully memorize the differences between wave types (often utilizing the first letter as a memory aide), textbooks rarely give tangible examples of how the two waves would "feel" to a person sitting on the ground. One reason for introducing the wave types is to explain how to calculate earthquake epicenters using seismograms and travel time charts -- very abstract representations of earthquakes. Even when the skill is mastered using paper-and-pencil activities or one of the excellent online interactive versions, locating an epicenter simply does not excite many of our students because it evokes little emotional impact, even in students located in earthquake-prone areas. Despite these limitations, huge numbers of students are mandated to complete the task. At the K-12 level, California requires that all students be able to locate earthquake epicenters in Grade 6; in New York, the skill is a required part of the Regent's Examination. Recent innovations in earthquake early warning systems around the globe give us the opportunity to address the same content standard, but with substantially more emotional impact on students. I outline a lesson about earthquakes focused on earthquake early warning systems. The introductory activities include video clips of actual earthquakes and emphasize the differences between the way P- and S-waves feel when they arrive (P arrives first, but is weaker). I include an introduction to the principle behind earthquake early warning (including a summary of possible uses of a few seconds warning about strong shaking) and show examples from Japan. Students go outdoors to simulate P-waves, S-waves, and occupants of two different cities who are talking to one another on cell phones. The culminating activity is for students to "design" an early warning system that will protect their school from nearby earthquakes. The better they design the system, the safer they will be. Each team of students receives a map of faults in the area and possible sites for real-time seismometer installation. Given a fixed budget, they must select the best sites for detecting a likely earthquake. After selecting their locations, teams face-off two-by-two in a tournament of simulated earthquakes. We created animations of a few simulated earthquakes for our institution and have plans to build a web-based version that will allow others to customize the location to their own location and facilitate the competition between teams. Earthquake early warning is both cutting-edge and has huge societal benefits. Instead of teaching our students how to locate epicenters after an earthquake has occurred, we can teach the same content standards while showing them that earthquake science can really save lives.

  15. 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

  16. Recondensation of chondritic material in the early solar system: Results of thermodynamic simulation

    NASA Technical Reports Server (NTRS)

    Dorofeyeva, V. A.; Makalkin, A. B.; Mironenko, M. V.; Vityazev, A. V.

    1993-01-01

    We have performed a thermodynamic simulation of the recondensation of evaporated meteoritic material. We suggest that evaporation and recondensation occurred in impact events during the intercollision of planetesimals during the early evolution of the solar system. The source materials adopted for our model are the chondrites CI Orgueil and H5 Richardton. These chondrites are representative examples of the two extremes regarding volatile content and oxidation state. We calculated equilibrium mineral compositions of the closed systems of the Orgueil's and Richardton's elemental composition at the P-T conditions characteristic of the explosion cloud formed at a planetesimal collision. The P-T conditions are as follows: 10(exp -4) bar, and 1500 and 2000 K. The results are presented.

  17. 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

  18. 3D simulations of the early stages of AGN jets: geometry, thermodynamics and backflow

    NASA Astrophysics Data System (ADS)

    Cielo, S.; Antonuccio-Delogu, V.; Macciò, A. V.; Romeo, A. D.; Silk, J.

    2014-04-01

    We investigate the interplay between jets from active galactic nuclei (AGNs) and the surrounding interstellar medium (ISM) through full 3D, high-resolution, adaptive mesh refinement simulations performed with the FLASH code. We follow the jet-ISM system for several Myr in its transition from an early, compact source to an extended one including a large cocoon. During the jet evolution, we identify three major evolutionary stages and we find that, contrary to the prediction of popular theoretical models, none of the simulations shows a self-similar behaviour. We also follow the evolution of the energy budget, and find that the fraction of input power deposited into the ISM (the AGN coupling constant) is of the order of a few per cent during the first few Myr. This is in broad agreement with galaxy formation models employing AGN feedback. However, we find that in these early stages, this energy is deposited only in a small fraction (<1 per cent) of the total ISM volume. Finally, we demonstrate the relevance of backflows arising within the extended cocoon generated by a relativistic AGN jet within the ISM of its host galaxy, previously proposed as a mechanism for self-regulating the gas accretion on to the central object. These backflows tend later to be destabilized by the 3D dynamics, rather than by hydrodynamic (Kelvin-Helmholtz) instabilities. Yet, in the first few hundred thousand years, backflows may create a central accretion region of significant extent, and convey there as much as a few millions of solar masses.

  19. Depression, illness perception and coping in rheumatoid arthritis

    Microsoft Academic Search

    Helen Murphy; Chris Dickens; Francis Creed; R. Bernstein

    1999-01-01

    This study aimed to establish the relationship between depression, illness perception, coping strategies, and adverse childhood events in rheumatoid arthritis patients. Sixty-two out-patients with rheumatoid arthritis (RA) completed the Hospital Anxiety and Depression Scale, Illness Perception Questionnaire, London Coping with Rheumatoid Arthritis Questionnaire, and Childhood Development Questionnaire, and underwent a clinical assessment of their physical state. Depressed patients were more

  20. The creation and persistence of a misaligned gas disc in a simulated early-type galaxy

    E-print Network

    van de Voort, Freeke; Keres, Dusan; Quataert, Eliot; Faucher-Giguere, Claude-Andre; Hopkins, Philip F

    2015-01-01

    Massive early-type galaxies commonly have gas discs which are kinematically misaligned with the stellar component. These discs feel a torque from the stars, however, and the angular momentum vectors are naively expected to align within a few dynamical times. We present results on the evolution of a misaligned gas disc in a cosmological 'zoom-in' simulation of a massive early-type galaxy from the Feedback In Realistic Environments (FIRE) project. This galaxy experiences a merger at z=0.3, which, together with a strong galactic wind, removes most of the gas disc that was in place. The galaxy subsequently reforms a gas disc through accretion of cold gas, but it is initially 120 degrees misaligned with the stellar rotation axis. This misalignment persists for about 2 Gyr before the gas-star misalignment angle drops below 20 degrees. This is about 150 times longer than the dynamical time in the central kpc and varies with galactocentric radius. The time it takes for the gaseous and stellar components to align is m...

  1. Radiation Magnetohydrodynamic Simulations of Protostellar Collapse: Nonideal Magnetohydrodynamic Effects and Early Formation of Circumstellar Disks

    NASA Astrophysics Data System (ADS)

    Tomida, Kengo; Okuzumi, Satoshi; Machida, Masahiro N.

    2015-03-01

    The transport of angular momentum by magnetic fields is a crucial physical process in the formation and evolution of stars and disks. Because the ionization degree in star-forming clouds is extremely low, nonideal magnetohydrodynamic (MHD) effects such as ambipolar diffusion and ohmic dissipation work strongly during protostellar collapse. These effects have significant impacts in the early phase of star formation as they redistribute magnetic flux and suppress angular momentum transport by magnetic fields. We perform three-dimensional nested-grid radiation magnetohydrodynamic simulations including ohmic dissipation and ambipolar diffusion. Without these effects, magnetic fields transport angular momentum so efficiently that no rotationally supported disk is formed even after the second collapse. Ohmic dissipation works only in a relatively high density region within the first core and suppresses angular momentum transport, enabling formation of a very small rotationally supported disk after the second collapse. With both ohmic dissipation and ambipolar diffusion, these effects work effectively in almost the entire region within the first core and significant magnetic flux loss occurs. As a result, a rotationally supported disk is formed even before a protostellar core forms. The size of the disk is still small, about 5 AU at the end of the first core phase, but this disk will grow later as gas accretion continues. Thus, the nonideal MHD effects can resolve the so-called magnetic braking catastrophe while keeping the disk size small in the early phase, which is implied from recent interferometric observations.

  2. A phenomenological particle-based platelet model for simulating filopodia formation during early activation.

    PubMed

    Pothapragada, Seetha; Zhang, Peng; Sheriff, Jawaad; Livelli, Mark; Slepian, Marvin J; Deng, Yuefan; Bluestein, Danny

    2015-03-01

    We developed a phenomenological three-dimensional platelet model to characterize the filopodia formation observed during early stage platelet activation. Departing from continuum mechanics based approaches, this coarse-grained molecular dynamics (CGMD) particle-based model can deform to emulate the complex shape change and filopodia formation that platelets undergo during activation. The platelet peripheral zone is modeled with a two-layer homogeneous elastic structure represented by spring-connected particles. The structural zone is represented by a cytoskeletal assembly comprising of a filamentous core and filament bundles supporting the platelet's discoid shape, also modeled by spring-connected particles. The interior organelle zone is modeled by homogeneous cytoplasm particles that facilitate the platelet deformation. Nonbonded interactions among the discrete particles of the membrane, the cytoskeletal assembly, and the cytoplasm are described using the Lennard-Jones potential with empirical constants. By exploring the parameter space of this CGMD model, we have successfully simulated the dynamics of varied filopodia formations. Comparative analyses of length and thickness of filopodia show that our numerical simulations are in agreement with experimental measurements of flow-induced activated platelets. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25532469

  3. Interleukin 6 and Rheumatoid Arthritis

    PubMed Central

    Yoshida, Yuji

    2014-01-01

    Interleukin-6 (IL-6) is a representative cytokine featuring pleiotropic activity and redundancy. A transient synthesis of IL-6 contributes to host defense against infectious agents and tissue injuries by inducing acute phase reactions and immunological and hematopoietic responses. However, uncontrolled persistent production of IL-6 may lead to the development of several immune-mediated diseases. Rheumatoid arthritis (RA) is a chronic disease with joint and systemic inflammation resulting from immunological abnormalities and it has been found that IL-6 plays a key role in the development of this disease. Clinical trials in various parts of the world of tocilizumab, a humanized anti-IL-6 receptor antibody, have proved its efficacy and tolerable safety either as monotherapy or in combination with disease-modifying antirheumatic drugs. As a result, it is currently used as a first-line biologic for the treatment of moderate-to-severe RA in more than 100 countries. Clarification of the mechanism(s) through which tocilizumab exerts its effect on RA and of the reason(s) why IL-6 is continuously produced in RA can be expected to lead to the best use of this agent for RA patients and aid in investigations into the pathogenesis of RA. PMID:24524085

  4. HLA-linked rheumatoid arthritis

    SciTech Connect

    Hasstedt, S.J.; Clegg, D.O.; Ingles, L.; Ward, R.H. [Univ. of Utah, Salt Lake City, UT (United States)

    1994-10-01

    Twenty-eight pedigrees were ascertained through pairs of first-degree relatives diagnosed with rheumatoid arthritis (RA). RA was confirmed in 77 pedigree members including probands; the absence of disease was verified in an additional 261 pedigree members. Pedigree members were serologically typed for HLA. We used likelihood analysis to statistically characterize the HLA-linked RA susceptibility locus. The genetic model assumed tight linkage to HLA. The analysis supported the existence of an HLA-linked RA susceptibility locus, estimated the lifetime penetrance as 41% in male homozygotes and as 48% in female homozygotes. Inheritance was recessive in males and was nearly recessive in females. In addition, the analysis attributed 78% of the variance within genotypes to genetic or environmental effects shared by siblings. The genetic model inferred in this analysis is consistent with previous association, linkage, and familial aggregation studies of RA. The inferred HLA-linked RA susceptibility locus accounts for approximately one-fifth of the RA in the population. Although other genes may account for the remaining familial RA, a large portion of RA cases may occur sporadically. 79 refs., 9 tabs.

  5. Vitamin D in rheumatoid arthritis.

    PubMed

    Cutolo, Maurizio; Otsa, Kati; Uprus, Maria; Paolino, Sabrina; Seriolo, Bruno

    2007-11-01

    The discovery of the vitamin D receptor (VDR) in the cells of the immune system and the fact that activated dendritic cells produce the vitamin D hormone suggested that vitamin D could have immunoregulatory properties. VDR, a member of the nuclear hormone receptor superfamily, was identified in mononuclear cells, dendritic cells, antigen-presenting cells, and activated T-B lymphocytes. In synthesis, the most evident effects of the D-hormone on the immune system seem to be in the downregulation of the Th1-driven autoimmunity. Low serum levels of vitamin D3 might be partially related, among other factors, to prolonged daily darkness (reduced activation of the pre vitamin D by the ultra violet B sunlight), different genetic background (i.e. vitamin D receptor polymorphism) and nutritional factors, and explain to the latitute-related prevalence of autoimmune diseases such as rheumatoid arthritis (RA), by considering the potential immunosuppressive roles of vitamin D. 25(OH)D3 plasma levels have been found inversely correlated at least with the RA disease activity showing a circannual rhythm (more severe in winter). Recently, greater intake of vitamin D was associated with a lower risk of RA, as well as a significant clinical improvement was strongly correlated with the immunomodulating potential in vitamin D-treated RA patients. PMID:17967727

  6. Comparative clinical utility of once-weekly subcutaneous abatacept in the management of rheumatoid arthritis

    PubMed Central

    Rakieh, Chadi; Conaghan, Philip G

    2014-01-01

    Biologic therapies in rheumatoid arthritis are now part of standard practice for disease that proves difficult to control with conventional disease-modifying anti-rheumatic drugs. While anti-tumor necrosis factor therapies have been commonly used, other targeted biologic therapies with different mechanisms of action are becoming increasingly available. Abatacept is a recombinant fusion protein that inhibits the T-cell costimulatory molecules required for T-cell activation. Intravenous abatacept has good clinical efficacy with an acceptably low toxicity profile in rheumatoid arthritis, but the subcutaneous mode of delivery has only recently become available. In this article, we examine key efficacy and safety data for subcutaneous abatacept in rheumatoid arthritis, incorporating evidence from five large Phase III studies that included people with an inadequate response to methotrexate and an inadequate response to biologic disease-modifying anti-rheumatic drugs. The results demonstrate that subcutaneous abatacept has efficacy and safety comparable with that of intravenous abatacept and adalimumab. In addition, inhibition of radiographic progression at year 1 in relatively early rheumatoid arthritis is consistent with that of adalimumab. Subcutaneous abatacept is well tolerated, with very low rates of discontinuation in both short-term and long-term follow-up. PMID:24812514

  7. 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

  8. 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.

  9. Mast cell involvement in rheumatoid arthritis.

    PubMed

    Kritas, S K; Saggini, A; Varvara, G; Murmura, G; Caraffa, A; Antinolfi, P; Toniato, E; Pantalone, A; Neri, G; Frydas, S; Rosati, M; Tei, M; Speziali, A; Saggini, R; Pandolfi, F; Theoharides, T C; Conti, P

    2013-01-01

    Autoimmunity is a failure of self-tolerance resulting in immune reactions against autologous antigen. Rheumatoid arthritis is characterized by inflammation of synovium associated with destruction of the join cartilage and bone. A role of mast cell-mediated inflammation and antibodies are involved in this disease. Numerous cytokines such as IL-1, TNF, IL-8, IL-33 and IFN gamma have been implicated in rheumatoid arthritis and in particular in the synovial joint fluid. Since TNF is believed to activates resident synovial cells to produce collagenase that mediate destruction of cartilage, antagonists against the inflammatory cytokine TNF have a beneficial effects in this disease. Here we review the interrelationship between rheumatoid arthritis and mast cell activation. PMID:24152834

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

    Microsoft Academic Search

    Suad Hannawi; Thomas H Marwick; Ranjeny Thomas

    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

  11. Insufficiency fractures of the distal tibia misdiagnosed as cellulitis in three patients with rheumatoid arthritis

    SciTech Connect

    Straaton, K.V.; Lopez-Mendez, A.; Alarcon, G.S. (Univ. of Alabama, Birmingham (USA))

    1991-07-01

    We describe 3 patients with rheumatoid arthritis who presented with diffuse pain, swelling, and erythema of the distal aspect of the lower extremity, suggestive of either cellulitis or thrombophlebitis, but were found to have insufficiency fractures of the distal tibia. The value of technetium-99m diphosphonate bone scintigraphy in the early recognition of these fractures and a possible explanation for the associated inflammatory symptoms are discussed.

  12. Microvascular function is preserved in newly diagnosed rheumatoid arthritis and low systemic inflammatory activity

    Microsoft Academic Search

    Izhar C. van Eijk; Erik H. Serné; Ben A. C. Dijkmans; Yvo Smulders; Michael Nurmohamed

    2011-01-01

    Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. Microvascular function has\\u000a been linked to several risk factors for cardiovascular disease and may be affected in RA. It is, however, presently unknown\\u000a at what point in the disease course the abnormalities in microvascular function occur. We determined whether microvascular\\u000a function is already disturbed in early disease-modifying antirheumatic drugs

  13. Chemokines and angiogenesis in rheumatoid arthritis

    PubMed Central

    Szekanecz, Zoltan; Pakozdi, Angela; Szentpetery, Agnes; Besenyei, Timea; Koch, Alisa E.

    2010-01-01

    In rheumatoid arthritis, chemokines mediate the migration of inflammatory leukocytes into the synovium. Among the four known chemokine families, CXC, CC chemokines and fractalkine seem to be of outstanding importance in this process. Angiogenesis, the formation of new vessels, is also important during the perpetuation of inflammation underlying rheumatoid arthritis. In this review, authors discuss the role of the most important chemokines and chemokine repetors in arthritis-associated neovascularization. The process and regulation of angiogenesis are described in this context as well. Apart from discussing the pathogenic role of chemokines and chemokine receptors in arthritic vessel formation, authors also review the important relevance of chemokines and angiogenesis for therapeutic intervention. PMID:19482623

  14. Psychological effects of living with rheumatoid arthritis.

    PubMed

    Ryan, Sarah

    2014-12-01

    Rheumatoid arthritis is a long-term inflammatory condition that can affect physical, psychological and social function. The condition is not curable - although drug therapy can be used to reduce inflammation - and patients often experience daily symptoms of joint pain and stiffness, fatigue and functional limitations. Patients may also experience psychological challenges. This article focuses on the psychological implications of living with rheumatoid arthritis, including reaction to diagnosis, anxiety and depression, body image, sexuality, self-esteem and social role. It aims to explore the role of the nurse in addressing these psychological challenges to optimise the physical and psychological status of each patient. PMID:25424112

  15. Clinical significance of anti-CCP antibodies in rheumatoid arthritis.

    PubMed

    Mimori, Tsuneyo

    2005-11-01

    A number of novel autoantibodies have been recently described in rheumatoid arthritis (RA), and their clinical significance and possible pathogenic roles have been discussed. In particular, new autoantibodies to citrullinated proteins such as filaggrin and its circular form (cyclic citrullinated peptide: CCP) are especially noteworthy because of their high sensitivity and high specificity. There are many studies that anti-CCP antibodies may serve as a powerful serologic marker for early diagnosis of RA and prognostic prediction of joint destruction. Anti-citrullinated protein antibodies are locally produced in RA joints, and citrullinated proteins (most are fibrins) are localized in RA synovial tissue. This finding strongly suggests a possibility that local citrullination of intraarticular proteins might be the initial event leading to autoantibody production in RA. Genetic factors such as a gene polymorphism of the citrullinating enzyme, PADI, might be associated with the breakage of self-tolerance and induction of autoimmunity against citrullinated proteins. PMID:16357447

  16. Estimating rheumatoid arthritis activity with infrared image analysis.

    PubMed

    Frize, Monique; Ogungbemile, Abiola

    2012-01-01

    This work describes the development of a new diagnostic tool to assess the severity of rheumatoid arthritis (RA) using infrared image collection and analysis. Early work showed that the temperature distribution of joints of hands and knees of patients with RA was statistically significantly different from that of normal subjects. Current work identified ankles as also significant for an assessment of RA. Moreover, the patients were classified in three levels of RA severity (High, Medium, and Low) using a C5.0 decision tree classifier with excellent results: Sensitivity (true positive cases) of 96 % and a specificity (true negative cases) of 92%. Future work will automate the image analysis and test clinically by comparing to MR as ground truth. PMID:22874260

  17. A rheumatoid arthritis study by Fourier transform infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Carvalho, Carolina S.; Silva, Ana Carla A.; Santos, Tatiano J. P. S.; Martin, Airton A.; dos Santos Fernandes, Ana Célia; Andrade, Luís E.; Raniero, Leandro

    2012-01-01

    Rheumatoid arthritis is a systemic inflammatory disease of unknown causes and a new methods to identify it in early stages are needed. The main purpose of this work is the biochemical differentiation of sera between normal and RA patients, through the establishment of a statistical method that can be appropriately used for serological analysis. The human sera from 39 healthy donors and 39 rheumatics donors were collected and analyzed by Fourier Transform Infrared Spectroscopy. The results show significant spectral variations with p<0.05 in regions corresponding to protein, lipids and immunoglobulins. The technique of latex particles, coated with human IgG and monoclonal anti-CRP by indirect agglutination known as FR and CRP, was performed to confirm possible false-negative results within the groups, facilitating the statistical interpretation and validation of the technique.

  18. A Simulation Study to Assess the Potential of Real-Time GPS for Tsunami Early Warning in Chile

    NASA Astrophysics Data System (ADS)

    Chen, Kejie; Babeyko, Andrey Y.; Hoechner, Andreas; Ge, Maorong

    2014-05-01

    Global Positioning System (GPS) has been proved to be a powerful tool for measuring co-seismic ground displacement with application to earthquake rupture inversion. Due to the fact that most of the tsunamis are triggered by large earthquakes, GPS could contribute to tsunami early warning by helping to resolve for the tsunami source in almost real-time. Recently, this became a core of the concept of a 'GPS-Shield for Tsunami Early Warning'. In present study we extend this concept to the Chilean Pacific continental margin. Chile is situated at the western margin of the South American plate which experiences constant tectonic forcing due to the actively subducted Nazca oceanic plate. This ongoing subduction makes almost the whole Chilean coast to be vulnerable to earthquake and tsunami threats. New Chilean tsunami early warning system is expected to incorporate the novel real-time GPS-component for fast source inversion. We use numerical simulation technique to evaluate the potential of the coastal real-time GPS arrays for reliable early warning. We provide start-to-end simulations of the related physical processes (earthquake rupture, ground shaking, tsunami generation and propagation) together with their sensor (GPS) imaging and processing. In particular, co-seismic GPS observations are simulated using Bernese 5.2 software. For GPS data processing, both Bernese 5.2 and (real-time) PANDA are adopted for comparison. We demonstrate our 'close-loop' simulation workbench together with main results reflecting the importance of the real-time GPS component for the tsunami early warning in Chile. Special attention is paid to the uncertainty propagation through the early warning chain.

  19. Discrete Element Model for Simulations of Early-Life Thermal Fracturing Behaviors in Ceramic Nuclear Fuel Pellets

    SciTech Connect

    Hai Huang; Ben Spencer; Jason Hales

    2014-10-01

    A discrete element Model (DEM) representation of coupled solid mechanics/fracturing and heat conduction processes has been developed and applied to explicitly simulate the random initiations and subsequent propagations of interacting thermal cracks in a ceramic nuclear fuel pellet during initial rise to power and during power cycles. The DEM model clearly predicts realistic early-life crack patterns including both radial cracks and circumferential cracks. Simulation results clearly demonstrate the formation of radial cracks during the initial power rise, and formation of circumferential cracks as the power is ramped down. In these simulations, additional early-life power cycles do not lead to the formation of new thermal cracks. They do, however clearly indicate changes in the apertures of thermal cracks during later power cycles due to thermal expansion and shrinkage. The number of radial cracks increases with increasing power, which is consistent with the experimental observations.

  20. Retrospect on the tsunami simulation efforts for the German-Indonesian Tsunami Early Warning System

    NASA Astrophysics Data System (ADS)

    Rakowsky, Natalja; Androsov, Alexey; Harig, Sven; Immerz, Antonia; Behrens, Jörn; Danilov, Sergey; Hiller, Wolfgang; Schröter, Jens

    2014-05-01

    Starting in 2005, the GITEWS project (German-Indonesian Tsunami Early Warning System) established from scratch a fully operational tsunami warning system at BMKG in Jakarta. GITEWS was succeeded in 2011 by the smaller project PROTECTS for training the Indonesian staff and consolidating the technical system. With the official end in March 2014, it is time to draw a balance and evaluate the approach. This presentation focuses on the contribution of the tsunami modelling group at the Alfred Wegener Institute. We will give a short overview on the developments of the numerical tsunami simulation model TsunAWI, of the scenario database built with TsunAWI, and of the simulation module SIM that interfaces the database to the decision support system. Some distinctive experiences will be highlighted. Topics include the modeling part as well as the matching process after the database is already set up. On the modeling side, unstructured mesh generation with focus on local bathymetric features and inclusion of precise coastline position as well as numerical parametrization and post processing are covered. The matching of pre calculated scenarios with incoming data in case of a tsunamigenic earthquake is performed in the simulation system SIM, which processes the data of multiple sensors and employs various metrics to limit the choice of possible scenarios from the database. One challenge was that the development of the matching algorithm had to start without having access to real sensor data except seismic information on epicenter and magnitude. Therefore, the algorithm is designed with robustness in mind. Still, the conservative approach allows to narrow down the scenario selection even with limited sensor information. Given more experience in the typical behaviour of sensor data in real events, the algorithm parameters can easily be calibrated towards a more restrictive scenario selection. Another challenge was to ensure the quality control of the data products derived from all 4500 scenarios that currently fill the database. Though we can rely on the high quality of TsunAWI, that does not produce numerical artifacts provided model parameters are calibrated and the computational grid is built with care, manual checking remains essential. During GITEWS and PROTECTS, tools were developed to allow for a semi-automatic process of visualizing, checking, and annotating scenarios.

  1. Pain management in patients with rheumatoid arthritis.

    PubMed

    Durham, Catherine O; Fowler, Terri; Donato, AnneMarie; Smith, Whitney; Jensen, Elizabeth

    2015-05-15

    Rheumatoid arthritis (RA) is one of the most common inflammatory conditions in the United States affecting approximately 1 million adults. This article briefly reviews the evidence-based diagnosis of RA, mainstays of treatment to prevent joint destruction, and pain management. PMID:25882452

  2. Rat bite fever mimicking rheumatoid arthritis.

    PubMed

    Legout, L; Senneville, E; Mulleman, D; Solau-Gervais, E; Flipo, R M; Mouton, Y

    2005-01-01

    We report a case of Streptobacillus moniliformis polyarthritis mimicking a rheumatoid arthritis, in a pet shop employee. In culture of fluid joint growth a curious Gram-negative bacillus was identified by polymerase chain reaction as Streptobacillus moniliformis. The outcome was good after surgical debridment and rifampin-clindamycin combination during 4 weeks. PMID:16012023

  3. Aerobic Exercise Prescription for Rheumatoid Arthritics.

    ERIC Educational Resources Information Center

    Evans, Blanche W.; Williams, Hilda L.

    The use of exercise as a general treatment for rheumatoid arthritics (RA) has included range of motion, muscular strength, water exercise and rest therapy while virtually ignoring possible benefits of aerobic exercise. The purposes of this project were to examine the guidelines for exercise prescription in relation to this special population and…

  4. 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

  5. T cell receptor genes in rheumatoid arthritis

    Microsoft Academic Search

    Jan P. Dutz; Agnes Chan; Tak Mak; Katherine A. Siminovitch; Laurence A. Rubin

    1989-01-01

    Rheumatoid arthritis is an oft debilitating chronic disease of an autoimmune nature. Although the putative antigen remains unknown, the recent elucidation of the structure and functional relationships of the trimolecular complex governing the immune response to antigen, facilitates the development of novel approaches to the treatment of RA and enhances our understanding of the etiopathogenesis of this disorder and autoimmunity

  6. Ulceration of the cornea in rheumatoid arthritis.

    PubMed Central

    Jayson, M I; Easty, D L

    1977-01-01

    Five patients with melting of the cornea in association with rheumatoid arthritis are described. The arthritis was often inactive and without systemic manifestations, in contrast to that seen in association with scleritis. In 3 there was evidence of reduced tear formation, but in none was tear production absent. In 3 patients the lesions healed during treatment with azathioprine or penicillamine. Images PMID:921342

  7. Intracellular Signaling Pathways in Rheumatoid Arthritis

    PubMed Central

    Malemud, Charles J

    2013-01-01

    Dysfunctional intracellular signaling involving deregulated activation of the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) and “cross-talk” between JAK/STAT and the stress-activated protein kinase/mitogen-activated protein kinase (SAPK/MAPK) and Phosphatidylinositide-3-Kinase/AKT/mammalian Target of Rapamycin (PI-3K/AKT/mTOR) pathways play a critical role in rheumatoid arthritis. This is exemplified by immune-mediated chronic inflammation, up-regulated matrix metalloproteinase gene expression, induction of articular chondrocyte apoptosis and “apoptosis-resistance” in rheumatoid synovial tissue. An important consideration in the development of novel therapeutics for rheumatoid arthritis will be the extent to which inhibiting these signal transduction pathways will sufficiently suppress immune cell-mediated inflammation to produce a lasting clinical remission and halt the progression of rheumatoid arthritis pathology. In that regard, the majority of the evidence accumulated over the past decade indicated that merely suppressing pro-inflammatory cytokine-mediated JAK/ STAT, SAPK/MAPK or PI-3K/AKT/mTOR activation in RA patients may be necessary but not sufficient to result in clinical improvement. Thus, targeting aberrant enzyme activities of spleen tyrosine kinase, sphingosine kinases-1, -2, transforming growth factor ?-activated kinase-1, bone marrow kinase, and nuclear factor-?B-inducing kinase for intervention may also have to be considered. PMID:24619558

  8. 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

  9. Independent associations of total and high molecular weight adiponectin with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with rheumatoid arthritis: a cross-sectional study

    PubMed Central

    2013-01-01

    Introduction Whether adiponectin levels associate with atherogenesis in RA is uncertain. We examined the independent relationships of total and high molecular weight (HMW) adiponectin concentrations with cardiometabolic risk and surrogate markers of enhanced early atherogenesis in black and white patients with RA. Methods We determined total and HMW adiponectin concentrations and those of endothelial activation molecules including soluble E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), in 210 (119 black and 91 white) RA patients. Associations were determined in potential confounder and mediator adjusted mixed regression models. Results Total and HMW adiponectin concentrations related similarly to metabolic risk factors and endothelial activation. In all patients, total and HMW adiponectin concentrations associated paradoxically with high systolic, diastolic and mean blood pressure (partial R = 0.155 to 0.241, P ?0.03). Ethnic origin did not impact on these relationships (interaction P ?0.09). Total and HMW adiponectin concentrations associated with those of glucose in white and black patients respectively (partial R = -0.304, P = 0.006 and -0.246, P = 0.01). In black but not white participants, total and HMW adiponectin concentrations also related favorably to lipid profiles (partial R = 0.292 to 0.360, P ?0.003 for HDL cholesterol concentrations, -0.269 to -0.299, P ?0.006 for triglyceride concentrations and -0.302 to -0.390, P ?0.002 for total-HDL cholesterol ratio) and the number of metabolic risk factors (partial R = -0.210 to -0.238, P ?0.03). In white but not black patients, total and HMW adiponectin concentrations associated paradoxically with overall endothelial activation as estimated by a standard z-score of endothelial activation molecule concentrations (partial R = 0.262, P = 0.01 and 0.252, P = 0.02); in the respective models, the extent of effect of total and HMW adiponectin concentrations on endothelial activation was larger in white compared to black participants (standardized ? (SE) = 0.260 (0.107) versus -0.106 (0.107), P = 0.01 and 0.260 (0.120) versus -0.100 (0.111), P = 0.02). The HMW-total adiponectin ratio related inconsistently to metabolic risk factors and not to endothelial activation. Conclusion In this study, total and HMW adiponectin concentrations associated with increased blood pressure parameters, and in white patients additionally with endothelial activation. The potential mechanism(s) underlying these paradoxical relationships between adiponectin concentrations and cardiovascular risk in RA merit further investigation. PMID:24286214

  10. Development of sarcoidosis in etanercept-treated rheumatoid arthritis patients

    Microsoft Academic Search

    Kilian Verschueren; Els Van Essche; Patrick Verschueren; Veerle Taelman; Rene Westhovens

    2007-01-01

    We report two rheumatoid arthritis patients developing sarcoidosis possibly induced by etanercept. Both women, aged 46 and\\u000a 53, had erosive, rheumatoid-factor-positive rheumatoid arthritis (RA) for 7 and 6 years, respectively. The eldest had received\\u000a infliximab for over a year with good response, which was stopped because of a perfusion reaction. She developed a cough and\\u000a dyspnea after 6 months of etanercept treatment.

  11. Dealing with uncertainty in the simulation-based situation assessment of the GITEWS tsunami early warning system

    NASA Astrophysics Data System (ADS)

    Behrens, J.; Androsov, A.; Harig, S.; Klaschka, F.; Pranowo, W. S.; Schröter, J.; Hiller, W.

    2009-04-01

    The hazard assessment in the simulation-based German-Indonesian Tsunami Early Warning System (GITEWS) relies on a novel multi-sensor quick assimilation technique, and a large number of detailed pre-computed tsunami scenarios. In order to obtain reliable and accurate information about the hazard situation, thorough evaluation of uncertainty is necessary. We present a rational methodology to evaluate and propagate uncertainty through the diverse steps of the early warning process. First, we propose a scheme for quantifying uncertainty from data, we then propagate this uncertainty through the modelling and simulation phase, and finally add several uncertainty measures for the assimilation phase. It turns out that quantitative uncertainty measures may help in the decision making process.

  12. 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.

  13. Using simulation in an objects-early approach to CS1 and CS2 Owen Astrachan

    E-print Network

    Astrachan, Owen

    of two simulations we have used in our courses: a simulation of the card game war and a queueing rather than revolutionary | based on organizing programs around modules and abstract data types that has

  14. 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.

  15. 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.

    2014-05-01

    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. 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 pre-industrial. It is shown that dynamic vegetation enhances the orbitally triggered summer precipitation anomaly by approximately 20% in the Sahara/Sahel region (10° N-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.

  16. 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

  17. Efficacy of compression gloves in rheumatoid arthritis.

    PubMed

    Culic, D D; Battaglia, M C; Wichman, C; Schmid, F R

    1979-12-01

    Twenty-three patients with rheumatoid arthritis whose disease had become stabilized while receiving non-steroidal, anti-inflammatory drugs and/or gold salt injections entered an 8 week crossover study in which the effect of a compression glove worn during sleep was compared to a loosely fitting glove made of the same material. Improvement in hand symptoms was greater with the compression glove than with the control glove as regards morning stiffness, pain, night time throbbing, numbness or heaviness and a subjective assessment of swelling (p = 0.01). In addition, swelling of the proximal interphalangeal joints was slightly reduced (p = 0.05). These data suggest that the night time use of compression gloves in patients with rheumatoid arthritis can improve hand symptoms and exert a mild, transiently beneficial effect upon the degree of hand swelling. PMID:517640

  18. COX2 inhibitors in rheumatoid arthritis

    Microsoft Academic Search

    John S. Sundy

    2001-01-01

    The selective cyclooxygenase 2 (COX-2) inhibitors have emerged as an important option in the treatment of rheumatoid arthritis\\u000a (RA). Rofecoxib and celecoxib, the selective COX-2 inhibitors currently available, have shown efficacy in reducing symptoms\\u000a of RA comparable with that of traditional nonsteroidal antiinflammatory drugs (NSAIDs). The primary advantage of selective\\u000a COX-2 inhibitors relates to reduced gastrointestinal (GI) toxicity. Gastroduodenal ulcers

  19. Bronchiectasis and rheumatoid arthritis: a clinical study

    Microsoft Academic Search

    M J McMahon; D R Swinson; S Shettar; R Wolstenholme; C Chattopadhyay; P Smith; P Johns; N H Crosby

    1993-01-01

    OBJECTIVES--To examine the relation between rheumatoid arthritis (RA) and bronchiectasis (BR). METHODS--Disease activity, outcome, extra-articular manifestations, and laboratory features were compared in 32 patients with BR and RA (RA-BR group), 32 matched patients with RA without BR (RA group), and 31 patients with BR but without arthritis (BR group). RESULTS--In 30 of the 32 (94%) patients with RA-BR, BR preceded

  20. Rheumatoid arthritis association at 6q23

    PubMed Central

    Thomson, Wendy; Barton, Anne; Ke, Xiayi; Eyre, Steve; Hinks, Anne; Bowes, John; Donn, Rachelle; Symmons, Deborah; Hider, Samantha; Bruce, Ian N; Wilson, Anthony G; Marinou, Ioanna; Morgan, Ann; Emery, Paul; Carter, Angela; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Strachan, David; Worthington, Jane

    2009-01-01

    The Wellcome Trust Case Control Consortium (WTCCC) identified nine single SNPs putatively associated with rheumatoid arthritis at P = 1 × 10 -5 - 5 × 10-7 in a genome-wide association screen. One, rs6920220, was unequivocally replicated (trend P = 1.1 × 10-8) in a validation study, as described here. This SNP maps to 6q23, between the genes oligodendrocyte lineage transcription factor 3 (OLIG3) and tumor necrosis factor-?-induced protein 3 (TNFAIP3). PMID:17982455

  1. Cutaneous manifestations associated with rheumatoid arthritis

    Microsoft Academic Search

    T. Yamamoto

    2009-01-01

    Rheumatoid arthritis presents various cutaneous manifestations, either specific or nonspecific skin features, which are induced\\u000a by the activation of inflammatory cells (neutrophils, lymphocytes, macrophages), vasculopathy, vasculitis, acral deformity,\\u000a drugs, and so on. These include (1) specific findings, (2) findings due to vascular impairment, (3) findings due to immune\\u000a dysfunction, (4) characteristic neutrophilic conditions, and (5) miscellaneous conditions. On the other

  2. New agents for scintigraphy in rheumatoid arthritis

    Microsoft Academic Search

    Marjolein H. W. Bois; Ernest K. J. Pauwels; Ferdinand C. Breedveld

    1995-01-01

    Radiopharmaceuticals have been used as investigative tools for the detection and treatment of arthritis activity in rheumatoid arthritis (RA) since the 1950s. Against the background of the pathophysiology of RA, the current status of joint scintigraphy and possible future developments are reviewed. Both non-specific (radiolabelled leucocytes and technetium-99m labelled human immunoglobulin) and specific targeting radiopharmaceuticals (including radiolabelled antibodies) are considered.

  3. Abatacept in the treatment of rheumatoid arthritis

    Microsoft Academic Search

    Maya H Buch; Edward M Vital; Paul Emery

    2008-01-01

    T-cell biology has regained importance in the pathogenesis of rheumatoid arthritis. Despite the significant improvements associated with the introduction of tumor necrosis factor-? blockade, reasonable proportions of failures and suboptimal responses have been reported, necessitating a search for alternative targeted therapies. This has included drug therapy designed to interrupt T-cell activation via the co-stimulation pathway. Abatacept is a recombinant fusion

  4. The mass and angular momentum distribution of simulated massive early-type galaxies to large radii

    NASA Astrophysics Data System (ADS)

    Wu, Xufen; Gerhard, Ortwin; Naab, Thorsten; Oser, Ludwig; Martinez-Valpuesta, Inma; Hilz, Michael; Churazov, Eugene; Lyskova, Natalya

    2014-03-01

    We study the dark and luminous mass distributions, circular velocity curves (CVCs), line-of-sight kinematics and angular momenta for a sample of 42 cosmological zoom simulations of galaxies with stellar masses from 2.0 × 1010 to 3.4 × 1011 M? h-1. Using a temporal smoothing technique, we are able to reach large radii. We find the following. The dark matter halo density profiles outside a few kpc follow simple power-law models, with flat dark matter CVCs for lower mass systems, and rising CVCs for high-mass haloes. The projected stellar density distributions at large radii can be fitted by Sérsic functions with n ? 10, larger than for typical early-type galaxies (ETGs). The massive systems have nearly flat total (luminous plus dark matter) CVCs at large radii, while the less massive systems have mildly decreasing CVCs. The slope of the circular velocity at large radii correlates with circular velocity itself. The dark matter fractions within the projected stellar half-mass radius Re are in the range 15-30 per cent and increase to 40-65 per cent at 5Re. Larger and more massive galaxies have higher dark matter fractions. The fractions and trends with mass and size are in agreement with observational estimates, even though the stellar-to-total mass ratio is ˜2-3 times higher than estimated for ETGs. The short axes of simulated galaxies and their host dark matter haloes are well aligned and their short-to-long axis ratios are correlated. The stellar root mean square velocity vrms(R) profiles are slowly declining, in agreement with planetary nebulae observations in the outer haloes of most ETGs. The line-of-sight velocity fields {bar{v}} show that rotation properties at small and large radii are correlated. Most radial profiles for the cumulative specific angular momentum parameter ?(R) are nearly flat or slightly rising, with values in [0.06, 0.75] from 2Re to 5Re. A few cases show local maxima in |{bar{v}}|/? (R). These properties agree with observations of ETGs at large radii. Stellar mass, ellipticity at large radii ?(5Re) and ?(5Re) are correlated: the more massive systems have less angular momentum and are rounder, as for observed ETGs. More massive galaxies with a large fraction of accreted stars have radially anisotropic velocity distributions outside Re. Tangential anisotropy is seen only for galaxies with high fraction of in situ stars.

  5. 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

  6. Rheumatoid arthritis seropositive for the rheumatoid factor is linked to the protein tyrosine phosphatase nonreceptor 22-620W allele

    PubMed Central

    Dieudé, Philippe; Garnier, Sophie; Michou, Laëtitia; Petit-Teixeira, Elisabeth; Glikmans, Elodie; Pierlot, Céline; Lasbleiz, Sandra; Bardin, Thomas; Prum, Bernard; Cornélis, François

    2005-01-01

    The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes for lymphoid tyrosine phosphatase LYP, involved in the negative regulation of early T-cell activation. An association has recently been reported between the PTPN22-620W functional allele and rheumatoid factor-positive (RF+) rheumatoid arthritis (RA), among other autoimmune diseases. Expected linkage proof for consistency cannot be definitely produced by an affected sib-pair (ASP) analysis. Our aim was therefore to search for linkage evidence with the transmission disequilibrium test. DNA from the French Caucasian population was available for two samples of 100 families with one RA patient and both parents, and for 88 RA index cases from RA ASP families. Genotyping was carried out by PCR-restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, genotype relative risk and ASP-based analysis. The transmission disequilibrium test of the PTPN22-620W allele revealed linkage and association for RF+ RA (61% of transmission, P = 0.037). The genotype relative risk showed the risk allele in 34% of RF+ RA patients and in 24% of controls derived from nontransmitted parental chromosomes (P = 0.047, odds ratio = 1.69, 95% confidence interval = 1.03–2.78). The ASP investigation showed no enriched risk allele in RA multiplex families, resulting in a lack of power of ASP analysis, explaining the published negative results. This study is the first to show linkage of PTPN22 to RF+ RA, consistent with PTPN22 as a new RA gene. PMID:16277672

  7. 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".

  8. Recovering the geographic origin of early modern humans by realistic and spatially explicit simulations

    E-print Network

    Batzoglou, Serafim

    evidence globally favor a complete re- placement of previous representatives of the genus Homo by early nuclear genes (Hawks et al. 2000), or the inference of pre-H. sapiens range expansions from current

  9. Additive hindfoot arthrodesis for rheumatoid hindfoot disease: a clinical study of patient outcomes and satisfaction.

    PubMed

    Ohly, Nicholas E; Breusch, Steffen J

    2013-12-01

    Advanced rheumatoid hindfoot disease causes significant pain and disability. Hindfoot arthrodesis is a useful procedure but is often overlooked as a treatment option. The objective of this study was to report the improvements in patients' health, pain, functional ability and satisfaction following this procedure. Thirty-seven patients with rheumatoid arthritis (RA) were recruited from the outpatient clinic and underwent 42 hindfoot arthrodesis procedures by a single surgeon. Outcome measures were SF12 score, Manchester-Oxford Foot Questionnaire index score, visual analogue pain score and satisfaction scores, as well as radiographic assessment. Assessment was undertaken at the pre-admission clinic and at 6 and 12 months post-operatively. Statistically significant improvements were seen at 6 and 12 months in all measured outcomes. The union rate was 97.6%. The satisfaction rate was 92.5%. The complication rate was 7.1%. The functional benefit and outcome scores are comparable to those reported following hip and knee replacement in patients with RA. The findings of this study provide evidence that hindfoot arthrodesis should be considered a worthwhile surgical treatment in the rheumatoid patient with advanced hindfoot disease. Healthcare professionals involved in the management of these patients should be aware of the potential benefits of this procedure and refer early to a foot and ankle surgeon specialist when conservative treatment modalities have failed. PMID:23900577

  10. 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

  11. Heparan Sulfate Differences in Rheumatoid Arthritis versus Healthy Sera

    PubMed Central

    López-Hoyos, Marcos; Seo, Youjin; Andaya, Armann; Leary, Julie A.

    2015-01-01

    Heparan sulfate (HS) is a complex and highly variable polysaccharide, expressed ubiquitously on the cell surface as HS proteoglycans (HSPGs), and found in the extracellular matrix as free HS fragments. Its heterogeneity due to various acetylation and sulfation patterns endows a multitude of functions. In animal tissues, HS interacts with a wide range of proteins to mediate numerous biological activities; given its multiple roles in inflammation processes, characterization of HS in human serum has significant potential for elucidating disease mechanisms. Historically, investigation of HS was limited by its low concentration in human serum, together with the complexity of the serum matrix. In this study, we used a modified mass spectrometry method to examine HS disaccharide profiles in the serum of 50 women with rheumatoid arthritis (RA), and compared our results to 51 sera from healthy women. Using various purification methods and online LC-MS/MS, we discovered statistically significant differences in the sulfation and acetylation patterns between populations. Since early diagnosis of RA is considered important in decelerating the disease's progression, identification of specific biomolecule characterizations may provide crucial information towards developing new therapies for suppressing the disease in its early stages. This is the first report of potential glycosaminoglycan biomarkers for RA found in human sera, while acknowledging the obvious fact that a larger population set, and more stringent collection parameters, will need to be investigated in the future. PMID:25217862

  12. Elk Velvet Antler in Rheumatoid Arthritis: Phase II Trial

    Microsoft Academic Search

    Marion Allen; Kathleen Oberle; Michael Grace; Anthony Russell

    2002-01-01

    The purpose of this phase II clinical trial was to examine safety of elk velvet antler taken concurrently with rheumatoid arthritis medications and to determine efficacy by dose to enable sample size estimation and dose standardization for a larger study. Forty patients with stage II rheumatoid arthritis were randomly assigned to 1 of 4 arms of 10 patients each. One

  13. Certain Infections Linked to Reduced Risk of Rheumatoid Arthritis

    MedlinePLUS

    ... Preidt Thursday, February 5, 2015 Related MedlinePlus Pages Bacterial Infections Rheumatoid Arthritis THURSDAY, Feb. 5, 2015 (HealthDay News) -- ... HealthDay . All rights reserved. More Health News on: Bacterial Infections Rheumatoid Arthritis Recent Health News Page last updated ...

  14. [Rheumatoid arthritis and myocardiopathy. A patient awaiting a heart transplant].

    PubMed

    Vázquez Fuentes, Noelia; Querol Gutiérrez, José Javier; Miralles Ibarra, José María; de Torres, Rafael Merino; Querol Gutiérrez, Juan Carlos; Laza Y Laza, Enrique Manuel

    2007-07-01

    Cardiovascular pathology is common in rheumatoid arthritis. However, myocardial affection is unusual and clinical disease is rare. We report a case of dilated cardiomyopathy in a patient with rheumatoid arthritis and progressive heart failure that required inclusion into a heart transplantation list. PMID:21794426

  15. 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

  16. Fibrocyte activation in rheumatoid arthritis

    PubMed Central

    Galligan, Carole L.; Siminovitch, Katherine A.; Keystone, Edward C.; Bykerk, Vivian; Perez, Omar D.

    2010-01-01

    Objectives. RA is a common, relapsing autoimmune disease primarily affecting the joints. Fibroblast-like synovial (FLS) cells are thought to be responsible for pannus formation and secretion of factors that recruit leucocytes to affected joints, thereby promoting bone and cartilage destruction. Fibrocytes are multipotent circulating stem cells that may have a role in RA pathogenesis, perhaps as the precursors of the FLS cells, or by regulating FLS cell function. Methods. We utilized multidimensional phospho-specific flow cytometry to characterize the activation status of peripheral blood (PB) fibrocytes derived from human RA patients at different stages of disease and from mice with CIA. Results. Human PB fibrocytes from RA patients exhibited phosporylation activation of the p44/42 and p38 MAP kinases (MAPKs), and STAT3 (signal transducer and activator of transcription) and STAT-5 early in disease, within the first year of diagnosis. Similarly, in murine CIA, an increase in the total number of PB phosphoSTAT5-positive fibrocytes was observed at early time points in disease. Notably, in the affected paws of mice with CIA, we identified an increased number of fibrocytes, in contrast to the paws of control mice. Conclusions. These data suggest that activated fibrocytes may influence the disease process in RA and may serve as surrogate markers for disease in the PB of affected patients. PMID:19858121

  17. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis

    Microsoft Academic Search

    Akari Suzuki; Xiaotian Chang; Shinya Tokuhiro; Tetsuji Sawada; Masakatsu Suzuki; Miyuki Nagasaki; Makiko Nakayama-Hamada; Reimi Kawaida; Mitsuru Ono; Masahiko Ohtsuki; Hidehiko Furukawa; Shinichi Yoshino; Masao Yukioka; Shigeto Tohma; Tsukasa Matsubara; Shigeyuki Wakitani; Ryota Teshima; Yuichi Nishioka; Akihiro Sekine; Aritoshi Iida; Atsushi Takahashi; Tatsuhiko Tsunoda; Yusuke Nakamura; Kazuhiko Yamamoto; Ryo Yamada

    2003-01-01

    Individuals with rheumatoid arthritis frequently have autoantibodies to citrullinated peptides, suggesting the involvement of the peptidylarginine deiminases citrullinating enzymes (encoded by PADI genes) in rheumatoid arthritis. Previous linkage studies have shown that a susceptibility locus for rheumatoid arthritis includes four PADI genes but did not establish which PADI gene confers susceptibility to rheumatoid arthritis. We used a case-control linkage disequilibrium

  18. Early warnings of the potential for malaria transmission in rural Africa using the hydrology, entomology and malaria transmission simulator (HYDREMATS)

    PubMed Central

    2010-01-01

    Background 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. 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. Methods 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. Results 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. Conclusions HYDREMATS can be used to make reasonable predictions of mosquito populations and vectorial capacity, and provide early warnings of the potential for malaria epidemics in Africa. PMID:21073726

  19. Disseminated Herpes Zoster Mimicking Rheumatoid Vasculitis in a Rheumatoid Arthritis Patient on Etanercept

    Microsoft Academic Search

    S. Tresch; R. M. Trüeb; J. Kamarachev; L. E. French; G. F. L. Hofbauer

    2009-01-01

    Tumor necrosis factor-? (TNF?)-blocking agents are immunomodulating agents introduced for treatment of a variety of chronic inflammatory disease conditions. Adverse effects include an increased incidence of infections. Clinically, these infections often have atypical presentations that may hamper prompt diagnosis. In our report of a patient on etanercept therapy for rheumatoid arthritis, the correct diagnosis was delayed because disseminated herpes zoster

  20. Hand bone mass in rheumatoid arthritis: A review of the literature

    PubMed Central

    Kilic, Gamze; Ozgocmen, Salih

    2015-01-01

    Rheumatoid arthritis (RA) is a common chronic inflammatory disease and periarticular osteoporosis or osteopenia of the inflamed hand joints is an early feature of RA. Quantitative measurement of hand bone loss may be an outcome measure for the detection of joint destruction and disease progression in early RA. This systematic review examines the published literature reporting hand bone mass in patients with RA, particularly those using the dual X-ray absorptiometry (DXA) methods. The majority of the studies reported that hand bone loss is associated with disease activity, functional status and radiological progression in early RA. Quantitative measurement of hand bone mineral density by DXA may be a useful and practical outcome measure in RA and may be predictive for radiographic progression or functional status in patients with early RA. PMID:25621215

  1. Frequency dependence of dynamic compliance in patients with rheumatoid arthritis.

    PubMed Central

    Hills, E A; Davies, S; Geary, M

    1979-01-01

    An investigation of lung function was carried out in 99 randomly selected patients with calssic or definite rheumatoid arthritis and in 60 control subjects matched for age, sex, and smoking habits. Mean FEV1 and mean VC were both significantly lower in the rheumatoid patients due to significant differences for women but mean FEV/VC ratio was 73.0% in the rheumatoid group and 72.1% in the control. Steady-state transfer factor was significantly greater in the normal men than in the comparable rheumatoid group, but there was no difference for women. After excluding patients with FEV1 less than 80% predicted normal and patients with low compliance, 72 rheumatoid patients and 45 controls provided series of tracings that could be assessed for a fall in Cdyn of 20% between 20 cycles and 60 cycles a minute. Dynamic compliance was not significantly different in any group at any rate of respiration. Fourteen of 72 rheumatoid patients and three of 45 controls showed frequency dependence (FDC). After the age of 50 the prevalence in the rheumatoid groupwas 11/38 and in the control group 2/27. This difference was significant (P less than 0.05). FDC was not consistently related to other abnormalities of lung function or to the duration, severity, or treatment of the rheumatoid arthritis. In various categories of smoking habits, dust exposure, or allergic tendency, the prevalence was always greater in the rheumatoid group. This provides evidence of patchy involvement of small airways, or alveoli and connective tissue, by the rheumatoid process. PMID:542915

  2. Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor

    Microsoft Academic Search

    Timothy R. D. J. Radstake; C. G. J. Sweep; Paco Welsing; Barbara Franke; Sita H. H. M. Vermeulen; Anneke Geurts-Moespot; Thierry Calandra; Rachelle Donn

    2005-01-01

    OBJECTIVE: To study whether genetic variants of macrophage migration inhibitory factor (MIF), the MIF -173G>C and CATT(5-8) alleles, are associated with disease severity and levels of circulating MIF in patients with rheumatoid arthritis (RA). METHODS: Genotyping was performed in patients with early RA and in healthy controls. Demographic data, disease activity, and outcome measurements were compared between patients with and

  3. Ethnicity may be a reason for lipid changes and high Lp(a) levels in rheumatoid arthritis

    Microsoft Academic Search

    Mustafa Cesur; Zeynep Ozbalkan; Mehtap Akcil Temel; Ya?ar Karaarslan

    2007-01-01

    There are so many studies that suggest the changes in lipid profiles and lipoprotein (a) [Lp(a)] are associated with early\\u000a atherosclerosis in rheumatoid arthritis (RA). But there are some opposite studies also. Because of marked ethnicity differences\\u000a in the distribution of Lp(a), we aimed to investigate the associations of Lp(a) levels and lipid changes in Turkish RA patients.\\u000a There were

  4. 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

  5. Adalimumab in the treatment of rheumatoid arthritis.

    PubMed

    Voulgari, Paraskevi V; Kaltsonoudis, Evripidis; Papagoras, Charalampos; Drosos, Alexandros A

    2012-12-01

    Adalimumab (ADA), a fully human monoclonal antibody against TNF-? is indicated for the treatment of rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, Crohn's disease, ulcerative colitis and psoriasis. In RA, it may be prescribed in combination with methotrexate or other disease-modifying antirheumatic drugs or as monotherapy. Studies comparing ADA with other TNF-? inhibitors are limited and are based mainly on meta-analyses of randomised controlled trials and large observational cohorts. In this study, the effectiveness and safety of ADA is compared with that of etanercept and infliximab. PMID:22954150

  6. Cerebral complications in juvenile rheumatoid arthritis

    PubMed Central

    Jan, James E.; Hill, Robert H.; Low, Morton D.

    1972-01-01

    A study of 170 patients with juvenile rheumatoid arthritis and a review of the literature indicate that this disease can significantly affect the central nervous system. Signs of CNS dysfunction were observed in 13 children. During the acute toxic stages the EEG is abnormal in many cases. Other manifestations of toxic encephalopathy such as irritability, drowsiness, stupor, convulsions and marked meningismus may be evident in severe cases. Meningitis is often suspected but ruled out by the finding of normal CSF. Steroids can rapidly improve the condition of these children. If `unexplained' seizures occur during the chronic stage, the diagnosis of cerebral vasculitis should be entertained. PMID:4665094

  7. Total knee arthroplasty considerations in rheumatoid arthritis.

    PubMed

    Danoff, Jonathan R; Moss, Garrett; Liabaud, Barthelemy; Geller, Jeffrey A

    2013-01-01

    The definitive treatment for advanced joint destruction in the late stages of rheumatoid arthritis can be successfully treated with total joint arthroplasty. Total knee arthroplasty has been shown to be a well-proven modality that can provide pain relief and restoration of mobility for those with debilitating knee arthritis. It is important for rheumatologists and orthopedic surgeons alike to share an understanding of the special considerations that must be addressed in this unique population of patients to ensure success in the immediate perioperative and postoperative periods including specific modalities to maximize success. PMID:24151549

  8. Total Knee Arthroplasty Considerations in Rheumatoid Arthritis

    PubMed Central

    Danoff, Jonathan R.; Geller, Jeffrey A.

    2013-01-01

    The definitive treatment for advanced joint destruction in the late stages of rheumatoid arthritis can be successfully treated with total joint arthroplasty. Total knee arthroplasty has been shown to be a well-proven modality that can provide pain relief and restoration of mobility for those with debilitating knee arthritis. It is important for rheumatologists and orthopedic surgeons alike to share an understanding of the special considerations that must be addressed in this unique population of patients to ensure success in the immediate perioperative and postoperative periods including specific modalities to maximize success. PMID:24151549

  9. Treatment of rheumatoid arthritis: a global perspective on the use of antirheumatic drugs

    PubMed Central

    Envalds, Minja; Pincus, Theodore

    2008-01-01

    Modern therapy for rheumatoid arthritis (RA) is based on knowledge of the severity of the natural history of the disease. RA patients are approached with early and aggressive treatment strategies, methotrexate as an anchor drug, biological targeted therapies in those with inadequate response to methotrexate, and “tight control,” aiming for remission and low disease activity according to quantitative monitoring. This chapter presents a rationale for current treatment strategies for RA with antirheumatic drugs, a review of published reports concerning treatments in clinical cohorts outside of clinical trials, and current treatments at 61 sites in 21 countries in the QUEST-RA database. PMID:18437286

  10. Successful leukocytapheresis therapy in a patient with rheumatoid arthritis on maintenance hemodialysis.

    PubMed

    Maeshima, Keisuke; Torigoe, Masataka; Iwakura, Mikako; Yamanaka, Kunitoshi; Ishii, Koji

    2015-01-01

    We report the case of a 44-year-old female undergoing maintenance hemodialysis in whom early-phase rheumatoid arthritis (RA) was successfully treated by leukocytapheresis (LCAP). The effects of prednisone, tacrolimus, and etanercept were limited, but LCAP was highly effective and its efficacy continued even after cessation of LCAP. Moreover, remission was maintained for 2 years after discontinuation of medication. LCAP may be an important treatment option for RA patients with end-stage renal failure who are on hemodialysis. PMID:24517518

  11. Tsunami Simulations With Unstructured Grids in Support of a Tsunami Early Warning System for the Indian Ocean

    NASA Astrophysics Data System (ADS)

    Harig, S.; Chaeroni, C.; Androsov, A.; Behrens, J.; Braune, S.; Mentrup, L.; Schröter, J.

    2007-12-01

    A Finite Element Model for simulations of Tsunami waves (TsunAWI) has been developed. It is part of the German Indonesian Tsunami Early Warning System (GITEWS). Model results will be the main source for the prediction of arrival times and expected wave heights. The unstructured triangular grid has a relatively low resolution in the ocean interior (about 10 km) coastal regions however are very well resolved (up to 80 m). This flexibility allows for a good representation of the wave propagation in the deep ocean as well as inundation processes without the need of nesting different grids. Numerical experiments simulating the Indian Ocean Tsunami generated by the earthquake of Dec. 26 in 2004 have been conducted. The role of the model bathymetry and topography (based on the GEBCO dataset as well as data from the SRTM satellite mission and ship cruises) has been investigated. The inundation obtained in the simulations were compared to field measurements as well as to satellite images of Banda Aceh region. Furthermore the results were compared to simulations of the same event by the finite difference model TUNAMI- N3 with three nested grids and resolutions ranging from 900 m in the coarsest grid to 90 m in the finest nested grid. It turned out that the two models coincide fairly well with respect to wave propagation and inundation. However in both approaches a good knowledge of topography and bathymetry especially in the near shore range turned out to be crucial for realistic results.

  12. 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.

  13. Simulation of a Stratospheric Intrusion Using the Lagrangian Particle Transport Model FLEXPART, Combined With Observed Surface Impacts Over the United States in Early May 1999

    Microsoft Academic Search

    S. J. Reid; O. R. Cooper; A. Stohl; A. O. Langford; A. Wimmers

    2003-01-01

    This paper reports observations and a model simulation of an exceptionally-strong tropopause fold in early May 1999 which impacted the surface of Colorado and the south-central United States. The model simulation was performed using a special version of the Lagrangian particle dispersion model FLEXPART, which revealed the evolution of the fold eastward across the United States during the subsequent week.

  14. Early maturation processes in coal. Part 2: Reactive dynamics simulations using the ReaxFF reactive force field on Morwell Brown coal structures

    E-print Network

    Goddard III, William A.

    Early maturation processes in coal. Part 2: Reactive dynamics simulations using the ReaxFF reactive force field on Morwell Brown coal structures Elodie Salmon a , Adri C.T. van Duin b , François Lorant Brown coal using the ReaxFF reactive force field. We find that these reactive MD simulations

  15. Early diagnostic suggestions improve accuracy of GPs: a randomised controlled trial using computer-simulated patients

    PubMed Central

    Kostopoulou, Olga; Rosen, Andrea; Round, Thomas; Wright, Ellen; Douiri, Abdel; Delaney, Brendan

    2015-01-01

    Background Designers of computerised diagnostic support systems (CDSSs) expect physicians to notice when they need advice and enter into the CDSS all information that they have gathered about the patient. The poor use of CDSSs and the tendency not to follow advice once a leading diagnosis emerges would question this expectation. Aim To determine whether providing GPs with diagnoses to consider before they start testing hypotheses improves accuracy. Design and setting Mixed factorial design, where 297 GPs diagnosed nine patient cases, differing in difficulty, in one of three experimental conditions: control, early support, or late support. Method Data were collected over the internet. After reading some initial information about the patient and the reason for encounter, GPs requested further information for diagnosis and management. Those receiving early support were shown a list of possible diagnoses before gathering further information. In late support, GPs first gave a diagnosis and were then shown which other diagnoses they could still not discount. Results Early support significantly improved diagnostic accuracy over control (odds ratio [OR] 1.31; 95% confidence interval [95%CI] = 1.03 to 1.66, P = 0.027), while late support did not (OR 1.10; 95% CI = 0.88 to 1.37). An absolute improvement of 6% with early support was obtained. There was no significant interaction with case difficulty and no effect of GP experience on accuracy. No differences in information search were detected between experimental conditions. Conclusion Reminding GPs of diagnoses to consider before they start testing hypotheses can improve diagnostic accuracy irrespective of case difficulty, without lengthening information search. PMID:25548316

  16. 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

  17. Immunocytomorphopathological studies on the pathogenesis of rheumatoid arthritis.

    PubMed

    Ciobanu, A; H?l?l?u, F L; Laky, D; Ciobanu, I R; Dinulescu, I; St?nculescu, S; Stroescu, I

    1996-01-01

    Thirty cases of rheumatoid arthritis were submitted to cytomorphological, histopathological (HE, VG, PAS Alcian, Gömöri, Safranine O), histoenzymological (Acid Phosphatase, chondroitin-sulphatase, Peroxidase) and immunological (rheumatoid factor (RF)) studies; circulating immune complexes, anti-collagen antibodies II, Reactive C protein (CRP), Complementary C3 fraction were also assessed. The synoviocytogram of the rheumatoid synovial fluid (SF) indicated a cytosis with polynucleosis and ragocytosis compared to the hydroarthrosic SF defined by lymphocytosis (47.8%). Enzymologically, especially for high titres of rheumatoid factor, a phosphatase and peroxidase activity was observed in polymorphonuclear cells of a ragocytary type and in phagocytic mononuclear cells. The severe forms of rheumatoid arthritis (RA) were correlated histopathologically with chronic villous synovitis associated with some processes of obliterant vascularitis, fibrosis and sclerosis. At the level of synovio-cartilage junction, fissures and a homogenization of the cartilaginous fundamental substance in the vicinity of disintegrated synovial structures were noticed. Histoenzymologically, a lysosomal and oxidative activity was found in chondrocytes and in synovial macrophages. Immunological assessments (73 serum and 60 synovial fluid samples) showed pathological values of circulating immune complexes, anti-collagen antibodies and C reactive protein. The complementary synovial depletion of the C3 fraction underlines the immune character of the rheumatoid synovitis. The immunocytomorphologic data correlation demonstrates the involvement of immunologic and enzymatic factors in the evolution of Rheumatoid Arthritis. PMID:9038384

  18. Early stages of the recovery stroke in myosin II studied by molecular dynamics simulations

    PubMed Central

    Baumketner, Andrij; Nesmelov, Yuri

    2011-01-01

    The recovery stroke is a key step in the functional cycle of muscle motor protein myosin, during which pre-recovery conformation of the protein is changed into the active post-recovery conformation, ready to exersice force. We study the microscopic details of this transition using molecular dynamics simulations of atomistic models in implicit and explicit solvent. In more than 2 ?s of aggregate simulation time, we uncover evidence that the recovery stroke is a two-step process consisting of two stages separated by a time delay. In our simulations, we directly observe the first stage at which switch II loop closes in the presence of adenosine triphosphate at the nucleotide binding site. The resulting configuration of the nucleotide binding site is identical to that detected experimentally. Distribution of inter-residue distances measured in the force generating region of myosin is in good agreement with the experimental data. The second stage of the recovery stroke structural transition, rotation of the converter domain, was not observed in our simulations. Apparently it occurs on a longer time scale. We suggest that the two parts of the recovery stroke need to be studied using separate computational models. PMID:21922589

  19. Early stages of the recovery stroke in myosin II studied by molecular dynamics simulations.

    PubMed

    Baumketner, Andrij; Nesmelov, Yuri

    2011-12-01

    The recovery stroke is a key step in the functional cycle of muscle motor protein myosin, during which pre-recovery conformation of the protein is changed into the active post-recovery conformation, ready to exersice force. We study the microscopic details of this transition using molecular dynamics simulations of atomistic models in implicit and explicit solvent. In more than 2 ?s of aggregate simulation time, we uncover evidence that the recovery stroke is a two-step process consisting of two stages separated by a time delay. In our simulations, we directly observe the first stage at which switch II loop closes in the presence of adenosine triphosphate at the nucleotide binding site. The resulting configuration of the nucleotide binding site is identical to that detected experimentally. Distribution of inter-residue distances measured in the force generating region of myosin is in good agreement with the experimental data. The second stage of the recovery stroke structural transition, rotation of the converter domain, was not observed in our simulations. Apparently it occurs on a longer time scale. We suggest that the two parts of the recovery stroke need to be studied using separate computational models. PMID:21922589

  20. MicroRNAs in rheumatoid arthritis.

    PubMed

    Salehi, Eisa; Eftekhari, Rahil; Oraei, Mona; Gharib, Alvand; Bidad, Katayoon

    2015-04-01

    The role of genetic and epigenetic factors in the development of rheumatic diseases has been an interesting field of research over the past decades all around the world. Research on the role of microRNAs (miRNAs) in rheumatoid arthritis (RA) has been active and ongoing, and investigations have attempted to use miRNAs as biomarkers in disease diagnosis, prognosis, and treatment. This review focuses on experimental researches in the field of miRNAs and RA to present the data available up to this date and includes researches searched by keywords "microRNA" and "rheumatoid arthritis" in PubMed from 2008 to January 2015. All references were also searched for related papers. miRNAs are shown to act as proinflammatory or anti-inflammatory agents in diverse cell types, and their role seems to be regulatory in most instances. Researchers have evaluated miRNAs in patients compared to controls or have investigated their role by overexpressing or silencing them. Multiple targets have been identified in vivo, in vitro, or in silico, and the researches still continue to show their efficacy in clinical settings. PMID:25736037

  1. 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

  2. Histopathological and histoenzimological investigations of the rheumatoid articular cartilage.

    PubMed

    Ciobanu, A; Ciobanu, I R; H?l?l?u, F; Laky, D; Dinulescu, I; St?nculescu, D; Stoicescu, M; Stroescu, I

    1994-01-01

    Twenty seven biopsies of articular cartilage taken intraoperatively from patients with Rheumatoid arthritis (RA) and from control patients with traumas were examined using histopathological techniques (HE, VG, PAS-Alcian, Gömöri, Safranine 0) and histoenzymological techniques (Acid phosphatase-lysomal marker, Chondroitinsulphatase, Peroxidase). Histopathologically, the rheumatoid articular cartilage appears with superficial and deep cartilaginous fissures, frequent perichondrocytic gaps associated with modification of the tinctorial activity. At the pannus synovia-cartilage junction we found invasive and destructive synovial inflammatory infiltrates penetrating and eroding the cartilage. Histoenzymologically, the rheumatoid chondrocytes have a high lysosomal potential (phosphatasic, chondroitinsulphatasic) and highly oxidative potential (peroxidasic) specific for lesion modifications. PMID:7640371

  3. Genetic Markers of Cardiovascular Disease in Rheumatoid Arthritis

    PubMed Central

    Rodríguez-Rodríguez, Luis; López-Mejías, Raquel; García-Bermúdez, Mercedes; González-Juanatey, Carlos; González-Gay, Miguel A.; Martín, Javier

    2012-01-01

    Cardiovascular (CV) disease is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). It is the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases. Besides traditional CV risk factors and chronic inflammation, a number of studies have confirmed the role of genetic factors in the development of the atherogenesis observed in RA. In this regard, besides a strong association between the HLA-DRB1?04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G > A, rs1800629) of the TNFA locus, the rs1801131 polymorphism (A > C; position + 1298) of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA. Despite considerable effort to decipher the genetic basis of CV disease in RA, further studies are required to better establish the genetic influence in the increased risk of CV events observed in patients with RA. PMID:22927710

  4. Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).

    PubMed

    O'Dwyer, David N; Armstrong, Michelle E; Cooke, Gordon; Dodd, Jonathan D; Veale, Douglas J; Donnelly, Seamas C

    2013-10-01

    Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD. PMID:23916467

  5. Rheumatoid arthritis: genetic variants as biomarkers of cardiovascular disease.

    PubMed

    Rodriguez-Rodriguez, Luis; López-Mejias, Raquel; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; González-Gay, Miguel A; Martín, Javier

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature mortality, severe morbidity, and functional impairment leading to considerable financial burden for both patients and society. Since disease progression and complications can differ from one patient to another, genetic markers are of potential relevance for identifying those individuals at a higher risk of more severe disease. RA is a complex polygenic disease. Cardiovascular (CV) disease due to accelerated atherogenesis is the most common cause of premature mortality in patients with RA. Several studies support the implication of genetic factors in the development of CV disease in RA. In addition to the strong association between alleles of the HLA-DRB1*04 shared epitope and both subclinical and clinically evident CV disease, genes implicated in inflammation and metabolism, such as TNFA, MTHFR, and CCR5, seem to be associated with a higher risk of CV disease in patients with RA. We propose the use of these genetic variants as molecular biomarkers that could help to predict disease outcome at diagnosis of RA and, therefore, to optimize the treatment and management of other risk factors from an early stage of the disease. PMID:25163740

  6. Prevalence of methotrexate intolerance in rheumatoid arthritis and psoriatic arthritis

    PubMed Central

    2013-01-01

    Introduction The aim of this study was to determine the prevalence of gastrointestinal and behavioural symptoms occurring before (anticipatory/associative) and after methotrexate (MTX) administration, termed MTX intolerance, in rheumatoid (RA) and psoriatic arthritis (PsA). Methods Methotrexate Intolerance Severity Score (MISS), previously validated in juvenile idiopathic arthritis patients, was used to determine MTX intolerance prevalence in 291 RA/PsA patients. The MISS consisted of four domains: abdominal pain, nausea, vomiting and behavioural symptoms, occurring upon, prior to (anticipatory) and when thinking of MTX (associative). MTX intolerance was defined as ?6 on the MISS with ?1 point on anticipatory and/or associative and/or behavioural items. Results A total of 123 patients (42.3%) experienced at least one gastrointestinal adverse effect. The prevalence of MTX intolerance was 11%. MTX intolerance prevalence was higher in patients on parenteral (20.6%) than on oral MTX (6.2%) (p?early detection of MTX intolerance, in order to intervene timely and avoid discontinuation of an effective treatment. PMID:24345416

  7. [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

    2014-10-24

    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

  8. 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).

  9. 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.

  10. A meta-analysis of the efficacy and toxicity of combining disease-modifying anti-rheumatic drugs in rheumatoid arthritis based on patient withdrawal

    Microsoft Academic Search

    E. H. S. Choy; C. Smith; C. J. Dore; D. L. Scott

    2005-01-01

    Introduction. Combinations of disease-modifying anti-rheumatic drugs (DMARDs) are increasingly used to treat rheumatoid arthritis (RA). Early trials showed their toxicity while recent trials suggest superior efficacy. Trials of DMARD combinations have enrolled different types of patient (early or established RA), used different designs (step-up, parallel or step-down) and utilized a range of outcome measures. We undertook a systematic review of

  11. 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

  12. The performance of field scientists undertaking observations of early life fossils while in simulated space suit

    NASA Astrophysics Data System (ADS)

    Willson, D.; Rask, J. C.; George, S. C.; de Leon, P.; Bonaccorsi, R.; Blank, J.; Slocombe, J.; Silburn, K.; Steele, H.; Gargarno, M.; McKay, C. P.

    2014-01-01

    We conducted simulated Apollo Extravehicular Activity's (EVA) at the 3.45 Ga Australian 'Pilbara Dawn of life' (Western Australia) trail with field and non-field scientists using the University of North Dakota's NDX-1 pressurizable space suit to overview the effectiveness of scientist astronauts employing their field observation skills while looking for stromatolite fossil evidence. Off-world scientist astronauts will be faced with space suit limitations in vision, human sense perception, mobility, dexterity, the space suit fit, time limitations, and the psychological fear of death from accidents, causing physical fatigue reducing field science performance. Finding evidence of visible biosignatures for past life such as stromatolite fossils, on Mars, is a very significant discovery. Our preliminary overview trials showed that when in simulated EVAs, 25% stromatolite fossil evidence is missed with more incorrect identifications compared to ground truth surveys but providing quality characterization descriptions becomes less affected by simulated EVA limitations as the science importance of the features increases. Field scientists focused more on capturing high value characterization detail from the rock features whereas non-field scientists focused more on finding many features. We identified technologies and training to improve off-world field science performance. The data collected is also useful for NASA's "EVA performance and crew health" research program requirements but further work will be required to confirm the conclusions.

  13. A 3D simulation of the early winter distribution of reactive chlorine in the north polar vortex

    SciTech Connect

    Douglass, A.; Rood, R. (NASA/Goddard Space Flight Center, Greenbelt, MD (United States)); Waters, J.; Froidevaux, L.; Read, W.; Elson, L. (California Institute of Technology, Pasadena (United States)); Geller, M.; Chi, Y. (State Univ. of New York, Stony Brook (United States)); Cerniglia, M.; Steenrod, S.

    1993-06-18

    This paper presents the results of 3D simulations of the formation of reactive chlorine on polar stratospheric clouds in the southern polar vortex. The purpose behind these simulations is to compare calculations with measurements of the microwave limb sounder (MLS) carried on the upper atmosphere research satellite (UARS), which showed regions of enhanced ClO in early December 1991, in regions south of areas where temperatures would support the formation of polar stratospheric clouds. The presently accepted model is that reactive chlorine is formed by rapid chemical reactions on the surfaces of particles in polar stratospheric clouds, from gases such as HCl and ClONO[sub 2]. It is then converted to ClO by photochemical processes. The simulations look at cyclonic and anticyclonic circulation patterns in the region of polar stratospheric cloud formation, and the impact this circulation has on the transport of reactive chlorine northward or southward from its creation to regions where it is converted to ClO.

  14. Effect of simulated and real weightlessness on early regeneration stages of Brassica napus protoplasts.

    PubMed

    Skagen, E B; Iversen, T H

    2000-01-01

    Results from experiments using protoplasts in space, performed on the Biokosmos 9 satellite in 1989 and on the Space Shuttle on the IML-1-mission in 1992 and S/MM-03 in 1996, are presented. This paper focuses on the observation that the regeneration capacity of protoplasts is lower under micro-g conditions than under 1 g conditions. These aspects have been difficult to interpret and raise new questions about the mechanisms behind the observed effects. In an effort to try to find a key element to the poor regeneration capacity, ground-based studies were initiated focusing on the effect of the variable organization and quantity of corticular microtubules (CMTs) as a consequence of short periods of real and simulated weightlessness. The new results demonstrated the capacity of protoplasts to enter division, confirming the findings in space that this was affected by gravity. The percentage of dividing cells significantly decreased as a result of exposure to simulated weightlessness on a 2-D clinostat. Similar observations were made when comparing the wall components, which confirmed that the reconstitution of the cell wall was retarded under both space conditions and simulated weightlessness. The peroxidase activity in protoplasts exposed to microgravity was slightly decreased in both 0 g and 1 g flight samples compared with the ground controls, whereas activity in the protoplasts exposed to simulated weightlessness was similar to activity in the 1 g control. The observation that protoplasts had randomized and more sparse corticular microtubules when exposed to various forms of simulated and real weightlessness on a free-fall machine on the ground could indicate that the low division capacity in 0 g protoplasts was correlated with an abnormal CMT array in these protoplasts. This study has increased our knowledge of the more basic biochemical and cell biological aspects of g effects. This is an important link in preparation for the new space era, when it will be possible to follow the growth of single cells and tissue cultures for generations under microgravity conditions on the new International Space Station, which will be functional on a permanent basis from the year 2003. PMID:11758568

  15. Quantitative lung SPECT applied on simulated early COPD and humans with advanced COPD

    PubMed Central

    2013-01-01

    Background Reduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), reflected as inhomogeneities in the single-photon emission computed tomography (SPECT) lung image, is correlated to disease advancement. An analysis method for measuring these inhomogeneities is proposed in this work. The first aim was to develop a quantitative analysis method that could discriminate between Monte Carlo simulated normal and COPD lung SPECT images. A second aim was to evaluate the ability of the present method to discriminate between human subjects with advanced COPD and healthy volunteers. Methods In the simulated COPD study, different activity distributions in the lungs were created to mimic the healthy lung (normal) and different levels of COPD. Gamma camera projections were Monte Carlo simulated, representing clinically acquired projections of a patient who had inhaled 125 MBq 99mTc-Technegas followed by a 10-min SPECT examination. Reconstructions were made with iterative ordered subset expectation maximisation. The coefficient of variance (CV) was calculated for small overlapping volumes covering the 3D reconstructed activity distribution. A CV threshold value (CVT) was calculated as the modal value of the CV distribution of the simulated normal. The area under the distribution curve (AUC), for CV values greater than CVT, AUC(CVT), was then calculated. Moreover, five patients with advanced emphysema and five healthy volunteers inhaled approximately 75 MBq 99mTc-Technegas immediately before the 20-min SPECT acquisition. In the human study, CVT was based on the mean CV distribution of the five healthy volunteers. Results A significant difference (p < 0.001) was found between the Monte-Carlo simulated normal and COPD lung SPECT examinations. The present method identified a total reduction of ventilation of approximately 5%, not visible to the human eye in the reconstructed image. In humans the same method clearly discriminated between the five healthy volunteers and five patients with advanced COPD (p < 0.05). Conclusions While our results are promising, the potential of the AUC(CVT) method to detect less advanced COPD in patients needs further clinical studies. PMID:23597059

  16. Association of MHC and rheumatoid arthritis: HLA polymorphisms in phenotypic variants of rheumatoid arthritis

    Microsoft Academic Search

    Cornelia M Weyand; Jörg J Goronzy

    2000-01-01

    Genes in the human leukocyte antigen (HLA) region remain the most powerful disease risk genes in rheumatoid arthritis (RA). Several allelic variants of HLA-DRB1 genes have been associated with RA, supporting a role for T-cell receptor-HLA-antigen interactions in the pathologic process. Disease-associated HLA-DRB1 alleles are similar but not identical and certain allelic variants are preferentially enriched in patient populations with

  17. Is juvenile rheumatoid arthritis\\/juvenile idiopathic arthritis different from rheumatoid arthritis?

    Microsoft Academic Search

    Sampath Prahalad; David N Glass

    2002-01-01

    CHAPTER SUMMARY: The chronic arthropathies of childhood share clinical and pathological features with rheumatoid arthritis (RA) in adults. Both are autoimmune diseases characterized by a destructive arthropathy. Both are likely to be complex genetic traits, with autoantibodies and with a type-1-T-helper-cell cytokine profile in disease tissues. In common with other autoimmune diseases, both have associations and linkage with human keukocyte

  18. The TRIDEC Virtual Tsunami Atlas - customized value-added simulation data products for Tsunami Early Warning generated on compute clusters

    NASA Astrophysics Data System (ADS)

    Löwe, P.; Hammitzsch, M.; Babeyko, A.; Wächter, J.

    2012-04-01

    The development of new Tsunami Early Warning Systems (TEWS) requires the modelling of spatio-temporal spreading of tsunami waves both recorded from past events and hypothetical future cases. The model results are maintained in digital repositories for use in TEWS command and control units for situation assessment once a real tsunami occurs. Thus the simulation results must be absolutely trustworthy, in a sense that the quality of these datasets is assured. This is a prerequisite as solid decision making during a crisis event and the dissemination of dependable warning messages to communities under risk will be based on them. This requires data format validity, but even more the integrity and information value of the content, being a derived value-added product derived from raw tsunami model output. Quality checking of simulation result products can be done in multiple ways, yet the visual verification of both temporal and spatial spreading characteristics for each simulation remains important. The eye of the human observer still remains an unmatched tool for the detection of irregularities. This requires the availability of convenient, human-accessible mappings of each simulation. The improvement of tsunami models necessitates the changes in many variables, including simulation end-parameters. Whenever new improved iterations of the general models or underlying spatial data are evaluated, hundreds to thousands of tsunami model results must be generated for each model iteration, each one having distinct initial parameter settings. The use of a Compute Cluster Environment (CCE) of sufficient size allows the automated generation of all tsunami-results within model iterations in little time. This is a significant improvement to linear processing on dedicated desktop machines or servers. This allows for accelerated/improved visual quality checking iterations, which in turn can provide a positive feedback into the overall model improvement iteratively. An approach to set-up and utilize the CCE has been implemented by the project Collaborative, Complex, and Critical Decision Processes in Evolving Crises (TRIDEC) funded under the European Union's FP7. TRIDEC focuses on real-time intelligent information management in Earth management. The addressed challenges include the design and implementation of a robust and scalable service infrastructure supporting the integration and utilisation of existing resources with accelerated generation of large volumes of data. These include sensor systems, geo-information repositories, simulations and data fusion tools. Additionally, TRIDEC adopts enhancements of Service Oriented Architecture (SOA) principles in terms of Event Driven Architecture (EDA) design. As a next step the implemented CCE's services to generate derived and customized simulation products are foreseen to be provided via an EDA service for on-demand processing for specific threat-parameters and to accommodate for model improvements.

  19. IgG rheumatoid factors and anti-nuclear antibodies in rheumatoid vasculitis.

    PubMed Central

    Quismorio, F P; Beardmore, T; Kaufman, R L; Mongan, E S

    1983-01-01

    We studied the distribution and characteristics of circulating rheumatoid factors (RF) and anti-nuclear antibodies (ANA) in 30 rheumatoid arthritis (RA) patients who had polyarthritis alone (group I), 28 RA patients with polyarthritis and extra-articular disease (group II), 28 RA patients with systemic vasculitis (group III) and 60 healthy matched controls. IgG RF occurred more frequently and in higher serum titres in group III (100%) than RA patients in group I (40%), or in group II (18%) or in normal controls (5.8%). The serum titre of IgM RF was higher in vasculitis patients than in other RA patients. ANA were found in 74% of all RA patients and although the frequency did not differ in the three patient groups, the serum titre was significantly higher in the vasculitis group. Antibodies to extractable nuclear antigen were found only in group III (18.7%). Antibodies to histones were also more prevalent in group III than in the other RA groups. The serological abnormalities in rheumatoid vasculitis differed quantitatively as well as qualitatively from other RA patients. PMID:6602676

  20. Antibodies Act Jointly to Promote Inflammation in Rheumatoid Arthritis

    MedlinePLUS

    ... 2000 1999 Spotlight on Research 2014 September 2014 Antibodies Act Jointly to Promote Inflammation in Rheumatoid Arthritis Two types of antibody molecules act in concert to stimulate inflammation in ...

  1. BRAF Drives Synovial Fibroblast Transformation in Rheumatoid Arthritis

    PubMed Central

    Weisbart, Richard H.; Chan, Grace; Heinze, Emil; Mory, Rachel; Nishimura, Robert N.; Colburn, Keith

    2010-01-01

    Synovial fibroblasts destroy articular cartilage and bone in rheumatoid arthritis, but the mechanism of fibroblast transformation remains elusive. Because gain-of-function mutations of BRAF can transform fibroblasts, we examined BRAF in rheumatoid synovial fibroblasts. The strong gain-of-function mutation, V600R, of BRAF found in melanomas and other cancers was identified in first passage synovial fibroblasts from two of nine rheumatoid arthritis patients and confirmed by restriction site mapping. BRAF-specific siRNA inhibited proliferation of synovial fibroblasts with V600R mutations. A BRAF aberrant splice variant with an intact kinase domain and partial loss of the N-terminal autoinhibitory domain was identified in fibroblasts from an additional patient, and fibroblast proliferation was inhibited by BRAF-specific siRNA. Our finding is the first to establish mechanisms for fibroblast transformation responsible for destruction of articular cartilage and bone in rheumatoid arthritis and establishes a new target for therapeutic intervention. PMID:20843808

  2. 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

  3. Relativistic Particle-In-Cell Simulation Studies of Prompt and Early Afterglows from GRBs

    E-print Network

    K. -I. Nishikawa; P. Hardee; Y. Mizuno; M. Medvedev; B. Zhang; D. H. Hartmann; G. J. Fishman

    2008-02-18

    Nonthermal radiation observed from astrophysical systems containing relativistic jets and shocks e.g. gamma-ray bursts (GRBs) active galactic nuclei (AGNs) and microquasars commonly exhibit power-law emission spectra. Recent PIC simulations of relativistic electron-ion (or electron-positron) jets injected into a stationary medium show that particle acceleration occurs within the downstream jet. In collisionless relativistic shocks particle (electron, positron and ion) acceleration is due to plasma waves and their associated instabilities (e.g. the Weibel (filamentation) instability) created in the shock region. The simulations show that the Weibel instability is responsible for generating and amplifying highly non-uniform small-scale magnetic fields. These fields contribute to the electron's transverse deflection behind the jet head. The resulting ``jitter'' radiation from deflected electrons has different properties compared to synchrotron radiation which assumes a uniform magnetic field. Jitter radiation may be important for understanding the complex time evolution and/or spectra in gamma-ray bursts, relativistic jets in general and supernova remnants.

  4. Effects of simulated weightlessness on meiosis. Fertilization, and early development in mice

    NASA Technical Reports Server (NTRS)

    Wolgemuth, D. J.

    1986-01-01

    The initial goal was to construct a clinostat which could support mammalian cell culture. The clinostat was selected as a means by which to simulate microgravity conditions within the laboratory, by constant re-orientation of cells with respect to the gravity vector. The effects of this simulated microgravity on in-vitro meiotic maturation of oocytes, using mouse as the model system, was investigated. The effects of clinostat rotation on fertilization in-vitro was then examined. Specific endpoints included examining the timely appearance of male and female pronuclei (indicating fertilization) and the efficiency of extrusion of the second polar body. Particular attention was paid to detecting anomalies of fertilization, including parthenogenetic activation and multiple pronuclei. Finally, for the preliminary studies on mouse embryogenesis, a key feature of the clinostat was modified, that of the position of the cells during rotation. A means was found to immobilize the cells during the clinostat reotation, permitting the cells to remain at the axis of rotation yet not interfering with cellular development.

  5. New Relativistic Particle-In-Cell Simulation Studies of Prompt and Early Afterglows from GRBs

    NASA Technical Reports Server (NTRS)

    Nishikawa, Ken-ichi; Hardee, P.; Mizuno, Y.; Zhang, B.; Medvedev, M.; Hartmann, D.; Fishman, J. F.; Preece, R.

    2008-01-01

    Nonthermal radiation observed from astrophysical systems containing relativistic jets and shocks, e.g., gamma-ray bursts (GRBs), active galactic nuclei (AGNs), and Galactic microquasar systems usually have power-law emission spectra. Recent PIC simulations of relativistic electron-ion (electro-positron) jets injected into a stationary medium show that particle acceleration occurs within the downstream jet. In the collisionless relativistic shock particle acceleration is due to plasma waves and their associated instabilities (e.g., the Buneman instability, other two-streaming instability, and the Weibel (filamentation) instability) created in the shocks are responsible for particle (electron, positron, and ion) acceleration. The simulation results show that the Weibel instability is responsible for generating and amplifying highly nonuniform, small-scale magnetic fields. These magnetic fields contribute to the electron's transverse deflection behind the jet head. The 'jitter' radiation from deflected electrons has different properties than synchrotron radiation which is calculated in a uniform magnetic field. This jitter radiation may be important to understanding the complex time evolution and/or spectral structure in gamma-ray bursts, relativistic jets, and supernova remnants.

  6. Relativistic Particle-In-Cell Simulation Studies of Prompt and Early Afterglows from GRBs

    NASA Technical Reports Server (NTRS)

    Nishikawa, Ken-Ichi; Hardee, Philip; Mizuno, Yosuke; Fishman, Gerald

    2008-01-01

    Nonthermal radiation observed from astrophysical systems containing relativistic jets and shocks, e.g., gamma-ray bursts (GRBs), active galactic nuclei (AGNs), and Galactic microquasar systems usually have power-law emission spectra. Recent PIC simulations of relativistic electron-ion (electro-positron) jets injected into a stationary medium show that particle acceleration occurs within the downstream jet. In the collisionless relativistic shock particle acceleration is due to plasma waves and their associated instabilities {e.g., the Weibel (filamentation) instability) created in the shocks are responsible for particle (electron, positron, and ion) acceleration. The simulation results show that the Weibel instability is responsible for generating and amplifying highly nonuniform, small-scale magnetic fields. These magnetic fields contribute to the electron's transverse deflection behind the jet head. The "jitter" radiation from deflected electrons has different properties than synchrotron radiation which is calculated in a uniform magnetic field. This jitter radiation may be important to understanding the complex time evolution and/or spectral structure in gamma-ray bursts, relativistic jets, and supernova remnants.-/

  7. Relativistic Particle-in-Cell Simulation Studies of Prompt and Early Afterglows Observed by GLAST

    NASA Technical Reports Server (NTRS)

    Mizuno, Y.; Nishikawa, K.-I.; Hardee, P.; Fishman, G. J.; Preece, R.

    2007-01-01

    Nonthermal radiation observed from astrophysical systems containing relativistic jets and shocks, e.g., gamma-ray bursts (GRBs), active galactic nuclei (AGNs), and Galactic microquasar systems usually have power-law emission spectra. Recent PIC simulations using injected relativistic electron-ion (electro-positron) jets show that acceleration occurs within the downstream jet. Shock acceleration is a ubiquitous phenomenon in astrophysical plasmas. Plasma waves and their associated instabilities (e.g., the Buneman instability, other two-streaming instability, and the Weibel instability) created in the shocks are responsible for particle (electron, positron, and ion) acceleration. The simulation results show that the Weibel instability is responsible for generating and amplifying highly nonuniform, small-scale magnetic fields. These magnetic fields contribute to the electron's transverse deflection behind the jet head. The "'jitter" radiation from deflected electrons has different properties than synchrotron radiation which is calculated in a uniform magnetic field. This jitter radiation may be important to understanding the complex time evolution and/or spectral structure in gamma-ray bursts, relativistic jets, and supernova remnants.

  8. Three cases of rheumatoid arthritis with laryngeal stridor

    Microsoft Academic Search

    James E. Peters; Christopher J. Burke; Vanessa H. Morris

    2011-01-01

    The purpose of this is case-based review is to report a series of patients with rheumatoid arthritis who developed stridor\\u000a and highlight this potentially life-threatening manifestation of the disease. We report three cases from the Rheumatology\\u000a Department of University College Hospital, London and review the literature on the prevalence, clinical presentation, histopathological\\u000a features and treatment of laryngeal involvement in rheumatoid

  9. Rheumatoid factor (antigammaglobulin) in women: effects of oral contraceptives use of its prevalence.

    PubMed

    Sponzilli, E E; Ramcharan, S; Wingerd, J

    1976-01-01

    A total of 14,856 women, including 921 pregnant subjects, were tested for rheumatoid factor; 4,562 were using oral contraceptives at the time of testing. The prevalence of rheumatoid factor increased directly with age. The age-adjusted prevalence of rheumatoid factor was lower in oral contraceptive users than in nonusers but this difference was not statistically significant. Rheumatoid factor remained positive in 39% of subjects undergoing retesting after an average interval of 16 months. Those women with higher titers of rheumatoid factor were more likely to remain positive (81%). Of the women having positive tests, 5.4% were identified as having rheumatoid disease. PMID:59601

  10. 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

  11. Role of osteopontin in rheumatoid arthritis.

    PubMed

    Zhang, Fangjie; Luo, Wei; Li, Yusheng; Gao, Shuguang; Lei, Guanghua

    2015-04-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness, and destruction of synovial joints, leading to severe disability and premature mortality. RA is a multifactorial disease with genetic, environmental, and stochastic components related to its susceptibility. It has been demonstrated that the expression of osteopontin (OPN) is upregulated in the RA patients. Numerous studies have indicated that the full-length OPN or even OPN fragments, such as thrombin-cleaved OPN and its receptors, play the key roles in RA pathogenesis. Therapeutic application of siRNA to target OPN or neutralizing antibodies related to OPN epitopes in RA animal models are in progress, and some results are encouraging. However, there is a long way to go along with the clinical trials. This review focuses on the recent development in research associated with the OPN role in the pathogenesis of RA and provides insights concerning the OPN targeting as therapeutic approaches for patients with RA. PMID:25163663

  12. Rheumatoid arthritis susceptibility genes: An overview

    PubMed Central

    Korczowska, Izabela

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease sustained by genetic factors. Various aspects of the genetic contribution to the pathogenetics and outcome of RA are still unknown. Several genes have been indicated so far in the pathogenesis of RA. Apart from human leukocyte antigen, large genome wide association studies have identified many loci involved in RA pathogenesis. These genes include protein tyrosine phosphatase, nonreceptor type 22, Peptidyl Arginine Deiminase type IV, signal transducer and activator of transcription 4, cytotoxic T-lymphocyte-associated protein 4, tumor necrosis factor-receptor associated factor 1/complement component 5, tumor necrosis factor and others. It is important to determine whether a combination of RA risk alleles are able to identify patients who will develop certain clinical outcomes, such myocardium infarction, severe infection or lymphoma, as well as to identify patients who will respond to biological medication therapy. PMID:25232530

  13. 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)

  14. Genetics of rheumatoid arthritis: confronting complexity

    PubMed Central

    Gregersen, Peter K

    1999-01-01

    The genetic basis for rheumatoid arthritis (RA) is likely to be extremely complex. Even the role of MHC genes remains to be fully defined, and may involve interactive genetic effects. The difficulty of precisely defining the clinical phenotype, as well as underlying genetic heterogeneity, complicates the problem. In addition, stochastic genetic or physiologic events may contribute to the low penetrance of susceptibility genes. This situation parallels developing paradigms for other autoimmune disorders, in which many different genes each appear to contribute a small amount to overall risk for disease, and where severity and specific phenotypic subtypes are subject to genetic effects. The completion of the human genome project, along with advances in informatics, will be required to reach a deeper understanding of RA. It is likely that this will involve an iterative and interactive process between several different scientific disciplines. PMID:11094412

  15. 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.

  16. 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

  17. Thermodynamic equilibrium solubility measurements in simulated fluids by 96-well plate method in early drug discovery.

    PubMed

    Bharate, Sonali S; Vishwakarma, Ram A

    2015-04-01

    An early prediction of solubility in physiological media (PBS, SGF and SIF) is useful to predict qualitatively bioavailability and absorption of lead candidates. Despite of the availability of multiple solubility estimation methods, none of the reported method involves simplified fixed protocol for diverse set of compounds. Therefore, a simple and medium-throughput solubility estimation protocol is highly desirable during lead optimization stage. The present work introduces a rapid method for assessment of thermodynamic equilibrium solubility of compounds in aqueous media using 96-well microplate. The developed protocol is straightforward to set up and takes advantage of the sensitivity of UV spectroscopy. The compound, in stock solution in methanol, is introduced in microgram quantities into microplate wells followed by drying at an ambient temperature. Microplates were shaken upon addition of test media and the supernatant was analyzed by UV method. A plot of absorbance versus concentration of a sample provides saturation point, which is thermodynamic equilibrium solubility of a sample. The established protocol was validated using a large panel of commercially available drugs and with conventional miniaturized shake flask method (r(2)>0.84). Additionally, the statistically significant QSPR models were established using experimental solubility values of 52 compounds. PMID:25740159

  18. Use of monoclonal antibodies to detect disease associated HLA-DRB1 alleles and the shared epitope in rheumatoid arthritis

    PubMed Central

    Wicks, I.; McColl, G.; D'Amico, A.; Dougherty, L.; Tait, B.

    1997-01-01

    OBJECTIVE—To use a panel of monoclonal antibodies (Mab) which recognise HLA class II alleles associated with rheumatoid arthritis for fluorescence activated cell sorter (FACS) analysis of peripheral blood mononuclear cells (PBMNC) from patients with early and established rheumatoid arthritis and to compare these results against DNA oligotyping of HLA class II molecules in the same patients.?METHODS—27 patients (18 from an early arthritis clinic, nine with established rheumatoid arthritis) were studied using both techniques. PBMNC were stained with Mab which recognise the shared epitope, the HLA-DRB1*04 molecule and its *0401, *0404 subtypes in the presence of bound peptide. Mab stained cells were analysed by FACS. Genomic DNA was prepared from PBMNC and used for DNA oligotyping and sequencing by standard methods.?RESULTS—FACS analysis of Mab stained PBMNC gave identical results to those obtained by DNA oligotyping in 26/27 patients. The antibodies identified the shared epitope in 14/14 cases and the presence of an HLA-DRB1*04 molecule in 12/12 cases. HLA-DRB1*0404 was identified in 4/4 cases. HLA-DRB1*0401 was identified in 5/6 cases. One patient oligotyped as HLA-DRB1*0401, but consistently failed to react with the *0401 Mab. DNA sequencing of the second exon of the HLA-DRB1*0401 allele in this patient confirmed a normal HLA-DRB1*0401 genotype.?CONCLUSIONS—FACS analysis of PBMNC stained with Mab recognising the shared epitope and rheumatoid arthritis associated HLA susceptibility molecules provides a rapid, reliable, and more accessible alternative to DNA oligotyping. The apparent discordance between phenotypic and genetic analysis of HLA-DRB1*0401 in one patient, may reflect variability in HLA-DRB1*0401 gene expression or in class II peptide presentation.?? PMID:9068289

  19. Anti-CCP antibody and rheumatoid factor concentrations predict greater disease activity in men with rheumatoid arthritis

    Microsoft Academic Search

    Benjamin J Miriovsky; Kaleb Michaud; Geoffrey M Thiele; James R ODell; Grant W Cannon; Gail Kerr; J Steuart Richards; Dannette Johnson; Liron Caplan; Andreas Reimold; Roderick Hooker; Ted R Mikuls

    2010-01-01

    ObjectiveTo examine associations of anti-cyclic citrullinated peptide (aCCP) antibody and rheumatoid factor (RF) concentrations with future disease activity in men with rheumatoid arthritis (RA).MethodsOutcome measures were examined in male US veterans with RA and included (1) proportion of observations in remission (disease activity score (DAS28) ?2.6); (2) remission for ?3 consecutive months; and (3) area under the curve (AUC) for

  20. A 3D simulation of the early winter distribution of reactive chlorine in the north polar vortex

    NASA Technical Reports Server (NTRS)

    Douglass, A.; Rood, R.; Waters, J.; Froidevaux, L.; Read, W.; Elson, L.; Geller, M.; Chi, Y.; Cerniglia, M.; Steenrod, S.

    1993-01-01

    Early in December 1991, high values of ClO are seen by the Microwave Limb Sounder (MLS) on the Upper Atmosphere Research Satellite at latitudes south of areas of temperatures cold enough to form polar stratospheric clouds (PSCs). A 3D simulation shows that the heterogeneous conversion of chlorine reservoirs to reactive chlorine on the surfaces of PSCs (processing) takes place at high latitudes. Often the processed air must be transported to lower latitudes, where the reactive chlorine is photochemically converted to ClO, to be observed by MLS. In this simulation, one incidence of cold temperatures is associated with an anticyclone, and a second with a cyclone. The transport of processed air associated with the anticyclone is marked by shearing; a decrease in the maximum of the processed air is accompanied by growth of the area influenced by the processing. In contrast, the air processed in the cyclonic event spreads more slowly. This shows that transport and shearing is a crucial element to the evolution of reactive chlorine associated with a processing event. In particular, transport and shearing, as well as photochemical processes, can cause variations in observed ClO.

  1. Color matrix display simulation based upon luminance and chromatic contrast sensitivity of early vision

    NASA Technical Reports Server (NTRS)

    Martin, Russel A.; Ahumada, Albert J., Jr.; Larimer, James O.

    1992-01-01

    This paper describes the design and operation of a new simulation model for color matrix display development. It models the physical structure, the signal processing, and the visual perception of static displays, to allow optimization of display design parameters through image quality measures. The model is simple, implemented in the Mathematica computer language, and highly modular. Signal processing modules operate on the original image. The hardware modules describe backlights and filters, the pixel shape, and the tiling of the pixels over the display. Small regions of the displayed image can be visualized on a CRT. Visual perception modules assume static foveal images. The image is converted into cone catches and then into luminance, red-green, and blue-yellow images. A Haar transform pyramid separates the three images into spatial frequency and direction-specific channels. The channels are scaled by weights taken from human contrast sensitivity measurements of chromatic and luminance mechanisms at similar frequencies and orientations. Each channel provides a detectability measure. These measures allow the comparison of images displayed on prospective devices and, by that, the optimization of display designs.

  2. 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.

  3. Marine methane cycle simulations for the period of early global warming

    SciTech Connect

    Elliott, S.; Maltrud, M.; Reagan, M.T.; Moridis, G.J.; Cameron-Smith, P.J.

    2011-01-02

    Geochemical environments, fates, and effects are modeled for methane released into seawater by the decomposition of climate-sensitive clathrates. A contemporary global background cycle is first constructed, within the framework of the Parallel Ocean Program. Input from organics in the upper thermocline is related to oxygen levels, and microbial consumption is parameterized from available rate measurements. Seepage into bottom layers is then superimposed, representing typical seabed fluid flow. The resulting CH{sub 4} distribution is validated against surface saturation ratios, vertical sections, and slope plume studies. Injections of clathrate-derived methane are explored by distributing a small number of point sources around the Arctic continental shelf, where stocks are extensive and susceptible to instability during the first few decades of global warming. Isolated bottom cells are assigned dissolved gas fluxes from porous-media simulation. Given the present bulk removal pattern, methane does not penetrate far from emission sites. Accumulated effects, however, spread to the regional scale following the modeled current system. Both hypoxification and acidification are documented. Sensitivity studies illustrate a potential for material restrictions to broaden the perturbations, since methanotrophic consumers require nutrients and trace metals. When such factors are considered, methane buildup within the Arctic basin is enhanced. However, freshened polar surface waters act as a barrier to atmospheric transfer, diverting products into the deep return flow. Uncertainties in the logic and calculations are enumerated including those inherent in high-latitude clathrate abundance, buoyant effluent rise through the column, representation of the general circulation, and bacterial growth kinetics.

  4. 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

  5. Efficacy, safety and mechanism of action of modified-release prednisone in rheumatoid arthritis

    PubMed Central

    Clarke, Lynsey

    2012-01-01

    Glucocorticoids (GCs) provide a powerful and widely used anti-inflammatory and disease-modifying therapy for rheumatoid arthritis (RA). However, concerns about adverse effects are driving efforts to find ‘safer’ GC or GC analogues. One novel approach has been to change the timing of GC delivery, targeting the early hours of the morning to suppress the observed circadian peak in interleukin-6 (IL-6). The CAPRA-1 study has shown that this produces a clinically useful beneficial improvement in morning stiffness and mechanistic studies have shown that this correlates with a strong suppression of the IL-6 early morning peak. With no obvious additional adverse reactions, this improvement in the therapeutic ratio offers additional treatment options in RA, and perhaps in other inflammatory diseases that show circadian variation in symptoms. PMID:22850902

  6. 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 ...

  7. 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 ...

  8. 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, ...

  9. Periodontal status of rheumatoid arthritis patients in khartoum state

    PubMed Central

    2011-01-01

    Background Few studies have investigated the periodontal condition among Rheumatoid arthritis in Sudan. The present study described the periodontal condition among Sudanese patients suffering from rheumatoid arthritis and to compare them with those of non-rheumatic subjects. Methods A group of eighty rheumatoid arthritis patients was selected from Patient's Rheumatoid Clinics in Khartoum State during the period of January to May 2010. A control group of eighty patients with the same age and gender was selected for the study. Both Rheumatoid arthritis patients and the control group were examined for their plaque index, gingival index, and clinical attachment loss. Results The results revealed that there were no significant differences in plaque and gingival index among study and control groups, with mean plaque index of (1.25 ± 0.4) for patients and (1.17 ± 0.28) for the control group (p-value is 0.3597). The mean gingival index was (1.2 ± 0.24) for the patients and (1.2 ± 0.33) for the control (p = is 0.3049). The results showed statistically significant differences in clinical attachment loss between study and control groups, with mean clinical attachment loss of (1.03 ± 0.95) for the study group and (0.56 ± 0.63) for the control group (p = 0.0002). The study revealed that no association exists between the type of drug used to treat rheumatoid arthritis (NSAIDs & DMARDs) and the periodontal parameters (plaque index, gingival index, and clinical attachment loss). Conclusion A significant relationship between periodontal disease and Rheumatoid Arthritis does exist, but no difference between plaque and gingival index has been detected among study and control groups. PMID:22035090

  10. 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

  11. Limited Wegener's granulomatosis presenting as lung nodules in a patient with rheumatoid arthritis: a case report

    Microsoft Academic Search

    Sushma Pai; Mukta Panda

    2008-01-01

    BACKGROUND: Rheumatoid arthritis has varied pleuroparenchymal manifestations. Wegener's granulomatosis can develop in an established case of rheumatoid arthritis and this association although previously reported is very rare. CASE PRESENTATION: A 60-year-old lady had been diagnosed with rheumatoid arthritis on the basis of her clinical symptoms and serological tests which were positive RA factor and anti-CCP antibodies. Her rheumatoid arthritis activity

  12. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci

    Microsoft Academic Search

    Eli A Stahl; Soumya Raychaudhuri; Elaine F Remmers; Gang Xie; Stephen Eyre; Brian P Thomson; Yonghong Li; Fina A S Kurreeman; Alexandra Zhernakova; Anne Hinks; Candace Guiducci; Robert Chen; Lars Alfredsson; Christopher I Amos; Kristin G Ardlie; Anne Barton; John Bowes; Elisabeth Brouwer; Noel P Burtt; Joseph J Catanese; Jonathan Coblyn; Marieke J H Coenen; Karen H Costenbader; Lindsey A Criswell; J Bart A Crusius; Jing Cui; Paul I W de Bakker; Philip L De Jager; Bo Ding; Paul Emery; Edward Flynn; Pille Harrison; Lynne J Hocking; Tom W J Huizinga; Daniel L Kastner; Xiayi Ke; Annette T Lee; Xiangdong Liu; Paul Martin; Ann W Morgan; Leonid Padyukov; Marcel D Posthumus; Timothy R D J Radstake; David M Reid; Mark Seielstad; Michael F Seldin; Nancy A Shadick; Sophia Steer; Paul P Tak; Wendy Thomson; Annette H M van der Helm-van Mil; Irene E van der Horst-Bruinsma; C Ellen van der Schoot; Piet L C M van Riel; Michael E Weinblatt; Anthony G Wilson; Gert Jan Wolbink; B Paul Wordsworth; Cisca Wijmenga; Elizabeth W Karlson; Rene E M Toes; Niek de Vries; Ann B Begovich; Jane Worthington; Katherine A Siminovitch; Peter K Gregersen; Lars Klareskog; Robert M Plenge

    2010-01-01

    To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at

  13. Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation.

    PubMed

    Martinez, Emily M; Yoshida, Miya C; Candelario, Tara Lynne T; Hughes-Fulford, Millie

    2015-03-15

    Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (?g) conditions. Scientists on the ground use two models of simulated ?g (s?g): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true ?g when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true ?g and s?g on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2r?, Ifn?, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that s?g models provide an excellent test bed for scientists to develop baseline studies and augment true ?g in spaceflight experiments. Ultimately, s?g and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders. PMID:25568077

  14. Gestational and early postnatal exposure to simulated high altitude does not modify postnatal body mass growth trajectory in the rat.

    PubMed

    Bozzini, Carlos E; Champin, Graciela M; Bozzini, Clarisa; Alippi, Rosa M

    2014-09-01

    Postnatal hypoxia blunts body mass growth. It is also known that the quality of the fetal environment can influence the subsequent adult phenotype. The main purpose of the study was to determine whether gestational hypoxia and early postnatal hypoxia are able to blunt growth when the offspring is raised under normoxia. Hypobaric hypoxia was induced in simulated high altitude (SHA) chambers in which air was maintained at 380?mmHg (5450?m). Mature Sprague-Dawley rats of both sexes were divided in normoxic (NX) and hypoxic (HX) groups and, in the case of the HX group, maintained for 1 month at 5450?m. Mating was then allowed under NX or HX conditions. Offspring were NX-NX, NX-HX, HX-HX, or HX-NX: the first term indicates NX or HX during both gestation and the first 30 days of life; the second term indicates NX or HX during postnatal life between days 30 and 133. Body mass (g) was measured periodically and body mass growth rate (BMGR, g/d) was estimated between days 33 and 65 of postnatal life. Results can be summarized as follows: 1) BM was significantly higher in NX than in HX rats at weaning; 2) BMGR was not significantly different between NX-NX and HX-NX rats, and between HX-HX and NX-HX animals; and 3) BMGR was significantly higher in rats living under NX conditions than in those living under HX conditions during postnatal life. Data suggest that that hypobaric hypoxia during gestational and early postnatal development of rats does not alter the regulation of body mass growth in rats when compared to that seen under sea-level conditions. PMID:25184739

  15. 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

  16. [Low-field magnetic resonance imaging for rheumatoid arthritis].

    PubMed

    Ostendorf, B; Edelmann, E; Kellner, H; Scherer, A

    2010-02-01

    Magnetic resonance imaging (MRI) as a cross-sectional imaging procedure allows a three-dimensional representation of musculature, ligaments, tendons, capsules, synovial membranes, bones and cartilage with high resolution quality. An activity assessment is further possible by application of a contrast medium (gadolinium-DTPA) to differentiate between active and chronic inflammatory processes. Evidence of a bone marrow edema detected by MRI in patients with rheumatoid arthritis (RA) can be interpreted as a prognostic and predictive factor for the development of bone erosions. On the basis of these advantages MRI is being employed more and more in the early diagnosis of inflammatory joint diseases. Semi-quantitative scores for analysis and grading of findings have already been developed and are in clinical use. Because MRI technical performances are invariably reproducible they can be practically retrieved in the course of examination which is particularly relevant in rheumatology. Therapy response or progression can thus be adequately displayed. Open, dedicated low-field MRI with a low signal strength of 0.2 Tesla (T) has been known since the 90s and now represents new MRI examination options in rheumatology. Smaller devices with lower acquisition and maintenance expenses as well as considerably more convenience due to the device itself result in a higher subjective acceptability by the patients as well as objectively more data records of low-field MRI scans of RA, which underline the significance of this new technical method. The German Society for Rheumatology (DGRh), represented by the Committee for "Diagnostic Imaging", meets this development with the release of recommendations and standards for the procedures of low-field MRI and their scoring and summarizes the most important technical data and information on clinical indications. PMID:19894053

  17. Rheumatoid arthritis and schizophrenia: a negative association at a dimensional level

    Microsoft Academic Search

    P. Gorwood; J. Pouchot; P. Vinceneux; X. Puéchal; R. M. Flipo; M. De Bandt; J. Adès

    2004-01-01

    There is wide evidence for a decreased risk of rheumatoid arthritis in patients with schizophrenia. Nevertheless, very few studies have looked at the risk of schizophrenia in a group of patients with rheumatoid arthritis.We prospectively investigated, with the SCL-90R, 220 consecutive outpatients with rheumatoid arthritis and 196 consecutive outpatients with various medical conditions, half of them suffering from psoriatic arthritis

  18. 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.

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

    PubMed Central

    Bogoch, Earl R.

    2008-01-01

    Total knee arthroplasty frequently is required during early adulthood in patients with advanced juvenile rheumatoid arthritis. We queried patients on issues of importance to them, asked whether they were satisfied with surgical outcomes, and ascertained their postoperative status. We retrospectively reviewed 14 adult patients (22 knees) with severe juvenile rheumatoid arthritis who were treated with primary total knee arthroplasty between 1989 and 2001. All patients were evaluated by pain and stiffness visual analog scales, range of motion, the Patient-Specific Index, Hospital for Special Surgery knee score, WOMAC Osteoarthritis Index, EuroQuol in five dimensions, and SF-36 Health Survey. Preoperative scores were assessed by recall. Patients had a minimum followup of 2 years (mean, 8 years; range, 2–13 years). Quality of life improved after TKA as measured by the Patient-Specific Index. Eighteen of 22 patients rated themselves satisfied with the functional outcome of their surgery; all patients were satisfied with pain relief. Final SF-36, EuroQuol in five dimensions, and WOMAC scores were low compared with age-matched population norms. A mean postoperative flexion arc of 77° (range, 30°–130°) was observed. Total knee arthroplasty had a major positive impact on quality of life as reported by patients. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18196390

  20. A double blind randomised trial of low power laser treatment in rheumatoid arthritis.

    PubMed Central

    Heussler, J K; Hinchey, G; Margiotta, E; Quinn, R; Butler, P; Martin, J; Sturgess, A D

    1993-01-01

    OBJECTIVES--To define the value of low power laser treatment in small joint rheumatoid arthritis. METHODS--Twenty five women with active disease were recruited. The metacarpophalangeal and proximal interphalangeal joints of one hand were treated with 12 J/cm2 for 30 s with a gallium-aluminium-arsenate laser. The other hand received a sham laser treatment designed so that neither therapist nor patient could distinguish the active laser from the sham laser. Each patient received 12 treatments over four weeks. The following parameters were measured: pain as assessed by visual analogue scale; range of joint movements; grip strength; duration of early morning stiffness, joint circumference, Jebsen's hand assessment; drug usage; total swollen joint counts; Arthritis Impact Measurement Scales; three phase bone scans; haematological and serological tests. RESULTS--A total of 72% of patients reported pain relief but this reduction was reported equally in both hands. No significant changes were seen in other clinical, functional, scintigraphic, or laboratory features. Neither patients nor staff were able to detect which hand was treated with the active laser. CONCLUSION--When this specific laser and dose regimen was used, low power laser treatment had no objective effect on patients with rheumatoid arthritis. It did appear to produce analgesia through a powerful placebo effect. PMID:8257205

  1. 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.

  2. Abatacept in the treatment of rheumatoid arthritis.

    PubMed

    Posadas, Augusto; Lisse, Jeffrey; Sarkar, Sujata

    2009-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory arthritis affecting 1% of the population. The immunologic dysfunction underlying this immune disorder is complex and intricate with the involvement of various immune cells as well as cytokines and surface molecules. While inhibition of TNF-alpha has changed the outlook of patients with this disorder, it regulates only one aspect of the inflammatory cascade associated with RA. This is corroborated by experience in the clinic, where a significant proportion of the patients do not have clinical benefit with such therapies. Furthermore, a number of patients experience blunting of the initial therapeutic benefits of TNF-alpha-targeted therapies. Thus, a different approach to regulate the immune dysfunction associated with RA is necessary. T cells are considered important in the pathogenesis of RA and abatacept, a fusion protein, was developed to abolish the activation of the T cell by blocking its interaction with the antigen-presenting cell. Abatacept has demonstrated promising clinical improvements in patients with RA. Although clinical experience with this new drug is limited and its mechanism of action remains to be understood, the data on the safety profile are reassuring. PMID:20476895

  3. Bone Remodelling Markers in Rheumatoid Arthritis

    PubMed Central

    Fardellone, Patrice; Séjourné, Alice; Paccou, Julien; Goëb, Vincent

    2014-01-01

    Bone loss in rheumatoid arthritis (RA) patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin), serum aminoterminal propeptide of type I collagen (PINP), serum carboxyterminal propeptide of type I collagen (ICTP), bone alkaline phosphatase (BAP), osteocalcin (OC), and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX), N-terminal telopeptide of type 1 collagen (I-NTX), pyridinolines (DPD and PYD), and tartrate-resistant acid phosphatase (TRAP). Bone resorption can be seen either in periarticular bone (demineralization and erosion) or in the total skeleton (osteoporosis). Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics. PMID:24839355

  4. Utilizing Regulatory T Cells Against Rheumatoid Arthritis

    PubMed Central

    Haque, Mohammad; Fino, Kristin; Lei, Fengyang; Xiong, Xiaofang; Song, Jianxun

    2014-01-01

    Regulatory T (Treg) cells are essential for normal immune surveillance systems, and their dysfunction leads to development of diseases, such as autoimmune disorders. CD4+CD25+ Treg cells are well-known suppressive cells, which express the transcription factor Foxp3, are indispensable for the maintenance of immune self-tolerance and homeostasis by suppressing aberrant or excessive immune response. Other Foxp3? Treg cells include Tr1, Th3, CD8+CD28?/?, and Qa1-restricted T cells; however, the contribution of these Treg cells to self-tolerance, immune homeostasis as well as preventing autoimmunity is not well defined. Here, we discuss the phenotypes and function of Foxp3+ Treg cells and the potential use of such Treg cells against rheumatoid arthritis (RA). Of note, even though most expanded populations of Foxp3+ Treg cells exhibit suppressive activity, tissue-associated or antigen-specific Treg cells appear superior in suppressing local autoimmune disorders such as RA. In addition, utilizing tissue-associated Foxp3+ Treg cells from stem cells may stable Foxp3 expression and avoid induction of a potentially detrimental systemic immunosuppression. PMID:25152867

  5. Tofacitinib Prevents Radiographic Progression in Rheumatoid Arthritis

    PubMed Central

    Kim, Joon Wan; Choi, In Ah; Lee, Eun Young; Song, Yeong Wook

    2013-01-01

    Tofacitinib, a novel Janus kinase inhibitor, may prevent structural damage in rheumatoid arthritis (RA). In this cohort study, we compared radiographic progression of hand joints between 21 RA patients who took tofacitinb for 18 months in a phase IIb and its extension study and 42 patients who took conventional disease modifying antirheumatic drugs (DMARDs), using simple erosion narrowing score. For tofacitinib group, changes before and after the treatment were also compared. The changes of erosion and sum scores were significantly less in tofacitinib than DMARDs group (for erosion, -0.60 ± 1.83 vs 0.51 ± 1.77, P = 0.038; for sum, -0.50 ± 1.72 vs 1.57 ± 4.13, P = 0.012). Joint space narrowing score (JSN) was also less in tofacitinib group (0.095 ± 0.58 vs 1.06 ± 2.60, P = 0.055). In tofacitinib group, yearly rates of both erosion and JSN were significantly decreased after administration of tofacitinib (For erosion, 0.62 ± 0.93 to -0.14 ± 0.48, P = 0.009; for JSN, 0.47 ± 0.64 to 0.03 ± 0.40, P = 0.032), as was change of sum score (1.09 ± 1.27 to -0.10 ± 0.63, P < 0.001). In conclusion, tofacitinib may prevent structural damage caused by RA. PMID:23960438

  6. Genetics and epigenetics of rheumatoid arthritis.

    PubMed

    Viatte, Sebastien; Plant, Darren; Raychaudhuri, Soumya

    2013-03-01

    Investigators have made key advances in rheumatoid arthritis (RA) genetics in the past 10 years. Although genetic studies have had limited influence on clinical practice and drug discovery, they are currently generating testable hypotheses to explain disease pathogenesis. Firstly, we review here the major advances in identifying RA genetic susceptibility markers both within and outside of the MHC. Understanding how genetic variants translate into pathogenic mechanisms and ultimately into phenotypes remains a mystery for most of the polymorphisms that confer susceptibility to RA, but functional data are emerging. Interplay between environmental and genetic factors is poorly understood and in need of further investigation. Secondly, we review current knowledge of the role of epigenetics in RA susceptibility. Differences in the epigenome could represent one of the ways in which environmental exposures translate into phenotypic outcomes. The best understood epigenetic phenomena include post-translational histone modifications and DNA methylation events, both of which have critical roles in gene regulation. Epigenetic studies in RA represent a new area of research with the potential to answer unsolved questions. PMID:23381558

  7. 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.

  8. 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

  9. Early-season effects of solar UV-B enhancement on plant canopy structure, simulated photosynthesis and competition

    SciTech Connect

    Barnes, P.W.; Flint, S.D.; Caldwell, M.M. (Southwest Texas State Univ., San Marcos, TX (United States))

    1994-06-01

    Mixed-species stands of wheat (Triticum aestivum) and wild oat (Avena fatua) were exposed to enhanced solar UV-B radiation simulating a 20% reduction in column ozone to assess the timing and seasonal development of the UV-B-induced alterations in competitive balance between these species. Results from two years of field studies revealed that UV-B enhancement did not significantly affect the magnitude or timing of seeding emergence of the combined-species LAI of 4-week old mixtures (near 2 for both years). The UV-B did, however, significantly increase (5-9%) the relative proportion of the mixture LAI contributed by wheat which then resulted in a 6-8% increase in its calculated relative light interception and canopy carbon gain. These findings, and others indicate that the effects of enhanced UV-B on competitive balance are realized very early during canopy development and suggest that UV-B-induced alterations in seedling growth may have peristent and significant consequences for light competition later in the growing season.

  10. Combining effects of polymorphism of tumor necrosis factor ? 5?-flanking region and HLA-DRB1 on radiological progression in patients with rheumatoid arthritis

    Microsoft Academic Search

    Naomi Ichikawa; Shigeru Kotake; Masayuki Hakoda; Kenshi Higami; Aya Kawasaki; Takefumi Furuya; Yuki Nanke; Naoyuki Tsuchiya; Katsushi Tokunaga; Naoyuki Kamatani

    2009-01-01

    We examined whether polymorphisms upstream of the TNF-? gene (TNFA) were associated with the radiological progression of rheumatoid arthritis (RA). One hundred and twenty-three patients with\\u000a early RA (disease duration <1 year) were enrolled in a prospective follow-up study. The laboratory findings (ESR, CRP, and\\u000a RF) were evaluated every 2 months for 2 years. Radiological progression in hands\\/wrists and feet was evaluated every

  11. 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

  12. Influence of cigarette smoking on disease outcome in rheumatoid arthritis.

    PubMed

    Harrison, Beverley J

    2002-03-01

    Cigarette smoking is a well-known risk factor for rheumatoid arthritis. However, the influence of smoking on disease outcome has only been investigated very recently, and the data are not clear-cut. Smoking has a number of important effects on the immune system and sex hormones that may influence disease pathogenesis. Smoking has also been shown to affect disease outcome in other inflammatory diseases. The major focus of this review is to explore the relationship between smoking and severity of rheumatoid arthritis in detail. PMID:11845011

  13. 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.

  14. Etanercept-induced sarcoidosis in rheumatoid arthritis: FDG PET findings.

    PubMed

    Nakajima, Reiko; Abe, Koichiro; Nakajima, Ayako; Nishikawa, Toshio; Sakai, Shuji

    2015-01-01

    We report the F-FDG PET/CT findings of an etanercept-induced sarcoidosis in a patient with rheumatoid arthritis. A 68-year-old woman with rheumatoid arthritis who had been treated with etanercept and methotrexate showed multiple lung nodules and hilar lymph node swellings on CT. She underwent FDG PET/CT for cancer screening. Intense FDG uptakes were found in the multiple lung nodules, bilateral hilar lymph nodes, a periurethral masslike lesion, and cranial meningeal nodules. A histopathological examination revealed epithelioid granuloma with multinucleated giant cells, which was compatible with sarcoidosis. PMID:25188646

  15. Cell-cell Interactions in Rheumatoid Arthritis Synovium

    PubMed Central

    Gizinski, Alison; Morgan, Rachel; Lundy, Steven K

    2010-01-01

    Synopsis Understanding the pathogenesis of joint inflammation and destruction in rheumatoid arthritis involves dissection of the cellular and molecular interactions that occur in synovial tissue. Development of effective targeted therapies has been based on progress in achieving such insights. Safer and more specific approaches to treatment could flow from discovery of cell-cell interaction pathways that are relatively specific for inflammation of the joint, and less important in defense against systemic infection. This chapter highlights selected cell-cell interactions in rheumatoid arthritis synovium that may be worthy of evaluation as future therapeutic targets. PMID:20510236

  16. DNA methylome signature in rheumatoid arthritis

    PubMed Central

    Nakano, Kazuhisa; Whitaker, John W; Boyle, David L; Wang, Wei; Firestein, Gary S

    2012-01-01

    Objectives Epigenetics can influence disease susceptibility and severity. While DNA methylation of individual genes has been explored in autoimmunity, no unbiased systematic analyses have been reported. Therefore, a genome-wide evaluation of DNA methylation loci in fibroblast-like synoviocytes (FLS) isolated from the site of disease in rheumatoid arthritis (RA) was performed. Methods Genomic DNA was isolated from six RA and five osteoarthritis (OA) FLS lines and evaluated using the Illumina HumanMethylation450 chip. Cluster analysis of data was performed and corrected using Benjamini–Hochberg adjustment for multiple comparisons. Methylation was confirmed by pyrosequencing and gene expression was determined by qPCR. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. Results RA and control FLS segregated based on DNA methylation, with 1859 differentially methylated loci. Hypomethylated loci were identified in key genes relevant to RA, such as CHI3L1, CASP1, STAT3, MAP3K5, MEFV and WISP3. Hypermethylation was also observed, including TGFBR2 and FOXO1. Hypomethylation of individual genes was associated with increased gene expression. Grouped analysis identified 207 hypermethylated or hypomethylated genes with multiple differentially methylated loci, including COL1A1, MEFV and TNF. Hypomethylation was increased in multiple pathways related to cell migration, including focal adhesion, cell adhesion, transendothelial migration and extracellular matrix interactions. Confirmatory studies with OA and normal FLS also demonstrated segregation of RA from control FLS based on methylation pattern. Conclusions Differentially methylated genes could alter FLS gene expression and contribute to the pathogenesis of RA. DNA methylation of critical genes suggests that RA FLS are imprinted and implicate epigenetic contributions to inflammatory arthritis. PMID:22736089

  17. Prevalence of rheumatoid arthritis in France: 2001

    PubMed Central

    Guillemin, F; Saraux, A; Guggenbuhl, P; Roux, C; Fardellone, P; Le Bihan, E; Cantagrel, A; Chary-Valckenaere, I; Euller-Ziegler, L; Flipo, R; Juvin, R; Behier, J; Fautrel, B; Masson, C; Coste, J

    2005-01-01

    Background: Prevalence estimates of rheumatoid arthritis (RA) vary across Europe. Recent estimates in southern European countries showed a lower prevalence than in northern countries. Objectives: To estimate the prevalence of RA in France in a multiregional representative sample in the year 2001. Methods: A two stage random sample was constituted in seven areas (20 counties) from the national telephone directory of households and by the next birthday method in each household. Patient-interviewers, member of self help groups, were trained to administer telephone surveys using a validated questionnaire for case detection of inflammatory rheumatism, and conducted the survey under quality control. All suspected cases of RA were confirmed by their rheumatologist or by clinical examination. Prevalence estimates after probability sampling correction were standardised for age and sex (national census 1999). Results: An average response rate of 64.7% (two stages combined) led to a total of 9395 respondents. Standardised prevalence was 0.31% (95% confidence interval 0.18 to 0.48) for RA, 0.51% in women and 0.09% in men, with a higher age-specific prevalence in the 65–74 year age band. A geographical analysis of county clustering showed significant variation across the country. Conclusion: This national multiregional cooperative study demonstrates the usefulness of working in association with patients of self help groups. It showed a similar prevalence of RA to that of the spondyloarthropathies estimated concomitantly during the survey. It provides a reliable basis for definition of population targets for healthcare delivery and drug treatments. PMID:15800010

  18. Development of macromolecular prodrug for rheumatoid arthritis?

    PubMed Central

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

    2012-01-01

    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

  19. Genetics of Rheumatoid Arthritis — A Comprehensive Review

    PubMed Central

    Kurkó, Júlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T.; Mikecz, Katalin

    2013-01-01

    The “Bermuda triangle” of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11–37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci — Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively — have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics. PMID:23288628

  20. Genetics of rheumatoid arthritis - a comprehensive review.

    PubMed

    Kurkó, Júlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T; Mikecz, Katalin; Szekanecz, Zoltán

    2013-10-01

    The "Bermuda triangle" of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11-37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci - Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively - have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics. PMID:23288628

  1. Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients.

    PubMed

    Rowley, D; Gutteridge, J M; Blake, D; Farr, M; Halliwell, B

    1984-06-01

    Thiobarbituric acid (TBA)-reactive material is present in serum and knee joint synovial fluid from rheumatoid patients, consistent with lipid peroxidation occurring in vivo. The amount of TBA-reactive material in synovial fluid correlates with the concentration of iron salts present as determined by the bleomycin method, presumably because iron is an important catalyst of radical reactions in vivo. There appear to be significant correlations between the contents of TBA-reactive material and bleomycin-detectable iron in synovial fluid and the activity of rheumatoid arthritis as assessed with a clinical index of local inflammation and with various laboratory parameters. PMID:6723205

  2. [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

  3. Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: common target, common therapies.

    PubMed

    Assefnia, Shahin; Dakshanamurthy, Sivanesan; Guidry Auvil, Jaime M; Hampel, Constanze; Anastasiadis, Panos Z; Kallakury, Bhaskar; Uren, Aykut; Foley, David W; Brown, Milton L; Shapiro, Lawrence; Brenner, Michael; Haigh, David; Byers, Stephen W

    2014-03-30

    Cadherin-11 (CDH11), associated with epithelial to mesenchymal transformation in development, poor prognosis malignancies and cancer stem cells, is also a major therapeutic target in rheumatoid arthritis (RA). CDH11 expressing basal-like breast carcinomas and other CDH11 expressing malignancies exhibit poor prognosis. We show that CDH11 is increased early in breast cancer and ductal carcinoma in-situ. CDH11 knockdown and antibodies effective in RA slowed the growth of basal-like breast tumors and decreased proliferation and colony formation of breast, glioblastoma and prostate cancer cells. The repurposed arthritis drug celecoxib, which binds to CDH11, and other small molecules designed to bind CDH11 without inhibiting COX-2 preferentially affect the growth of CDH11 positive cancer cells in vitro and in animals. These data suggest that CDH11 is important for malignant progression, and is a therapeutic target in arthritis and cancer with the potential for rapid clinical translation. PMID:24681547

  4. Simulation of the early startup period of high-temperature heat pipes from the frozen state by a rarefied vapor self-diffusion model

    NASA Technical Reports Server (NTRS)

    Cao, Y.; Faghri, A.

    1993-01-01

    The heat pipe startup process is described physically and is divided into five periods for convenience of analysis. The literature survey revealed that none of the previous attempts to simulate the heat pipe startup process numerically were successful, since the rarefied vapor flow in the heat pipe was not considered. Therefore, a rarefied vapor self-diffusion model is proposed, and the early startup periods, in which the rarefied vapor flow is dominant within the heat pipe, are first simulated numerically. The numerical results show that large vapor density gradients existed along the heat pipe length, and the vapor flow reaches supersonic velocities when the density is extremely low. The numerical results are compared with the experimental data of the early startup period with good agreement.

  5. Nonsteroidal anti-inflammatory drugs for rheumatoid arthritis during pregnancy

    PubMed Central

    Florescu, Ana; Koren, Gideon

    2005-01-01

    QUESTION I am treating two pregnant patients who have rheumatoid arthritis with nonsteroidal anti-inflammatory drugs. Are these medications safe at high doses during pregnancy? ANSWER While these medications do not appear to increase overall rates of congenital malformations, they do increase the risk of ductus arteriosus constriction or closure. PMID:16060172

  6. Tracheobronchomalacia due to amyloidosis in a patient with rheumatoid arthritis

    Microsoft Academic Search

    Franktien Turkstra; Rico N. P. M. Rinkel; Hagen Biermann; Paul van der Valk; Alexandre E. Voskuyl

    2008-01-01

    In this case report, we describe a patient with longstanding rheumatoid arthritis who developed tracheobronchomalacia with\\u000a fatal outcome. Despite negative antemortem biopsies of abdominal fat and tongue, amyloid was found postmortem in the trachea\\u000a and appeared to be associated with tracheobronchomalacia.

  7. Myasthenia gravis associated with penicillamine treatment for rheumatoid arthritis

    Microsoft Academic Search

    R C Bucknall; E N Glick; J Woodland; D W Zutshi

    1975-01-01

    Four patients with rheumatoid arthritis (R.A.) developed myasthenia gravis after taking penicillamine. In one patient withdrawal of the drug was followed by spontaneous remission of the myasthenia, and in two the dose of anticholinesterase was subsequently reduced. In the fourth patient continuing penicillamine treatment was associated with increasingly severe myasthenic features, but on withdrawal of the drug these resolved. As

  8. Premises for immune interventional therapy in rheumatoid arthritis.

    PubMed Central

    Mackay, I. R.; Rowley, M. J.

    1988-01-01

    Consideration of rheumatoid arthritis (RA) as an autoimmune disease includes initiating event(s), genetic predisposition, immune regulatory derangements, and effector cycles of articular damage. The initiating event is still unknown. Collagen type 2 has good claims as a rheumatogenic autoantigen which perpetuates disease. The association of HLA DR4 with rheumatoid arthritis is in part explainable by the affinity of binding of the rheumatogenic antigen to a hypervariable portion of MHC Class II molecules with selective presentation of this complex to T cell receptors. Immune regulatory derangements include lymphokine-induced aberrant expression of MHC Class II molecules on synovial tissues, the presence of a 'resistant' subset of B cells (CD5 + ve), failure of anti-idiotypic control of autoantibodies (not well established as yet in rheumatoid arthritis), and defective immune suppression, revealed by low counts in synovial fluids of a suppressor-inducer subset of CD4 + ve T cells. The many possibilities for therapeutic immune intervention would include polyclonal or monoclonal antibody to block (a) receptors for antigen on B or T lymphocytes (but this would require knowledge of the rheumatoid arthritis-inducing antigen), (b) the CD4 complex on helper T lymphocytes, (c) MHC Class II (Ia) molecules, for which there are excellent prototypes in experimental immunopathology, or (d) lymphokines or their receptors. Induction of suppression by 'tolerogenic vaccines' is experimentally validated, but only for diseases for which an autoantigen can be identified. PMID:3074285

  9. Developments in the clinical understanding of rheumatoid arthritis

    Microsoft Academic Search

    Josef S Smolen; Daniel Aletaha

    2009-01-01

    The changes occurring in the field of rheumatoid arthritis (RA) over the past decade or two have encompassed new therapies and, in particular, a new look at the clinical characteristics of the disease in the context of therapeutic improvements. It has been shown that composite disease activity indices have special merits in following patients, that disease activity governs the evolution

  10. Macrophage migration inhibitory factor in rheumatoid arthritis: clinical correlations

    Microsoft Academic Search

    E. F. Morand; M. Leech; H. Weedon; C. Metz; R. Bucala; M. D. Smith

    2002-01-01

    Objective. Cytokines play an important role in the pathology of rheumatoid arthritis (RA). Macrophage migration inhibitory factor (MIF) is a cytokine with a broad spectrum of actions, including induction of monocyte tumour necrosis factor a (TNF-a). Evidence of the expression and proinflammatory activity of MIF has recently been demonstrated in RA synovium and in animal models of RA. We wished

  11. Home Care Guide on Juvenile Rheumatoid Arthritis (For Parents).

    ERIC Educational Resources Information Center

    Giesecke, Linda L.; And Others

    The booklet, written by the medical staff of a children's hospital, provides information for parents of children with juvenile rheumatoid arthritis (JRA). Arthritis is a swelling of the joint(s) in children and lasts for over 6 weeks (sometimes many years). Aspirin is the main medicine given for JRA, and it works not only to control pain but also,…

  12. Rehabilitation in rheumatoid arthritis and ankylosing spondylitis: differences and similarities

    Microsoft Academic Search

    Sophia Rehabilitation; Theodora P. M. Vliet Vlieland; Linda C. Li; Vliet Vlieland

    The aim of the paper is to summarize and compare the best available evi- dence concerning the effectiveness of rehabilitative interventions and provide an overview of recommendations or in- ternational guidelines on non-pharma- cological treatments in rheumatoid ar- thritis (RA) and ankylosing spondylitis (AS). It was found that, compared to RA, there are relatively fewer non-pharma- cological intervention studies in

  13. Genetic and genomic studies of PADI4 in rheumatoid arthritis

    Microsoft Academic Search

    S. M. J. Harney; C. Meisel; A.-M. Sims; P. Y. Woon; B. P. Wordsworth; M. A. Brown

    2005-01-01

    Objectives. Strong genetic association of rheumatoid arthritis (RA) with PADI4 (peptidyl arginine deiminase) has previously been described in Japanese, although this was not confirmed in a subsequent study in the UK. We therefore undertook a further study of genetic association between PADI4 and RA in UK Caucasians and also studied expression of PADI4 in the peripheral blood of patients with

  14. CIITA is not associated with risk of developing rheumatoid arthritis

    Microsoft Academic Search

    P G Bronson; P P Ramsay; M F Seldin; P K Gregersen; L A Criswell; L F Barcellos

    2011-01-01

    The major histocompatibility complex (MHC) class II transactivator gene (CIITA) encodes an important transcription factor regulating genes required for human leukocyte antigen (HLA) class II MHC-restricted antigen presentation. MHC genes, particularly HLA class II, are strongly associated with risk of developing rheumatoid arthritis (RA). Given the strong biological relationship between CIITA and HLA class II genes, a comprehensive investigation of

  15. Genetic interaction in the susceptibility of rheumatoid arthritis

    Microsoft Academic Search

    Nina A Daha; Annemiek Willemze; David B Robinson; Kiem G Oen; Irene Smolik; Donna Hart; Wendimagegn Ghidey; Jeanine J Houwing-Duistermaat; KA Siminovitch; Tom WJ Huizinga; Hani S El-Gabalawy; René EM Toes

    2011-01-01

    IntroductionRecent advances have revolutionised the identification of genes underlying common diseases. For rheumatoid arthritis (RA), over 20 genes have been identified to associate to disease susceptibility. The strongest of these genetic associations is with particular genes within the human leucocyte antigen (HLA) region. To date, however, little is known about underlying relations between genes on a genetic level, which provides

  16. Rheumatoid arthritis, Proteus, anti-CCP antibodies and Karl Popper

    Microsoft Academic Search

    Alan Ebringer; Taha Rashid; Clyde Wilson

    2010-01-01

    Rheumatoid arthritis (RA) is a crippling joint disease affecting over 20million people worldwide. The cause of RA is most probably linked to the triad of microbial trigger, genetic association and autoimmunity and can be explained using the philosophical method of Karl Popper or Popperian sequences. Ten “Popper sequences” have been identified which point to the urinary microbe Proteus mirabilis as

  17. Apoptosis as a therapeutic tool in rheumatoid arthritis

    Microsoft Academic Search

    Richard M. Pope

    2002-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory synovitis that is dominated by the presence of macrophages, lymphocytes and synovial fibroblasts, which leads to the destruction of bone and cartilage. The effectiveness of therapies that are directed against tumour-necrosis factor and interleukin-1 has identified macrophages as a crucial target for therapeutic intervention. However, not all patients respond to these therapies, and

  18. Therapy Insight: managing cardiovascular risk in patients with rheumatoid arthritis

    Microsoft Academic Search

    Jon T Giles; Wendy Post; Roger S Blumenthal; Joan M Bathon

    2006-01-01

    Chronic low-grade inflammation was recognized during the past decade as an important risk factor for the development of atherosclerosis and, more recently, for the development of heart failure. Patients with rheumatoid arthritis (RA) are at increased risk of morbidity and mortality from ischemic cardiovascular events and heart failure. Epidemiologic and clinical studies indicate that RA is an independent risk factor

  19. Socioeconomic impact of rheumatoid arthritis in Morocco

    Microsoft Academic Search

    Hanan Rkain; Fadoua Allali; Imane Jroundi; Najia Hajjaj-Hassouni

    2006-01-01

    Objective. – To estimate the socioeconomic impact of rheumatoid arthritis (RA) in Morocco.Materials and methods. – We identified 100 consecutive patients (88 women and 12 men) with RA receiving follow-up either at a teaching hospital or from office-based physicians. For each patient, we recorded direct costs, indirect costs (productivity losses), and intangible costs (deterioration in the social domain of quality

  20. Views on Exercise Maintenance: Variations Among Patients With Rheumatoid Arthritis

    Microsoft Academic Search

    Emma Swardh; Gabriele Biguet; Christina H Opava

    2008-01-01

    Background and Purpose. Individuals with rheumatoid arthritis (RA) often have to make changes in exercise behavior in order to gain and sustain health benefits. The purpose of this study was to explore and describe ways of understand- ing exercise maintenance among individuals with RA who had already started to exercise. Participants. Fourteen women and 4 men with RA of at

  1. Occupational therapy for rheumatoid arthritis: A systematic review

    Microsoft Academic Search

    Esther M. J. Steultjens; Joost Dekker; Lex M. Bouter; Dirkjan van Schaardenburg; Marie-Antoinette H. van Kuyk; Cornelia H. M. van den Ende

    2002-01-01

    Patients with rheumatoid arthritis (RA) show a reduction in physical capacities compared with healthy persons. Symptoms such as pain, fatique, stiffness, and decreased muscle strength cause difficulties with daily activities such as grooming and dressing, cooking a meal, cleaning, shopping, work, and leisure activities. The physical, personal, familial, social, and vocational consequences of RA are extensive. Occupational therapy (OT) is

  2. Development of anti-TNF therapy for rheumatoid arthritis

    Microsoft Academic Search

    Marc Feldmann

    2002-01-01

    The aetiology of systemic, autoimmune, chronic inflammatory diseases — such as rheumatoid arthritis — is not known, and their pathogenesis is complex and multifactorial. However, progress in the characterization of intercellular mediators — proteins that are now known as cytokines — has led to the realization that one cytokine, tumour-necrosis factor (TNF; previously known as TNF-?), has an important role

  3. Antigen microarrays profiling of autoantibodies in rheumatoid arthritis

    Microsoft Academic Search

    W. Huebner; Brian A. Kidd; Beren H. Tomooka; Byung J. Lee; Bonnie Bruce; James F. Fries; G. Sonderstrup; Paul Monach; Jan W. Drijfhout; Walther J. van Venrooij; Paul J. Utz; Mark C. Genovese

    2005-01-01

    Objective. Because rheumatoid arthritis (RA) is a heterogeneous autoimmune disease in terms of disease manifestations, clinical outcomes, and therapeutic re- sponses, we developed and applied a novel antigen microarray technology to identify distinct serum anti- body profiles in patients with RA. Methods. Synovial proteome microarrays, con- taining 225 peptides and proteins that represent candi- date and control antigens, were developed.

  4. The early phase of psoriatic arthritis

    Microsoft Academic Search

    Dennis McGonagle; Zoe Ash; Laura Dickie; Michael McDermott; Sibel Zehra Aydin

    2011-01-01

    Evaluation of the preclinical phases of the classic autoimmune diseases including rheumatoid arthritis has been facilitated by the availability of autoantibody and genetic markers that point firmly towards the early dysregulation of the adaptive immune responses. The association of psoriatic disease with the human leucocyte antigen—Cw0602 (HLA-Cw0602) gene has likewise led to the perception that autoimmunity has a pivotal role

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

    NASA Astrophysics Data System (ADS)

    Adi Aizudin Bin Radin Nasirudin, Radin; Meier, Reinhard; Ahari, Carmen; Sievert, Matti; Fiebich, Martin; Rummeny, Ernst J.; No"l, Peter B.

    2011-03-01

    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 analyzing tool and a clinical evaluation study. Our analyzing tool extends the capability of existing OI tools. We include many features in the tool, such as region-based image analysis, hyper perfusion curve analysis, and multi-modality image fusion to aid clinicians in localizing and determining the intensity of inflammation in joints. Additionally, image data management options, such as the full integration of PACS/RIS, are included. In our clinical study we demonstrate how OI facilitates the detection of active inflammation in rheumatoid arthritis. The preliminary clinical results indicate a sensitivity of 43.5%, a specificity of 80.3%, an accuracy of 65.7%, a positive predictive value of 76.6%, and a negative predictive value of 64.9% in relation to clinical results from MRI. The accuracy of inflammation detection serves as evidence to the potential of OI as a useful imaging modality for early detection of active inflammation in patients with rheumatoid arthritis. With our in-house developed tool we extend the usefulness of OI imaging in the clinical arena. Overall, we show that OI is a fast, inexpensive, non-invasive and nonionizing yet highly sensitive and accurate imaging modality.-

  6. Radiographic estimation in seropositive and seronegative rheumatoid arthritis

    PubMed Central

    Sahatçiu-Meka, Vjollca; Rexhepi, Sylejman; Manxhuka-Kërliu, Suzana; Rexhepi, Mjellma

    2011-01-01

    Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis, diagnosed with negative rheumatoid factor tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis (RA). Our aim was to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis, regarding some radiological and clinical parameters, applied for the first time on patients from Kosovo. Two hundred fifty patients with rheumatoid arthritis according to the American College of Rheumatology criteria were retrospectively studied by analysis the radiographic damage and clinical parameters of the disease, using a data base. All examinees were between 25-60 years of age (Xb=49.96, SD=10.37) with disease duration between 1-27 years (Xb = 6.41, SD=6.47). All patients underwent a standardised evaluation radiographs. Baseline standardised poster anterior radiographs of hands and feet and radiographs of other joints, depending on indications, were assessed. Erythrocyte sedimentation rate values correlated with the radiological damages and statistical difference was found for seronegative subset (r=0.24, p<0.01). Longer duration of the disease resulted in the increase of radiological changes in both subsets (r=0.66, p<0.01) seronegative, (r=0.49, p<0.01) seropositive. Anatomic changes of IInd and IIIrd level were nearly equally distributed in both subsets, 76 (60.8%) seronegative, 75 (60%) seropositive. Radiological damages are nearly equal in both subsets, elevate in relation to the duration of the disease and correlate with ESR values. Regarding the sero-status, differences within sex, with some exceptions, are not relevant. Although there are some definite quantitative and qualitative differences regarding sero-status, obviously there is a great deal of overlap between the two groups. PMID:21875421

  7. Rheumatoid arthritis, Proteus, anti-CCP antibodies and Karl Popper.

    PubMed

    Ebringer, Alan; Rashid, Taha; Wilson, Clyde

    2010-02-01

    Rheumatoid arthritis (RA) is a crippling joint disease affecting over 20 million people worldwide. The cause of RA is most probably linked to the triad of microbial trigger, genetic association and autoimmunity and can be explained using the philosophical method of Karl Popper or Popperian sequences. Ten "Popper sequences" have been identified which point to the urinary microbe Proteus mirabilis as the cause of RA: Popper sequence 1 establishes that HLA-DR4 lymphocytes injected into a rabbit evoke specific antibodies against Proteus bacteria. Popper sequence 2 establishes that antibodies to Proteus bacteria are present in RA patients from 14 different countries. Popper sequence 3 establishes that antibodies to Proteus bacteria in RA patients are disease specific since no such antibodies are found in other conditions. Popper sequence 4 establishes that when RA patients have high titres of antibodies to Proteus such bacteria are found in urinary cultures. Popper sequence 5 establishes that only Proteus bacteria and no other microbes evoke significantly elevated antibodies in RA patients. Popper sequence 6 establishes that the "shared epitope" EQR(K)RAA shows "molecular mimicry" with the sequence ESRRAL found in Proteus haemolysin. Popper sequence 7 establishes that Proteus urease contains a sequence IRRET which has "molecular mimicry" with LRREI found in collagen XI of hyaline cartilage. Popper sequence 8 establishes that sera obtained from RA patients have cytopathic properties against sheep red cells coated with the cross-reacting EQR(K)RAA and LRREI self-antigen peptides. Popper sequence 9 establishes that Proteus sequences in haemolysin and urease as well as the self antigens, HLA-DR1/4 and collagen XI, each contain an arginine doublet, thereby providing a substrate for peptidyl arginine deiminase (PAD) to give rise to citrulline, which is the main antigenic component of CCP, antibodies to which are found in early cases of RA. Popper sequence 10 establishes that antibodies to Proteus come not only from sequences crossreacting to self antigens but also from non-crossreacting sequences, thereby indicating that active RA patients have been exposed to infection by Proteus. The ten Popper sequences establish that RA is most probably caused by Proteus upper urinary tract infections, which can possibly be treated with anti-Proteus therapy. PMID:19895906

  8. 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

  9. Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene

    PubMed Central

    Michou, Laëtitia; Lasbleiz, Sandra; Rat, Anne-Christine; Migliorini, Paola; Balsa, Alejandro; Westhovens, René; Barrera, Pilar; Alves, Helena; Pierlot, Céline; Glikmans, Elodie; Garnier, Sophie; Dausset, Jean; Vaz, Carlos; Fernandes, Manuela; Petit-Teixeira, Elisabeth; Lemaire, Isabelle; Pascual-Salcedo, Dora; Bombardieri, Stefano; Dequeker, Jan; Radstake, Timothy R.; Van Riel, Piet; van de Putte, Leo; Lopes-Vaz, Antonio; Prum, Bernard; Bardin, Thomas; Dieudé, Philippe; Cornélis, François

    2007-01-01

    The tyrosine phosphatase PTPN22 allele 1858T has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. RA is the most frequent of those multifactorial diseases. The RA association was usually restricted to serum rheumatoid factor positive disease (RF+). No interaction was shown with HLA-DRB1, the first RA gene. Many case-control studies replicated the RA association, showing an allele frequency increase of ?5% on average and large variations of population allele frequencies (2.1–15.5%). In multifactorial diseases, the final proof for a new susceptibility allele is provided by departure from Mendel's law (50% transmission from heterozygous parents). For PTPN22–1858T allele, convincing linkage proof was available only for type 1 diabetes. We aimed at providing this proof for RA. We analyzed 1,395 West European Caucasian individuals from 465 “trio” families. We replicated evidence for linkage, demonstrating departure from Mendel's law in this subset of early RA onset patients. We estimated the overtransmission of the 1858T allele in RF+ families: T = 63%, P < 0.0007. The 1858T allele frequency increased from 11.0% in controls to 17.4% in RF+ RA for the French Caucasian population and the susceptibility genotype (1858T/T or T/C) from 20.2% to 31.6% [odds ratio (OR) = 1.8 (1.2–2.8)]. In conclusion, we provided the linkage proof for the PTPN22–1858T allele and RF+ RA. With diabetes and RA, PTPN22 is therefore a “linkage-proven” autoimmunity gene. PTPN22 accounting for ?1% of the RA familial aggregation, many new genes could be expected that are as many leads to definitive therapy for autoimmune diseases. PMID:17237219

  10. Influence of tumor necrosis factor ? in rheumatoid arthritis

    PubMed Central

    Kulp, Werner; Corzillus, Michael; Greiner, Wolfgang; Pientka, Ludger; Siebert, Uwe; von der Schulenburg, Johann-Matthias; Wasem, Jürgen

    2005-01-01

    Objective Rheumatoid arthritis (RA) is the most prevalent inflammatory rheumatic disorder. It is a chronic and incurable disease that leads to painful inflammation, often irreversible joint damage, and eventually to functional loss. Conventional treatment is based on unspecific immunosuppressive agents, e.g. Methotrexate, Azathioprin or Gold. However, the longterm outcomes of these approaches have been poor with frequently ongoing inflammatory disease activity, functional decline, and temporary or permanent work disability. More recently, antagonists of the human cytokine Tumor Necrosis Factor ? (TNF-?) have been introduced that are potent suppressors of inflammatory processes. Infliximab is a chimeric antibody against TNF-?. Etanercept is a soluble human TNF-? receptor. The report assesses the efficacy of TNF-?-antagonists to down-regulate inflammation, improve functional status and prevent joint damage in RA with particular regard to the following indications: Treatment of severe, refractory and ongoing disease activity despite adequate use of conventional antirheumatic agents; and treatment of early RA before conventional treatment failure has been demonstrated. Methods A systematic review of the literature is been performed using established electronic databases. The literature search is supplemented by a hand search of journals and publications relevant to RA, reviews of websites of national and international rheumatologic expert societies, as well as contacts to manufacturers. A priori defined inclusion and exclusion criteria are used for literature selection. Analysis and evaluation of included publications are based on standardised criteria sets and checklists of the German Scientific Working Group for Technology Assessment in Health Care. Results Health Technology Assessment reports and metaanalyses cannot be identified. A total of 12 clinical trials are analysed, as well as national and international expert recommendations and practice guidelines. Numerous non-systematic reviews are found and analysed for additional sources of information that is not identified through the systematic search. Case reports and safety assessements are considered as well. A total of 137 publications is included. The primary outcome measures in clinical trials are suppression of inflammatory disease activity and slowing of structural joint damage. Clinical response is usually measured by standardised response criteria that allow a semi-quantitative classification of improvement from baseline by 20%, 50%, or 70%. In patients with RA refractory to conventional treatment, TNF-?-antagonists are unequivocally superior to Methotrexate with regard to disease activity, functional status and prevention of structural damage. In patients with early RA, TNF-?-antagonists show a more rapid onset of anti-inflammatory effects than Methotrexate. However, differences in clinical response rates and radiologic progression disappear after a few months of treatment and are no longer statistically significant. Serious adverse events are rare in clinical trials and do not occur significantly more often than in the control groups. However, case reports and surveillance registries show an increased risk for serious infectious complications, particularly tuberculosis. Expert panels recommend the use of TNF-?-antagonists in patients with active refractory RA after failure of conventional treatment. Studies that compare Infliximab and Etanercept are lacking. There are no pharmacoeconomic studies although decision analytic models of TNF-?-antagonists for the treatment of RA exist. Based on the results of the models, a combination therapy with Hydroxychloroquin (HCQ), Sulfaslazin (SASP) and Methotrexate as well as Etanercept/Methotrexate can be considered a cost-effective treatment for Methotrexate-resistant RA. Conclusions TNF-?-antagonists are clearly effective in RA patients with no or incomplete response to Methotrexate and superior to continuous use of Methotrexate. It refers to both, reduction of

  11. Inhibiting citrullination in rheumatoid arthritis: taking fuel from the fire

    PubMed Central

    2012-01-01

    Citrullination is a post-translational modification catalysed by peptidylarginine deiminase and is a common feature of inflammation. The presence of anti-citrullinated protein/peptide antibodies (ACPA), however, is unique to rheumatoid arthritis. Several lines of evidence suggest that ACPA are important in the pathogenesis of rheumatoid arthritis. A popular hypothesis for this pathogenesis is a two-hit model. The first hit gives rise to ACPA, and the second hit, an unrelated episode of synovial inflammation accompanied by citrullination, is perpetuated by the pre-existing antibodies. This model suggests that reducing citrullination might ameliorate disease. Recent findings indicate that citrullination closely correlates with inflammation, and that glucocorticoids decrease peptidylarginine deiminase expression independent of their other anti-inflammatory effects. PMID:22380578

  12. Efficacy and safety of tofacitinib for treatment of rheumatoid arthritis

    PubMed Central

    Lundquist, Lisa M; Cole, Sabrina W; Sikes, Martha L

    2014-01-01

    Tofacitinib is the first in a new class of nonbiologic disease-modifying antirheumatic drugs (DMARDs), a targeted, synthetic DMARD, approved for the treatment of rheumatoid arthritis (RA) as monotherapy or in combination with methotrexate or other non-biologic DMARD. Tofacitinib, an orally administered Janus kinase (JAK) inhibitor, decreases T-cell activation, pro-inflammatory cytokine production, and cytokine signaling by inhibiting binding of type?I?cytokine receptors family and ?-chain cytokines to paired JAK1/JAK3 receptors. The net effect of tofacitinb’s mechanism of action is decreased synovial inflammation and structural joint damage in RA patients. To date, six phase 3 trials have been conducted to evaluate the safety and efficacy of tofacitinib under the oral rheumatoid arthritis triaLs (ORAL) series. This review describes the pharmacology of the novel agent, tofacitinib, and details the safety and efficacy data of the ORAL trials. PMID:25232526

  13. Synovial fluid antigen-presenting cell function in rheumatoid arthritis.

    PubMed Central

    Viner, N J; Gaston, J S; Bacon, P A

    1993-01-01

    We have previously demonstrated enhanced synovial fluid (SF) antigen-presenting cell (APC) function in inflammatory arthritis patients selected on the basis of marked SF mononuclear cell (MNC) responsiveness to reactive arthritis-associated bacteria (Clin Exp Immunol 1990; 79:189-94). In this study we have assessed whether similarly enhanced synovial APC function is present in other inflammatory arthritis patients by using two assay systems to study 18 rheumatoid arthritis patients whose MNC responsiveness had not been determined in advance. We demonstrate that rheumatoid SF APC are much more potent than peripheral blood (PB) APC in stimulating the responses of autologous PB T cells to a range of recall antigens. In addition, SF APC are shown to be efficient stimulators of the antigen-specific responses of MHC-compatible, cloned T cells. Enhanced synovial APC function is thus likely to be a general feature of inflammatory arthritis and may play an important role in its pathogenesis. PMID:8485910

  14. Rheumatoid forefoot deformity: pathophysiology, evaluation and operative treatment options.

    PubMed

    Louwerens, Jan Willem K; Schrier, Joost C M

    2013-09-01

    Despite recent advances in pharmacological management of rheumatoid arthritis, forefoot deformity, with its symptoms, remains a common problem, often requiring operative treatment. Typical deformities in these patients comprise hallux valgus and deformity of the lesser metatarsophalangeal (MTP) joints and toes. With regard to the lesser rays the standard operative procedure, advocated for the disabling forefoot pain in these patients, remains metatarsal head resection. It should be considered that with increasing success of pharmacological treatment the degree of forefoot deformity in these patients is becoming less and that resection of the lesser MTP joints is becoming more and more superfluous. This supports a trend towards metatarsal head-preserving surgery. The optimal treatment of the hallux deformity remains unclear. Fusion of the first MTP joint is, generally, recommended. This article will discuss the current surgical options in rheumatoid forefoot pathology. PMID:23892468

  15. 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

  16. Iguratimod for the treatment of rheumatoid arthritis in Japan.

    PubMed

    Tanaka, Keiichi; Yamaguchi, Tomonobu; Hara, Masako

    2015-05-01

    Iguratimod (IGU), a small-molecule compound, was developed as a disease-modifying antirheumatic drug in Japan. The pharmacological studies showed that inhibition of the production of cytokines and immunoglobulins mainly contributes to its improvement effect on animal arthritis models. The first clinical study of IGU in Japanese patients with rheumatoid arthritis was started in 1992 and Phase III studies were started in 1998. From the results of Phase II studies, a dose-escalating regimen was recommended to relieve the side effects. In a double-blind study comparing the efficacy and safety of the drug with those of placebo and salazosulfapyridine, it was confirmed that IGU was superior to placebo and was not inferior to salazosulfapyridine. Furthermore, a double-blind controlled trial of IGU in combination with methotrexate revealed an efficacious and manageable safety profile. IGU would be widely used as a new option for rheumatoid arthritis treatment and combination drug with methotrexate. PMID:25797025

  17. Cells of the synovium in rheumatoid arthritis. Chondrocytes

    PubMed Central

    Otero, Miguel; Goldring, Mary B

    2007-01-01

    Rheumatoid arthritis (RA) is one of the inflammatory joint diseases in a heterogeneous group of disorders that share features of destruction of the extracellular matrices of articular cartilage and bone. The underlying disturbance in immune regulation that is responsible for the localized joint pathology results in the release of inflammatory mediators in the synovial fluid and synovium that directly and indirectly influence cartilage homeostasis. Analysis of the breakdown products of the matrix components of joint cartilage in body fluids and quantitative imaging techniques have been used to assess the effects of the inflammatory joint disease on the local remodeling of joint structures. The role of the chondrocyte itself in cartilage destruction in the human rheumatoid joint has been difficult to address but has been inferred from studies in vitro and in animal models. This review covers current knowledge about the specific cellular and biochemical mechanisms that account for the disruption of the integrity of the cartilage matrix in RA. PMID:18001488

  18. Genotyping in rheumatoid arthritis: a game changer in clinical management?

    PubMed

    Pratt, Arthur G; Isaacs, John D

    2015-03-01

    Rheumatoid arthritis (RA) is a genetically complex disease of immune dysregulation characterized by painful inflammation of synovial joints. Despite advances in its management afforded by biologic drug development, efforts to improve outcomes for patients are confounded by the condition's heterogeneous pathobiology, and consequent variability in therapeutic responses. Great strides have been made in understanding the genetic epidemiology of rheumatoid arthritis since its association with the HLA locus was established in the 1980s, with over 100 additional disease-associated variants now confirmed through cumulative genome-wide association studies. Yet translation of this new knowledge for patient benefit - whether as a route to predicting disease risk, drug development or personalized medicine - has been slow. To address this, collaborating teams of interdisciplinary scientists will need to pool resources, including ever larger, well-characterized patient cohorts and sophisticated biostatistical approaches. Recent advances suggest that the fruits of these endeavors are beginning to come within reach. PMID:25644535

  19. Frequency-domain inverse Monte Carlo simulation for the diagnosis of the early cervical cancer based on NIR diffuse measurement

    NASA Astrophysics Data System (ADS)

    Zhao, Huijuan; Zhang, Shunqi; Wang, Zhaoxia; Miao, Hui; Du, Zhen; Jiang, Jingying

    2008-02-01

    This article aims at the optical parameter reconstruction technology for the frequency- domain measurement of near-infrared diffused light. For mimicking the cervix, a cylindrical model with hole in the middle is used in the simulation and experiments. Concerning the structure of the cervix, Monte-Carlo simulation is adopted for describing the photon migration in tissue and Perturbation Monte-Carlo is used for the reconstruction of the optical properties of cervix. The difficulties in the reconstruction of cervical optical properties with frequency domain measurement are the description of the tissue boundary, expression of the frequency-domain signal, and development of rapid reconstruction method for clinical use. To get the frequency domain signal in Monte Carlos simulation, discrete Fourier transformation of the photon migration history in time-domain is employed. By combining the perturbation Monte-Carlo simulation and the LM optimization technology, a rapid reconstruction algorithm is constructed, by which only one Monte-Carlo simulation is needed. The reconstruction method is validated by simulation and experiments on solid phantom. Simulation results show that the inaccuracy in reconstruction of absorption coefficient is less than 3% for a certain range of optical properties. The algorithm is also proved to be robust to the initial guess of optical properties and noise. Experimental results showed that the absorption coefficient can be reconstructed with inaccuracy of less than 10%. The absorption coefficient reconstruction for one set of measurement data can be fulfilled within one minute.

  20. Antiphospholipid antibodies in rheumatoid arthritis: Identifying the dominoes

    Microsoft Academic Search

    Debbie A. Gladd; Ewa Olech

    2009-01-01

    Antiphospholipid antibodies (aPL) occur in a variety of autoimmune, malignant, and infectious diseases, with or without the\\u000a thrombotic or obstetric sequelae that characterize the antiphospholipid syndrome. Although many studies have focused on the\\u000a clinical implications of aPL in systemic lupus erythematosus, few have specifically addressed the questions facing rheumatologists\\u000a caring for rheumatoid arthritis patients who are concomitantly positive for aPL.

  1. Association of MICA polymorphism with rheumatoid arthritis patients in Koreans

    Microsoft Academic Search

    Jee Won Mok; Yun Jong Lee; Jeong Yeon Kim; Eun Bong Lee; Yeong Wook Song; Myoung Hee Park; Kyung Sook Park

    2003-01-01

    To investigate whether genetic variations of MICA are associated with susceptibility to rheumatoid arthritis (RA), the (GCT)n microsatellite polymorphism of the transmembrane domain was analyzed in 144 Korean patients with RA and in 297 unrelated healthy controls. The allele frequency of MICA*A9 significantly decreased in RA patients compared with controls (9.0% vs. 15.3%, odds ratio [OR] = 0.55, p =

  2. Genetic markers of treatment response in rheumatoid arthritis

    Microsoft Academic Search

    Joanna Wesoly; Judith A. M. Wessels; Henk-Jan Guchelaar; Tom W. J. Huizinga

    2006-01-01

    Rheumatoid arthritis patients exhibit a considerable interindividual variability in response to drug treatment. Although many\\u000a disease-related and demographic factors have been studied to predict treatment outcome, the effective disease-modifying antirheumatic\\u000a drug (DMARD) therapy is not yet allocated based on factors that predict efficacy. Individual genetic characteristics are thought\\u000a to play an important role in treatment response; therefore, current research aims

  3. Increased prevalence of diastolic dysfunction in rheumatoid arthritis

    Microsoft Academic Search

    Kimberly P Liang; Elena Myasoedova; Cynthia S Crowson; John M Davis; Véronique L Roger; Barry L Karon; Daniel D Borgeson; Terry M Therneau; Richard J Rodeheffer; Sherine E Gabriel

    2010-01-01

    ObjectiveTo compare the prevalence of left ventricular (LV) diastolic dysfunction in subjects with and without rheumatoid arthritis (RA), among those with no history of heart failure (HF), and to determine risk factors for diastolic dysfunction in RA.MethodsA cross-sectional, community-based study comparing cohorts of adults with and without RA and without a history of HF was carried out. Standard two-dimensional\\/Doppler echocardiography

  4. Skewed X chromosome inactivation in rheumatoid arthritis women

    Microsoft Academic Search

    Doua F Azzouz; Onur Emre Onat; Nathalie Balandraud; Sami B Kanaan; Jean Roudier; Tayfun Ozcelik; Nathalie C Lambert

    2011-01-01

    Background and objectivesIt has long been recognised that women have a greater prevalence of autoimmune diseases. Rheumatoid arthritis (RA) does not escape this rule with a women:men ratio of 3:1.X chromosome inactivation (XCI) is a dosage compensation mechanism used by mammals to ensure that XX females and XY males equalise X chromosome gene expression. As a consequence, females are a

  5. Humanized mice as a model for rheumatoid arthritis

    Microsoft Academic Search

    Rüdiger Eming; Kevin Visconti; Frances Hall; Chiyoko Sekine; Kayta Kobayashi; Qun Chen; Andrew Cope; Satoshi Kanazawa; Matija Peterlin; Antonius Rijnders; Annemieke Boots; Jan Meijerink; Grete Sønderstrup

    2002-01-01

    CHAPTER SUMMARY: Genetic susceptibility to rheumatoid arthritis (RA), a common autoimmune disease, is associated with certain HLA-DR4 alleles. Treatments are rarely curative and are often tied to major side effects. We describe the development of a humanized mouse model wherein new, less toxic, vaccine-like treatments for RA might be pretested. This model includes four separate transgenes: HLA-DR*0401 and human CD4

  6. Improving adherence to medical regimens for juvenile rheumatoid arthritis

    PubMed Central

    Rapoff, Michael A; Lindsley, Carol B

    2007-01-01

    Poor adherence to medical regimens can compromise the efficacy of treatments for children and adolescents with juvenile rheumatoid arthritis (JRA). The purpose of this review is to describe medical regimens for the treatment of JRA and the rates of adherence to these regimens. We also summarize and critically the few research studies aimed at improving adherence to regimens for JRA. Finally, we summarize strategies for enhancing adherence in clinical practice. PMID:17550635

  7. Elk velvet antler in rheumatoid arthritis: phase II trial.

    PubMed

    Allen, Marion; Oberle, Kathleen; Grace, Michael; Russell, Anthony

    2002-01-01

    The purpose of this phase II clinical trial was to examine safety of elk velvet antler taken concurrently with rheumatoid arthritis medications and to determine efficacy by dose to enable sample size estimation and dose standardization for a larger study. Forty patients with stage II rheumatoid arthritis were randomly assigned to 1 of 4 arms of 10 patients each. One group received placebo and the other 3 groups received 2, 4, or 6 capsules (215 mg) of elk velvet antler with appropriate placebos to total 6 capsules daily. All subjects continued to take their arthritis medications. Outcome variables were reported adverse events and health status. At 1 month, there were no significant differences between groups in number of adverse events or health status. The greatest improvement was in the 6 elk velvet antler group, the least was in the placebo group. Differences were not statistically significant. It was concluded that elk velvet antler can be taken safely in conjunction with a number of rheumatoid arthritis medications and should be studied further to assess efficacy. PMID:12003439

  8. Does rheumatoid arthritis disease activity correlate with weather conditions?

    PubMed

    Savage, E M; McCormick, D; McDonald, S; Moore, O; Stevenson, M; Cairns, A P

    2015-05-01

    To determine whether rheumatoid arthritis disease activity correlates with changing weather conditions. A longitudinal analysis of 133 patients attending the Department of Rheumatology, Musgrave Park Hospital, Belfast was performed. Participants had a diagnosis of rheumatoid arthritis and were receiving subcutaneous anti-TNF therapy (Adalimumab or Etanercept) for a period of >6 months. Data were collected at five time points. This included tender joint count, swollen joint count, patient visual analogue score (VAS), erythrocyte sedimentation rate, C-reactive protein, VAS, and DAS-28 (Disease Activity Score). Each weather factor (maximum, minimum temperature, pressure, rainfall, sunshine, humidity, and wind-speed) was analysed against each patients' DAS-28 score at five time points, using an analysis of covariance. A significant correlation was noted between low DAS-28 and increased hours of sunshine (p < 0.001). Sunny conditions were associated with a DAS-28 reduction of 0.037 (95 % CI -0.059, -0.016) p < 0.001. A significant correlation between humidity and DAS-28 was also noted (p = 0.016). Increased humidity was associated with an increased DAS-28 of 0.007 (95 % CI 0.001, 0.013) p = 0.016. Higher temperatures were associated with a non-significant decrease in DAS-28 (p = 0.16). In this study, rheumatoid arthritis disease activity (as measured by DAS-28) was significantly lower in both more sunny and less humid conditions. PMID:25342437

  9. Continuous monitoring of haemodynamic parameters in humans during the early phase of simulated diving with and without breathholding

    Microsoft Academic Search

    Daniel Duprez; Marc De Buyzere; Jan Trouerbach; Willem Ranschaert; Denis L. Clement

    2000-01-01

    This study examined the integrative changes of blood pressure (BP) and stroke volume (SV) leading to the initial biphasic\\u000a heart rate (f\\u000a c) response (first 15?s) in simulated diving manoeuvres with and without breathholding (BH). Simulated diving was studied in\\u000a ten young healthy volunteers by application of a gel-filled pack at 0C and 18C on the forehead with and without

  10. Simulated NASA Satellite Data Products for the NOAA Integrated Coral Reef Observation Network/Coral Reef Early Warning System

    NASA Technical Reports Server (NTRS)

    Estep, Leland; Spruce, Joseph P.

    2007-01-01

    This RPC (Rapid Prototyping Capability) experiment will demonstrate the use of VIIRS (Visible/Infrared Imager/Radiometer Suite) and LDCM (Landsat Data Continuity Mission) sensor data as significant input to the NOAA (National Oceanic and Atmospheric Administration) ICON/ CREWS (Integrated Coral Reef Observation System/Coral Reef Early Warning System). The project affects the Coastal Management Program Element of the Applied Sciences Program.

  11. Familial rheumatoid arthritis: linkage of HLA to disease susceptibility locus in four families where proband presented with juvenile rheumatoid arthritis.

    PubMed Central

    Rossen, R D; Brewer, E J; Sharp, R M; Ott, J; Templeton, J W

    1980-01-01

    The occurrence of a chronic seronegative polyarthritis has been studied in four families in which the proband presented with some form of juvenile rheumatoid arthritis. In these families, histocompatibility testing suggested that susceptibility to arthritis was controlled by a dominant allele with variable penetrance and expressivity at the rheumatoid-like arthritis, first locus (RLA-1). The combined lod scores for the four families (2.70) indicated that the odds in favor of genetic linkage between the major histocompatibility complex and the postulated disease susceptibility gene, RLA-1, were 500:1. In one family, a recombinant event permitted localization of RLA-1 centromeric to HLA-D. Of major interest was the fact that there was significant pleomorphism in the clinical manifestations of arthritis in affected individuals. In some, symptoms first occurred in childhood and in others, in adult life. Even among those with childhood-onset arthritis, different types of juvenile rheumatoid arthritis were observed within the same family. PMID:6766468

  12. Alpha 1 antitrypsin (PI) phenotypes in two rheumatic diseases: a reappraisal of the association of PI subtypes in rheumatoid arthritis

    Microsoft Academic Search

    S S Papiha; B Pal; D Walker; P Mangion; M A Hossain

    1989-01-01

    alpha 1 Antitrypsin phenotypes were determined by isoelectric focusing in 225 adult white patients with rheumatoid arthritis (RA), 60 patients with severe rheumatoid arthritis (grade III and IV), 17 sibling pairs--HLA identical but discordant for rheumatoid arthritis, and 122 random patients with Sjögren's syndrome. No significant increase in non-M phenotypes was found in either of the groups of patients with

  13. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis

    Microsoft Academic Search

    M Otero; R Lago; R Gomez; F Lago; C Dieguez; J J Go?mez-Reino; O Gualillo

    2006-01-01

    Background: Rheumatoid arthritis is a chronic autoimmune inflammatory condition characterised by polyarthritis and severe change in body mass and neuroendocrine environment.Objectives: To investigate plasma levels of adipocytokines (leptin, adiponectin, visfatin and resistin) in patients with rheumatoid arthritis and to compare them with levels in healthy controls.Methods: Adiponectin, resistin, visfatin and leptin concentrations were measured in 31 patients with rheumatoid arthritis

  14. 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.

  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. Macular blood flow during pregnancy in patients with early diabetic retinopathy measured by blue-field entoptic simulation

    Microsoft Academic Search

    Timo Hellstedt; Risto Kaaja; Kari Teramo; Ilkka Immonen

    1996-01-01

    • Purpose: To study macular capillary blood flow velocity during pregnancy and postpartum in diabetic women with minimal diabetic retinopathy. • Methods: Macular capillary blood velocity was measured using the blue-field entoptic simulation technique in 17 type I diabetic pregnant women with minimal background retinopathy and 10 healthy pregnant women at the 12th and 32nd–36th weeks of pregnancy and 3

  17. Viruses and lymphocytes in rheumatoid arthritis. II. Examination of lymphocytes and sera from patients with rheumatoid arthritis for evidence of retrovirus infection.

    PubMed Central

    Hart, H; McCormick, J N; Marmion, B P

    1979-01-01

    The possible involvement of retroviruses in the aetiology of rheumatoid arthritis (RA) was investigated. Retrovirus antigens were not expressed on rheumatoid synovial and peripheral blood lymphocytes as judged by membrane immunofluorescence, radioimmunoassay, and complement-mediated cytotoxicity. The specific antiretroviral (anti-RD-144 and anti-SSAV) sera used in this study were produced in rabbits immunised with viral antigens grown in a homologous system (rabbit cells and medium supplemented with normal rabbit serum), avoiding non-specific immunofluorescence previously detected with donated antiretroviral sera. Immune complexes lodged in the rheumatoid synovial membranes did not contain, and other cells within the membranes did not express, retroviral antigens. Antibodies cross-reacting with primate retrovirus antigens were sought in sera from patients with 'autoimmune' diseases by means of solid phase radioimmunoassay. There were no retrovirus antibodies in the 3 groups of patients studied, that is, those with rheumatoid arthritis, systemic lupus erythematosus, and with non-RA conditions. Absorption of rheumatoid factor did not alter this conclusion. These results give little support to the hypothesis that activation of endogenous human retroviruses or an infection with horizontally transmitted retroviruses is associated with the rheumatoid process. PMID:395909

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

    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.

  19. 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

  20. 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

  1. 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

  2. Database of tsunami scenario simulations for Western Iberia: a tool for the TRIDEC Project Decision Support System for tsunami early warning

    NASA Astrophysics Data System (ADS)

    Armigliato, Alberto; Pagnoni, Gianluca; Zaniboni, Filippo; Tinti, Stefano

    2013-04-01

    TRIDEC is a EU-FP7 Project whose main goal is, in general terms, to develop suitable strategies for the management of crises possibly arising in the Earth management field. The general paradigms adopted by TRIDEC to develop those strategies include intelligent information management, the capability of managing dynamically increasing volumes and dimensionality of information in complex events, and collaborative decision making in systems that are typically very loosely coupled. The two areas where TRIDEC applies and tests its strategies are tsunami early warning and industrial subsurface development. In the field of tsunami early warning, TRIDEC aims at developing a Decision Support System (DSS) that integrates 1) a set of seismic, geodetic and marine sensors devoted to the detection and characterisation of possible tsunamigenic sources and to monitoring the time and space evolution of the generated tsunami, 2) large-volume databases of pre-computed numerical tsunami scenarios, 3) a proper overall system architecture. Two test areas are dealt with in TRIDEC: the western Iberian margin and the eastern Mediterranean. In this study, we focus on the western Iberian margin with special emphasis on the Portuguese coasts. The strategy adopted in TRIDEC plans to populate two different databases, called "Virtual Scenario Database" (VSDB) and "Matching Scenario Database" (MSDB), both of which deal only with earthquake-generated tsunamis. In the VSDB we simulate numerically few large-magnitude events generated by the major known tectonic structures in the study area. Heterogeneous slip distributions on the earthquake faults are introduced to simulate events as "realistically" as possible. The members of the VSDB represent the unknowns that the TRIDEC platform must be able to recognise and match during the early crisis management phase. On the other hand, the MSDB contains a very large number (order of thousands) of tsunami simulations performed starting from many different simple earthquake sources of different magnitudes and located in the "vicinity" of the virtual scenario earthquake. In the DSS perspective, the members of the MSDB have to be suitably combined based on the information coming from the sensor networks, and the results are used during the crisis evolution phase to forecast the degree of exposition of different coastal areas. We provide examples from both databases whose members are computed by means of the in-house software called UBO-TSUFD, implementing the non-linear shallow-water equations and solving them over a set of nested grids that guarantee a suitable spatial resolution (few tens of meters) in specific, suitably chosen, coastal areas.

  3. Molecular Characterization of Rheumatoid Arthritis with Magnetic Resonance Imaging

    PubMed Central

    Gu, Jeffrey T.; Nguyen, Linda; Chaudhari, Abhijit J.; MacKenzie, John D.

    2012-01-01

    Several recent advances in the field of magnetic resonance imaging (MRI) may transform the detection and monitoring of rheumatoid arthritis (RA). These advances depict both anatomic and molecular alterations from RA. Previous techniques could detect specific end products of metabolism in vitro, or were limited to providing anatomic information. This review focuses on the novel molecular imaging techniques of hyperpolarized carbon-13 (13C) MRI, MRI with iron labeled probes, and fusion of MRI with positron emission tomography. These new imaging approaches go beyond the anatomic description of RA and lend new information into the status of this disease by giving molecular information. PMID:22648081

  4. 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

  5. Cardiovascular complications of Rheumatoid Arthritis - Assessment, prevention and treatment

    PubMed Central

    Kaplan, Mariana J.

    2010-01-01

    Synopsis Morbidity and mortality rates are higher in individuals with rheumatoid arthritis (RA) than in the general population. Ischemic heart disease and heart failure now represent one of the most common causes of death in RA. Indeed, RA appears to represent an independent risk factor for ischemic heart disease, similar to diabetes mellitus. However, no clear guidelines with regards to cardiovascular disease diagnosis and prevention in RA have been developed. This review highlights recent investigations on the assessment, prevention and treatment of cardiovascular disease in RA. PMID:20510241

  6. Recent advances in the genetics of rheumatoid arthritis

    Microsoft Academic Search

    Chris Deighton; Lindsey A. Criswell

    2006-01-01

    Recent progress in defining the role of genetic factors in rheumatoid arthritis (RA) has been remarkable. Anticyclic citrullinated\\u000a peptide (anti-CCP) antibody-positive disease appears to be immunogenetically distinct from anti-CCP-negative disease, with\\u000a the former subgroup primarily responsible for association and linkage with the HLA-DRB1 shared epitope (SE). There is preliminary\\u000a evidence that non-HLA genes contribute differentially to anti-CCP-positive and negative disease.

  7. Representative sample of rheumatoid synovium: a morphometric study.

    PubMed Central

    Kennedy, T D; Plater-Zyberk, C; Partridge, T A; Woodrow, D F; Maini, R N

    1988-01-01

    The synovium from 11 patients with rheumatoid arthritis, who were undergoing joint surgery, was assessed using histological and morphometric techniques. Histological examination confirmed previous reports that the intensity of the cellular reaction varied throughout the synovium, and the morphometric method reflected this variability sensitively. The method was shown to be reproducible and allowed areas of similar cellular density to be defined. From these defined areas a total of 2.5 mm2 of synovium equivalent to 12 fields at x250 required analysis to reflect the variation in the cellular reaction. It would be feasible to collect this amount of material using an arthroscope. Images Fig 2 PMID:3170771

  8. Rheumatoid arthritis educational series: a nurse-led project.

    PubMed

    Lemon, Joyce; Marichal-Williams, Blanca; Blum, Eileen; Bracero, Maria

    2012-01-01

    Nurses in the rheumatology clinic at New York University Hospital for Joint Diseases realized a need to provide patients with rheumatoid arthritis with more healthcare information than was routinely given during clinic visits. This project goal was to support patient involvement in decision making and encourage participation in treatment planning. To address these concerns, a team of staff registered nurses developed an educational program based on various arthritis-related topics. This article shares the experiences of these nurses as they developed and led a patient education project. Various elements of the project are discussed, including institutional history, program needs, project start-up, challenges, outcomes, and the lessons learned. PMID:22828520

  9. Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations

    PubMed Central

    Lehmann, Eldon D.; Tarín, Cristina; Bondia, Jorge; Teufel, Edgar; Deutsch, Tibor

    2009-01-01

    Introduction AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described. Methods This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done. Results Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as well as for insulin doses up to 50 IU. Discussion The methodology to be adopted for implementing the generic absorption model within AIDA has been overviewed, and the first plasma insulin profiles based on this approach have been demonstrated. Ideas for future work and development are discussed. It is expected that an updated release of AIDA (v4.5), based on this collaborative approach, will become available for free—in due course—via the www.2aida.org Web site. Readers who wish to be informed when the new software is launched can join the very low volume AIDA announcement list by sending a blank email note to subscribe@2aida.org. PMID:20046665

  10. Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study

    Microsoft Academic Search

    Jennie Ursum; Markus MJ Nielen; Dirkjan van Schaardenburg; Ann R van der Horst; Rob J van de Stadt; Ben AC Dijkmans; Dörte Hamann

    2008-01-01

    INTRODUCTION: The aim of our study was to investigate the association between arthritic disease activity and antibodies to mutated citrullinated vimentin (anti-MCV), because such a relation has been suggested. METHODS: Anti-MCV levels were measured in 162 patients with early arthritis (123 with rheumatoid arthritis and 39 with undifferentiated arthritis) at baseline and at 1 and 2 years of follow up.

  11. Simulated Surface Energy Budgets Over the Southeastern US: The GHCC Satellite Assimilation System and the NCEP Early Eta

    NASA Technical Reports Server (NTRS)

    Lapenta, William M.; Suggs, Ron; McNider, Richard T.; Jedlovec, Gary

    1999-01-01

    A technique has been developed for assimilating GOES-derived skin temperature tendencies and insolation into the surface energy budget equation of a mesoscale model so that the simulated rate of temperature change closely agrees with the satellite observations. A critical assumption of the technique is that the availability of moisture (either from the soil or vegetation) is the least known term in the model's surface energy budget. Therefore, the simulated latent heat flux, which is a function of surface moisture availability, is adjusted based upon differences between the modeled and satellite-observed skin temperature tendencies. An advantage of this technique is that satellite temperature tendencies are assimilated in an energetically consistent manner that avoids energy imbalances and surface stability problems that arise from direct assimilation of surface shelter temperatures. The fact that the rate of change of the satellite skin temperature is used rather than the absolute temperature means that sensor calibration is not as critical. An advantage of this technique for short-range forecasts (0-48h) is that it does not require a complex land-surface formulation within the atmospheric model. As a result, we can avoid having to specify land surface characteristics such as vegetation resistances, green fraction, leaf area index, soil physical and hydraulic characteristics, stream flow, runoff, and the vertical and horizontal distribution of soil moisture.

  12. Association between the TNFRII 196R allele and diagnosis of rheumatoid arthritis

    PubMed Central

    Goëb, Vincent; Dieudé, Philippe; Vittecoq, Olivier; Mejjad, Othmane; Ménard, Jean-François; Thomas, Marlène; Gilbert, Danièle; Boumier, Patrick; Pouplin, Sophie; Daragon, Alain; Fardellone, Patrice; Tron, François; Cornélis, François; Le Loët, Xavier

    2005-01-01

    Tumour necrosis factor (TNF)-? plays a key role in the pathogenesis of rheumatoid arthritis (RA). It binds to two receptors, namely TNF receptor (TNFR)I and TNFRII. Several studies have suggested an association between TNFRII 196R/R genotype and RA. The objective of the present study was to evaluate the predictive value of the TNFRII 196R allele for RA diagnosis and prognosis in a cohort of patients with very early arthritis. We followed up a total of 278 patients recruited from the community, who had swelling of at least two joints that had persisted for longer than 4 weeks but had been evolving for less than 6 months, and who had not received disease-modifying antirheumatic drugs or steroid therapy. At 2 years, patients were classified according to the American College of Rheumatology criteria. All patients were genotyped with respect to TNFRII 196M/R polymorphism. Radiographs of hands and feet (read according to the modified Sharp method) and the Health Assessment Questionnaire were used to quantify structural and functional severity. The cohort of 278 patients was found to include 156 and 122 RA and non-RA patients, respectively. The TNFRII 196R allele was found to be associated with RA (P = 0.002). However, progression of radiographic severity and Health Assessment Questionnaire scores over 1 year did not differ between carriers of the 196R allele and noncarriers. Our findings suggest that the TNFRII 196R allele may be associated with RA diagnosis but that it does not predict early radiographic progression or functional severity in patients with very early, unclassified arthritis. PMID:16207322

  13. Low-level laser therapy in different stages of rheumatoid arthritis: a histological study.

    PubMed

    Alves, Ana Carolina Araruna; de Carvalho, Paulo de Tarso Camillo; Parente, Marcio; Xavier, Murilo; Frigo, Lucio; Aimbire, Flávio; Leal Junior, Ernesto Cesar Pinto; Albertini, Regiane

    2013-02-01

    Rheumatoid arthritis (RA) is an autoimmune inflammatory disease of unknown etiology. Treatment of RA is very complex, and in the past years, some studies have investigated the use of low-level laser therapy (LLLT) in treatment of RA. However, it remains unknown if LLLT can modulate early and late stages of RA. With this perspective in mind, we evaluated histological aspects of LLLT effects in different RA progression stages in the knee. It was performed a collagen-induced RA model, and 20 male Wistar rats were divided into 4 experimental groups: a non-injured and non-treated control group, a RA non-treated group, a group treated with LLLT (780 nm, 22 mW, 0.10 W/cm(2), spot area of 0.214 cm(2), 7.7 J/cm(2), 75 s, 1.65 J per point, continuous mode) from 12th hour after collagen-induced RA, and a group treated with LLLT from 7th day after RA induction with same LLLT parameters. LLLT treatments were performed once per day. All animals were sacrificed at the 14th day from RA induction and articular tissue was collected in order to perform histological analyses related to inflammatory process. We observed that LLLT both at early and late RA progression stages significantly improved mononuclear inflammatory cells, exudate protein, medullary hemorrhage, hyperemia, necrosis, distribution of fibrocartilage, and chondroblasts and osteoblasts compared to RA group (p?early as well as in late progression stages of RA. PMID:22538842

  14. A transient peak of infections during onset of rheumatoid arthritis: a 10-year prospective cohort study

    PubMed Central

    Arleevskaya, Marina I; Gabdoulkhakova, Aida G; Filina, Yulia V; Miftakhova, Regina R; Bredberg, Anders; Tsybulkin, Anatoly P

    2014-01-01

    Objectives The role of infection in rheumatoid arthritis (RA) has not been determined. We aimed to document the infectious burden and some aspects of antibacterial immunity in a large and prospective cohort study of RA patients in the early and late stages of the disease and in their relatives predisposed to RA. Setting Clinical and laboratory examination of all individuals enrolled in the study was performed in the Republican Clinical Hospital, Kazan, Russia. Participants 376 patients with RA, 251 healthy first-degree relatives and 227 healthy controls without a family history of autoimmune disease (all females) were examined twice annually over more than 10?years. Primary and secondary outcome measures The following parameters were investigated: type, duration and frequency of infections, bacterial colonisation and serum levels of IgG to bacteria, serum levels of total Ig, plasma cytokine levels, granulocyte reactive oxygen species production, lysozyme activity and phagocytosis. Results There were no significant differences in infection rate between healthy controls (median 14?days/year) and RA patients (13). However, infection rates were higher (p<0.001) in healthy relatives (53) and early stage patients (62), which groups also showed heavy bacterial skin colonisation. In contrast, late stage patients had fewer infection days (12; p<0.001) than healthy controls, although bacterial colonisation was still heavy. Phagocyte function and antibacterial antibody generation, together with compensatory cytokine production, were observed to be subnormal in the healthy relatives as well as in RA patients. Conclusions We observed a marked increase in overall infections at the time of RA onset, and signs of a defective antibacterial defence mechanism, contrasting with fewer infections in the late RA stage. It can be speculated that frequent early infections initiate a compensatory immune hyper-reactivity which reduces the infection load while stimulating the development of RA in predisposed individuals. PMID:25180052

  15. Can remission be maintained with or without further drug therapy in rheumatoid arthritis?

    PubMed

    Saleem, B; Nizam, S; Emery, P

    2006-01-01

    Remission is now the accepted goal of management in rheumatoid arthritis (RA). This article highlights the controversies surrounding the definition of remission and reviews the potential of current treatment options to achieve remission. Defining "true" remission can be difficult based on current criteria, which do not consider structural and physical function. Nonetheless, considerable advances in recent years have made the concept of remission a realistic goal. In early RA, substantial and largely irreversible radiographic damage is seen in 60% of patients within the first 2 years of diagnosis. Early therapeutic intervention would ideally lead to reduction in long-term disability in RA and likelihood of inducing and maintaining remission.Long-term maintenance therapy with disease-modifying antirheumatic drugs (DMARDs) has been shown to be effective in preventing flares of disease. Stopping therapy for short periods does not necessarily lead to flares, but the effect on long-term radiographic damage and potential to achieve similar levels of disease control following reinstatement of therapy is not established. Early use of tumour necrosis factor (TNF)-antagonist therapy (e.g. infliximab) has been shown to lead to significant improvement in disease activity measures (clinical and radiologic outcomes) when compared to monotherapy or combination DMARD and corticosteroid therapies. Response was shown to be sustained in 70% of patients receiving TNF-blocking therapy 1 year after stopping treatment. This suggests the significant role of TNF-blocking therapy in enabling sustainable remission without need for long-term administrations, which has important implications for favourable health economics. At present, little published evidence exists on the effects of withdrawal of TNF-blocking therapy in patients with established RA in remission. In conclusion, evidence indicates that remission is a realistic goal, but more evidence is required to establish optimal treatment strategies and define criteria for remission that include imaging and immunological as well as clinical assessment of the disease state. PMID:17083760

  16. Rheumatoid arthritis and schizophrenia: a negative association at a dimensional level.

    PubMed

    Gorwood, P; Pouchot, J; Vinceneux, P; Puéchal, X; Flipo, R M; De Bandt, M; Adès, J

    2004-01-01

    There is wide evidence for a decreased risk of rheumatoid arthritis in patients with schizophrenia. Nevertheless, very few studies have looked at the risk of schizophrenia in a group of patients with rheumatoid arthritis. We prospectively investigated, with the SCL-90R, 220 consecutive outpatients with rheumatoid arthritis and 196 consecutive outpatients with various medical conditions, half of them suffering from psoriatic arthritis (a medical condition close to rheumatoid arthritis). The SCL-90R appears to be a valuable tool to distinguish patients with schizophrenia from the outpatients of our sample, the former having more "paranoid ideation" (p = 0.004) and more "psychoticism" (p < 0.001) than the latter. The "paranoid ideation" dimension was significantly lower (25% decrease) in the sample of patients with rheumatoid arthritis compared to the combined control group (p = 0.005), ratings under the median value being more frequent in the former group (p = 0.025). Confounding factors might not explain this difference according to the regression logistic analysis performed. As patients with rheumatoid arthritis have a lower score of paranoid ideation than controls in our sample, even after controlling for age, gender and severity of the disease, these data represent further evidence for a decreased risk of schizophrenia in individuals with rheumatoid arthritis. PMID:14693349

  17. Analysis of rheumatoid factors by a biotin-avidin based isotype-specific ELISA.

    PubMed

    Kemp, M; Husby, S; Jensenius, J C; Rasmussen, G G; Svehag, S E

    1985-10-01

    A one day enzyme immunoassay for the detection of rheumatoid factors of the IgG, IgM, and IgA class is described. The assay utilizes rabbit IgG as solid-phase reactant and the biotin-avidin interaction for the coupling of enzyme to indicator antibody. Three different indicator antibodies discriminated effectively between rheumatoid arthritis patients and normal subjects. F(ab')2 fragments of goat antibodies were found best suited for the test. Rheumatoid factor activity was expressed in U/ml by comparing samples to an internal standard, which was related to the WHO international reference serum for rheumatoid arthritis. Rheumatoid factor activity (U/ml) in the IgM-specific assay showed a close correlation to the latex agglutination titer. Avidity indices estimated from the slopes of the dose response curves of test sera were significantly higher for rheumatoid arthritis patients than for a group of healthy persons, indicating a higher avidity of the rheumatoid factors in the patients' sera. PMID:4083017

  18. Management of cardiovascular risk in patients with rheumatoid arthritis: evidence and expert opinion

    PubMed Central

    van den Oever, Inge A.M.; van Sijl, Alper M.

    2013-01-01

    The risk of cardiovascular morbidity and mortality is increased in rheumatoid arthritis. The classical cardiovascular risk factors, including smoking, hypertension, dyslipidaemia, insulin resistance and diabetes mellitus, obesity and physical inactivity do not appear to explain the excess cardiovascular risk in rheumatoid arthritis, although they do contribute, albeit in a different way or to a lesser extent, to rheumatoid arthritis in comparison with the general population. A very important link between rheumatoid arthritis and cardiovascular disease is inflammation as it plays a key role in all stages of atherosclerosis: from endothelial dysfunction to plaque rupture and thrombosis. It also has an influence on and accentuates some traditional cardiovascular risk factors, such as dyslipidaemia, obesity and insulin resistance. To date, the exact pathophysiologic mechanism by which this relation between cardiovascular disease and rheumatoid arthritis can be explained is not completely clear. Cardiovascular risk management in rheumatoid arthritis is mandatory. Unfortunately, the way this should be done remains a point of discussion. In this review issues regarding cardiovascular risk in rheumatoid arthritis and its management will be addressed, according to evidence presented in the latest studies and our own experience-based opinion. PMID:23904862

  19. Effects of therapeutically induced affect arousal on depressive symptoms, pain and beta-endorphins among rheumatoid arthritis patients.

    PubMed

    Beutler, L E; Daldrup, R J; Engle, D; Oro'-Beutler, M E; Meredith, K; Boyer, J T

    1987-06-01

    The relationship among therapeutically induced affective arousal, depressive symptoms, pain and beta-endorphin levels were explored on 6 patients with chronic, active rheumatoid arthritis. An ABA, n of 1 study methodology was utilized, replicated 5 times. This procedure allowed the analysis of individualized changes across time in response to the therapeutic regimen. The results indicated that the treatment regimen activated the beta-endorphin system, particularly during the early and late phases of treatment. However, beta-endorphin response had little effect on reports of subjective pain. Depressive symptoms were affected positively by the treatment but were not strongly correlated to the beta-endorphin response. The results suggest that pain and depression represent independent systems and that beta-endorphin levels serve more as stress markers than analgesics in chronic, organic pain. PMID:2956558

  20. Permittivity and Performance of Dielectric Pads with Sintered Ceramic Beads in MRI: Early Experiments and Simulations at 3 T

    PubMed Central

    Luo, Wei; Lanagan, Michael T.; Sica, Christopher T.; Ryu, YeunChul; Oh, Sukhoon; Ketterman, Matthew; Yang, Qing X.; Collins, Christopher M.

    2014-01-01

    Passive dielectric materials have been used to improve aspects of MRI by affecting the distribution of radiofrequency electromagnetic fields. Recently, interest in such materials has increased with the number of high-field MRI sites. Here, we introduce a new material composed of sintered high-permittivity ceramic beads in deuterated water. This arrangement maintains the ability to create flexible pads for conforming to individual subjects. The properties of the material are measured and the performance of the material is compared to previously used materials in both simulation and experiment at 3 T. Results show that both permittivity of the beads and effect on signal-to-noise ratio and required transmit power in MRI are greater than those of materials consisting of ceramic powder in water. Importantly, use of beads results in both higher permittivity and lower conductivity than use of powder. PMID:22890908

  1. Application of Liposomes in Treatment of Rheumatoid Arthritis: Quo Vadis

    PubMed Central

    Singh, Sachin Kumar; Gulati, Monica

    2014-01-01

    The most common treatments for rheumatoid arthritis include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease modifying antirheumatic drugs (DMARDs), and some biological agents. However, none of the treatments available is able to achieve the ultimate goal of treatment, that is, drug-free remission. This limitation has shifted the focus of treatment to delivery strategies with an ability to deliver the drugs into the synovial cavity in the proper dosage while mitigating side effects to other tissues. A number of approaches like microemulsions, microspheres, liposomes, microballoons, cocrystals, nanoemulsions, dendrimers, microsponges, and so forth, have been used for intrasynovial delivery of these drugs. Amongst these, liposomes have proven to be very effective for retaining the drug in the synovial cavity by virtue of their size and chemical composition. The fast clearance of intra-synovially administered drugs can be overcome by use of liposomes leading to increased uptake of drugs by the target synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging trends of this promising technology. PMID:24688450

  2. Predictors of frequent oral analgesic use in rheumatoid arthritis

    PubMed Central

    Gupta, Esha das; Tee, Huey Shin; Sakthiswary, Rajalingham

    2014-01-01

    Objective: The main objective of this study was to determine the predictors of frequent oral analgesic use among Rheumatoid Arthritis (RA) patients who were prescribed with the above medication on an ‘as-needed’ basis. Methods: Patients with RA were recruited consecutively from the Rheumatology outpatient clinics in this cross-sectional study. The sociodemographic data, frequency of oral analgesic intake, Patient Global Assessment (PGA) scores and HAQ (Health Assessment Questionnaire) scores were determined by interviewing the subjects. Subjects were divided into 2 groups; frequent users (3 days and above in a week) and less frequent users (less than 3 days in a week). Results: In a total of 112 subjects, 39 (34.8%) were frequent analgesic users. Both the HAQ and PGA scores were significantly higher among the frequent users (p<0.05). Using multivariate analysis, the HAQ scores (p=0.015, odds ratio 3.161 [95% confidence interval of 1.246-8.015]) and PGA scores (p=0.039 odds ratio 1.291 [95% confidence interval of 1.012-1.646]) were found to be independent predictors of frequent analgesic use. Conclusions: Our study confirms that the frequency of analgesic intake in Rheumatoid Arthritis has a significant relationship with patient-reported functional capacity and well being. PMID:25225510

  3. Amyloid Goiter Associated with Amyloidosis Secondary to Rheumatoid Arthritis

    PubMed Central

    Uzum, Gungor; Kaya, Fatih Oner; Uzum, Ayse Kubat; Kucukyilmaz, Meltem; Duzkoylu, Yigit; Leblebici, Cem; Koc, Oguz

    2013-01-01

    Amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. The most common forms of systemic amyloidosis are primary amyloidosis (PA) of light chains and secondary amyloidosis (SA) caused by chronic inflammatory diseases such as rheumatoid arthritis (RA). Although involvement of the thyroid gland by amyloid is a relatively common phenomenon, clinically significant enlargement of the thyroid owing to amyloid deposition is a rare occurrence. In SA, the deposition of amyloid associated (AA) protein is associated with atrophy of thyroid follicles. The clinical picture of these patients is characterized by rapid, painless thyroid gland enlargement which may be associated with dysphagia, dyspnea, or hoarseness. Thyroid function is not impaired in most cases. Although amyloid goitre secondary to systemic amyloidosis due to chronic inflammatory diseases is relatively common, specifically related to RA is much more uncommon one and it is reported less in the literature. In this report, A 52-old-year female patient with amyloid goiter associated with amyloidosis secondary to rheumatoid arthritis is presented. PMID:24368922

  4. Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation

    SciTech Connect

    Field, E.H.; Strober, S.; Hoppe, R.T.; Calin, A.; Engleman, E.G.; Kotzin, B.L.; Tanay, A.S.; Calin, H.J.; Terrell, C.P.; Kaplan, H.S.

    1983-08-01

    Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values.

  5. [Mechanisms of osteoporosis development in patients with rheumatoid arthritis].

    PubMed

    Matuszewska, Agnieszka; Szechi?ski, Jacek

    2014-01-01

    Rheumatoid arthritis (RA) is progressive, chronic, autoimmune, systemic connective tissue disease. It affects 0,5-1% population. RA manifests as inflammation of symmetrical mainly small and medium joints with synovial hypertrophy, extra-articular lesions and systemic complications. Depending on intensity and duration of RA in imaging studies the patients demonstrate narrowing of articular fissures, presence of geodes, erosions, subluxations and/or synostoses. Progressive bone mass loss in the joint involved by the morbid process and in the entire skeleton was also described. Local (periarticular) osteoporosis is linked to the presence of cytokines and growth factors, which regulate reciprocal interactions between osteoclasts, osteoblasts and immune system cells. In the inflamed joint accumulate synoviocytes of fibroblast phenotype, synoviocytes of macrophage phenotype, antigen presenting cells, lymphocytes T, activated lymphocytes B, plasma cells and neutrophils. Increased expression of receptor activator of nuclear factor ?B (RANKL), macrophage-colony stimulating factor (M-CSF), presence of TNF?, IL-1, IL-6, IL-7, IL-17 influences pathological loss of bone mass. Rheumatoid arthritis is an important risk factor of generalised osteoporosis and fractures, involved in FRAX (fracture risk assessment) algorythm. Generalised osteoporosis in patients with RA has a multifactorial aetiology. Its development reflects effects of both: factors linked to the disease (presence of proinflammatory cytokines, disability of the patients, applied therapy) and classical risk factors of osteoporosis (e.g. advanced age, sex, post-menopausal period, genetic predisposition, low peak bone mass, low body weight, deficiency of calcium and vitamin D, tobacco smoking). PMID:24491906

  6. [Surgical aspects of the cervical spine in rheumatoid arthritis].

    PubMed

    Grob, D

    2004-10-01

    Approximately 20% percent of the patients with rheumatoid arthritis show pathology in the cervical spine. The translational instability between axis and atlas might be painful and leads in the long term to myelopathic changes due to chronic traumatization of the myelon. Ongoing osseous resorption of the lateral masses of the atlas cause upward migration of the dens into the foramen magnum. In the subaxial cervical spine, the inflammatory process causes instability and deformity. Neck pain is the most common indication for surgery, but neurological symptoms with myelopathy or radicular deficits might be the primary cause for surgery. Neurophysiological investigation is suitable to obtain objective results. Stabilization of the atlantoaxial segment is the most common procedure for treatment of atlantoaxial instability. It is performed by screw fixation technique from a posterior approach. In case of severe occipitocervical dislocation, the fixation has to be extended to the occiput. Persistent dislocation or compression by the dislocated dens has to be treated by transoral decompression. In the subaxial spine, instabilities may be treated by posterior plate fixation with lateral mass screws or pedicle screws. Concomitant nar-rowing of the spinal canal should be approached by anterior decompression with corpectomy and/or posterior laminectomy. The timing of surgery in rheumatoid patients is crucial to obtain satisfactory clinical results. PMID:15375655

  7. 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

  8. Therapy gloves for patients with rheumatoid arthritis: a review.

    PubMed

    Nasir, Siti Hana; Troynikov, Olga; Massy-Westropp, Nicola

    2014-12-01

    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

  9. Simulating the formation of massive seed black holes in the early Universe. I: An improved chemical model

    E-print Network

    Glover, Simon

    2015-01-01

    The direct collapse model for the formation of massive seed black holes in the early Universe attempts to explain the observed number density of supermassive black holes (SMBHs) at $z \\sim 6$ by assuming that they grow from seeds with masses M > 10000 solar masses that form by the direct collapse of metal-free gas in atomic cooling halos in which H2 cooling is suppressed by a strong extragalactic radiation field. The viability of this model depends on the strength of the radiation field required to suppress H2 cooling, $J_{\\rm crit}$: if this is too large, then too few seeds will form to explain the observed number density of SMBHs. In order to determine $J_{\\rm crit}$ reliably, we need to be able to accurately model the formation and destruction of H2 in gas illuminated by an extremely strong radiation field. In this paper, we use a reaction-based reduction technique to analyze the chemistry of H2 in these conditions, allowing us to identify the key chemical reactions that are responsible for determining the...

  10. 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

  11. 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.

  12. Spontaneous talar and calcaneal fracture in rheumatoid arthritis: a case report

    PubMed Central

    Spina, Antonio; Clemente, Alberto; Vancini, Chiara; Fejzo, Majlinda; Campioni, Paolo

    2011-01-01

    Rheumatoid arthritis (RA) leads to a progressive weakening of the skeleton which may result in bone fractures. However, spontaneous fractures (exclusive of stress fractures, vertebral collapse, and superficial articular fragmentation) in patients with rheumatoid arthritis have been only occasionally reported in the medical literature. A case of spontaneous talar and calcaneal fracture in rheumatoid arthritis is described. Bone lesions were identified on radiographs, MR images and scintigraphy in a patient with right ankle pain. The absence of episodes of acute trauma, and the presence of acute clinical manifestations should guide the clinical suspicion. PMID:22470803

  13. Applying Evidence In The Care Of Patients With Rheumatoid Hand And Wrist Deformities

    PubMed Central

    Rehim, Shady A.; Chung, Kevin C.

    2014-01-01

    The traditional approach in managing rheumatoid hand deformities is based on the individual surgeon’s experiences. In the current era of evidence-based medicine (EBM), formulating treatment for the rheumatoid hand fits perfectly within the framework of EBM by leveraging the best evidence from the literature, incorporating surgeons’ experience, and considering patients’ preferences. In this special article, we use a case example to illustrate how EBM can be practiced within the framework of treating rheumatoid hand deformities by distilling the best evidence from the literature to guide surgeons in a rational approach for treating this common condition. PMID:23783062

  14. Erosive rheumatoid arthritis is associated with antibodies that activate PAD4 by increasing calcium sensitivity

    PubMed Central

    Darrah, Erika; Giles, Jon T; Ols, Michelle L; Bull, Herbert G; Andrade, Felipe; Rosen, Antony

    2013-01-01

    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 clearly active in vivo (e.g. in RA synovial fluid) where calcium concentrations are much lower. In this study, we have discovered a novel subset of anti-PAD4 autoantibodies (identified by their cross-reactivity with PAD3) which strikingly increase the catalytic efficiency of PAD4 by decreasing the enzyme’s requirement for calcium into the physiologic range. Patients with these novel 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

  15. Primary Hepatic Lymphoma in a Patient with Rheumatoid Arthritis Treated with Methotrexate

    PubMed Central

    Tatsumi, Goichi; Ukyo, Naoya; Hirata, Hirokazu; Tsudo, Mitsuru

    2014-01-01

    Primary hepatic lymphoma (PHL) has rarely been reported in patients with immunosuppression. We herein describe a case of Epstein-Barr virus- (EBV-) positive PHL in a 67-year-old Japanese woman receiving methotrexate (MTX) treatment for rheumatoid arthritis (RA). The patient, who had been receiving MTX therapy for more than 6 years, presented with low-grade fever and abdominal pain. Initial laboratory tests showed mildly elevated liver enzymes with normal levels of alpha-fetoprotein and carcinoembryonic antigen, and computed tomography scans revealed multiple hepatic tumors with no lymph-node swelling. Examination of liver specimens obtained via ultrasonography-guided needle biopsy indicated EBV-positive diffuse large B cell lymphoma; therefore, she was diagnosed with PHL. MTX was discontinued, and she was carefully monitored thereafter owing to the prolonged history of MTX administration for RA. Rapid progression of PHL was observed; therefore 10 days after the PHL diagnosis, she received 6 cycles of R-THP-COP (rituximab, cyclophosphamide, pirarubicin, vincristine, and prednisolone) therapy and achieved complete remission for more than 1 year. Although MTX-associated lymphoproliferative disorders often show remission after withdrawal of MTX, early diagnosis and treatment are essential for PHL in patients with RA treated with MTX, because of the aggressive nature of the disease. PMID:25610674

  16. Recommendations for the use of ultrasound in rheumatoid arthritis: literature review and SONAR score experience.

    PubMed

    Zufferey, Pascal; Tamborrini, Giorgio; Gabay, Cem; Krebs, Andreas; Kyburz, Diego; Michel, Beat; Moser, Urs; Villiger, Peter M; So, Alexander; Ziswiler, Hans Rudolf

    2013-01-01

    Ultrasound (US) has become a useful tool in the detection of early disease, differential diagnosis, guidance of treatment decisions and treatment monitoring of rheumatoid arthritis (RA). In 2008, the Swiss Sonography in Arthritis and Rheumatism (SONAR) group was established to promote the use of US in inflammatory arthritis in clinical practice. A scoring system was developed and taught to a large number of Swiss rheumatologists who already contributed to the Swiss Clinical Quality Management (SCQM) database, a national patient register. This paper intends to give a Swiss consensus about best clinical practice recommendations for the use of US in RA on the basis of the current literature knowledge and experience with the Swiss SONAR score. Literature research was performed to collect data on current evidence. The results were discussed among specialists of the Swiss university centres and private practice, following a structured procedure. Musculoskelatal US was found to be very helpful in establishing the diagnosis and monitoring the evolution of RA, and to be a reliable tool if used by experienced examiners. It influences treatment decisions such as continuing, intensifying or stepping down therapy. The definite modalities of integrating US into the diagnosis and monitoring of RA treatments will be defined within a few years. There are, however, strong arguments to use US findings as of today in daily clinical care. Some practical recommendations about the use of US in RA, focusing on the diagnosis and the use of the SONAR score, are proposed. PMID:24363082

  17. Prognosis in rheumatoid arthritis. A longitudinal study of newly diagnosed younger adult patients.

    PubMed

    Feigenbaum, S L; Masi, A T; Kaplan, S B

    1979-03-01

    The course of rheumatoid arthritis was analyzed in 50 newly-diagnosed adults followed prospectively for an average of over five years. Eighteen patients had no swelling and no erosion (outcome 1), 22 patients had swelling without erosion (outcome 2) and 10 patients had erosion (outcome 3). Computer-assisted data screening and multivariate analytic technics were employed to derive a simple index from entry data which correlated closely with the patients' subsequent articular course. The index included six entry items: positive rhematoid factor; two or more swollen upper extremity joints on examination (2 points each); history of Raynaud's-like symptoms; malaise or weakness at the onset of arthritis; white race and female sex (1 point each). This index was 80 per cent accurate over-all in classifying patients into the three mutually exclusive articular outcome categories. Zero to 2 points on entry predicted no swelling, 3 to 5 points swelling without erosion and 6 to 8 points the development of bony erosion. Although results must be qualified to this patient population in the early stages of disease, the analytic approaches developed promise to assist with a broad range of clinical research and medical care delivery problems. PMID:433943

  18. Emerging Role of Endosomal Toll-Like Receptors in Rheumatoid Arthritis

    PubMed Central

    Thwaites, Ryan; Chamberlain, Giselle; Sacre, Sandra

    2013-01-01

    Toll-like receptors (TLRs) and their downstream signaling pathways have been comprehensively characterized in innate immunity. In addition to this function, these receptors have also been suggested to be involved in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Murine in vivo models and human in vitro tissue models of RA have provided a wealth of information on the potential activity of TLRs and components of the downstream signaling pathways. Whilst most early work investigated the cell surface TLRs, more recently the focus has moved to the endosomal TLRs 3, 7, 8, and 9. These receptors recognize self and foreign double-stranded RNA and single-stranded RNA and DNA. The development of therapeutics to inhibit the endosomal TLRs or components of their signaling cascades may represent a way to target inflammation upstream of cytokine production. This may allow for greater specificity than existing therapies including cytokine blockade. Here, we review the current information suggesting a role for the endosomal TLRs in RA pathogenesis and the efforts to target these receptors therapeutically. PMID:24474949

  19. Type I IFNs as biomarkers in rheumatoid arthritis: towards disease profiling and personalized medicine.

    PubMed

    Rodríguez-Carrio, Javier; López, Patricia; Suárez, Ana

    2015-04-01

    RA (rheumatoid arthritis) is a chronic rheumatic condition hallmarked by joint inflammation and destruction by self-reactive immune responses. Clinical management of RA patients is often hampered by its heterogeneous nature in both clinical presentation and outcome, thereby highlighting the need for new predictive biomarkers. In this sense, several studies have recently revealed a role for type I IFNs (interferons), mainly IFN?, in the pathogenesis of a subset of RA patients. Genetic variants associated with the type I IFN pathway have been linked with RA development, as well as with clinical features. Moreover, a role for IFN? as a trigger for RA development has also been described. Additionally, a type I IFN signature has been associated with the early diagnosis of RA and clinical outcome prediction in patients undergoing biological drug treatment, two challenging issues for decision-making in the clinical setting. Moreover, these cytokines have been related to endothelial damage and vascular repair failure in different autoimmune disorders. Therefore, together with chronic inflammation and disease features, they could probably account for the increased cardiovascular disease morbidity and mortality of these patients. The main aim of the present review is to provide recent evidence supporting a role for type I IFNs in the immunopathology of RA, as well as to analyse their possible role as biomarkers for disease management. PMID:25630235

  20. 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

  1. The effects of simulated solar UVB radiation on early developmental stages of the Northwestern Salamander (Ambystoma gracile) from three lakes

    USGS Publications Warehouse

    Calfee, Robin D.; Little, Edward E.; Pearl, Christopher A.; Hoffman, Robert L.

    2010-01-01

    Solar ultraviolet radiation (UV) has received much attention as a factor that could play a role in amphibian population declines. UV can be hazardous to some amphibians, but the resultant effects depend on a variety of environmental and behavioral factors. In this study, the potential effects of UV on the Northwestern Salamander, Ambystoma gracile, from three lakes were assessed in the laboratory using a solar simulator. We measured the survival of embryos and the survival and growth of larvae exposed to four UV treatments in controlled laboratory studies, the UV absorbance of egg jelly, oviposition depths in the lakes, and UV absorbance in water samples from the three lakes. Hatching success of embryos decreased in the higher UV treatments as compared to the control treatments, and growth of surviving larvae was significantly reduced in the higher UVB irradiance treatments. The egg jelly exhibited a small peak of absorbance within the UVB range (290–320 nm). The magnitude of UV absorbance differed among egg jellies from the three lakes. Oviposition depths at the three sites averaged 1.10 m below the water surface. Approximately 66% of surface UVB radiation was attenuated at 10-cm depth in all three lakes. Results of this study indicate that larvae may be sensitive to UVB exposure under laboratory conditions; however, in field conditions the depths of egg deposition in the lakes, absorbance of UV radiation by the water column, and the potential for behavioral adjustments may mitigate severe effects of UV radiation.

  2. Low-mass galaxy assembly in simulations: regulation of early star formation by radiation from massive stars

    NASA Astrophysics Data System (ADS)

    Trujillo-Gomez, Sebastian; Klypin, Anatoly; Colín, Pedro; Ceverino, Daniel; Arraki, Kenza S.; Primack, Joel

    2015-01-01

    Despite recent success in forming realistic present-day galaxies, simulations still form the bulk of their stars earlier than observations indicate. We investigate the process of stellar mass assembly in low-mass field galaxies, a dwarf and a typical spiral, focusing on the effects of radiation from young stellar clusters on the star formation (SF) histories. We implement a novel model of SF with a deterministic low efficiency per free-fall time, as observed in molecular clouds. Stellar feedback is based on observations of star-forming regions, and includes radiation pressure from massive stars, photoheating in H II regions, supernovae and stellar winds. We find that stellar radiation has a strong effect on the formation of low-mass galaxies, especially at z > 1, where it efficiently suppresses SF by dispersing cold and dense gas, preventing runaway growth of the stellar component. This behaviour is evident in a variety of observations but had so far eluded analytical and numerical models without radiation feedback. Compared to supernovae alone, radiation feedback reduces the SF rate by a factor of ˜100 at z ? 2, yielding rising SF histories which reproduce recent observations of Local Group dwarfs. Stellar radiation also produces bulgeless spiral galaxies and may be responsible for excess thickening of the stellar disc. The galaxies also feature rotation curves and baryon fractions in excellent agreement with current data. Lastly, the dwarf galaxy shows a very slow reduction of the central dark matter density caused by radiation feedback over the last ˜7 Gyr of cosmic evolution.

  3. Effects of simulated solar UVB radiation on early developmental stages of the northwestern salamander (Ambystoma gracile) from three lakes

    USGS Publications Warehouse

    Calfee, R.D.; Little, E.E.; Pearl, C.A.; Hoffman, R.L.

    2010-01-01

    Solar ultraviolet radiation (UV) has received much attention as a factor that could play a role in amphibian population declines. UV can be hazardous to some amphibians, but the resultant effects depend on a variety of environmental and behavioral factors. In this study, the potential effects of UV on the Northwestern Salamander, Ambystoma gracile, from three lakes were assessed in the laboratory using a solar simulator. We measured the survival of embryos and the survival and growth of larvae exposed to four UV treatments in controlled laboratory studies, the UV absorbance of egg jelly, oviposition depths in the lakes, and UV absorbance in water samples from the three lakes. Hatching success of embryos decreased in the higher UV treatments as compared to the control treatments, and growth of surviving larvae was significantly reduced in the higher UVB irradiance treatments. The egg jelly exhibited a small peak of absorbance within the UVB range (290-320 nm). The magnitude of UV absorbance differed among egg jellies from the three lakes. Oviposition depths at the three sites averaged 1.10 m below the water surface. Approximately 66 of surface UVB radiation was attenuated at 10-cm depth in all three lakes. Results of this study indicate that larvae may be sensitive to UVB exposure under laboratory conditions; however, in field conditions the depths of egg deposition in the lakes, absorbance of UV radiation by the water column, and the potential for behavioral adjustments may mitigate severe effects of UV radiation. Copyright 2010 Society for the Study of Amphibians and Reptiles.

  4. Incidence of Rheumatoid Arthritis in the Southern part of Denmark from 1995 to 2001

    PubMed Central

    Pedersen, Jens K; Svendsen, Anders J; Hørslev-Petersen, Kim

    2007-01-01

    We estimated the incidence of rheumatoid arthritis in the southern part of Denmark from 1995 to 2001. At a rheumatology hospital serving a population of about 200 000 people over the age of 15, medical records were scrutinized. As case definition we used the tree and list format of 1987 American College of Rheumatology criteria for rheumatoid arthritis. The mean annual incidence rate per 100 000 person years was 40 in females, 21 in males, and 31 in females and males combined. The incidence of rheumatoid arthritis in Denmark is in accordance with recent studies from North America, the UK, and Northern European countries. The aetiology of rheumatoid arthritis is unknown but this study indicates that in these populations the exposure to non-genetic host and environmental aetiological factors is similar. PMID:19088896

  5. 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...

  6. Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis

    NASA Astrophysics Data System (ADS)

    Trentham, David E.; Dynesius-Trentham, Roselynn A.; Orav, E. John; Combitchi, Daniel; Lorenzo, Carlos; Sewell, Kathryn Lea; Hafler, David A.; Weiner, Howard L.

    1993-09-01

    Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.

  7. MD Anderson study finds biologic therapies for rheumatoid arthritis not associated with increased cancer risk

    Cancer.gov

    Biologic therapies developed in the last decade for rheumatoid arthritis are not associated with an increased risk of cancer when compared with traditional treatments for the condition, according to new research from The University of Texas MD Anderson Cancer Center.

  8. Lipid imbalance in individuals predisposed to rheumatoid arthritis: possible relationship with common infections.

    PubMed

    Arleevskaya, M I; Zabotin, A I; Gabdulkhakova, A G; Semenova, O M; Tsibulkin, A P

    2013-10-01

    Lipid balance was studied in female patients with late rheumatoid arthritis, their healthy female relatives liable to autoimmune diseases, and healthy women without family history of autoimmune diseases. Previous studies showed that the relatives of patients with rheumatoid arthritis suffered from frequent stubborn common infections, which prompted us to analyze the relationship between lipid metabolism and the infectious syndrome parameters. Blood serum and cells were collected for analysis when females had no clinical symptoms of infections (in all groups) or laboratory signs of inflammatory process (in the relatives and controls). Proatherogenic shifts in serum lipid composition presumably associated with frequent lasting infections were detected in individuals liable to rheumatoid arthritis development. Elevated cholesterol content in mononuclear leukocytes in this group could lead, in turn, to dysfunctions of these cells and augment the defects of anti-infection defense. The parameters of lipid balance in patients with late rheumatoid arthritis were close to the age-specific norm. PMID:24288765

  9. 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)...

  10. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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)...

  11. 21 CFR 866.5775 - Rheumatoid factor immuno-logical test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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)...

  12. 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

  13. 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

  14. 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

  15. A Functional RANKL Polymorphism Associated with Younger Age at Onset of Rheumatoid Arthritis

    PubMed Central

    Tan, Wenfeng; Wu, Hui; Zhao, Jian; Derber, Lezlie A.; Lee, David M.; Shadick, Nancy A.; Conn, Doyt L.; Smith, Edwin A.; Gersuk, Vivian H.; Nepom, Gerald T.; Moreland, Larry W.; Furst, Daniel E.; Thompson, Susan D.; Jonas, Beth L.; Holers, V. Michael; Glass, David N.; Chen, Pojen P.; Bridges, S. Louis; Weinblatt, Michael E.; Paulus, Harold E.; Tsao, Betty P.

    2010-01-01

    Objective We previously reported association of co-occurrence of HLA-DRB1 shared epitope (SE) and RANKL SNPs with younger age of RA onset in 182 rheumatoid factor positive (RF) European American (EA) early RA patients. Here, we fine-mapped the 48 kb RANKL region in the extended 210 EA RF-positive early RA cohort, sought replication of RA-associated SNPs in additional 501 EA and 298 African-Americans (AA) RA cohorts, and explored functional consequences of RA-associated SNPs. Methods SNP genotyping was conducted using pyrosequencing or TaqMan PCR assays. Associations of rs7984870 with RANKL expression in plasma, PBMC and isolated T cells were quantified using ELISA and RT-PCR. Site-directed mutagenesis of rs7984870 within the 2kb RANKL promoter was performed to drive the luciferase reporter gene in osteoblast and stromal cell lines. Interaction of DNA and protein was determined by electrophoretic mobility shift assay. Results A single promoter SNP rs7984870 was consistently significantly associated with earlier age of RA onset in 3 independent seropositive (RF or anti-cyclic citrullinated peptide antibody positive) RA cohorts but not in seronegative RA patients. The risk C allele of rs7984870 conferred 2-fold higher plasma RANKL levels in RF-positive RA patients, significantly elevated RANKL mRNA expression in activated normal T cells, and increased promoter activity after stimulation in vitro via differential binding to transcription factor SOX5. Conclusion The RANKL promoter allele that increased transcriptional levels upon stimulation might promote interaction between activated T cells and dendritic cells, predisposing to younger RA onset in seropositive EA and/or AA individuals. PMID:20533289

  16. Hypoglossal nerve palsy from cervical spine involvement in rheumatoid arthritis: 3 case reports

    Microsoft Academic Search

    Lisa D. Blankenship; Jeffrey R. Basford; Jeffrey A. Strommen; Renee J. Andersen

    2002-01-01

    Blankenship LD, Basford JR, Strommen JA, Andersen RJ. Hypoglossal nerve palsy from cervical spine involvement in rheumatoid arthritis: 3 case reports. Arch Phys Med Rehabil 2002;83:269-72. Rheumatoid arthritis (RA) involvement of the cervical spine is a well-known but perhaps underappreciated phenomenon. Neurologic complications of this involvement include pain, myelopathy, and cranial nerve (CN) palsies. However, hypoglossal nerve palsy (CN XII)

  17. Life-threatening stridor presenting in a patient with rheumatoid involvement of the larynx.

    PubMed Central

    McGeehan, D F; Crinnion, J N; Strachan, D R

    1989-01-01

    A case of a female patient with extensive rheumatoid arthritis who presented to the Accident and Emergency Department with life-threatening stridor is described. Although clinical involvement of the larynx is found in over a third of patients with severe rheumatoid arthritis, acute airways obstruction is fortunately a very rare complication. Stridor is probably precipitated in the acute situation in such patients as a result of upper respiratory tract infection. PMID:2610804

  18. Intraductal papillary mucinous neoplasia- a challenging diagnosis in a patient with paraneoplastic rheumatoid arthritis. Case report.

    PubMed

    Grigorescu, Ioana; Cismaru, Andrei; Chira, Romeo; Catinean, Adrian; Dumitrascu, Dan Lucian

    2015-03-01

    Intraductal papillary mucinous neoplasias (IPMNs) of the pancreas are potentially malignant tumors, and associated also with extrapancreatic carcinomas. We present the case of a 80 year old man with IPMN and late onset of rheumatoid arthritis. The particularity of this case is the discordance between the clinical picture and the imaging worrisome features, together with the surgery-requiring mixed-type of IPMN, despite the late possible paraneoplastic onset of rheumatoid arthritis. PMID:25745669

  19. Prolonged low-dose corticosteroid therapy and osteoporosis in rheumatoid arthritis

    Microsoft Academic Search

    V J Hajiroussou; M Webley

    1984-01-01

    Thirty-one patients with rheumatoid arthritis maintained on prednisolone 5 mg daily for an average period of 9.4 years were assessed radiologically to determine the degree of osteoporosis in their spine and peripheral skeleton. They were compared with a control group of 32 rheumatoid patients who had never received corticosteroids. The steroid-treated patients had more severe osteoporosis than the controls, though

  20. Cardiovascular disease is associated with extra-articular manifestations in patients with rheumatoid arthritis

    Microsoft Academic Search

    Oscar-Danilo Ortega-Hernandez; Ricardo Pineda-Tamayo; Aryce L. Pardo; Adriana Rojas-Villarraga; Juan-Manuel Anaya

    2009-01-01

    The objective of this study was to examine the clinical and genetic variables associated with extra-articular rheumatoid arthritis\\u000a (ExRA). This was a cross-sectional study in which 538 Northwestern Colombian patients with rheumatoid arthritis (RA) were\\u000a included. Information about demographics and clinical characteristics including disease activity, inflammatory markers, co-morbidities,\\u000a cardiovascular (CV) risk factors, history of familial autoimmunity and therapy was recorded.

  1. 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

  2. Cervical spine disease in rheumatoid arthritis: incidence, manifestations, and therapy.

    PubMed

    Kim, Han Jo; Nemani, Venu M; Riew, K Daniel; Brasington, Richard

    2015-02-01

    Cervical spine involvement in patients with rheumatoid arthritis (RA) and other inflammatory arthropathies is common. While the radiographic features can be dramatic in untreated disease, patients may remain asymptomatic making treatment decisions challenging. Further, subtle clinical presentations can belie serious myelopathy because peripheral joint involvement can make interpreting the physical exam difficult. While new pharmacologic therapies have drastically reduced the morbidity of the widespread joint destruction that occurs in RA, patients remain at risk for symptomatic occipitocervical, atlantoaxial, or subaxial instability causing myelopathy, deformity, and premature death. In this review, we discuss the clinical presentation of RA patients with cervical spine disease as well as the indications and outcomes of surgical treatment. PMID:25663179

  3. [Changes in the hepatobiliary system in juvenile rheumatoid arthritis].

    PubMed

    Gasanov, A M; Kurchakova, T V; Shakhbazian, I E

    1991-01-01

    The authors submit the results of echographic investigation of 42 children aged from 4 to 15 years old with juvenile rheumatoid arthritis (JRA). All the patients were distributed into three groups. Signs of affection of the hepatobiliary system were revealed in 60% of the patients, predominantly with the articular form of the disease and in 78.5% of the children with the articular -visceral form. The most grave changes were noted in the group of patients with JRA complicated by secondary amyloidosis (100%). The data obtained are compared with the clinico-laboratory indices, the form of the disease, peculiarity of therapy as a result of which a relationship between the mentioned signs and the character of JRA lesions is established. A high informativeness of the echographic method especially in the diagnosis of secondary amylosis is confirmed. PMID:1925259

  4. 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

  5. miRNAs and related polymorphisms in rheumatoid arthritis susceptibility.

    PubMed

    Chatzikyriakidou, Anthoula; Voulgari, Paraskevi V; Georgiou, Ioannis; Drosos, Alexandros A

    2012-07-01

    The epigenetic mechanisms in regulation of genes' expression seem to be another field of research that gains land in genetic association studies of rheumatoid arthritis (RA) susceptibility factors. Recently, a new class of molecules has been discovered, the microRNAs (miRNAs). miRNAs are related to post-transcriptional regulation of genes' expression. Different expression patterns of mir-146a, miRNA-155, miRNA-124a, mir-203, mir-223, mir-346, mir-132, mir-363, mir-498, mir-15a, and mir-16 were documented in several tissue sample types of RA patients. The polymorphisms of these miRNAs and their gene targets, which previously have been associated with RA or other autoimmune diseases, are also reviewed. Finally, using web-based tools we propose polymorphisms of the discussed miRNAs and their gene-targets that worth to be studied for their role in RA predisposition. PMID:22100329

  6. Zingiber officinale: A Potential Plant against Rheumatoid Arthritis

    PubMed Central

    Al-Nahain, Abdullah; Jahan, Rownak

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease particularly affecting elderly people which leads to massive bone destruction with consequent inflammation, pain, and debility. Allopathic medicine can provide only symptomatic relief. However, Zingiber officinale is a plant belonging to the Zingiberaceae family, which has traditionally been used for treatment of RA in alternative medicines of many countries. Many of the phytochemical constituents of the rhizomes of this plant have therapeutic benefits including amelioration of RA. This review attempts to list those phytochemical constituents with their reported mechanisms of action. It is concluded that these phytochemicals can form the basis of discovery of new drugs, which not only can provide symptomatic relief but also may provide total relief from RA by stopping RA-induced bone destruction. As the development of RA is a complex process, further research should be continued towards elucidating the molecular details leading to RA and drugs that can stop or reverse these processes by phytoconstituents of ginger. PMID:24982806

  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. CIITA is not associated with risk of developing rheumatoid arthritis.

    PubMed

    Bronson, P G; Ramsay, P P; Seldin, M F; Gregersen, P K; Criswell, L A; Barcellos, L F

    2011-04-01

    The major histocompatibility complex (MHC) class II transactivator gene (CIITA) encodes an important transcription factor regulating genes required for human leukocyte antigen (HLA) class II MHC-restricted antigen presentation. MHC genes, particularly HLA class II, are strongly associated with risk of developing rheumatoid arthritis (RA). Given the strong biological relationship between CIITA and HLA class II genes, a comprehensive investigation of CIITA variation in RA was conducted. This study tested 31 CIITA single-nucleotide polymorphisms in 2542 RA cases and 3690 controls (N=6232). All individuals were of European ancestry, as determined by ancestry informative genetic markers. No evidence for association between CIITA variation and RA was observed after a correction for multiple testing was applied. This is the largest study to fully characterize common genetic variation in CIITA, including an assessment of haplotypes. Results exclude even a modest role for common CIITA polymorphisms in susceptibility to RA. PMID:21248776

  9. Rheumatoid Arthritis—Atlanto-Axial Subluxation and Its Clinical Presentation

    PubMed Central

    Robinson, H. S.

    1966-01-01

    The clinical picture, radiological findings and treatment of 22 patients with atlantoaxial subluxation and rheumatoid arthritis are described. This lesion, untreated, may result in damage to the spinal cord, paresis or sudden death. Occipital headache, present in 13 of 22 patients, was often aggravated by working with the head in forward flexion. Paresthesias were present in six patients. The spine of the axis was often prominent. In three patients there was objective evidence of cord compression with sensory and/or pyramidal signs. In eight the lesion was asymptomatic and discovered by routine lateral radiography in flexion, the position of maximum subluxation. Conservative treatment involved the continuous use of a cervical collar to limit neck flexion. This usually relieved subjective symptoms including headaches. Successful surgical fixation was performed in two individuals. Surgical indications included acute or chronic cord compression or severe symptoms unrelieved by a collar. ImagesFig. 2Fig. 3Fig. 4Fig. 5 PMID:5907320

  10. [Health economic aspects of a stratified medicine for rheumatoid arthritis].

    PubMed

    Frank, M; Mittendorf, T

    2013-02-01

    Up to now stratified therapy concepts have not played an important role in the treatment of patients with rheumatoid arthritis; however, a high heterogeneity regarding the effectiveness of therapies and occurrence of side effects in patients with the same indications provokes research efforts aiming at identifying and developing diagnostic biomarkers. Comprehensive diagnostics could lead to improved patient-oriented therapy algorithms and hence, a higher patient-relevant benefit could be achieved. Furthermore, costs for non-effective therapy options could be reduced, which might improve the cost-effectiveness of single active agents, especially biologicals. For the pharmaceutical industry an enhanced stratification of pharmaceuticals leads to smaller patient target groups and smaller markets on the one hand but on the other hand it may result in higher chances of receiving approval as well as higher reimbursement prices. PMID:23223870

  11. 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

  12. Angiotensin II in inflammation, immunity and rheumatoid arthritis.

    PubMed

    Chang, Y; Wei, W

    2015-02-01

    Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that is characterized by increased cardiovascular morbidity and mortality, independent of the traditional risk factors for cardiovascular disease. Although classically known for its role in the regulation of circulatory homeostasis, angiotensin II (Ang II) is recognized to act as a powerful proinflammatory mediator. Some research has showed that Ang II plays important roles in autoimmune diseases, including RA, systemic lupus erythematosus and multiple sclerosis. Ang II blockers prove effective in reducing inflammation and autoimmunity in rheumatic diseases and their relative safety, together with their effects for reducing the cardiovascular disease risk, suggest that Ang II blockers may at least act as effective adjunctive therapy for disease control in patients with RA. The present review focuses systematically on the potential impact of Ang II and its receptors on inflammation and immunomodulation in patients with RA. PMID:25302847

  13. Restless Legs Syndrome as a Comorbidity in Rheumatoid Arthritis

    PubMed Central

    Gjevre, John A.; Taylor Gjevre, Regina M.

    2013-01-01

    Rheumatoid arthritis (RA) is a multisystem disease with a complex immunologic pathophysiology. Likewise, sleep disorders can involve a complicated interplay between the neurologic pathways, immune system, and respiratory system. Recent studies have shown an elevated prevalence of sleep abnormalities in connective tissue disorders compared to the general population. Restless legs syndrome (RLS) may be present in up to 30% of RA patients. These findings may be related to cytokine release and other immunomodulatory responses. TNF-? levels relate to sleep physiology and anti-TNF-? therapy may improve sleep patterns. Most of the patients with this disorder can distinguish their RLS sensations from their arthritic symptoms. RLS is a common comorbidity seen with RA, and prompt recognition and treatment can improve patient quality of life. PMID:23840943

  14. Cross-linking of IgGs bound on circulating neutrophils leads to an activation of endothelial cells: possible role of rheumatoid factors in rheumatoid arthritis-associated vascular dysfunction

    PubMed Central

    2013-01-01

    Background Rheumatoid arthritis is characterized by the presence of circulating auto-antibodies, including rheumatoid factors, which recognize the Fc portion of IgGs. The neutrophil is the most abundant circulating leukocyte and it expresses high levels of Fc?Rs on its surface. The aim of the present study was to examine the capacity of circulating human neutrophils to be activated by rheumatoid factors and the consequences of these events on endothelium. Methods Neutrophil-bound IgGs were cross-linked with anti-human IgGs to mimick the presence of circulating rheumatoid factors and Fc?Rs-dependent signalling events and functions were examined. The IgG and IgM composition of rheumatoid factors isolated from the serum of RA patients was characterized. Adhesion of neutrophils to endothelial cells was quantified in response to the addition of rheumatoid factors. Results Cross-linking of IgGs bound on neutrophils leads to Fc?Rs-dependent tyrosine phosphorylation, mobilisation of intracellular calcium and the extracellular release of superoxide anions and lysozyme. Incubation of endothelial cells with the supernatant of activated neutrophils increases ICAM-1 expression and IL-8 production by endothelial cells. Finally, rheumatoid factors enhance neutrophil adhesion to endothelial cells. Conclusions Our results show that activation of neutrophils’ Fc?Rs by rheumatoid factors could participate in rheumatoid arthritis-associated vascular damage. PMID:23902799

  15. Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis

    PubMed Central

    2012-01-01

    Introduction Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation, in the presence of specific autoimmunity. As a result, the present study examined the possibility that effective antirheumatic treatment will decrease the level of synovial citrullination. Methods Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patients before and 2 weeks after an intraarticular glucocorticoid injection, and eight healthy volunteers. Synovial inflammation was assessed with double-blind semiquantitative analysis of lining thickness, cell infiltration, and vascularity by using a 4-point scale. Expression of citrullinated proteins (CPs) with the monoclonal antibody F95 and peptidylarginine deiminase (PAD) 2 and 4 was assessed immunohistochemically with double-blind semiquantitative analysis. In vitro synovial fluid (SF), peripheral blood (PB), mononuclear cells (MCs), and synovial explants obtained from RA patients were incubated with dexamethasone and analyzed with immunohistochemistry for expression of CP as well as PAD2 and PAD4 enzymes. Results The presence of synovial CP was almost exclusive in RA compared with healthy synovium and correlated with the degree of local inflammation. Treatment with glucocorticoids but not methotrexate alters expression of synovial CP and PAD enzymes, in parallel with a decrease of synovial inflammation. Ex vivo and in vitro studies suggest also a direct effect of glucocorticoids on citrullination, as demonstrated by the decrease in the level of citrullination and PAD expression after incubation of SFMC and synovial explants with dexamethasone. Conclusion Synovial citrullination and PAD expression are dependent on local inflammation and targeted by glucocorticoids. PMID:22284820

  16. A Broad Analysis of IL1 Polymorphism and Rheumatoid Arthritis

    PubMed Central

    Johnsen, Alyssa K.; Plenge, Robert M.; Butty, Vincent; Campbell, Christopher; Dieguez-Gonzalez, Rebeca; Gomez-Reino, Juan J.; Shadick, Nancy; Weinblatt, Michael; Gonzalez, Antonio; Gregersen, Peter K.; Benoist, Christophe; Mathis, Diane

    2008-01-01

    Objective It has been suggested that polymorphisms in IL1 are correlated with severe and/or erosive rheumatoid arthritis (RA), but the implicated alleles have differed among studies. The aim of this study was to perform a broad and well-powered search for association between allelic polymorphism in IL1A and IL1B and the susceptibility to or severity of RA. Methods Key coding and regulatory regions in IL1A and IL1B were sequenced in 24 patients with RA, revealing 4 novel single-nucleotide polymorphisms (SNPs) in IL1B. These and a comprehensive set of 24 SNPs tagging most of the underlying genetic diversity were genotyped in 3 independent RA case-control sample sets and 1 longitudinal RA cohort, totaling 3,561 patients and 3,062 control subjects. Results No fully significant associations were observed. Analysis of the discovery case-control sample sets indicated a potential association of IL1B promoter region SNPs with susceptibility to RA (for RA3/A, odds ratio [OR] 1.27, P = 0.0021) or with the incidence of radiographic erosions (for RA4/C, OR 1.56, P = 0.036), but these findings were not replicated in independent case-control samples. No association with rheumatoid factor, anti-cyclic citrullinated peptide, or the Disease Activity Score in 28 joints was found. None of the associations previously observed in other studies were replicated here. Conclusion In spite of a broad and highly powered study, we observed no robust, reproducible association between IL1A/B variants and the susceptibility to or severity of RA in white individuals of European descent. Our results provide evidence that, in the majority of cases, polymorphism in IL1A and IL1B is not a major contributor to genetic susceptibility to RA. PMID:18576312

  17. Rituximab therapy in Greek patients with rheumatoid arthritis

    PubMed Central

    Tsiakalos, Aristotelis P; Avgoustidis, Nestor K; Moutsopoulos, Haralampos M

    2008-01-01

    Objective: An open-label, prospective, uncontrolled study created to investigate clinical response, serological changes and side effects in Greek patients with rheumatoid arthritis (RA), after B-cell depletion with rituximab. Methods: Patients with high disease activity (disease activity score [DAS]-28 > 5.1) were selected for treatment with rituximab and received two infusions, 1 gr each, 2 weeks apart. Different disease parameters (visual analog scale, DAS-28, C-reactive protein [CRP], erythrocyte sedimentation rate, health assessment questionnaire, complement (C3), C4, rheumatoid factor [RF], anti-cyclic citrullinated peptide antibody [anti-CCP], swollen joint count, tender joint count, immunoglobulin M [IgM], IgG, IgA) were performed at base line, 2, 4, and 6 months post-treatment. Response was defined according to the American College of Rheumatology (ACR) criteria. Results: Seventeen patients received therapy. Treatment led to a reduction in various disease parameters. ACR20 was achieved in 41.11% of patients by week 8, 52.94% by week 16, and 82.35% by week 24. ACR50 was achieved in 5.88% by week 8, 41.17% by week 16, and 64.7% by week 24. ACR70 was achieved only by week 24 in 23.52% of patients. Statistical analysis has shown no differences in clinical response, between RF positive/negative patients, and anti-CCP-positive/negative patients, while decline of RF was better correlated with reduction of DAS-28 than with anti-CCP. Conclusions: Rituximab is a well tolerated and effective treatment in RA. Response was not correlated to RF or anti-CCP positivity. Decline of RF was associated with clinical response and reduction of DAS-28 and CRP. PMID:19707469

  18. Inverse Association between Air Pressure and Rheumatoid Arthritis Synovitis

    PubMed Central

    Furu, Moritoshi; Nakabo, Shuichiro; Ohmura, Koichiro; Nakashima, Ran; Imura, Yoshitaka; Yukawa, Naoichiro; Yoshifuji, Hajime; Matsuda, Fumihiko; Ito, Hiromu; Fujii, Takao; Mimori, Tsuneyo

    2014-01-01

    Rheumatoid arthritis (RA) is a bone destructive autoimmune disease. Many patients with RA recognize fluctuations of their joint synovitis according to changes of air pressure, but the correlations between them have never been addressed in large-scale association studies. To address this point we recruited large-scale assessments of RA activity in a Japanese population, and performed an association analysis. Here, a total of 23,064 assessments of RA activity from 2,131 patients were obtained from the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Detailed correlations between air pressure and joint swelling or tenderness were analyzed separately for each of the 326 patients with more than 20 assessments to regulate intra-patient correlations. Association studies were also performed for seven consecutive days to identify the strongest correlations. Standardized multiple linear regression analysis was performed to evaluate independent influences from other meteorological factors. As a result, components of composite measures for RA disease activity revealed suggestive negative associations with air pressure. The 326 patients displayed significant negative mean correlations between air pressure and swellings or the sum of swellings and tenderness (p?=?0.00068 and 0.00011, respectively). Among the seven consecutive days, the most significant mean negative correlations were observed for air pressure three days before evaluations of RA synovitis (p?=?1.7×10?7, 0.00027, and 8.3×10?8, for swellings, tenderness and the sum of them, respectively). Standardized multiple linear regression analysis revealed these associations were independent from humidity and temperature. Our findings suggest that air pressure is inversely associated with synovitis in patients with RA. PMID:24454853

  19. Prevalence of rheumatoid arthritis in Italy: the Chiavari study

    PubMed Central

    Cimmino, M.; Parisi, M.; Moggiana, G.; Mela, G.; Accardo, S.

    1998-01-01

    OBJECTIVE—To ascertain the prevalence of rheumatoid arthritis (RA) in an Italian general population.?METHODS—The study was performed in the years 1991-92 in Chiavari, a small town located on the Ligurian coast, and involved 4456 subjects aged 16 years or more from four general practices. The subjects received a postal questionnaire developed to detect patients with current or past inflammatory joint diseases. The age and sex distribution of the sample were similar to those of the Italian population from the 1992 census. Patients reporting a history of joint swelling in at least a pair of symmetrical joints were reviewed by a rheumatologist. The clinical records of non-responders and responders who failed to attend the clinic were also reviewed.?RESULTS—3294 of 4456 (73.9%) subjects answered to the questionnaire. The mean (SD) age of the 3294 responders was 48.3 (19.3) years; 53.7% of them were female. Swelling in at least two symmetrical joints was reported by 230 subjects (7%). Among them, 11 patients fulfilling the 1987 ARA criteria for RA were identified. The prevalence of RA was 0.33% (95% CI 0.13, 0.53) in the general population, 0.13% (95% CI 0, 0.31) in men, and 0.51% (95% CI 0.18, 0.84) in women.?CONCLUSIONS—These data are consistent with the results of three earlier studies published in the fifties in the Italian literature and confirm that the prevalence of RA is low in Italy and has remained unchanged in the last 40 years.?? Keywords: rheumatoid arthritis; prevalence; epidemiology; Italy PMID:9741317

  20. [Lymphocytic subpopulations implicated in the rheumatoid rosette phenomenon].

    PubMed

    Sany, J; Clot, J; Sip, H M; Charmasson, E; Serre, H

    1975-05-01

    The significance of the phenomenon of rheumatoid rosettes (RR) was studied in 21 subjects suffering from rheumatoid polyarthritis (RP) and in 16 controls. Certain technical factors influenced the prevalence of RR. Thus the number of RR increased in the RP patients and the controls with increase in the number of sensitized 0 Rhesus - red corpuscules; nevertheless there was a significant difference between the results obtained with the RP patients and the controls. The length of incubation and the temperature played an important role: prolonged contact times (30 min to one night), particularly at 4C considerably increased the numbers of RR, which reached 10 per cent both, in the controls and in the RP patients. The separation of lymphocytes by filtration through nylon according to Greaves' technique was followed by a study of the T cells (E rosettes), the B cells (surface immunoglobulins), and the RR. In all cases (RP and controls), the numbers of RR increased after filtration through nylon which retained the B cells. Separation of the lymphocytes by the centrifuging of the E rosettes showed that the proportion of RR was clearly higher in a population rich in B lymphocytes and lower in a population rich in T lymphocytes. Futhermore, filtration through nylon of cell suspensions rich in B lymphocytes showed a considerable rise in the RR and parallel drop in the number of B cells. Reduction of the RR by centrifuging did not affect the numbers of T or B cells. In the light of these results, it seems that the cell responsible for the formation of the RR does not have the characteristics of either the T or the B lymphocytes: a lymphocyte carring a receptor for the fragment Fc of the immunoglobulins (K cells) could be involved. In this case, the RR should be related to the EA rosettes of which they perhaps represent and active fraction. PMID:806958

  1. Adhesion of rheumatoid lymphocytes to mucosal endothelium: the gut revisited.

    PubMed

    Kadioglu, A; Sheldon, P

    1996-03-01

    By a study of the adhesion of rheumatoid mononuclear cells, we have sought to clarify the homing properties and origins of cells likely to be involved in the pathogenesis of this disease. The adhesion of mononuclear cells from patients with rheumatoid arthritis (RA) was enumerated by an in vitro adherence assay using frozen sections of endothelium-containing gut lamina propria (EGLP) from porcine small intestine. Preliminary studies verified the involvement of known adhesion molecules by inhibition assays using monoclonal antibodies Meca-367, Mel-14 and Hermes-3. Twenty-five paired samples of peripheral blood (PB) and synovial fluid (SF) were studied, plus six from synovial membrane (SM) and eight from patients with other diseases. There was a significantly greater degree of adherence to EGLP by SF cells than PB (mean adherence 266 +/- 22 cells/mm(2), compared to 136 +/- 13 cells/mm(2), respectively, the majority of which were CD8+ cells; P=0.02, Mann-Whitney U-test for 25 paired samples). The results of the monoclonal antibody inhibition assays were in keeping with the involvement of homing receptors to gut endothelium in our assay system. Synovial fluid lymphocytes from RA patients exhibited adhesion properties more in keeping with lymphocytes of mucosal than of lymph node origin. Synovial membrance lymphocytes, by contrast, showed poor adherence to endothelium-containing lamina propria. The gut, as an immune lymphoid organ, may thus play a contributory role in this disease, possibly through the pathological seeding of cells into the synovial space. PMID:8620295

  2. Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors

    PubMed Central

    Mewar, Devesh; Wilson, Anthony G

    2011-01-01

    Advances in our understanding of the key mediators of chronic inflammation and tissue damage characteristic of rheumatoid arthritis (RA) have resulted in the development of novel therapies primarily targeting pro-inflammatory cytokines. Inhibitors of tumour necrosis factor (TNF) are the most widely used of the biological therapies at present with five different agents currently available; four are based on monoclonal anti-TNF antibodies and a soluble TNF receptor-Fc fusion protein. Long-term use of these molecules has proven to be highly effective in the majority of patients; however, around one-third have a suboptimal response potentially leading to further cartilage and bone damage, furthermore these agents are expensive compared with conventional therapies such as methotrexate. Many recent studies have attempted to identify therapeutic response biomarkers of TNF inhibitors which could be used to improve therapeutic targeting. The presence of rheumatoid factor and anti-cyclic citullinated protein antibodies, present in around 65% of RA patients, are associated with a poorer response to anti-TNF agents. Poorer response is also associated with levels of C-reactive protein and cartilage degradation product at initiation of treatment. Intriguingly, genetic studies of variants of TNF and of genes encoding members of the Toll-like receptors, nuclear factor-kappa B and p38 mitogen-activated protein kinase signalling families have been associated with response to individual anti-TNF agents. Continued advances in technologies such as ultra high throughput sequencing and proteomics should facilitate the discovery of additional biomarkers of response to anti-TNF resulting in improved disease control and quality of life for RA patients and reduced costs for healthcare funders. PMID:21039421

  3. RADB: a database of rheumatoid arthritis-related polymorphisms.

    PubMed

    Zhang, Ruijie; Luan, Meiwei; Shang, Zhenwei; Duan, Lian; Tang, Guoping; Shi, Miao; Lv, Wenhua; Zhu, Hongjie; Li, Jin; Lv, Hongchao; Zhang, Mingming; Liu, Guiyou; Chen, He; Jiang, Yongshuai

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease that has a complex genetic basis. Therefore, it is important to explore the genetic background of RA. The extensive recent application of polymorphic genetic markers, especially single nucleotide polymorphisms, has presented us with a large quantity of genetic data. In this study, we developed the Database of Rheumatoid Arthritis-related Polymorphisms (RADB), to integrate all the RA-related genetic polymorphisms and provide a useful resource for researchers. We manually extracted the RA-related polymorphisms from 686 published reports, including RA susceptibility loci, polymorphisms associated with particular clinical features of RA, polymorphisms associated with drug response in RA and polymorphisms associated with a higher risk of cardiovascular disease in RA. Currently, RADB V1.0 contains 3235 polymorphisms that are associated with 636 genes and refer to 68 countries. The detailed information extracted from the literature includes basic information about the articles (e.g., PubMed ID, title and abstract), population information (e.g., country, geographic area and sample size) and polymorphism information (e.g., polymorphism name, gene, genotype, odds ratio and 95% confidence interval, P-value and risk allele). Meanwhile, useful annotations, such as hyperlinks to dbSNP, GenBank, UCSC, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway, are included. In addition, a tool for meta-analysis was developed to summarize the results of multiple studies. The database is freely available at http://www.bioapp.org/RADB. Database URL: http://www.bioapp.org/RADB. PMID:25228593

  4. Interleukin17: the missing link between T-cell accumulation and effector cell actions in rheumatoid arthritis?

    Microsoft Academic Search

    Lisa K Stamp; Michael J James; Leslie G Cleland

    2004-01-01

    The prominence of T cells and monocyte\\/macrophages in rheumatoid synovium suggests T cells may localize and amplify the effector functions of monocyte\\/macrophages in rheumatoid disease. However, while T cells are abundant in rheumatoid joints, classic T-cell derived cytokines are scarce, especially when compared to the levels of monokines IL-1? and TNF-?. For this reason, it has been speculated that monocyte\\/macrophages

  5. Mannan Binding Lectin (MBL) genotypes coding for high MBL serum levels are associated with rheumatoid factor negative rheumatoid arthritis in never smokers

    Microsoft Academic Search

    Saedis Saevarsdottir; Bo Ding; Kristjan Steinsson; Gerdur Grondal; Helgi Valdimarsson; Lars Alfredsson; Lars Klareskog; Leonid Padyukov

    2011-01-01

    Introduction  Previous studies have provided inconsistent results on whether variants in the MBL2 gene, coding for the complement-activating mannan-binding lectin (MBL) protein, associate with rheumatoid arthritis (RA).\\u000a We re-evaluated this in context of the main environmental and genetic risk factors (smoking, HLA-DRB1 'shared epitope' (SE),\\u000a PTPN22*620W), which predispose to rheumatoid factor (RF) and\\/or anti-citrullinated-protein antibody (ACPA)-positive RA.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  In this population-based EIRA

  6. Cryptococcosis of lumbar vertebra in a patient with rheumatoid arthritis and scleroderma: case report and literature review

    PubMed Central

    2013-01-01

    Background Although cryptococcosis mainly occurs in the central nervous system and lungs in immunocompromised hosts, it can involve any body site or structure. Here we report the first case of primary cryptococcosis of a lumbar vertebra without involvement of the central nervous system or lungs in a relatively immunocompromised individual with rheumatoid arthritis and scleroderma. Case presentation A 40-year-old Chinese woman with rheumatoid arthritis diagnosed 1 year beforehand and with a subsequent diagnosis of scleroderma was found to have an isolated cryptococcal infection of the fourth lumbar vertebra. Her main complaints were severe low back and left leg pain. Cryptococcosis was diagnosed by CT-guided needle biopsy and microbiological confirmation; however, serum cryptococcal antigen titer was negative. After 3 months of antifungal therapy with fluconazole the patient developed symptoms and signs of scleroderma, which was confirmed on laboratory tests. After taking fluconazole for 6 months, the progressive destruction of the lumbar vertebral body had halted and the size of an adjacent paravertebral mass had decreased substantially. On discharge symptoms had resolved and at an annual follow-up there was no evidence of recurrence on the basis of symptoms, signs or imaging investigations. Conclusion Although cryptococcosis of the lumbar vertebra is extremely rare, it should be considered in the differential diagnosis for patients with lumbar vertebral masses to avoid missed diagnosis, misdiagnosis and diagnostic delay. Early treatment with antifungals proved to be a satisfactory alternative to surgery in this relatively immunocompromised patient. Any residual spinal instability can be treated later, once the infection has resolved. PMID:23496879

  7. Mandibular condyle lesions related to age at onset and subtypes of juvenile rheumatoid arthritis in 15-year-old children.

    PubMed

    Karhulahti, T; Ylijoki, H; Rönning, O

    1993-10-01

    The severity of lesions in the temporomandibular joint (TMJ) area and their association with age at onset, the various forms of juvenile rheumatoid arthritis (JRA), and certain serologic tests for rheumatoid factor (RF), antinuclear antibodies (ANA), and human leukocyte antigen (HLA)-B27 were determined in 15-yr-old children. The series comprised 121 JRA children, 78 girls and 43 boys, in whom an analysis had recently been made of the relation of TMJ lesions to jaw movement and occlusal status. The mean age at onset was 7.3 yr, the girls contracting JRA earlier than the boys. Also, the girls with lesions in the TMJ area were significantly younger than those with no lesions. TMJ abnormalities were found in 50% of cases with a pauciarticular or systemic onset, but in 72% of those representing the polyarticular subtype. Flattened condyles and grave lesions were equally represented in all subgroups and in both sexes. A crossover from onset type to present diagnosis was found in 30% of the cases, mostly from pauciarticular to polyarthritis, which also increased the risk of TMJ lesions from 50 to 60%. RF, ANA, or HLA-B27 alone did not seem to be associated with a risk of TMJ abnormalities. Maximal opening capacity is more restricted in patients with early onset or a polyarticular mode of JRA. Since the TMJ is affected in more than half of JRA children, regular measurements of maximal movements of the mandible or roentgenologic examinations of the TMJ are essential for their optimal treatment. PMID:8248736

  8. The effects of galaxy shape and rotation on the X-ray haloes of early-type galaxies - II. Numerical simulations

    NASA Astrophysics Data System (ADS)

    Negri, Andrea; Posacki, Silvia; Pellegrini, Silvia; Ciotti, Luca

    2014-12-01

    By means of high-resolution 2D hydrodynamical simulations, we study the evolution of the hot interstellar medium (ISM) for a large set of early-type galaxy models, characterized by various degrees of flattening and internal rotation. The galaxies are described by state-of-the-art axisymmetric two-component models, tailored to reproduce real systems; the dark matter haloes follow the Navarro-Frenk-White or the Einasto profile. The gas is produced by the evolving stars, and heated by Type Ia supernovae. We find that, in general, the rotation field of the ISM in rotating galaxies is very similar to that of the stars, with a consequent negligible heating contribution from thermalization of the ordered motions. The relative importance of flattening and rotation in determining the final X-ray luminosity LX and temperature TX of the hot haloes is a function of the galactic mass. Flattening and rotation in low-mass galaxies favour the establishment of global winds, with the consequent reduction of LX. In medium- to high-mass galaxies, flattening and rotation are not sufficient to induce global winds; however, in the rotating models, the nature of the gas flows is deeply affected by conservation of angular momentum, resulting in a reduction of both LX and TX.

  9. A study of the early-stage evolution of relativistic electron-ion shock using three-dimensional particle-in-cell simulations

    NASA Astrophysics Data System (ADS)

    Choi, E. J.; Min, K.; Nishikawa, K.-I.; Choi, C. R.

    2014-07-01

    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.

  10. Tsunami early warning in the Mediterranean: role, structure and tricks of pre-computed tsunami simulation databases and matching/forecasting algorithms

    NASA Astrophysics Data System (ADS)

    Armigliato, Alberto; Pagnoni, Gianluca; Tinti, Stefano

    2014-05-01

    The general idea that pre-computed simulated scenario databases can play a key role in conceiving tsunami early warning systems is commonly accepted by now. But it was only in the last decade that it started to be applied to the Mediterranean region, taking special impulse from initiatives like the GDACS and from recently concluded EU-funded projects such as TRIDEC and NearToWarn. With reference to these two projects and with the possibility of further developing this research line in the frame of the FP7 ASTARTE project, we discuss some results we obtained regarding two major topics, namely the strategies applicable to the tsunami scenario database building and the design and performance assessment of a timely and "reliable" elementary-scenario combination algorithm to be run in real-time. As for the first theme, we take advantage of the experience gained in the test areas of Western Iberia, Rhodes (Greece) and Cyprus to illustrate the criteria with which a "Matching Scenario Database" (MSDB) can be built. These involve 1) the choice of the main tectonic tsunamigenic sources (or areas), 2) their tessellation with matrices of elementary faults whose dimension heavily depend on the particular studied area and must be a compromise between the needs to represent the tsunamigenic area in sufficient detail and of limiting the number of scenarios to be simulated, 3) the computation of the scenarios themselves, 4) the choice of the relevant simulation outputs and the standardisation of their formats. Regarding the matching/forecast algorithm, we want it to select and combine the MSDB elements based on the initial earthquake magnitude and location estimate, and to produce a forecast of (at least) the tsunami arrival time, amplitude and period at the closest tide-level sensors and in all needed forecast points. We discuss the performance of the algorithm in terms of the time needed to produce the forecast after the earthquake is detected. In particular, we analyse the different contributions of a number of factors such as the efficient code development and availability of cutting-edge hardware to run the code itself, the wise selection of the MSDB outputs to be combined, the choice of the forecast points where water elevation time series must be taken into account, and few others.

  11. 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

  12. Impact of screening and early detection of impaired fasting glucose tolerance and type 2 diabetes in Canada: a Markov model simulation

    PubMed Central

    Mortaz, Soroush; Wessman, Christine; Duncan, Ross; Gray, Rachel; Badawi, Alaa

    2012-01-01

    Background Type 2 diabetes mellitus (T2DM) is a major global health problem. An estimated 20%–50% of diabetic subjects in Canada are currently undiagnosed, and around 20%–30% have already developed complications. Screening for high blood glucose levels can identify people with prediabetic conditions and permit introduction of timely and effective prevention. This study examines the benefit of screening for impaired fasting glucose (IFG) and T2DM. If intervention is introduced at this prediabetic stage, it can be most effective in delaying the onset and complications of T2DM. Methods Using a Markov model simulation, we compare the cost-effectiveness of screening for prediabetes (IFG) and T2DM with the strategy of no screening. An initial cohort of normoglycemic, prediabetic, or undiagnosed diabetic adults with one or more T2DM risk factors was used to model the strategies mentioned over a 10-year period. Subjects without known prediabetes or diabetes are screened every 3 years and persons with prediabetes were tested for diabetes on an annual basis. The model weighs the increase in quality-adjusted life-years (QALYs) associated with early detection of prediabetes and earlier diagnosis of T2DM due to lifestyle intervention and early treatment in asymptomatic subjects. Results Costs for each QALY gained were $2281 for conventional screening compared with $2890 for no screening. Thus, in this base-case analysis, conventional screening with a frequency of once every 3 years was favored over no screening. Furthermore, conventional screening was more favorable compared with no screening over a wide range of willingness-to-pay thresholds. Changing the frequency of screening did not affect the overall results. Screening persons without diabetes or prediabetes on an annual basis had small effects on the cost-effectiveness ratios. Screening with a frequency of once every 5 years resulted in the lowest cost per QALY ($2117). Lack of screening costs the health care system $4812 more than the cost of screening once every 5 years. Conclusion The increased cost per QALY of not screening is due to the costs of complications caused downstream of T2DM. By ensuring that IFG screening occurs every 3 years for those without prediabetes and every year for those with prediabetes, the health and financial benefits related to T2DM are improved in Canada. PMID:22553425

  13. Measurement of plasma concentrations of polymorphonuclear elastase-alpha 1 proteinase inhibitor (elastase-alpha 1 antitrypsin) in patients with rheumatoid arthritis: interference by rheumatoid factor

    Microsoft Academic Search

    R E Banks; S W Evans; K F Taylor; H A Bird; J T Whicher

    1990-01-01

    The plasma concentration of granulocyte elastase in complex with alpha 1 proteinase inhibitor was determined in 32 patients with rheumatoid arthritis and eight with seronegative spondarthritis complicated by peripheral joint synovitis. Most patients had concentrations of complex which were within the range of the control group when measured by an 'in-house' enzyme linked immunosorbent assay, though several of the patients

  14. 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

  15. Cytokine expression and cytokine-based T cell profiling in South Indian rheumatoid arthritis.

    PubMed

    Mariaselvam, Christina Mary; Aoki, Masayuki; Salah, Sofiane; Boukouaci, Wahid; Moins-Teisserenc, Hélène; Charron, Dominique; Krishnamoorthy, Rajagopal; Tamouza, Ryad; Negi, Vir Singh

    2014-10-01

    Rheumatoid arthritis (RA), a chronic inflammatory disease affects up to 1% of the general population. Early diagnosis and treatment are limited by the absence of specific and reliable diagnostic/prognostic biomarkers. This study was carried out in 48 Tamil South Indian RA patients and 49 healthy controls (HC) to identify any cytokine signature(s) that could potentially serve as biomarkers. Expression profiles of Th1, Th2, Th17 and Tregs cell type-specifying cytokines and transcription factors were analyzed using real time quantitative PCR (qPCR) assay. To explore if such expression profiles mirror their steady state plasma levels, a bead-based multiplex fluorescent assay was carried out. We found that the expression of transcription factors T-bet (for Th1), GATA-3 (for Th2) and FoxP3 (for Tregs) were significantly lower in patients than in healthy controls (P<0.0001) similar to lowering of IFN? (P=0.004) and IL-10 (P=0.04). The transcript levels of IL-12p40 and TNF-? were higher among patients as compared to HC (P<0.0001 and P=0.02, respectively). Circulating levels of assessed cytokines were in general higher in RA patients as compared to controls. These alterations in the expression of transcription factors and cytokines highlight the underlying dysregulation of T cell subsets in RA that reflects a predominantly inflammatory phenotype. Despite dissecting these cellular and molecular processes, no specific signature that could be of diagnostic and/or prognostic value was identified. Additional longitudinal follow-up studies, especially on newly diagnosed treatment-naïve patients are warranted to uncover clinically useful biomarkers of RA. PMID:25017474

  16. The supplementary therapeutic DMARD role of low-dose glucocorticoids in rheumatoid arthritis

    PubMed Central

    2014-01-01

    The management of rheumatoid arthritis (RA) is primarily based on the use of disease-modifying antirheumatic drugs (DMARDs), mainly comprising synthetic chemical compounds (that is, methotrexate or leflunomide) and biological agents (tumor necrosis factor inhibitors or abatacept). On the other hand, glucocorticoids (GCs), used for decades in the treatment of RA, are effective in relieving signs and symptoms of the disease, but also interfere with radiographic progression, either as monotherapy or in combination with conventional synthetic DMARDs. GCs exert most of their biological effects through a genomic action, using the cytosolic GC receptor and then interacting with the target genes within target cells that can result in increased expression of regulatory - including anti-inflammatory - proteins (transactivation) or decreased production of proinflammatory proteins (transrepression). An inadequate secretion of GCs from the adrenal gland, in relation to stress and inflammation, seems to play an important role in the pathogenesis and disease progression of RA. At present there is clear evidence that GC therapy, especially long-term low-dose treatment, slows radiographic progression by at least 50% when given to patients with early RA, hence satisfying the conventional definition of a DMARD. In addition, long-term follow-up studies suggest that RA treatment strategies which include GC therapy may favorably alter the disease course even after their discontinuation. Finally, a low-dose, modified night-release formulation of prednisone, although administered in the evening (replacement therapy), has been developed to counteract the circadian (night) rise in proinflammatory cytokine levels that contributes to disease activity, and might represent the way to further optimize the DMARD activity exerted by GCs in RA. PMID:25608624

  17. IgA related disorders in rheumatoid arthritis.

    PubMed

    Pillemer, S R; Reynolds, W J; Yoon, S J; Perera, M; Newkirk, M; Klein, M

    1987-10-01

    Serum monomeric and polymeric IgA, IgA rheumatoid factor (IgA-RF) and IgA containing circulating immune complexes (IgA-CIC) were studied in 192 patients with rheumatoid arthritis (RA) to explore the relationships among IgA related abnormalities and to investigate their potential associations with disease activity, immunoregulatory disorders and effect of treatments. Total serum IgA and polymeric IgA (p-IgA) levels were elevated in 23 and 11% of patients with RA, respectively. Their respective mean concentrations in serum were significantly elevated compared to normal values (p less than 0.001 and p less than 0.004). A preferential increase in polymeric rather than monomeric IgA was observed. IgA-RF, detected by a solid phase ELISA, was found in 71% and was associated with decreased grip strength (p less than 0.005), active disease (p less than 0.05), increased p-IgA level (p less than 0.001), elevated p-IgA:total IgA ratio (p less than 0.05), the presence of IgA-CIC (p less than 0.005) and IgM-RF (p less than 0.005). Complement fixing IgA-CIC were detected in 40% of patients by IgA specific conglutinin and anti-C3 binding solid phase ELISA. High molecular weight IgA species precipitated by 2.5% polyethylene glycol from RA sera positive for IgA-CIC were shown to be IgA-RF complexed to IgG. Taken together, our results suggest that IgA-RF are essentially polymeric in nature and circulate as IgA-RF-IgG immune complexes. Although the presence of IgA-CIC was not associated with disease activity, IgA-CIC activated C3 and thus are potentially pathogenic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2963127

  18. An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis

    Microsoft Academic Search

    Shinya Tokuhiro; Xiaotian Chang; Akari Suzuki; Yuta Kochi; Tetsuji Sawada; Masakatsu Suzuki; Miyuki Nagasaki; Masahiko Ohtsuki; Mitsuru Ono; Hidehiko Furukawa; Masakazu Nagashima; Shinichi Yoshino; Akihiko Mabuchi; Akihiro Sekine; Susumu Saito; Atsushi Takahashi; Tatsuhiko Tsunoda; Yusuke Nakamura; Kazuhiko Yamamoto; Ryo Yamada

    2003-01-01

    Rheumatoid arthritis is a common inflammatory disease with complex genetic components. We investigated the genetic contribution of the cytokine gene cluster in chromosome 5q31 to susceptibility to rheumatoid arthritis in the Japanese population by case-control linkage disequilibrium (LD) mapping using single nucleotide polymorphisms (SNPs). Here we report that there is significant association between rheumatoid arthritis and the organic cation transporter

  19. 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.

  20. Determining Thermal Inactivation of Escherichia coli O157:H7 in Fresh Compost by Simulating Early Phases of the Composting Process ?

    PubMed Central

    Singh, Randhir; Kim, Jinkyung; Shepherd, Marion W.; Luo, Feng; Jiang, Xiuping

    2011-01-01

    A three-strain mixture of Escherichia coli O157:H7 was inoculated into fresh dairy compost (ca. 107 CFU/g) with 40 or 50% moisture and was placed in an environmental chamber (ca. 70% humidity) that was programmed to ramp from room temperature to selected composting temperatures in 2 and 5 days to simulate the early composting phase. The surviving E. coli O157:H7 population was analyzed by direct plating and enrichment. Optimal and suboptimal compost mixes, with carbon/nitrogen (C/N) ratios of 25:1 and 16:1, respectively, were compared in this study. In the optimal compost mix, E. coli O157:H7 survived for 72, 48, and 24 h in compost with 40% moisture and for 72, 24, and 24 h with 50% moisture at 50, 55, and 60°C, respectively, following 2 days of come-up time (rate of heating up). However, in the suboptimal compost mix, the pathogen survived for 288, 72, and 48 h in compost with 40% moisture and for 240, 72, 24 h in compost with 50% moisture at the same temperatures, respectively. Pathogen survival was longer, with 5 days of come-up time compared with 2 days of come-up. Overall, E. coli O157:H7 was inactivated faster in the compost with 50% moisture than in the compost with 40% at 55 and 60°C. Both moisture and come-up time were significant factors affecting Weibull model parameters. Our results suggest that slow come-up time at the beginning of composting can extend pathogen survival during composting. Additionally, both the C/N ratio and the initial moisture level in the compost mix affect the rate of pathogen inactivation as well. PMID:21498743

  1. Allele *2 of the HS1,2A enhancer of the Ig regulatory region associates with rheumatoid arthritis

    PubMed Central

    Tolusso, B; Frezza, D; Mattioli, C; Fedele, A L; Bosello, S; Faustini, F; Peluso, G; Giambra, V; Pietrapertosa, D; Morelli, A; Gremese, E; De Santis, M; Ferraccioli, G F

    2009-01-01

    Objective: To investigate the role of the HS1,2 enhancer polymorphisms as a new candidate marker for rheumatoid arthritis (RA) and to define the possible association with autoantibody positivity and clinical outcome. Methods: Genomic DNA was obtained from two cohorts of patients with RA (100 with early RA (ERA) and 114 with longstanding RA (LSRA)) and from 248 gender-matched controls from the same geographical area. Clinical and immunological characteristics were recorded for all the patients. Results: The percentage of the 2/2 genotype was higher in patients with ERA (27.0%), and in patients with LSRA (34.2%), than in controls (14.9%) (ERA: OR?=?2.11 (95% CI 1.20 to 3.70) vs controls; LSRA: OR?=?2.96 (95% CI 1.76 to 5.00) vs controls). A lower representation of allele *3 was present in patients with ERA (2.0%) than in controls (6.0%; OR?=?0.32 (95% CI 0.11 to 0.91)). No significant associations were found between polymorphisms and autoantibodies positivity. Conclusion: The HS1,2A allele *2 associates with early and longstanding RA. PMID:18952640

  2. Physical Leisure Participation and the Well-Being of Adults With Rheumatoid Arthritis: The Role of Sense of Belonging

    Microsoft Academic Search

    Steven E. Mock; Cory Fraser; Shannon Knutson; Andrea Prier

    2010-01-01

    Participation in physical leisure activities was tested as a coping resource among adults with rheumatoid arthritis. Drawing on sociological theory of social integration, sense of belonging was tested as a potential mediator to help explain any significant association found between physical leisure activity and well-being among a population-based sample of adults with rheumatoid arthritis. Greater frequency of physical leisure participation

  3. Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Patients with rheumatoid arthritis have subnormal vitamin B6 status, both quantitatively and functionally. Abnormal vitamin B6 status in rheumatoid arthritis has been associated with spontaneous tumor necrosis factor (TNF)-alpha production and markers of inflammation, including C-reactive protein an...

  4. Management of leg ulcers in patients with rheumatoid arthritis or systemic sclerosis: The importance of concomitant arterial and venous disease

    Microsoft Academic Search

    Jürg Hafner; Ernst Schneider; Günter Burg; Paolo C. Cassina

    2000-01-01

    Purpose: We assessed the etiology and the prevalence of peripheral arterial and venous disease in leg ulcers in patients with rheumatoid arthritis and systemic sclerosis and analyzed the outcome after treatment of macrovascular disease. Methods: A clinical study on 15 consecutive patients with chronic leg ulcers in collagen vascular disease (nine patients with rheumatoid arthritis, six patients with systemic sclerosis)

  5. Comparison of high and low intensity training in well controlled rheumatoid arthritis. Results of a randomised clinical trial

    Microsoft Academic Search

    C H van den Ende; J M Hazes; S le Cessie; W J Mulder; D G Belfor; F C Breedveld; B A Dijkmans

    1996-01-01

    OBJECTIVE: To investigate the benefit of intensive dynamic exercises in comparison to range of motion (ROM) and isometric exercises in rheumatoid arthritis. METHODS: 100 consecutive rheumatoid arthritis patients on stable medication were randomly assigned to (1) intensive dynamic group exercises which included full weight bearing exercises and conditioning exercises on a stationary bicycle while the heart rate was maintained at

  6. Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis

    PubMed Central

    Gomez-Puerta, Jose A.; Mócsai, Attila

    2013-01-01

    Tyrosine kinases (TK) are enzymes capable of transferring phosphate groups to tyrosine residues in cytoplasmic proteins or the intracellular domains of transmembrane receptors. TK play critical roles in diverse biological functions including cellular processes such as adhesion, motility, proliferation, cell cycle control, cell death, as well as biological functions at the whole-organism level such as growth and development, metabolism or immune defense. TK inhibitors including spleen TK (fostamatinib) and Janus kinases (tofacitinib) inhibitors are two novel oral therapies that have demonstrated short-term good clinical responses in active rheumatoid arthritis patients with and inadequate responses to methotrexate or other traditional (non-biologic) disease-modifying antirheumatic drugs (DMARDs). Those responses are comparable to responses rates from pivotal trials of TNF inhibitors. TK inhibitors are generally well tolerated but not free of adverse effects. Several side effects had been described including gastrointestinal symptoms, neutropenia, hypertension, elevated liver function test and lipid alterations among others. Owing to the limited duration of follow-up of patients treated with TK inhibitors, the long term safety profile of these drugs are unknown. PMID:23574525

  7. 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

  8. Posturography in patients with rheumatoid arthritis and osteoarthritis.

    PubMed

    Soko?owska, B; Czerwosz, L; Hallay-Suszek, M; Sadura-Sieklucka, T; Ksi??opolska-Or?owska, K

    2015-01-01

    The purpose of the paper was to investigate the usefulness of posturographic analysis in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). RA is a chronic inflammatory disorder responsible for destruction of active and passive components of joints. It is the most common autoimmune disease, and the second most common form of arthritis after OA. OA is a chronic disorder characterized by irreversible changes in the joint structure developing with advancing age. Both diseases lead to the destruction of many parts of the motor system, cause pain, weakness, and damage of ligaments, muscles, bones, and articular cartilage. The etiology of the diseases remains unknown. In the present study, evaluation of body balance in the standing position was performed by means of Pro-Med force plate system. Three posturographic tests were applied: with eyes open, closed, and with the biofeedback - under conscious visual control of body movements. The following posturographic parameters were measured: the radius of sways, the developed area, and the total length of posturograms, and also two directional components of sways: the length of left-right (in frontal plane) and forward-backward (in sagittal plane) motions. The results demonstrate that the biofeedback test is most useful in the evaluation of instability in rheumatic patients; it is more powerful than the other posturographic tests evaluated. PMID:25298260

  9. 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

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

    PubMed Central

    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

  11. Whole Body Bone Tissue and Cardiovascular Risk in Rheumatoid Arthritis

    PubMed Central

    Popescu, Claudiu; Bojinc?, Violeta; Opri?, Daniela

    2014-01-01

    Introduction. Atherosclerosis and osteoporosis share an age-independent bidirectional correlation. Rheumatoid arthritis (RA) represents a risk factor for both conditions. Objectives. The study aims to evaluate the connection between the estimated cardiovascular risk (CVR) and the loss of bone tissue in RA patients. Methods. The study has a prospective cross-sectional design and it includes female in-patients with RA or without autoimmune diseases; bone tissue was measured using whole body dual X-ray absorptiometry (wbDXA); CVR was estimated using SCORE charts and PROCAM applications. Results. There were 75?RA women and 66 normal women of similar age. The wbDXA bone indices correlate significantly, negatively, and age-independently with the estimated CVR. The whole body bone percent (wbBP) was a significant predictor of estimated CVR, explaining 26% of SCORE variation along with low density lipoprotein (P < 0.001) and 49.7% of PROCAM variation along with glycemia and menopause duration (P < 0.001). Although obese patients had less bone relative to body composition (wbBP), in terms of quantity their bone content was significantly higher than that of nonobese patients. Conclusions. Female patients with RA and female patients with cardiovascular morbidity have a lower whole body bone percent. Obese female individuals have higher whole body bone mass than nonobese patients. PMID:24808969

  12. Rheumatoid arthritis: Nuclear Medicine state-of-the-art imaging

    PubMed Central

    Rosado-de-Castro, Paulo Henrique; Lopes de Souza, Sergio Augusto; Alexandre, Dângelo; Barbosa da Fonseca, Lea Mirian; Gutfilen, Bianca

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease, which is associated with systemic and chronic inflammation of the joints, resulting in synovitis and pannus formation. For several decades, the assessment of RA has been limited to conventional radiography, assisting in the diagnosis and monitoring of disease. Nevertheless, conventional radiography has poor sensitivity in the detection of the inflammatory process that happens in the initial stages of RA. In the past years, new drugs that significantly decrease the progression of RA have allowed a more efficient treatment. Nuclear Medicine provides functional assessment of physiological processes and therefore has significant potential for timely diagnosis and adequate follow-up of RA. Several single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals have been developed and applied in this field. The use of hybrid imaging, which permits computed tomography (CT) and nuclear medicine data to be acquired and fused, has increased even more the diagnostic accuracy of Nuclear Medicine by providing anatomical localization in SPECT/CT and PET/CT studies. More recently, fusion of PET with magnetic resonance imaging (PET/MRI) was introduced in some centers and demonstrated great potential. In this article, we will review studies that have been published using Nuclear Medicine for RA and examine key topics in the area. PMID:25035834

  13. Impact of Temporomandibular Joint Pain in Rheumatoid Arthritis

    PubMed Central

    Ahmed, Neveen; Mustafa, Hamid Masoud; Catrina, Anca Irinel

    2013-01-01

    To investigate the impact of temporomandibular joint (TMJ) pain on daily activities and quality of life in relation to systemic inflammatory activity in patients with rheumatoid arthritis (RA), thirty-three consecutive outpatients with RA were included. TMJ pain intensity at rest, on maximum mouth opening, and on chewing was assessed on a 0–10 numerical rating scale. TMJ palpatory tenderness, degree of anterior open bite, the impact of TMJ pain on daily activities and quality of life were also assessed. The systemic inflammatory activity was estimated by the disease activity score 28 (DAS28), blood levels of inflammatory markers and number of painful musculoskeletal regions. TMJ pain at rest, on maximum mouth opening, and on chewing as well as DAS28 was correlated with the impact of the TMJ pain on daily activities and quality of life. Partial correlations showed a significant interaction between TMJ pain on movement and DAS28 that explained the TMJ pain impact on daily activities and quality of life to a significant degree. This study indicates that both current TMJ pain intensity and systemic inflammatory activity play roles in the impact of TMJ pain on daily living and quality of life in RA. PMID:24363501

  14. Novel, Biocompatible, Disease Modifying Nanomedicine of VIP for Rheumatoid Arthritis

    PubMed Central

    Sethi, Varun; Rubinstein, Israel; Kuzmis, Antonina; Kastrissios, Helen; Artwohl, James; Onyuksel, Hayat

    2013-01-01

    Despite advances in rheumatoid arthritis (RA) treatment, efficacious and safe disease-modifying therapy still represents an unmet medical need. Here we describe an innovative strategy to treat RA by targeting low doses of vasoactive intestinal peptide (VIP) self-associated with sterically stabilized micelles (SSMs). This spontaneous interaction of VIP with SSM protects the peptide from degradation or inactivation in biological fluids and prolongs circulation half-life. Treatment with targeted low doses of nano-sized SSM-VIP but not free VIP in buffer significantly reduced incidence and severity of arthritis in an experimental model, completely abrogating joint swelling and destruction of cartilage and bone. In addition, SSM associated VIP unlike free VIP had no side-effects on the systemic functions due to selective targeting to inflamed joints. Finally, low doses of VIP in SSM successfully downregulated both inflammatory and autoimmune components of RA. Collectively, our data clearly indicate that VIP-SSM should be developed to be used as a novel nanomedicine for the treatment of RA. PMID:23211088

  15. Inhibition of rheumatoid arthritis by blocking connective tissue growth factor.

    PubMed

    Nozawa, Kazuhisa; Fujishiro, Maki; Takasaki, Yoshinari; Sekigawa, Iwao

    2014-11-18

    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

  16. Identifying barriers to smoking cessation in rheumatoid arthritis.

    PubMed

    Aimer, Pip; Stamp, Lisa; Stebbings, Simon; Valentino, Natalia; Cameron, Vicky; Treharne, Gareth J

    2014-11-01

    Objectives: The aim of this study was to investigate disease-related issues which make smoking cessation challenging for patients with rheumatoid arthritis (RA). There is currently a lack of research on tailoring smoking cessation interventions for RA patients. Qualitative exploration is a necessary first step in planning targeted interventions. Methods: A qualitative mixed methods study was undertaken. Participants attended either a focus group or an individual interview and completed a set of standardized questionnaires. The sample consisted of 36 RA patients: 24 current smokers and 12 ex-smokers. The transcripts were analysed thematically using a critical realist approach to inductively identify themes. Results: Five key barriers to smoking cessation which are faced by RA patients were identified. Firstly, participants were unaware of the causative relationship between smoking and RA and hence did not perceive this as a reason to quit. Secondly, smoking was used as a distraction from pain. Thirdly, participants found it difficult to exercise and hence were unable to use exercise as an alternative distraction. Fourthly, smoking was used as a coping mechanism for the frustrations of living with RA. Fifthly, participants felt unsupported and isolated from other RA patients. Conclusions: Disease-related issues may hinder smoking cessation for RA patients. Through an understanding of patients' perspectives there is an opportunity to plan an effective targeted intervention that may increase the chance of smoking cessation in RA patients where smoking may adversely influence disease progression and comorbidities. © 2014 American College of Rheumatology. PMID:25370172

  17. Labour force participation among patients with rheumatoid arthritis

    PubMed Central

    Chorus, A.; Miedema, H.; Wevers, C.; van der Linden, S.

    2000-01-01

    OBJECTIVES—To assess work history and labour force participation among patients with rheumatoid arthritis (RA) in the Netherlands.?METHODS—A random sample of 1056 patients with RA aged 16-59 years from 17 rheumatology practices in the Netherlands was examined. Data on disease status and outcome were obtained by a questionnaire including standardised instruments, such as the Rapid Assessment of Disease Activity in Rheumatology (RADAR) and RAND-36 questionnaires. Labour force participation was defined as having a paid job.?RESULTS—Of the study group with a mean disease duration of 12 years, 35.7% held a paid job (men 56.7%; women 27.7%). When standardised for age, sex, and educational level, the labour force participation of patients with RA was 61.2% compared with 65.5% for the general population, which was not statistically significant. Disease duration of six years and more was negatively associated with labour force participation.?CONCLUSIONS—After controlling for the confounding effects of age, sex, and education, the labour force participation of patients with RA in the Netherlands is only slightly lower than that of the general population.?? PMID:10873966

  18. Indian Herbal Medicines: Possible Potent Therapeutic Agents for Rheumatoid Arthritis

    PubMed Central

    Rathore, Brijesh; Ali Mahdi, Abbas; Nath Paul, Bhola; Narayan Saxena, Prabhu; Kumar Das, Siddharth

    2007-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology and is mainly characterized by the progressive erosion of cartilage leading to chronic polyarthritis and joint distortion. Although the exact pathogenesis of the disease has yet not been elucidated, however, studies suggest that cellular proliferation of synoviocytes result in pannus formation which damages the cartilage and bone. Recent reports also support the role of free radicals in its pathogenesis. Apart from the conventional treatment strategies using nonsteroidal anti-inflammatory drugs, disease modifying antirheumatic drugs and glucocorticoids, newer and safer drugs are continuously being searched, as long term usage of these drugs have resulted in adverse effects. Alternative medicine provides another approach for treatment of RA and currently a number of medicinal plants are under scientific evaluation to develop a novel drug. There is a dire need to investigate the complete therapeutic potential and adverse effects, if any, of these herbals for providing newer and safer treatment options with minimum side effects. In this review we have tried to explore various Indian ancient Ayurvedic, Unani and Tibbi, as also some Chinese and Korean, herbals for their potential to treat RA. PMID:18392103

  19. 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

  20. Rheumatoid arthritis: Nuclear Medicine state-of-the-art imaging.

    PubMed

    Rosado-de-Castro, Paulo Henrique; Lopes de Souza, Sergio Augusto; Alexandre, Dângelo; Barbosa da Fonseca, Lea Mirian; Gutfilen, Bianca

    2014-07-18

    Rheumatoid arthritis (RA) is an autoimmune disease, which is associated with systemic and chronic inflammation of the joints, resulting in synovitis and pannus formation. For several decades, the assessment of RA has been limited to conventional radiography, assisting in the diagnosis and monitoring of disease. Nevertheless, conventional radiography has poor sensitivity in the detection of the inflammatory process that happens in the initial stages of RA. In the past years, new drugs that significantly decrease the progression of RA have allowed a more efficient treatment. Nuclear Medicine provides functional assessment of physiological processes and therefore has significant potential for timely diagnosis and adequate follow-up of RA. Several single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals have been developed and applied in this field. The use of hybrid imaging, which permits computed tomography (CT) and nuclear medicine data to be acquired and fused, has increased even more the diagnostic accuracy of Nuclear Medicine by providing anatomical localization in SPECT/CT and PET/CT studies. More recently, fusion of PET with magnetic resonance imaging (PET/MRI) was introduced in some centers and demonstrated great potential. In this article, we will review studies that have been published using Nuclear Medicine for RA and examine key topics in the area. PMID:25035834